(PDF) Continence: Bladder Neck versus Mid-Urethra

Continence

iii

Continence

Current Concepts and Treatment Strategies

Edited by

Gopal H. Badlani

Wake Forest University Baptist Medical Center, Winston Salem, NC, USA

G. Willy Davila

Cleveland Clinic Florida, Weston, FL, USA

Martin C. Michel

Academic Medical Center, Amsterdam, The Netherlands

Jean J.M.C.H. de la Rosette

Academic Medical Center, Amsterdam, The Netherlands

ISBN: 978-1-84628-510-3 e-ISBN: 978-1-84628-734-3

DOI: 10.1007/978-1-84628-734-3

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Editors

Gopal H. Badlani, MD

Department of Urology

Wake Forest University

Baptist Medical Center

Winston Salem, NC, USA

Martin C. Michel, MD, MAE

Department of Pharmacology and Pharmacotherapy

Academic Medical Center

University of Amsterdam

Amsterdam

The Netherlands

G. Willy Davila, MD

Department of Gynecology

Cleveland Clinic Florida

Weston, FL

USA

Jean J.M.C.H. de la Rosette, MD, PhD

Department of Urology

Academic Medical Center

University of Amsterdam

Amsterdam

The Netherlands

Foreword

Urinary incontinence and pelvic prolapse have

affected the quality of many lives over the years.

Only recently, however, has increased attention

to these areas led to a better understanding of

the epidemiology, pathophysiology, and newer

approaches to treatment, both from the pharma-

cological and device standpoint. This text is a

step forward in bringing these new innovations

together in a comprehensive and well-organized

manner. The editors have chosen an international

group of authors who are highly regarded in their

fields, and these authors have in turn provided

details in an easy to read format. The editors

themselves have provided a diversity of expertise

from the fields of urology, urogynecology, phar-

macology, and minimally invasive approaches.

This combination is unique. The latest concepts

in epidemiology, anatomy, and pathophysiology

are presented in the first two parts on the book.

Stress incontinence is totally reviewed from the

standpoint of all types of conservative, minimally

invasive, and not so minimally invasive therapies.

Urinary urgency incontinence likewise is reviewed

from the same standpoints, including a separate

section on contemporary views regarding the use

of intradetrusor or suburothelial botulinum toxin

injections. The section on pelvic organ prolapse

includes a thorough discussion of biomaterials, as

well as complete discussions of conservative and

surgical management of the various forms of pro-

lapse. Male urinary incontinence is included as a

separate part of the book, and there are two parts

devoted to “special situations and socioeconomic

considerations.” The special situations include

fistulas, postradiation incontinence, recurrent

incontinence, voiding dysfunction after surgery,

and the multioperated patient with recurrent

incontinence and/or prolapse; the socioeconomic

issues include the economic impacts of urinary

incontinence and prolapse and a well-thought

out contribution on community awareness and

education. All in all, this is a complete package,

unique in the field, and I recommend it to any

audience interested in the topic.

Alan J. Wein, MD, PhD (Hon)

Professor and Chair

Division of Urology

University of Pennsylvania Health System

and

Chief of Urology

Hospital of the University of Pennsylvania

v

Preface

When we first met to consider a proposal to put

together a book on urinary incontinence and pelvic

organ prolapse, the obvious question was “why

another book.” The answer was not easy but a need

was perceived based on the tremendous changes in

our understanding and the way we practice today

compared to even 5 years ago, let alone when we

were in training. The radical changes were initiated

by the infusion of new pharmaceutical agents in

bladder-driven incontinence and by the more recent

device-driven approaches to the urethral inconti-

nence in female and male population. The emerg-

ing field of kits for the pelvic organ prolapse is

further fueling the interest. Journal articles reflect

individual reports, reviews, and meta-analysis data;

however, to a reader a comprehensive book offers a

resource for reference, an aid to understanding for

new practitioners entering the field, or an expan-

sion of the horizons and/or a substantiation of their

reasons for practice in the field for the more expe-

rienced practitioners. We hope that this effort of

many international stars will fulfill these needs.

We have made a great effort to put together

authors who are progressive in their thoughts and

are willing to reflect the changes from established

patterns. This in no way minimizes the efforts of

others in the past, for it is upon their shoulders that

we climb in order to see farther.

There is one individual who toiled to make

this effort possible. Kaytan Amrute was the glue

that binds this book, so to this young individual,

who is just beginning his journey in the field of

urogynecology, the four of us express our deep

gratitude.

Individually, we would like to thank our families

who give up so much of their time to allow us to

put in this effort. We list their names jointly, as the

four of us remain bound together by this book.

Gopal Badlani, MD

G. Willy Davila, MD

Martin C. Michel, MD, MAE

Jean J.M.C.H. de la Rosette, MD, PhD

vii

Acknowledgments

For all their help and support during the long

editorial process, Dr. Badlani would like to thank

his hard-working colleague Kaytan Amrute;

G. Willy Davila would like to thank Kristin

Dunn; Martin C. Michel would like to thank

Karla Dabekaussen-Peters; and Jean J.M.C.H.

de la Rosette would like to thank Sonja van Rees

Vellinga.

This book is dedicated to our family members

who give up so much!

GB: Charu, Pooja and Chirag

WD: Carolyn, Claudia, Daniel and Will

MM: Martina and Liesel

JD: Pilar

Gopal H. Badlani, MD

G. Willy Davila, MD

Martin C. Michel, MD, MAE

Jean J.M.C.H. de la Rosette, MD, PhD

ix

Contents

Foreword ............................................................................................................................................. v

Preface ................................................................................................................................................. vii

Acknowledgments .............................................................................................................................. ix

Part I Introduction

1 Epidemiology of Urinary Incontinence ...................................................................................... 1

Marie Carmela M. Lapitan

Part II Current Concepts on Anatomy and Physiology

2 Neurophysiology of Micturition: What’s New? ........................................................................ 17

Apostolos Apostolidis and Clare J. Fowler

3 Continence: Bladder Neck versus Mid-Urethra ....................................................................... 35

Matthias Oelke and Jan-Paul Roovers

4 Pelvic Floor: Three-Dimensional Surgical Anatomy ................................................................ 41

Ardeshir R. Rastinehad and Gopal H. Badlani

5 Pelvic Floor Prolapse: Cause and Effect ................................................................................... 53

Matthew A. Barker and Mickey M. Karram

6 Hormonal Influences on Continence .......................................................................................... 65

Dudley Robinson and Linda Cardozo

Part III Management of Stress Urinary Incontinence

7 Pelvic Floor Rehabilitation ......................................................................................................... 87

Kari Bø

8 Pharmacotherapy of Stress Urinary Incontinence ................................................................... 99

David Castro-Diaz and Sergio Fumero

9 Radio Frequency Therapy for the Treatment of Female

Stress Urinary Incontinence ....................................................................................................... 109

Roger R. Dmochowski and Emily Cole

xi

xii Contents

10 Surgery for Stress Urinary Incontinence: Historical Review ................................................ 117

Matthew P. Rutman and Jerry G. Blaivas

11 Surgery for Stress Urinary Incontinence: Open Approaches ............................................... 133

Meidee Goh and Ananias C. Diokno

12 Surgery for Stress Urinary Incontinence: Minimally Invasive Procedures ......................... 149

Eric A. Hurtado and Rodney A. Appell

13 Surgery for Stress Urinary Incontinence: Midurethral Slings ............................................. 165

Demetri C. Panayi and Vik Khullar

Part IV Management of Urge Incontinence

14 Behavioral Treatments for Urge Incontinence ........................................................................ 179

Howard B. Goldstein and Kristene E. Whitmore

15 Pharmacotherapy of Urgency Incontinence ............................................................................ 191

Martin C. Michel

16 Alternative Therapies for Urinary Urgency Incontinence:

Acupuncture and Herbology..................................................................................................... 203

Sarit O. Aschkenazi and Peter K. Sand

17 Sacral Nerve Stimulation for Neuromodulation of the Lower Urinary Tract ..................... 217

Dennis J. A. J. Oerlemans and Philip E. V. Van Kerrebroeck

18 Peripheral Neuromodulation for the Treatment of Overactive Bladder .............................. 227

Anurag K. Das

19 Surgery for Urge Urinary Incontinence: Cystoplasty, Diversion .......................................... 231

Petros Sountoulides and M. Pilar Laguna

20 Botulinum Toxin: An Effective Treatment for Urge Incontinence ....................................... 257

Arun Sahai, Mohammad Shamim Khan, and Prokar Dasgupta

Part V Management of Pelvic Organ Prolapse

21 Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries ............ 277

Jill Maura Rabin

22 Surgery for Pelvic Organ Prolapse: An Historical Review ................................................... 301

Baharak Amir and Alfred E. Bent

23 Biomaterials: Natural and Synthetic Grafts ........................................................................... 313

Kaytan V. Amrute and Gopal H. Badlani

24 Pelvic Reconstructive Surgery: Vaginal Approach ................................................................. 329

Daniel Biller and G. Willy Davila

Contents xiii

25 Pelvic Reconstruction: Abdominal Approach ......................................................................... 341

Lawrence R. Lind and Harvey A. Winkler

26 Laparoscopic Sacrocolpopexy: Indications, Technique and Results .................................... 355

Jens J. Rassweiler, Ali S. Goezen, Walter Scheitlin,

Christian Stock, and Dogu Teber

27 Posterior Compartment Repair and Fecal Incontinence ....................................................... 367

Gil Levy and Brooke H. Gurland

Part VI Management of Male Incontinence

28 Primary Urge Incontinence....................................................................................................... 393

Craig V. Comiter

29 Pharmacotherapy of Male Incontinence ................................................................................. 411

Peter Tsakiris and Jean J.M.C.H. de la Rosette

30 Treatment for Male Incontinence: Historical Review ............................................................ 423

Drogo K. Montague

31 Treatment for Male Incontinence: Surgical Procedures (Post-TURP/RRP) ....................... 433

Rajeev Kumar and Ajay Nehra

Part VII Special Situations

32 Current Concepts and Treatment Strategies for Genitourinary Fistulas ............................ 453

Gamal M. Ghoniem and Carolyn F. Langford

33 Urologic Consequences of Pelvic Irradiation in Women ....................................................... 461

Mary M.T. South and George D. Webster

34 Recurrent Incontinence ............................................................................................................. 469

Jørgen Nordling

35 Multioperated Recurrent Incontinence/Prolapse ................................................................... 475

Giacomo Novara and Walter Artibani

36 Voiding Dysfunction after Female Anti-Incontinence Surgery ............................................. 493

Priya Padmanabhan and Victor W. Nitti

Part VIII Social Aspects of Incontinence

37 Economic Impact of Stress Urinary Incontinence and Prolapse:

Conservative, Medical, and Surgical Treatments ................................................................... 511

Lynn Stothers

38 Community Awareness and Education .................................................................................... 521

Diane K. Newman

Index .................................................................................................................................................... 533

Contributors

Baharak Amir, BSc, MD

Department of Obstetrics and Gynecology, IWK

Health Center, Dalhousie University, Halifax, NS,

Canada

Kaytan V. Amrute, MD, FACOG

Department of Obstetrics and Gynecology, Jacobi

Medical Center, Bronx, NY, USA

Apostolos Apostolidis, MD

2nd Department of Urology, Papageorgiou

Hospital, Aristotle University of Thessaloniki,

Thessaloniki, Greece

Rodney A. Appell, MD, FACS

Professor and Chief

Division of Voiding Dysfunction and Female

Urology, The Scott Department of Urology, Baylor

College of Medicine, Houston, Texas, USA

Walter Artibani, MD

Professor of Urology and Chief

Department of Oncological and Surgical Sciences,

Urology Clinic, University of Padova, Padova, Italy

Sarit O. Aschkenazi, MD

Department of Obstetrics and Gynecology,

Evanston Continence Center, Evanston Hospital–

Northwestern University, Evanston, IL, USA

Gopal H. Badlani, MD

Professor and Vice Chair

Department of Urology, Wake Forest University

Baptist Medical Center, Winston Salem, NC, USA

Matthew A. Barker, MD

Department of Obstetrics and Gynecology, Good

Samaritan Hospital, Cincinnati, OH, USA

Alfred E. Bent, MD

Head, Division of Gynecology and Professor

Department of Obstetrics and Gynecology, IWK

Health Center, Dalhousie University, Halifax, NS,

Canada

Daniel Biller, MD

Department of Obstetrics and Gynecology,

Vanderbilt University, Nashville, TN, USA

Jerry G. Blaivas, MD

Department of Urology, Weill Medical College,

Cornell University, New York, NY, USA

Kari Bø, PhD

Professor, PT and Exercise Scientist

Department of Sports Medicine, Norwegian School

of Sport Sciences, Oslo, Norway

Linda Cardozo, MD FRCOG

Professor of Urogynaecology

Department of Urogynaecology, King’s College

Hospital, London, UK

David Castro-Diaz, MD, PhD

Professor of Urology / Consultant Urologist

Department of Urology, University Hospital of the

Canary Islands, Tenerife, Spain

Emily Cole, MD

Department of Urologic Surgery, Vanderbilt

University Medical Center, Nashville, TN, USA

Craig V. Comiter, MD

Associate Professor

Department of Urology, Stanford University School

of Medicine, Stanford, CA, USA

xv

xvi Contributors

Jean J.M.C.H. de la Rosette, MD, PhD

Professor and Chairman

Department of Urology, Academic Medical Center,

University Hospital, Amsterdam, The Netherlands

Anurag K. Das, MD, FACS

Assistant Professor of Surgery

Division of Urology, Beth Israel Deaconess

Medical Center, Harvard Medical School, Boston,

MA, USA

Prokar Dasgupta, MSc(Urol), MD, DLS,

FRCS(Urol), FEBU

Consultant Urological Surgeon

and Hon. Senior Lecturer

Department of Urology, Guy’s Hospital, London,

UK

G. Willy Davila, MD

Chairman, Department of Gynecology

Head, Section of Urogynecology and

Reconstructive Pelvic Surgery

Cleveland Clinic Florida, Weston, FL, USA

Ananias C. Diokno, MD, FACS

Executive Vice President and Chief Medical Officer

William Beaumont Hospitals, Royal Oak, MI, USA

Roger R. Dmochowski, MD

Professor

Department of Urologic Surgery, Vanderbilt

University Medical Center, Nashville, TN, USA

Clare J. Fowler, MB, BS, MSc, FRCP

Department of Uro-Neurology, National Hospital

for Neurology and Neurosurgery, London, UK

Sergio Fumero, MD

Department of Urology, University Hospital of the

Canary Islands, Tenerife, Spain

Gamal M. Ghoniem, MD, FACS

Head, Section of Voiding Dysfunction, Female

Urology and Reconstruction

Clinical Professor of Surgery/Urology NSU,

OSU and USF

Chairman of Medical Student Education

Department of Urology, Cleveland Clinic Florida,

Weston, FL, USA

Ali S. Goezen, MD

Department of Urology, SLK Kliniken Heilbronn,

Teaching Hospital University, Heidelberg, Germany

Meidee Goh, MD, MPH

Huron Valley Urology Associates, Ypsilanti, MI,

USA

Howard B. Goldstein, DO, MPH

Department of Female Pelvic Medicine and

Reconstructive Surgery, UMDNJ-Robert Wood

Johnson Medical School, Cooper University

Hospital, Camden, NJ, USA

Brooke H. Gurland, MD

Staff Physician, Department of Colon & Rectal

Surgery, Center for Functional Bowel Disorder,

The Cleveland Clinic Foundation, 9500 Euclid

Avenue-Desk A30, Cleveland, OH, USA

Eric A. Hurtado, MD

Fellow

Division of Female Voiding Dysfunction

and Female Urology, The Scott Department

of Urology, Baylor College of Medicine, Houston,

Texas, USA

Mickey M. Karram, MD

Department of Obstetrics and Gynecology, Good

Samaritan Hospital, Cincinnati, OH, USA

Vik Khullar, BSc, MD, MRCOG, AKC

Consultant Urogynaecologist

Department of Urogynaecology, St. Mary’s

Hospital, Imperial College, London, UK

Rajeev Kumar, MD

Associate Professor of Urology

All India Institute of Medical Sciences, New Delhi,

India

Carolyn F. Langford, DO

Clinical Associate Urology

Department of Urology, Cleveland Clinic Florida,

Weston, FL, USA

M. Pilar Laguna, MD, PhD, FEBU

Department of Urology, Academic Medical Center,

University Hospital, Amsterdam, The Netherlands

Contributors xvii

Marie Carmela M. Lapitan, MD, FPUA, FPCS

Clinical Associate Professor

College of Medicine,

University of the Philippines, Manila

Research Assistant Professor

National Institutes of Health–Manila,

University of the Philippines, Manila

Consultant

Division of Urology, Department of Surgery,

Philippine General Hospital,

University of the Philippines, Manila

Philippines

Gil Levy, MD

Director, Center for Pelvic Floor Dysfunction and

Reconstructive Surgery

Chief, Division of Urogynecology and

Reconstructive Surgery

Department of Obstetrics and Gynecology,

Maimonides Medical Center, Brooklyn, NY, USA

Director, Division of Female Pelvic Medicine and

Reconstructive Surgery

Department of Obstetrics and Gynecology, Staten

Island University Hospital, Staten Island, NY, USA

Assistant Professor of Obstetrics and Gynecology

State University of New York (SUNY Downstate),

NY, USA

Lawrence R. Lind, MD, FACOG, FACS

Co-Chief of Urogynecology and Pelvic

Reconstructive Surgery

Division of Urogynecology, Department of

Obstetrics and Gynecology, North Shore–LIJ

Health System, Great Neck, NY, USA

Martin C. Michel, MD, MAE

Professor

Department of Pharmacology and

Pharmacotherapy, Academic Medical Center,

University Hospital, Amsterdam, The Netherlands

Drogo K. Montague, MD

Professor of Surgery and Director

Center for Genitourinary Reconstruction,

Department of Urology, Glickman Urological and

Kidney Institute, Cleveland Clinic Foundation,

Cleveland, OH, USA

Ajay Nehra, MD, FACS

Professor of Urology

Mayo Clinic College of Medicine, Rochester, MN,

USA

Diane K. Newman, MSN, ANP-BC, CRNP,

FAAN, BCIA-PMDB

Co-Director, Penn Center for Continence and

Pelvic Health

Director, Clinical Trials

Division of Urology, Department of Surgery,

University of Pennsylvania Medical Center,

Philadelphia, PA, USA

Victor W. Nitti, MD

Professor and Vice Chairman

Director of Female Pelvic Medicine and

Reconstructive Surgery, Department of Urology,

NYU Langone Medical Center, New York, NY,

USA

Jørgen Nordling, MD

Professor of Urology

Department of Urology, Herlev Hospital,

University of Copenhagen, Denmark

Giacomo Novara, MD, FEBU

Consultant Urologist

I.R.C.C.S. Istituto Oncologico Veneto (I.O.V.),

Department of Oncological and Surgical Sciences,

Urology Clinic, University of Padova,

Padova, Italy

Matthias Oelke, MD, FEBU

Vice-Chairman

Department of Urology, Hannover Medical School,

Hannover, Germany

Dennis J.A.J. Oerlemans, MD

Department of Urology, University Hospital of

Maastricht, Maastricht, The Netherlands

Priya Padmanabhan, MD

Fellow

Female Pelvic Medicine and Reconstructive

Surgery, Vanderbilt University School of Medicine,

Nashville, TN, USA

Demetri C. Panayi, MB.BS(Lon), BSc(Hons),

MRCOG

Subspecialty Trainee Urogynaecology

Department of Urogynaecology, St. Mary’s

Hospital, Imperial College, London, UK

Jill Maura Rabin, MD

Department of Obstetrics and Gynecology,

Division of Urogynecology, Long Island Jewish

Medical Center, New Hyde Park, NY, USA

xviii Contributors

Jens J. Rassweiler, MD

Professor of Urology

Department of Urology, SLK-Kliniken Heilbronn

GmbH, Teaching Hospital University, Heidelberg,

Germany

Ardeshir R. Rastinehad, DO

Smith Institute for Urology, North Shore LIJ

Health System, Long Island, New York USA

Dudley Robinson, MD, MRCOG

Consultant Urogynaecologist

Department of Urogynaecology, King’s College

Hospital, London, UK

Jan-Paul Roovers, MD, PhD

Department of Gynaecology and Obstetrics,

Academic Medical Center, University Hospital,

Amsterdam, The Netherlands

Matthew P. Rutman, MD

Assistant Professor

Department of Urology, Columbia University

Medical Center, New York, NY, USA

Arun Sahai, BSc(Hons), MRCS(Eng)

Specialist Registrar in Urology

Department of Urology, Guy's Hospital, London,

UK

Peter K. Sand, MD

Department of Obstetrics and Gynecology,

Evanston Continence Center, Evanston Hospital–

Northwestern University, Evanston, IL, USA

Walter Scheitlin, MD

Department of Urology, SLK Kliniken Heilbronn,

Teaching Hospital University, Heidelberg, Germany

Mohammad Shamim Khan, FRCS(Urol), FEBU

Consultant Urological Surgeon

Department of Urology, Guy’s Hopsital, London,

UK

Petros Sountoulides, MD, FEBU

Department of Urology, Academic Medical Center,

University Hospital, Amsterdam, The Netherlands

Mary M.T. South, MD

Urogynecology and Pelvic Reconstructive Surgery,

Department of Obstetrics and Gynecology,

University of Cincinnati College of Medicine,

Cincinnati, OH, USA

Christian Stock, MD

Department of Urology, SLK Kliniken Heilbronn,

Teaching Hospital University, Heidelberg, Germany

Lynn Stothers, MD, MHSc, FRCSC

Associate Professor of Surgery

Associate Member,

Department of Health Care and Epidemiology

Associate Member, Department of Pharmacology

Director of Research, Bladder Care Centre

Department of Urologic Sciences, Bladder Care

Centre, University of British Columbia, Vancouver,

BC, Canada

Dogu Teber, MD

Department of Urology, SLK Kliniken Heilbronn,

Teaching Hospital University,

Heidelberg, Germany

Peter Tsakiris, MD

Department of Urology, Academic Medical Center,

University Hospital, Amsterdam,

The Netherlands

Philip E.V. Van Kerrebroeck, MD, PhD

Department of Urology, University Hospital

Maastricht, Maastricht, The Netherlands

George D. Webster, MD

Department of Urology, Duke University Medical

Center, Durham, NC, USA

Kristene E. Whitmore, MD

Division Chief of Female Pelvic Medicine and

Reconstructive Surgery, and Urology

Drexel University College of Medicine,

Hahnemann University Hospital, Pelvic and Sexual

Health Institute, Philadelphia, PA, USA

Harvey A. Winkler, MD, FACOG

Co-Chief of Urogynecology and Pelvic

Reconstructive Surgery

Division of Urogynecology, Department of

Obstetrics and Gynecology, North Shore–LIJ

Health System, Great Neck, NY, USA

Part I

Introduction

3

Urinary incontinence (UI) is one of the priority health

issues recognized by the World Health Organization.

An understanding of the epidemiology of this condi-

tion effectively leads to a better appreciation of its

importance and its impact on the population and the

health care delivery system. The past two decades

have seen intensified research on the prevalence of UI

and the identification of its determinants.

The synthesis of the published literature on the

epidemiology of UI is complex because of the dif-

ferences in the definitions of UI used, the popula-

tion types included, and the methodology used [1] .

For the definition used, variance may be in the

severity or in the interval measured. The influence

of restrictions in the definition of UI insofar as

severity, frequency, and duration of the leakage is

apparent when comparing prevalence rates of UI

established in epidemiological studies to those in

clinical trials on treatment for UI, wherein rates

in the former are often higher than in the latter.

Particularly for surveys and cross-sectional studies,

the design and wording of the questionnaires,

response rates, and the timing of the study in rela-

tion to potential confounders, such as pregnancy,

childbirth, prostatectomy, and stroke can influence

the results. Advertising for incontinence medica-

tions and products to the public in recent years also

has been identified as influential in increasing the

reported prevalence of UI by increasing the will-

ingness of women to disclose the condition [2] .

Notwithstanding these issues, this chapter aims

to discuss the prevalence, incidence, and remission

rates of UI in a comprehensive and cohesive manner,

integrating all available information on the topic. It

also seeks to elaborate on potential risk factors for

the development of UI.

Prevalence of UI in the General

Population

Urinary incontinence is increasingly recognized

as a prevalent condition worldwide. Surveys per-

formed in large cohorts of community-dwelling

persons involving both men and women in all age

groups report overall prevalence rates ranging from

5 to 69%, with a majority of the studies citing the

prevalence between 25 and 45% among women

and 1 and 9% among men.

The 3rd International Consultation on Incontinence

generated a comprehensive report on the overall prev-

alence of adult women and men in the general popula-

tion. The epidemiology committee of the Consultation

cited a median prevalence range of 20–30% for

young women, 30–40% for women in the middle age

group, and 30–50% in the elderly [3] . Among men,

prevalence rates from 3 to 39% have been cited, with

increasing rates as the study population ages.

A significant difference is found between the

prevalence of UI among males and females.

Aggazzotti reported that the prevalence of UI was

significantly higher in women than in men (59.8%

vs. 39.2%) [4] . Such a difference in prevalence was

particularly apparent with increasing age. Women

had an almost twofold risk of being incontinent

(OR = 1.95 95% CI 1.24–3.06). In a survey of a

Chapter 1

Epidemiology of Urinary Incontinence

Marie Carmela M. Lapitan

4 M.C.M. Lapitan

Japanese community with 1,836 respondents, Ueda

and co-workers had found that women with UI were

five times more common as men [5] . In a survey of

nursing home residents, Nelson et al . established

that the male gender was a protective factor in the

occurrence of UI [OR = 0.8 (0.7–1.0)] [6] .

Prevalence of UI According to Type

Stress urinary incontinence (SUI), commonly defined

in the epidemiological literature as the presence of

involuntary leakage during periods of exertion such

as laughing, sneezing, and coughing, is the most

prevalent type in population-based trials, occurring

40–50% of the time [5, 7, 8] . It is the type of inconti-

nence that predominates among women, accounting

for as much as 65% of all types on UI in women.

Studies including women of all ages cite SUI as

the type of UI among 33–50% of the incontinent

population [9– 12] . Its rate in women is highest in

the young and middle-age group. Thereafter, there

is a relative decrease with increasing age. Among

elderly women, the proportion of SUI declines, at

times with rates approaching the other types. In

contrast, SUI is found to be the least common type

in men, with reported prevalence rates limited to

less than 10% across all age groups.

Urgency urinary incontinence (UUI) is fre-

quently defined as involuntary urine leakage asso-

ciated with a sudden desire to urinate and failing

to reach the toilet in time. It is one of the com-

ponents of the overactive bladder (OAB), which

includes symptoms such as urgency, nocturia, and

frequency. Approximately one third of patients

diagnosed to have OAB present with UUI [13] .

The overall prevalence of UUI across both sexes

and all age groups in the general population is

20–40% . It is consistently found to be the predomi-

nant UI type among men, accounting for 40–80% of

all UI types [5, 14– 16] . Among women, the propor-

tion with UUI is noted to be from 11 to 25%. Such

proportion increases beyond age 60 years [17– 19] .

Incidence and Remission Rates

Recent years have seen an increase in the number

of studies performed to determine the incidence

and remission rates of UI. Longitudinal studies

performed on varied populations showed annual

incidence rates ranging from 0.9 to 10%. The

MRC Incontinence Team followed up with more

than 39,000 people aged 40 years and above to

establish a 6.3% annual incidence rate for inconti-

nence. Studies that focused on SUI cited incidence

rates of 3.8–8.1% [20 , 21]. In a study of an older

population, Thom found a slightly higher incidence

among women compared to men (17.5 per 1,000

women vs. 12.2 per 1,000 men) [19] . For both

men and women, incidence increased with age.

However, incidence plateaus at age 40–50 years

among females [22].

Remission rates have been reported to be at 2.9–

6.8% annually [22, 23] . Remission rates decrease

with age and with severity. Compared to UUI, SUI

has been found to have higher remission rates [22] .

Data from the MESA study suggest that remission

rates among men are higher compared to women

[24 , 25], in congruence with the finding of the

MRC Incontinence study [20].

Prevalence in Specific Populations

UI Among the Elderly in Communities

and in Long-Term Care Facilities

The elderly in long-term care facilities are reported

to have higher prevalences of UI. Giorgiou et al.

reported prevalence rates of UI in nursing homes

and long-term wards as twice that of residential

homes (70 and 71% vs. 34%, respectively) [26].

Studies including residents in nursing homes in

the United States, Italy, and Japan showed UI

prevalence rates ranging from 54 to 72% [4, 6 , 27].

Landi and co-workers studied more than 5,000

frail elderly under a home-care program and found

an overall prevalence of 51% with similar rates

between males (49%) and women (52%) [28] .

Pregnancy-Related and Postpartum UI

Pregnant and postpartum women are a special

group with high prevalence rates of UI. Pregnancy-

associated UI generally is viewed as a transient con-

dition attributed to the many physiological changes

in the woman’s body such as fluctuating hormone

levels, increased urine production, and changes in

the position and relations of the pelvic structures

1. Epidemiology of Urinary Incontinence 5

brought about by the enlarging uterus occurring

during gestation. On the other hand, the develop-

ment of UI in the postpartum period is thought to

be a consequence of the alterations in the pelvic

floor anatomy after childbirth and is believed to be

persistent in a proportion of women.

A review of the published literature on the topic

by Mason revealed pregnancy-associated UI preva-

lence rates ranging from 27 to 67% [29] . A popu-

lation-based survey of 1,874 adult women revealed

an overall prevalence of pregnancy-associated UI

of 16.6% [30] . In an interview of 525 postpartum

women within 3 days of their delivery, 59.5%

admitted to experiencing UI during the pregnancy

[31]. This figure is very similar to the 59% preva-

lence in 717 women on their 34th week of gestation

reported by Mason and co-workers [29] . Chaliha

prospectively studied 549 women through their

first pregnancy and delivery and found the preva-

lence of SUI and UUI during pregnancy to be 8.0

and 35.7%, respectively [32] .

After delivery, a proportion of women will con-

tinue to experience UI, and a few will develop de

novo incontinence in the postpartum period. The

literature review of Mason cited postpartum incon-

tinence prevalence rates ranging from 5.8 to 42.6%

[29] . The wide range of rates may be due to the

differences in the timing of the survey and the defi-

nition of UI used. In a prospective study of more

than 500 pregnant women up to 12 months postpar-

tum, Burgio and co-workers showed UI prevalence

rates of 11.4, 9.3, 10.5, and 13.25% at 6 weeks, 3,

6, and 12 months postpartum, respectively [31].

Mason found a postpartum UI prevalence of 31%

at 8 weeks [29] . Chaliha’s group reported 2.2 and

12.4% of patients reporting SUI and UUI, respec-

tively, in the postnatal period [32] .

Many studies related pregnancy UI and postpar-

tum UI. The population-based survey of Foldspang

reported that UI during pregnancy predicted

the occurrence of postpartum UI, age-adjusted

OR = 9.2 (95% CI 6.5–13.0) for the first childbirth

and OR = 12.3 (95% CI 7.6–19.9) for the second

childbirth [30] . Attributable risk for persistent UI

after delivery by pregnancy UI was 56.1–67.6%.

The prospective study by Burgio et al. showed

a twofold increase in the risk for postpartum UI

for women who experienced incontinence during

pregnancy (OR = 2.1, 95% CI 1.29–3.45) [31]. The

5-year longitudinal study of Viktrup demonstrated

that UI during the first pregnancy was independ-

ently associated with long-lasting SUI after 5 years

(OR = 3.8, 95% CI 1.9–7.5) [21]. In the same study,

SUI in the postpartum period was associated with

greater odds for persistent SUI (OR = 4.5, 95% CI

2.5–13.2). The risk of long-lasting SUI and UUI

was found to be related to the time of onset and the

duration of the incontinence after pregnancy and

delivery in a “dose–response-like” manner.

Multivariate analyses of several factors to deter-

mine their association with postpartum UI have

been performed. Higher parity was associated with

increased likelihood for SUI following delivery

[29] . Vaginal delivery was found to be a consistent

predictor of postpartum UI in three studies, with

odds ratios ranging from 1.2 to 3.6 [21, 30, 31] .

Correlated with this observation, caesarean deliv-

ery was noted to be associated with lower rates of

postpartum UI [33, 34] . Forceps delivery and the

performance of an episiotomy were other obstetric

factors found to be independent predictors of post-

partum UI [21, 31, 34] .

Smoking (OR = 1.91, 95% CI 1.20–3.45) and

BMI (OR = 1.15, 95% CI 1.03–1.28) also were

found to be significantly associated with postpar-

tum UI [31] . Hvidman, on the other hand, did not

find the same association with BMI [33] .

Postprostatectomy Incontinence

Postprostatectomy incontinence is a distinctive

form of male UI. The accepted incidence of UI

following transurethral resection of the prostate is

1%. Higher figures are reported after radical pros-

tatectomy with overall prevalence ranging from

5 to 62%, with most studies citing rates between

10 and 30%. This very wide range of prevalence

rates may be explained by the same factors cited

to be responsible for the variation in the prevalence

of UI in the general population. In addition, rates

also are found to be influenced by the basis of the

diagnosis. Rates based on the symptoms reported

by patients are generally 2–3× higher than those

based on physicians’ observations. Several studies

have demonstrated that doctors underestimate post-

prostatectomy UI by as much as 75% [35– 37] .

Incontinence rates are observed to progressively

decline from the time of catheter removal after

prostatectomy and they plateau 1–2 years postop-

eration [38– 42] . Thus, it is important to emphasize

6 M.C.M. Lapitan

that studies presenting postprostatectomy inconti-

nence rates should have a minimum followup of 1

year to establish true and reliable rates.

Modifications in the techniques of radical pros-

tatectomy have been developed primarily to min-

imize the complication of UI. The variations

associated with lower incontinence rates include

the perineal (vs. the abdominal) approach [43,

44] and the preservation of neurovascular bundle

[45, 46] . Bladder neck preservation affords earlier

return to continence compared to bladder neck

resection, although continence rates at 1 year post-

operation do not significantly differ between the

two techniques [47] .

Age at time of prostatectomy may be a sig-

nificant factor associated with the occurrence of

postoperative UI [40, 43, 45, 46, 48] . Catalona’s

work has shown that the risk for postprostatectomy

UI doubles for every 10 years of age beginning at

age 40 years. Horie, however, noted that rather than

absolutely affecting likelihood of developing UI,

age determined the rate at which continence would

be achieved [39] . Older men were found to take

a longer time to achieve continence. On the other

hand, two studies found no relation between age

and postprostatectomy UI prevalence [35, 49] .

Risk Factors

Age

Increasing age is found consistently to be associ-

ated with increasing likelihood for UI. Aggazzotti

reported that the risk of UI increased by 1.34 times

every 5 years (OR 1.34, 95% CI 1.02–1.51) in the

general population [4] . Astudy on the elderly by

Brown and co-workers found similar odds for each

5 years of advancing age (OR 1.3, 95% CI 1.2–1.5)

[50] . A study by Nelson et al. found a more modest

association (OR 1.03, 95% CI 1.02–1.04) [6] .

An almost linear correlation between age and

risk for UI is found among men. For women, how-

ever, a somewhat different pattern has emerged

from several studies [12, 51, 52] . A peak in the

prevalence of UI among women in the range of

30–36% is seen during the middle ages of 50–60

years. A second peak is found in older age greater

than 65 years.

Race and Ethnicity

Evidence is increasing on the effect of race in the

prevalence of UI. Several studies have established race

as a significant predictor for UI [53, 54] and a signifi-

cant association between race and the type of UI (see

Table 1.1 ). Specifically, Caucasian whites were found

to be at a higher risk for SUI compared to African-

Americans and Asians. Brown and co-workers found

Caucasians nearly 3× at risk for SUI compared to

nonwhites (RR 2.8, 95% CI 1.6–5.0) [55] .

Urodynamic findings of lower maximal urethral

closing pressures and lower resting and straining

urethral angles found among Caucasians compared

to African-Americans support this difference in

prevalence [56, 57] . Howard and co-workers com-

pared white and black nulliparous women using

urodynamics and MRI of the pelvic floor [58] .

They found that blacks had 21% greater urethral

volume measured by MRI. Blacks also were noted

to have 29% higher mean urethral closure pres-

sure and 14% higher mean maximum urethral closure

Table 1.1. Studies comparing odds ratio for urinary incontinence among women of different races .

Study

Odds ratio (95% CI)

Blacks Hispanics Asians Caucasians Non-whites

Danforth 2006 [60] 0.49 (0.4–0.6) Not significant 0.57 (0.46–0.72) Reference

Lewis 2005 [59] 0.46 (0.38–0.56) 0.69 (0.52–0.92) Not studied Reference

Grodstein 2003 [61] 0.39 (0.31–0.50) 0.75 (0.56–1.00) 0.79 (0.61–1.02) Reference

Nygaard 2003 [80] Severe UI 0.30

(0.19–0.46)

Severe UI 0.29

(0.15–0.53)

Not studied Reference

Mild UI 0.42

(0.31–0.56)

Mild UI 0.50

(0.34–0.74)

Melville 2005 [12] Reference 0.68 (0.54–0.86)

Brown 1999 [55] 2.8 (1.6–5.0) Reference

1. Epidemiology of Urinary Incontinence 7

pressure, suggesting greater urethral sphincter capac-

ity. There also was 17% greater levator ani muscle

cross-sectional area at the level of the midurethra

and 24% greater pelvic floor muscle strength.

Correlated with this finding was the report of

Melville that indicated nonwhites to be 32% less

prone to have UI (RR 0.68, 95% CI 0.54–0.86)

[11] . The Health and Retirement Study, which

investigated older women in Florida, likewise

reported 54% (RR 0.46, 95% CI 0.38–0.56) and

31% (RR 0.69, 95% CI 0.52–0.92) lesser risk

of UI among blacks and Hispanics, respectively

[59] . The Nurses’ Health Study found a similar

trend among blacks (RR 0.49, 95% CI 0.4–0.6)

but did not find any lesser risk for Hispanics [60] .

One study even cited Hispanics having the highest

age-adjusted UI prevalence compared to the other

racial groups (Hispanics, whites, blacks, Asian-

Americans: 38, 30, 25, 19%, respectively) [54] .

Asians also were protected against UI by 43% (RR

0.57, 95% CI 0.46–0.72) [60] . An earlier report of

the Nurses’ Health Study in 2003 showed similar

findings [61] .

A higher risk of UUI was found in African-

Americans [53] . Duong explained this as a result of

the lower MCC in the urodynamic studies of black

women. On the other hand, Sze found similar rates

of UUI among blacks, whites, and Hispanics (19%

vs. 16% vs. 16%, p = 0.214) [62] .

No evidence was found to demonstrate any the

effect of race on UI prevalence among men, as all

studies on the topic have been limited to women.

Parity

One of the most consistent determinants of UI in

women is parity. Partial denervation of the pel-

vic floor muscle resulting from pudendal nerve

damage during childbearing is theorized to be

responsible for the association between UI and

parity. The results of several observational studies

on UI prevalence among women support such an

association.

In a population-based survey of elderly women,

Brown et al. found 30% higher odds for parous

women to report UI compared to nulliparous

women [50] . Similarly, Hagglund and co-workers

found that UI was more common among those

who have given birth to one child (27% vs. 23%,

p < 0.001) and among those who had two children

(42% vs. 23%, p < 0.001) compared to nulliparous

women [51] . In the Nurses’ Health Survey, increas-

ing odds for UI was found with each additional

birth [60] . Ushiroyama, in a study of 3,046 post-

menopausal women who consulted at a gynecol-

ogy clinic, found a significantly higher prevalence

among the parous women, particularly those who

have given birth to three to four children [63] .

Mode of Delivery and Other Obstetrical

Factors

One of the more controversial factors being studied

as a predictor of UI in women is the mode of child

delivery. Vaginal birth has been closely linked

with UI in women and several pathophysiological

mechanisms have been proposed to justify such an

association. These include tissue damage resulting

in impaired bladder neck support and the myogenic

changes of the levator ani muscles, including fibro-

sis. During caesarean delivery, the female pelvis is

spared from these insults.

Foldspang, in a study of women in the Danish

registry, noted increased prevalence of UI among

women who had given birth vaginally compared to

those who did not (22.9% vs. 9.0%) [30] . He also

noted UI immediately following vaginal childbirth

(OR = 4.3, 95% CI 3.3–5.7) and incontinence

during pregnancy (OR = 2.2, 95% CI 1.2–4.1) as

strong predictors of long-term SUI.

Although a majority of studies lendsupport to

the adverse effect of vaginal delivery on a woman’s

continence, the impact of caesarean delivery on

the risk for UI is not certain. Several papers have

shown that caesarean delivery is protective [34,

64] , with a lesser risk for UI among those who

had caesarean deliveries compared to those who

delivered vaginally.

Farrell prospectively studied 484 primaparous

women and noted higher risk of UI at 6 months

for patients who had spontaneous vaginal delivery

compared to those who had caesarean delivery (RR

2.1, 95% CI 1.1–3.7), for patients who had forceps

delivery compared to those who had spontaneous

vaginal delivery (RR 1.5, 95%CI 1.0–2.3), and for

patients who had caesarean delivery (RR 3.1, 95%

CI 1.7–5.9) [34] . Caesarean delivery protected

against UI (RR 0.6, 95% CI 0.3–1.0).

In a prospective study of more than 700 pregnant

women, Mason found no significant difference in

8 M.C.M. Lapitan

the prevalence of SUI in women who had a normal

vaginal delivery compared to those who had an

instrumental delivery [29] . There was a significant

reduction, however, in the prevalence of SUI in

women who had a caesarean section.

McKinnie, in contrast, noted that those who deliv-

ered by caesarean section exclusively did not have

a significantly different UI prevalence from those

who had one vaginal delivery [65] . As some women

who had had a caesarean section reported symptoms

of SUI, it appears that the protective effect is not

absolute. It is suggested that the protective effect of

caesarean delivery may be only for the short term, so

that the longer the interval from delivery to survey,

the difference in UI was not significant [66] . Wilson

et al. found that the protective effect of caesarean

delivery is lost after three deliveries [64] .

Other obstetric techniques (episiotomy, forceps,

perineal suturing) were not associated with UI in

the multivariate analysis of several studies [30 ,

32]. In contrast, Viktrup noted episiotomy during

the first delivery doubled the risk of having persist-

ent SUI 5 years after the delivery (OR 2.0, 95%

CI 0.9–4.1) [21] . Vacuum extraction, on the other

hand, was associated with increased odds of nearly

3× (OR 2.9, 95% CI 1.1–7.7).

Menopause

There is conflicting evidence from cross-sectional

surveys on the association between menopause and

UI in women. Some studies report a significant

association [67, 68] , while others do not [54, 69] .

Prospective longitudinal studies present more

consistent evidence. The Melbourne Women’s

Midlife Health Project prospectively studied the

association of problems with control of urine and

the menopausal transition over 7 years. It found

that becoming menopausal was not associated with

increased incidence of UI [70] . A survey by Chen

and co-workers of 1,253 randomly selected women

in the community yielded a similar conclusion that

storage dysfunctions, including UI, were not affected

by the pre- to postmenopausal transition, but rather

are closely associated with aging changes [71] .

Hysterectomy

Hysterectomy may cause damage to the urethral

and bladder supportive structures or to the pelvic

nerve plexus, which in turn may lead to UI. Indeed,

Brown and co-workers reported 40% higher odds

(OR 1.4, 95% CI 1.1–1.6) [55] for hysterectomized

elderly women to report UI than those who were

not. Similar odds were reported by Danforth (OR

1.23, 95% CI 1.13–1.33) [60] .

As a contrasting point, hysterectomy was not

found to be associated with UI by Holtendahl

and co-workers, who offered the explanation that

hysterectomy removes the weight of the uterus and

so may diminish pressure on urethra-supporting

structures [72] .

Obesity

Numerous studies have investigated the relation-

ship of UI occurrence and obesity or increased

body mass index (BMI). The stress placed on the

pelvic floor by the abdominal contents is the pri-

mary factor identified in the pathophysiology of

incontinence among overweight people. Richter

reported a striking 66.9% prevalence of UI among

180 morbidly obese women awaiting weight loss

surgery [73] . The Health and Retirement study

demonstrated that women with increased BMI had

a greater risk for mild (OR 1.17, 95% CI 1.07–

1.27) and severe UI (OR 1.44, 95% CI 1.26–1.64)

[59] . Brown reported obesity as having a 16%

attributable risk proportion for UI, with those who

havehigher BMI having increased odds of 1.6 (OR

1.6, 95% CI 1.4–1.7) [50] .

Cognitive and Functional Impairment

Particularly in the older population, limits in cogni-

tion and functional impairment have been associ-

ated with higher occurrences of UI. In a study of

community-dwelling frail elderly people, Landi

demonstrated limitations in activities of daily living

(ADL) to be independent predictors of UI in both

men and women [28] . Urinary incontinence was

found to be 2–5× more likely in those with impair-

ments in ADL. A survey of Mexican-Americans

65 years and older showed a significant association

between UI and impaired ADL (OR 1.4, 95% CI

1.0–2.0) [17] . A similar relationship was reported

by Holroyd-Leduc (OR 1.31, 95% CI 1.05–1.63)

[74] . The elderly persons who had suffered a

stroke were 27–37% more likely to be found to be

incontinent [28] . Among stroke patients, those with

1. Epidemiology of Urinary Incontinence 9

moderate to severe paresis were 3× more at risk of

having UI (OR 3.1, 95% CI 0.9–10.4) than those

with mild to no paresis [75] .

The prevalence of UI increases significantly with

a worsening of mental status. Several studies in

the elderly population have shown that those with

impaired cognition had increased odds of having

incontinence. A comprehensive study of stroke

patients by Jorgensen demonstrated a tendency for

older people with UI to have lower Mini-Mental

State Examination (MMSE) scores (OR 2.8, 95% CI

0.9–8.6) [76] . A survey of nursing home residents

by Nelson demonstrated a 50% increased likeli-

hood for those with dementia to have UI (OR 1.5,

95% CI 1.2–1.7) [6] . Aggazzotti stated that nursing

home residents lacking mental orientation had an

almost fourfold increased risk (OR 3.61, 95% CI

2.42–5.39) [4] . Landi showed that for the frail eld-

erly living in the community, both men and women

with higher cognitive performance scale scores (i.e.

greater impairment) were 2–6× more likely to have

UI [28] . Elderly females suffering from delirium

were found to have 66% higher odds of being incon-

tinent (OR 1.66, 95% CI 1.31–2.11) [54] .

Smoking

Smoking is one of the factors for UI occurrence

found in several studies. The repeated stress on

the pelvic floor with chronic coughing associ-

ated with smoking is believed to be the reason

for this finding. A survey of more than 1,500

Mexican-American women of 65 years and older

demonstrated a more than twofold increase in the

prevalence of UI among smokers (OR 2.1, 95% CI

1.5–2.8) [17] . The SWAN study [2] found current

smokers to have a greater likelihood of moderate to

severe incontinence (OR 1.38, 95% CI 1.04–1.82).

The Nurses Health Study reported very similar

odds ratio (OR 1.34, 95% CI 1.25–1.45) [60] . A

study on postpartum women found smoking to be

a strong predictor of UI, with smokers at 3× higher

odds (OR 2.9, 95% CI 1.37–3.85) of having UI 1

year after childbirth [31] .

Estrogen–Hormone Replacement

Elderly women on oral estrogens were found to

be 90% more likely to report UI than those who

were not (OR 1.9, 95% CI 1.5–2.4). A similar

risk (OR 2.0, 95% CI 1.3–3.1) was found in 1,584

women surveyed by Jackson and co-workers [76] .

Samuelsson found women on estrogen replace-

ment therapy almost 3× at risk of having UI (OR

2.9, 95% CI 1.4–5.9) [22] . Hagglund found higher

estrogen use in women more than 50 years of

age with UI compared to those without [51] . The

Melbourne Women’s Midlife Health Project also

showed a higher prevalence of UI among women

receiving hormone replacement therapy compared

to those who did not (23% vs. 15%) [70] .

The strongest evidence in literature relating

hormone replacement with UI in women is seen

in the placebo-controlled clinical trials on estrogen

replacement on menopausal women. After 3 years

of hormone replacement, significant differences

in the prevalence of UI were noted between those

receiving estrogen (28.1% vs. 19.1%) and combi-

nation estrogen–progesterone (25.5% vs. 14.1%)

compared to the respective placebo groups [77] .

A 3-year trial using estrogen as the standard com-

parator for a drug for osteoporosis among meno-

pausal women showed a significantly higher UI

rate in the group receiving estrogen compared to

the placebo group (7.0% vs. 1.3%) [78] .

Depression

Using data from a large population-based survey,

the Health and Retirement Survey found that

depression was significantly associated with the

prevalence of UI [11, 71, 79– 81] . Women with

severe incontinence were 80% more likely to be

depressed (OR 1.82, 95% CI 1.26–2.63), whereas

for women with mild incontinence the risk of

depression was 40% higher compared to those with

no incontinence (OR 1.41, 95% CI 1.06–1.87). In a

survey of nuns, Buchsbaum found a strong associa-

tion between UI and depression (OR 2.96, 95% CI

1.21–7.55) [79] .

Diabetes Mellitus

Physiological, microvascular, and neurological

complications of diabetes mellitus may result in

changes that impair the function for the conti-

nence mechanism. Several studies have reported

consistent results supporting this, citing 20–63%

increase in risk for UI among diabetics compared

to nondiabetics.

10 M.C.M. Lapitan

The large-scale longitudinal Nurses’ Health

Study showed that diabetics were 28% more at

risk (RR 1.28, 95% CI 1.18–1.39) of having UI

than those who were not diabetic [81] . It also

showed a 21% higher chance of developing inci-

dent UI (RR 1.21, 95% CI 1.03–1.43) associated

with diabetes mellitus. The Health and Retirement

Study, which surveyed more than 10,000 women

aged 50–90 years, found an impressive 63%

greater risk of having UI among insulin-requiring

diabetics (RR 1.63, 95% CI 1.28–2.09) and a

more modest 20% increase in chance among non–

insulin-requiring diabetics compared to nondiabet-

ics [59] . The SWAN study showed a 53% greater

likelihood of UI among diabetics (OR 1.55, 95%

CI 1.12–2.10) [2] .

Caffeine and Alcohol Intake

The impact of consumption of caffeine and alcohol

on the occurrence of UI has been the subject of

few studies. The ability of caffeine to produce an

excitatory effect on the detrusor smooth muscle

and induce a transient contraction has been cited as

the possible mechanism to explain the significant

association between detrusor instability and high

caffeine intake [82] . The EPICONT study had

found that tea drinkers were slightly at a higher risk

for all types of UI. On the other hand, coffee had

no effect on UI risk [83] . A community survey of

nearly 5,000 Chinese women over 20 years of age

showed a significant relationship between alcohol

consumption and SUI (OR 4.7, 95% CI = 1.1–20.2)

[84] . However, the majority of the epidemiological

surveys in the rest of the published literature have

not found any association between coffee, tea, or

alcohol intake and UI [9, 11, 55] .

Help Seeking for Incontinence

Despite high prevalence rates of UI, less than 30%

of affected people seek consultation [2, 5, 8– 10,

12, 52, 63] . Women, compared to men, were more

likely to discuss the problem with their doctor [8] .

Severity of incontinence was strongly associated

with the likelihood of seeking help from a health

care provider. Those suffering from UUI were

more likely to seek consult [63] .

Impact of UI on the Quality of Life

Urinary incontinence, though not life-threatening,

is acknowledged to be of considerable burden

to the affected individuals and their families.

Incontinence sufferers reported more physical dis-

comfort, were more worried about their health,

were more troubled and more frequently were

hindered in their social activities compared to

individuals who did not suffer from incontinence.

More severe UI was significantly associated with

higher BII scores, i.e., lower quality of life [85] .

Lower quality of life scores [86] and lower SF36

scores [7] were found among individuals with UI.

Kocak reported that incontinence had a severe

impact on the quality of life in 12% of those with

the condition [9] .

Urinary Incontinence and Mortality

Several studies involving the older population did

not find UI to be significantly associated with either

2- or 6-year mortality rates [24, 25, 59] . Likewise,

a study on more than 7,000 community-dwelling

people aged 70 years and above failed to show UI

to be an independent predictor of mortality (OR

0.90, 95% CI 0.67–1.21). Instead, UI was found to

be marker of frailty [87] . Nakanishi, on the other

hand, found that severe incontinence increased the

risk for mortality even after adjustment for poten-

tial confounders [88] .

Conclusion

Urinary incontinence is a common condition affect-

ing the entire adult population, although certain

groups are identified as having higher prevalence

rates. These include the elderly, pregnant and post-

partum women, andmen who underwent prostate-

ctomy. Several risk factors have been associated

with an increased likelihood of UI occurrence,

including age, parity, smoking, obesity, hormone

therapy with estrogens, diabetes mellitus, depres-

sion, and cognitive and functional impairment.

Urinary incontinence impacts greatly on the quality

of life and may be a signal of poor health status,

particularly in the elderly.

1. Epidemiology of Urinary Incontinence 11

References

1 . Hampel C , Artibani W , Espuna M , et al.

Understanding the burden of stress urinary inconti-

nence in Europe: A qualitative review of the litera-

ture . Eur Urol 2004 ; 46 : 15 – 27 .

2 . Sampselle C , Harlow S , Skurnick J , et al. Urinary

incontinence predictors and life impact in ethnically

diverse perimenopausel women . Obstet Gynecol

2002 ; 100 (6) : 1230 – 1238 .

3 . Hunskaar S , Burgio K , Clark A , et al. Epidemiology

of urinary and faecal incontinence and pelvic organ

prolapse. In : Abrams P , Cardozo L , Khoury S , Wein

A , editors. Incontinence 3rd edn . Paris : Health

Publication , 2005 : 255 – 312 .

4. Aggazzotti G, Pesce F, Grassi D, et al. Prevalence

of urinary incontinence among institutionalized

patients: A cross-sectional epidemiologic study

in a midsized city in northern Italy. Urology 200;

56(2):245–249.

5 . Ueda T , Tamaki M , Kageyama S , et al. Urinary

incontinence among community dwelling people

aged 40 years or older in Japan: Prevalence risk

factors, knowledge and self-perception . Int J Urol

2000 ; 7 : 95 – 103 .

6 . Nelson R , Fumer S , Jesudason V . Urinary incon-

tinence in Wisconsin skilled nursing facilities:

Prevalence and associations in common with fecal

incontinence . J Aging Health 2001 ; 13 (4) : 539 – 47 .

7 . Roe B , Doll H . Prevalence of urinary incontinence

and its relationship with health status . J Clin Nur

2000 ; 9 (2) : 178 – 87 .

8 . Muscatello DJ , Rissel C , Szonyi G . Urinary symp-

toms and incontinence in an urban community:

Prevalence and associated factor in older men and

women . Intern Med J 2001 ; 31 : 151—160 .

9 . Kocak I , Okyay P , Dundar M , et al. Female urinary

incontinence in the west of Turkey: Prevalence, risk

factors and impact on quality of life . Eur Urol 2005 ;

48 : 634 – 641 .

10 . Hunskaar S , Lose G , Sykes D , et al. The prevalence

of urinary incontinence in woman in four European

countries . BJU Int 2004 ; 93 : 324 – 330 .

11 . Melville J , Katon W , Delaney K , et al. Urinary

incontinence in US women: A population-based

study . Arch Intern Med 2005 ; 165 : 537 – 542 .

12 . Hannestad Y , Rortviet G , Sandvik H , Hunskaar S .

A community-based epidemiological survey of

female urinary incontinence . J Clin Epidemiol 2000 ;

53 : 1150 – 1157 .

13 . Tubaro A . Defining overactive bladder: Epidemiology

and burden of disease . Urology 2004 ; 64 (6 Suppl) : 2 – 6 .

14 . Damian J , Martin-Moreno JM , Lobo F , et al. Prevalence

of urinary incontinence among Spanish older people

living at home . Eur Urol 1998 ; 34 (4) : 333 – 338 .

15 . Diokno A , Brock B , Brown M , et al. Prevalence of

urinary incontinence and other urological symptoms

in the noninstitutionalized elderly . J Urol 1986 ;

136 (5) : 1022 – 1025 .

16 . Schulman C , Claes H , Matthis J . Urinary inconti-

nence in Belgium: A population-based epidemio-

logical survey . Eur Urol 1997 ; 32 (3) : 315 – 320 .

17 . Espino D , Palmer R , Miles T , et al. Prevalence and

severity urinary incontinence in elderly Mexican-

American woman . J Am Geriatr Soc 2003 ; 51 :

1580 – 1586 .

18 . Jackson S , Scholes D , Boyko E , et al. Urinary incon-

tinence and diabetes in postmenopausal women .

Diabetes Care 2005 ; 28 : 1730 – 1738 .

19 . Thom D . Variation in estimate of urinary inconti-

nence prevalence in the community: Effects of dif-

ference in definition, population characteristics and

study type . J Am Geriatr Soc 1998 ; 46 (4) : 1 – 15 .

20 . Dallosso H , Matthews R , McGrother C , et al. Diet

as a risk factor for the development of stress urinary

incontinence: A longitudinal study in women . Eur J

Clin Nutrition 2004 ; 58 : 920 – 926 .

21 . Viktrup L , Lose G . The risk of stress incontinence

5 years after first delivery . Am J Obstet Gynecol

2001 ; 185 (1) : 1 – 10 .

22 . Samuelsson E , Arne Victor F.T , Svardsudd K . Five-

year incidence and remission rates of female urinary

incontinence in a Swedish population less than 65

years old . Am J Obstet Gynecol 2000 ; 183 (3) : 1 – 12 .

23 . Moller LA , Lose G , Jorgensen T . Incidence and

remission rates of lower urinary tract symptoms at

one year in women aged 40–60: Longitudinal study .

BMJ 2000 ; 320 : 1429 – 1432 .

24 . Herzog AR , Diokno AC , Brown MB , et al. Two-year

incidence, remission, and change patterns of urinary

incontinence in noninstitutionalized older adults .

J Gerontol 1990 ; 45 (2) : M67 – M74

25 . McGrother C , Resnick M , Yalla S , et al. Epidemiology

and etiology of urinary incontinence in the elderly .

World J Urol 1998 ; 16 : S3 – S9 .

26 . Giorgiou A , Potter J , Brocklehurst J . Measuring the

quality of urinary continence care in long term care

facilities: An analysis of outcome indicators . Age

Ageing 2001 ; 30 : 63 – 66 .

27 . Toba K , Ouchi Y , Orimo H , et al. Urinary inconti-

nence in elderly inpatients in Japan: A comparison

between general and geriatric hospitals . Aging

1996 ; 8 (1) : 47 – 54 .

28 . Landi F , Cesari M , Russo A , Onder G , et al.

Potentially reversible risk factors and urinary incon-

tinence in frail older people living in community .

Age Ageing 2003 ; 32 : 194—199 .

29 . Mason L , Glenn S , Walton I , et al. The prevalence of

stress incontinence during pregnancy and following

delivery . Midwifery 1999 ; 15 : 120—128 .

12 M.C.M. Lapitan

30 . Foldspang A , Hvidman L , Mommsen S , et al.

Risk of postpartum urinary incontinence associated

with pregnancy and mode of delivery . Acta Obstet

Gynecol Scand 2004 ; 83 : 923 – 927 .

31 . Burgio K , Zyczynski H , Locher J , et al. Urinary

incontinence in the 12-month postpartum period .

Obstet Gynecol 2003 ; 102 : 1291 – 1298 .

32 . Chaliha C , Kalia V , Stanton S , et al. Antenatal

prediction urinary and fecal incontinence . Obstet

Gynecol 1999 ; 94 (5) : 689 – 694 .

33 . Hvidman L , Foldspang A , Mommsen A , et al.

Postpartum urinary incontinence . Acta Obstet

Gynecol Scand 2003 ; 82 : 556 – 563 .

34 . Farrell S , Allen V , Baskett T . Parturition and urinary

incontinence in primiparas . Obstet Gynecol 2001 ;

97 (3) : 350 – 356 .

35 . Donnellan S , Duncan H , MacGregor , et al.

Prospective assessment of incontinence after radical

retropubic prostatectomy: Objective and subjective

analysis . Urology 1997 ; 49 : 225 – 230 .

36 . Ojdeby G , Claezon A , Brekkan E , et al. Urinary

incontinence and sexual impotence after radical pros-

tatectomy . Scand J Urol Nephrol 1996 ; 30 : 473 – 477 .

37 . McCammon K , Kolm P , Main B , et al. Comparative

quality of life analysis after radical prostatectomy

or external beam radiation for localized prostate

cancer . Urology 1999 ; 54 : 509 – 516 .

38 . Walsh P , Marschke P , Ricker D , et al. Patient-reported

urinary continence and sexual function after anatomic

radical prostatectomy . Urology 2000 ; 55 : 58 – 61 .

39 . Horie S , Tobisu K , Fujimoto H , et al. Urinary

incontinence after non–nerve-sparing radical pros-

tatectomy with neoadjuvant androgen deprivation .

Urology 1999 ; 53 : 561 – 567 .

40 . Goluboff ET , Saidi JA , Mazer S , et al. Urinary con-

tinence after radical prostatectomy: The Columbia

experience . J Urol 1998 ; 159 : 1276 – 1280 .

41 . Lowe BA . Comparison of bladder neck preserva-

tion to bladder neck resection in maintaining post-

prostatectomy urinary incontinence . Urology 1996 ;

48 : 889 – 893 .

42 . Weldon VE , Tavel FR , Neuwirth H . Continence,

potency and morbidity after radical perineal prosta-

tectomy . J Urol 1997 ; 158 : 1470 – 145 .

43 . Gray M , Petroni G , Theodorescu D . Urinary func-

tion after radical prostatectomy: A comparison of

the retropubic and perineal approaches . Urology

1999 ; 53 : 881 – 891 .

44 . Bishoff JT , Motley G , Optenberg SA , et al. Incidence

of fecal and urinary incontinence following radical

perineal and retropubic prostatectomy in a national

population . J Urol 1998 ; 160 : 454 – 458 .

45 . Eastham JA , Kattan MW , Rogers E , et al. Risk fac-

tors for urinary incontinence after radical prostatec-

tomy . J Urol 1996 ; 156 : 1707 – 1713 .

46 . Van Kampen M , De Weerdt W , Van Poppel H , et al.

Prediction of urinary continence following radical

prostatectomy . Urol Int 1998 ; 60 : 80 – 84 .

47 . Poon M , Ruckle H , Bamshad DBR , et al. Radical

retropubic prostatectomy: Bladder neck preservation

versus reconstruction . J Urol 2000 ; 163 : 194 – 198 .

48 . Catalona WJ , Carvalhal GF , Mager DE , Smith

DS . Potency, continence and complication rates in

19,870 consecutive radical retropubic prostatecto-

mies . J Urol 1999 ; 162 : 433 – 438 .

49 . Kao TC , Garner D , Foley J , et al. Multicenter patient

self-reporting questionnaire on impotence, incon-

tinence and stricture after radical prostatectomy . J

Urol 2000 ; 163 : 858 – 864 .

50 . Brown J , Seeley D , Fong J , et al. Urinary incon-

tinence in older women: Who is at risk? Obstet

Gynecol 1996 ; 87 (5) : 715 – 721 .

51 . Hagglund D , Olsson H , Lepper J . Urinary inconti-

nence: An unexpected large problem among young

females. Results from a population-based study .

Family Practice 1999 ; 16 (5) : 506 – 509 .

52 . Lagace E , Hansen W , Hickner J . Prevalence and

severity of urinary incontinence in ambulatory adult.

An UPRnet study . J Fam Pract 1993 ; 6 (6) : 610 – 614 .

53 . Graham C , Mallett V . Race as a predictor of urinary

incontinence and pelvic organ prolapse . Am J Obstet

Gynecol 2001 ; 185 (1) : 1 – 8 .

54 . Thom D , Van den Eeden S , Ragins A , et al.

Differences in prevalence of urinary incontinence by

race/ethnicity . J Urol 2006 ; 175 (1) : 259 – 264 .

55 . Brown J , Grady D , Ouslander J , et al. Prevalence

of urinary incontinence and associated risk factors

in postmenopausal women . Obstet Gynecol 1999 ;

94 (1) : 66 – 70 .

56 . Duong T , Korn A . A comparison of urinary incon-

tinence among African-American, Asian, Hispanic,

and white women . Am J Obstet Gynecol 2001 ;

184 (6) : 1083 – 1086 .

57 . Mattox TF , Bhatia NN The prevalence of uri-

nary incontinence or prolapse among white and

Hispanic women . Am J Obstet Gynecol 1996 ;

174 (2) : 646 – 648 .

58 . Howard D , Delancey J , Tunn R , et al. Racial differ-

ences in the structure and function of the stress uri-

nary continence mechanism . Obstet Gynecol 2000 ;

95 (5) : 713 – 717 .

59 . Lewis C , Schrader R , Many A , et al. Diabetes and

urinary incontinence in 50- to 90-year-old women:

A cross-sectional population-based study . Am J

Obstet Gynecol 2005 ; 193 : 2154 – 2158 .

60 . Danforth K , Townsend M , Lifford K , et al. Risk

factors for urinary incontinence among middle-aged

women . Am J Obstet Gynecol 2006 ; 194 : 339 – 345 .

61 . Grodstein F , Fretts R , Lifford K , et al. Association of

age, race, and obstetric history with urinary symptoms

1. Epidemiology of Urinary Incontinence 13

among women in the Nurses’ Health Study . Am J

Obstet Gynecol 2003 ; 189 (2) : 428 – 434 .

62 . Sze E , Jones W , Ferguson J , et al. Prevalence

of urinary incontinence symptoms among black,

white and hispanic women . Obstet Gynecol 2002 ;

99 (4) : 572 – 575 .

63 . Ushiroyama T , Ikeda A , Ueki M . Prevalence,

incidence and awareness in the treatment of men-

opausal urinary incontinence . Maturitas 1999 ;

33 : 127 – 132 .

64 . Wilson PD , Herbison R , Herbison G , et al. Obstetric

practice and the prevalence of urinary incontinence

3 months after delivery . Br J Obstet Gynecol 1996 ;

103 : 154 – 161 .

65 . McKinnie V , Swift SE , Wang W , et al. The effect of

pregnancy and mode of delivery on the prevalence

of urinary and fecal incontinence . Am J Obstet

Gynecol 2005 ; 193 : 512 – 518 .

66 . MacLennan AH , Taylor AW , Wilson DH , et al. The

prevalence of pelvic floor discorders and their rela-

tionship to gender, age, parity and mode of delivery .

Br J Obstet Gynecol 2000 ; 107 (12) : 1460 – 1470 .

67 . Vinker S , Kaplan B , Nakar S , et al. Urinary incon-

tinence in women: Prevalence, characteristics and

effect on quality of life. A primary care clinic study .

Isr Med Assoc J 2001 ; 3 (9) : 663 – 668 .

68 . Kuh D , Cardozo L , Hardy R . Urinary incontinence in

middle aged women: Childhood enuresis and other

lifetime risk factors in a British prospective cohort .

J Epidemiol Commun Health 1999 ; 53 (8) : 453 – 458 .

69 . Dolan L , Casson K , McDonald P , Ashe R . Urinary

incontinence in Northern Ireland: A prevalence

study . BJU Int 1999 ; 83 : 760 – 766 .

70 . Sherburn M , Guthrie J , Dudley E , et al. Is inconti-

nence associated with menopause? Obstet Gynecol

2001 ; 98 (4) : 628 – 633 .

71 . Chen YC , Chen GD , Hu SW , et al. Occurrence of

storage and voiding dysfunction affected by meno-

pausal transition or associated with the normal age-

ing process . Menopause 2003 ; 10 (3) : 203 – 208 .

72 . Holtendahl K , Hunskaar S . Prevalence, 1-year inci-

dence and factors associated with urinary inconti-

nence: A population based study of women 50–74

years of age in primary care . Maturitas 1998 ;

28 : 205 – 211 .

73 . Richter H , Burgio K , Clements R , et al. Urinary and

anal incontinence in morbidly obese women con-

sidering weight loss surgery . Obstet Gynecol 2005 ;

106 (6) : 1272 – 1277 .

74 . Holroyd-Leduc J , Mehta K , Covinsky K . Urinary

incontinence and its association with death, nurs-

ing home admission and functional decline . J Am

Geriatr Soc 2004 ; 52 : 712 – 718 .

75 . Jorgensen L , Engstad T , Jacobsen B . Self-reported

urinary incontinence in noninstitutionalized long-

term stroke survivors: A population-based study .

Arch Phys Med Rehab 2005 ; 86 : 416 – 420 .

76 . Jackson S , Scholes D , Boyko E , et al. Urinary incon-

tinence and diabetes in postmenopausal women .

Diabetes Care 2005 ; 18 : 1730—1738 .

77 . Hendrix S , Cochrane B , Nygaard I , et al. Under-

standing the burden of stress urinary incontinence

in Europe: A qualitative review of the literature . Eur

Urol 2004 ; 46 : 15 – 27 .

78 . Goldstein S , Johnson S , Watts , et al. Incidence of

urinary incontinence in postmenopausal women

treated with raloxifene or estrogen . Menopause

2005 ; 12 (2) : 160 – 164 .

79 . Buchsbaum G , Chin M , Glantz C , Guzick D .

Prevalence of urinary incontinence and associated

risk factors in a cohort of nuns . Obstet Gynecol

2002 ; 100 (2) : 226 – 229 .

80 . Nygaard I , Turvey C , Burn T , et al. Urinary inconti-

nence and depression in middle-aged United States

women . Obstet Gynecol 2003 ; 101 : 49 – 56

81 . Lifford K , Curhan G , Hu F , et al. Type 2 diabetes

mellitus and risk of developing urinary inconti-

nence . J Am Geriatr Soc 2005 ; 53 : 1851 – 1857 .

82 . Arya , L , Myers D , Jackson N . Dietary caffeine

intake and the risk for detrusor instability: A case-

control study . Obstet Gynecol 2000 ; 96 : 85 – 89 .

83 . Hannestad YS , Rortveit G , Daltveit AK , Hunskaar

S . Are smoking and other lifestyle factors associated

with female urinary incontinence? The Norwegian

EPINCONT Study . Br J Obstet Gynecol 2003 ;

110 (3) : 247 – 254 .

84 . Song , YF , Zhang WJ , Song J , Xu B . Prevalence

and risk factors of urinary incontinence in Fuzhou

Chinese women . Chin Med J (Engl) 2005 ;

118 (11) : 887 – 892 .

85 . Vandoninck V , Bemelmans B , Mazzetta C , et al. The

prevalence of urinary incontinence in community-

dwelling married women: A matter of definition .

BJU Int 2004 ; 94 (9) : 1291 – 1295 .

86 . Araki I , Beppu M , Kajiwara M , et al. Prevalence and

impact of generic quality of life of urinary incon-

tinence in Japanese working women: Assessment

by ICI-Q questionnaire and SF-36 health survey .

Urology 2005 ; 66 : 88 – 93 .

87 . Holroyd-Leduc J , Mehta K , Covinsky K . Urinary

incontinence and its association with death, nurs-

ing home admission and functional decline . J Am

Geriatr Soc 2004 ; 52 : 712 – 718 .

88. Nakanishi N, Tatara K, Shinsho F, et al. Mortality in

relation to urinary and faecal incontinence in elderly

people living at home. Age Ageing 199; 28:301–306.

15

Part II

Current Concepts on Anatomy

and Physiology

17

Central Control of Micturition

The apparently simple repertoire of bladder func-

tion comprising the storage and periodic elimi-

nation of urine is under the complex regulatory

control of a neural system that involves three sets

of peripheral nerves (the T11–L2 originating sym-

pathetic hypogastric nerves, the S2–S4 originat-

ing parasympathetic pelvic nerves and the sacral

somatic pudendal nerves) [1– 3] , the sacral spinal

cord, and the higher brain centers located in the

brain stem, diencephalon, and cerebral cortices.

The central nervous system centers not only allow

for the perception of bladder fullness but also deter-

mine the “correctness” implicated in the social part

of the micturition act and coordinate the activities

of the striated and smooth muscles involved in the

micturition reflex. Such coordination is achieved

via a series of locally organized reflexes that use all

these types of peripheral nerves, interneurons, and

vesical parasympathetic ganglia to convey inhibi-

tory and excitatory input to maintain a reciprocal

relationship between the bladder and the urethral

outlet [4] .

Animal experiments in the cat have shown that

in spinal health, sensory stimuli associated with the

sensation of bladder fullness ascend via the spinal

cord to an integrative brain center—the periaquae-

ductal grey (PAG)—and are relayed to the pontine

micturition center (PMC), which promotes micturi-

tion via excitatory parasympathetic outflow to the

bladder [5, 6] . In humans, the use of functional

imaging technology such as single photon emis-

sion computerized tomography (SPECT), positron

emission tomography (PET) [7– 12] , and functional

magnetic resonance imaging (fMRI) [13] confirmed

that the PAG and the PMC are key centers in the

supraspinal control of micturition and continence.

In addition to the former centers, areas such as the

anterior cingulate gyrus, the prefrontal cortex, and

the insula appear to be involved in the perception

of a full versus empty bladder. One study reported

that activation of the medial premotor cortex,

basal ganglia, and cerebellum may be involved in

continence in health [13] , whereas another study

showed the thalamus was also activated when the

bladder was full [11] . A schematic representation

of possible connections between the brain areas

that appear to be involved in micturition control is

given in Fig. 2.1 (adapted from [14] ).

Functional imaging techniques are now being

applied in pathological conditions. Women with

urinary retention due to a primary disorder of ure-

thral sphincter relaxation (Fowler’s syndrome) had

activation of cortical regions without midbrain or

brain stem activity, in contrast to control subjects

[12] . Activity in the latter two areas was normalized

following sacral nerve stimulation [12] . Increased

activation of cortical areas but with a weak activa-

tion of the orbitofrontal cortex was seen in patients

with idiopathic detrusor overactivity (IDO) on fill-

ing as opposed to strong activation of the orbitofron-

tal cortex seen in control subjects [15] . Activation

of the primary motor cortex, the cerebellum, and

the cingulate gyrus also was seen in patients with

urgency incontinence during the first hours of sacral

Chapter 2

Neurophysiology of Micturition:

What’s New?

Apostolos Apostolidis and Clare J. Fowler

18 A. Apostolidis and C.J. Fowler

neuromodulation [16] . The significance of these

findings are being further investigated in light of

results from anxiety provocation studies showing

activation of similar areas in the prefrontal, cin-

gulate, and insular regions [17] . Similarly, studies

on the effect of distraction on painful conditions

showed activation of the PAG and the prefrontal,

cingulate, and thalamic areas [18] .

Reflex Mechanisms Involved

in Micturition Control

The bladder and the urethral sphincters exhibit

excitatory and inhibitory interactions via a series of

reflexes that are either organized at a spinal level or

have a more complicated central organization involv-

ing spinal and spinobulbospinal pathways. Reflexes

promoting urine storage are served by sympathetic

and somatic (pudendal) nerves that mediate efferent

input to the urethral sphincter and inhibitory input

to the bladder, whereas reflexes promoting micturi-

tion are served by parasympathetic nerves mediating

efferent input to the detrusor and inhibitory input to

the urethral sphincters [19] .

Evidence to support the presence of such reflexes

in humans has been provided by urodynamic stud-

ies [20] . During filling cystometry, a low detrusor

pressure is maintained until micturition threshold

is reached, in parallel with an increase in urethral

electromyographic activity. It is thought that para-

sympathetic afferent firing from the bladder during

filling activates the external urethral sphincter via

a synapse with sacral interneurons, which results

in stimulation of the pudendal urethral efferents

(the “guarding reflex”). In addition, in some spe-

cies a sympathetically mediated reflex is believed

to inhibit detrusor contraction and promote urethral

smooth muscle contraction during bladder filling

[4, 21] . When micturition threshold is reached and

voiding is initiated, urethral sphincter activity ceases

first, followed by a rise in detrusor pressure due to

detrusor contraction and flow of urine. Micturition is

further promoted by a bladder-to-bladder excitatory

Fig. 2.1. Schematic representation of possible connections and interactions existing among various brain structures

thought to be involved in micturition control (as in reference [14] ). The exact direction of interactions has yet to be

clarified. PAG = Periaqueductal gray

2. Neurophysiology of Micturition: What’s New? 19

reflex and a bladder-to-urethral sphincter inhibitory

reflex, which are activated when the bladder is full

[4, 21] .

The role of interneurons at various levels of the

spinal cord appears to be central in the regulation

of reflex activity, serving as integrating areas of

afferent projections from both the bladder and

the urethra [4, 21] . Using interneuronal path-

ways, pudendal afferent activity from the urethral

sphincter and also from other urogenital sites can

inhibit the excitatory parasympathetic outflow to

the bladder. In support, stimulation of pudendal

afferents has been shown to successfully suppress

the sensation of urgency [22] and improve urody-

namic parameters [23] in patients with IDO and

urgency incontinence. Similarly, peripheral affer-

ent stimulation (tibial nerve) effectively controlled

symptoms of overactive bladder [24] . It has been

recently proposed that a bladder–sphincter–bladder

reflex pathway in which the bladder-to-external

urethral sphincter excitatory reflex activates the

urethral sphincter-to-bladder inhibitory reflex via

interneuronal synapses facilitates urine storage [4] .

Inhibition of excitatory interneurons and pregan-

glionic parasympathetic neurons are proposed as

additional mechanisms contributing to suppression

of bladder activity and urine storage. It is possible

that such augmented inhibitory pathways constitute

part of the mechanism by which urinary retention

occurs in women with primary disorder of ure-

thral sphincter relaxation (Fowler’s syndrome). In

contrast, activation of excitatory interneurons and

preganglionic parasympathetic neurons contributes

to maintenance of bladder activity until completion

of bladder emptying. At the same time, activation

of interneurons by bladder afferents stimulates

parasympathetic efferent inhibitory activity to the

urethral smooth muscle.

The complete explanation for the surprising

observation that sacral nerve stimulation (SNS) is

effective in the treatment of both refractory detru-

sor overactivity [21] and urinary retention [25]

remains to be discovered. However, activation of

the bladder–sphincter–bladder reflex pathway now

is proposed as a possible mechanism by which

SNS suppresses detrusor contraction in conditions

of bladder overactivity [4, 21] . In women with

urinary retention, however, the initial pathophysi-

ology is different, i.e., an upregulated sphincter–

bladder reflex. Restoration of bladder sensation

and reactivation of activity in brain areas receiving

afferent input from the bladder suggests that, in

these cases, SNS suppresses inhibitory interneu-

rons and releases the bladder from that augmented

sphincter–bladder reflex.

In addition to the spinal control of the micturi-

tion reflexes, various areas of the brain are believed

to regulate reflex activity. In the cat, stimulation of

a lateral pontine area known as “the urine storage

center” results in an increase in sphincter EMG

activity and inhibition of detrusor smooth mus-

cle activity. Stimulation of a medial pontine area

considered to be the “PMC” results in inhibition

of sphincter EMG activity and increase in detru-

sor smooth muscle activity. In addition, Onuf’s

nucleus, which is involved in the regulation of the

activity of sphincter motoneurons, receives projec-

tions from bulbospinal pathways. Research into the

neurotransmitters involved in these pathways (nore-

pinephrine, serotonin) has demonstrated facilitatory

glutamatergic excitatory transmission to the sphinc-

ter motoneurons, and this resulted in the develop-

ment of oral pharmacotherapy (duloxetine) for the

treatment of stress urinary incontinence [26] .

Peripheral Control of Micturition

Bladder sensation is conveyed by two types of

afferent axons: the myelinated Aδ-fibers, which

are sensitive to mechanical stimuli, e.g., distension,

stretch, and the primarily nociceptive, unmyeli-

nated C-fibers. The latter have a high mechanical

threshold and do not normally respond to bladder

distension but do respond to noxious stimuli, such

as chemical irritation and cooling. Thus, in con-

ditions of health, it is the Aδ-fibers that convey

information about bladder filling, whereas C-fibers

remain largely quiescent. Afferent nerve endings

form a dense network in the bladder suburothe-

lium ( Fig.2.2 ), with occasional fibers penetrating

the basal lamina to appear in close apposition

to urothelial cells. The efferent parasympathetic

input, mediated by acetylcholine (ACh) receptors

in the bladder wall, results in contraction of the

detrusor muscle [19] .

Detrusor overactivity is the most common uro-

dynamic abnormality in suprasacral lesions; it

occurs in patients with spinal cord injury or mul-

tiple sclerosis, and therefore it is referred to as

20 A. Apostolidis and C.J. Fowler

neurogenic detrusor overactivity (NDO). Animal

studies have proposed that spinal NDO is related

to the emergence of an aberrant C-fiber–driven

sacral spinal reflex [27] . Following the disruption of

the spinobulbospinal pathways, capsaicin-sensitive

C-fiber afferents in the suburothelium undergo

plastic changes, including hypertrophy related to

an increase in neurofilament content, and increased

excitability associated with elevated expression of

tetrodotoxin-sensitive Na

2+ channels [19] , conse-

quently becoming sensitive to mechanical stimuli

(mechanosensitive). Such changes lead to increased

afferent firing to the spinal cord during bladder

distension, followed by increased parasympathetic

input to the bladder, and thus detrusor overactivity.

Such animal observations became the basis

for the use of deafferenting neurotoxins, such as

capsaicin (CAPS) and resiniferatoxin (RTX), in

the treatment of lower urinary tract symptoms

(LUTS). Clinical and basic research results from

these studies provided evidence for activation of a

similar, C-fiber–mediated spinal reflex in humans

with spinal NDO [19, 27] . Immunohistochemical

studies of the suburothelium of patients with spi-

nal NDO using general neuronal markers such as

PGP9.5 [28] and S100 [29] demonstrated increased

suburothelial innervation in patients compared to

controls. Intravesical application of either CAPS or

RTX reduced the suburothelial nerve fiber density

in patients who responded to treatment, suggesting

a pathophysiological role of the augmented subu-

rothelial nerve network in neurogenic overactive

bladders [28, 29] .

Immunohistochemical studies also have con-

firmed the presence of sensory receptors in subu-

rothelial nerves, such as the capsaicin or vanilloid

receptor [transient receptor potential vanilloid 1

(TRPV1)] and the ATP-gated purinergic receptor

P2X

3 ( Fig. 2.3 ), both of which have been associ-

ated with normal bladder mechanosensation in

animal experiments [32– 34] ; TRPV1-deficient ( −/− )

mice display enhanced short-term voluntary urina-

tion and increased frequency of non-voiding con-

tractions on urodynamics, increased cystometric

capacity, and inefficient voiding [32] . The P2X

3 −/−

mice exhibit increased cystometric capacity and

Fig. 2.2. Electron micrographs of the lamina propria space of the human bladder (courtesy of Professor D.N. Landon,

Institute of Neurology, University College London). Bladder biopsies were obtained via a flexible cystoscope, fixed

in 3% glutaraldehyde in 0.1 M Na cacodylate buffer, and processed routinely for transmission electron microscopy.

Ultrathin sections were obtained from the midpoint of each biopsy specimen. ( a ) Image of a section through part of

the nerve close to the inner surface of the detrusor muscle, showing small myelinated and unmyelinated axons and

their Schwann cells surrounded by a thin perineurial sheath (P). ( b ) Image of a section though the superficial aspect

of the lamina propria, showing the base of the urothelium (U), its basal lamina (BL), beneath which are layers of

flattened fibroblasts (F) and collagen fibrils. Among the latter structures, Schwann cells (S) and unmyelinated axons

(A) can be identified. Scale = 2 µm in both ( a ) and ( b )

2. Neurophysiology of Micturition: What’s New? 21

decreased frequency of voiding [33] . Patients

with NDO and, to a lesser degree, those with

IDO were found to have increased TRPV1- and

P2X

3 -immunoreactive (-IR) suburothelial innerva-

tion compared to controls [28, 35, 36] ( Fig. 2.4 ).

Intravesical instillations of RTX in NDO patients

resulted in dramatic decreases of TRPV1- and

P2X

3 -IR fibers only in clinical responders [28, 35]

and produced significant improvements in LUTS

and urodynamic parameters in some patients with

IDO [37] . As previous preclinical research had

characterized CAPS and RTX as C-fiber toxins, the

findings in human studies were considered to pro-

vide further evidence for a role of the suburothelial

C-fiber afferents expressing TRPV1 and/or P2X

3 in

the pathophysiology of NDO and IDO.

It recently was proposed that the TRPV1 located

in synaptic vesicles in DRG neurons is coexpressed

and interacts with proteins active in exocytosis,

such as synaptotagmin and snapin, a colocalization

that extends to the nerve axons [38] . The presence

of P2X

3 in terminal afferent boutons with complex

Urine

(pH changes, temperature changes, mechanical stretch)

b1

mf

def

TRPV1

TRPV

TRPV1 TRPV1

P2X3

M3

M3M3

M2

M2 M2M2

M2

ATP

NK1NK1

ATP/ACh

ACh

ATP

P2X3

P2Y2

α7α3

NGF

SP

NGF

P2Y6

P2Y4

P2X3

Fig. 2.3. A cartoon representation of identifiable ultrastructural components of the human bladder wall with known

or proposed locations of receptors and sites of release of neuropeptides and growth factors thought to be involved in

bladder mechanosensation, as updated from relevant figures in references [30] and [31] . Abbreviations: bl = basal

lamina of urothelium; mf = myofibroblast layer; det = detrusor muscle, see also [30] for more detailed explanation

of ultrastructural elements. It has been proposed that the urothelial–suburothelial pathways of bladder mechano-

sensation are served by a complex system of interactions between the release of neurotransmitters and actions on

respective receptors located on these structural constituents. All connections identified by arrows (see [31] for arrow

identification) are thought to be upregulated in detrusor overactivity. Identification of receptors, neuropeptides and

neurotransmitters: TRPV1 – transient receptor potential vanilloid 1; P2X

3 – ionotropic purinergic receptor type 3;

P2Y

2 /P2Y 4 /P2Y 6 – metabotropic purinergic receptors types 2, 4, and 6; M2/M3 – muscarinic acetylcholine receptors

types 2 and 3; α

3 / α

7 – nicotinic acetylcholine receptors types 3 and 7; NK1 – neurokinin receptor type 1 (SP recep-

tor); SP – Substance P; NGF – Nerve growth factor; ACh – acetylcholine; ATP – adenosine triphosphate

22 A. Apostolidis and C.J. Fowler

synaptic properties [39] and its colocalization with

TRPV1 in the CNS have been shown [40] , and

there is indirect evidence for colocalization with

TRPV1 in bladder suburothelial afferents [28, 35] .

Further to its role in normal and pathological

sensation of bladder fullness, the capsaicin recep-

tor TRPV1 also is known to be a thermal receptor

activated by temperatures higher than 43°C. In

the same superfamily of transient receptor poten-

tial (TRP) channels, another five thermoreceptors

have been identified, with distinct temperature

thresholds [41] . A bladder-cooling reflex has been

described in animals and humans, which is thought

to be mediated by C-fiber afferents [42– 44] . A recep-

tor sensitive to low temperatures and menthol that

possibly mediates this reflex recently was identi-

fied and cloned: the TRPM8 receptor [45, 46] .

Its presence was shown in suburothelial fiberlike

structures of both fine and thicker caliber in the

human bladder [47] . TRPM8 immunoreactivity

was significantly increased in fine-caliber axons

in patients with IDO compared to controls and

the numbers of immunoreactive axons and fibers

correlated significantly with frequency scores in

those patients [47] . As intravesical instillation of

menthol was shown to decrease threshold activa-

tion of C-fibers [43] , these findings were proposed

as a partial explanation for increased frequency in

IDO patients [47] . Interestingly, no correlation was

found with urgency scores.

Immunohistochemistry also has demonstrated

the presence of the sensory neuropeptides substance

P (SP) and calcitonin gene-related peptide (CGRP)

in suburothelial afferents [48, 49] . Substance P

has been shown to colocalize with glutamate in

primary afferent terminals [50] , whereas all SP-IR

fibers contain colocalized CGRP [49] and SP and

CGRP are found on more than 90% of TRPV1-

immunoreactive fibers that traverse the rat blad-

der wall [51] . Women with IDO were found to

have increased density of suburothelial SP- and

CGRP-immunoreactive fibers compared to con-

trols [49] , while treatment with intravesical vanil-

loids resulted in marked decrease of TRPV1, SP,

and CGRP immunoreactivity in the bladder wall of

rats [52] . Several animal studies support an asso-

ciation between SP-CGRP and bladder sensation;

SP levels in the rat bladder were found to inversely

correlate to the micturition threshold [52, 53] .

Increased SP and CGRP content of spinalized rat

bladders was significantly reduced after capsaicin

application and was associated with a decrease in

urodynamic-proven DO [54] . Increasing evidence

suggests a role of these neuropeptides also in

human bladder sensation, with urinary levels of SP

correlating with degree of urgency or bladder pain

[55– 57] .

Both SP and CGRP appear to be involved in

LUT neuromodulation via complex central and

peripheral interactions ( Fig. 2.3 ). Neurotrophic fac-

tors such as the nerve growth factor (NGF) and the

glial-derived neurotrophic factor (GDNF) regulate

the expression of TRPV1 and P2X

3, respectively,

via modulation of nociceptive dorsal root ganglion

0.0

Controls

Nerve density

NDO

*

IDO Controls NDO IDO

P2X3

*

TRPV1

0.5

1.0

1.5

0.00

0.25

0.50

0.75

Fig. 2.4. Suburothelial nerve immunoreactivity to the sensory receptors P2X

3 ( left ) and TRPV1 ( right ) was found to

be significantly increased in patients with NDO (* signifies a statistical P value of less than 0.05) and, to a lesser,

statistically non-significant degree, in patients with IDO when compared to control subjects

2. Neurophysiology of Micturition: What’s New? 23

cells expressing SP and CGRP [58, 59] . Substance

P also can induce directly the expression of NGF

[60] and has been shown to activate the nonselec-

tive cation TRP channels via a G-protein–coupled/

phospholipase C (PLC) pathway in afferent neu-

rons [61] . Experimental data on ganglion neurons

have suggested that SP, ATP, and ACh activate

nonselective cation channels by a common intra-

cellular metabolic process [62] . In turn, activation

of TRPV1 on small afferent nerves, as through

vanilloid application, promotes vesicular release

of SP and CGRP via an ATP-P2Y–mediated path-

way [63] . Further, SP has been associated with

sensitization of the P2X

3 and heteromeric P2X

2/3

receptors to the action of ATP via protein-kinase-

C–mediated phosphorylation [64] .

Ultrastructural studies have shown that subu-

rothelial nerves are packed with both clear and

dense-cored vesicles, whose contents have not been

identified yet ( Fig. 2.5 ). The presence of SP has

been reported in large granular synaptic vesicles

in axon terminals of the rat LUT [65] and human

bladder [48] , and CGRP was found to colocalize

with SP in synaptic vesicles in peripheral sensory

nerves [66] .

However, traditionally, clear vesicles are believed

to contain ACh in cholinergic nerve endings [67,

68] . In addition, the association of clear vesicles

with large, dense-cored vesicles also is known to

occur in cholinergic nerves [69] , whose terminals

are reported to release ACh and ATP or a related

purine [70, 71] . The presence of muscarinic ACh

receptors (MAChRs) in nerve fibers in the subu-

rothelium and mainly the detrusor recently has

been demonstrated in human overactive and painful

bladders [72] ( Fig. 2.3 ). This study also has claimed

the presence of MAChRs types 2 and 3 in subu-

rothelial cells with long bipolar processes, thought

to be myofibroblastlike [72] . Immmunoreactivity

for both types of MAChRs in these suburothelial

cells was found to be increased in IDO bladders

compared to controls. Furthermore, a shift was

noted in mediation of detrusor contractions in

NDO bladders from M3AChRs to M2AChRs,

implying a possible functional role for M2AChRs

in bladder disease states [73] . In health, despite the

M2AChRs outnumbering the M3AChRs by a ratio

of 3:1, in vitro experiments have shown that detru-

sor contractions are mediated by the M3AChRs

[74] . Activation of muscarinic type 1 receptors

may facilitate the release of other transmitters; the

facilitatory mechanisms were found to be enhanced

in the rat overactive bladder [75] .

Muscarinic receptors also have been identi-

fied in the human bladder urothelium [72, 76] ,

which represents the main nonneuronal source of

ACh release during bladder filling [77] ( Fig. 2.3 ).

Urothelial release of ACh increases with detru-

sor stretch [77] . It was proposed that in health a

basal release of ACh from the urothelium dur-

ing bladder filling acts on smooth muscle cells’

MACh receptors to regulate bladder tone or even

on MACh receptors in suburothelial nerves [77] .

However, the presence of functional muscarinic

receptors in the urothelium implies a possible

autocrine role for urothelially released ACh, and a

yet unidentified urothelium-derived inhibitory fac-

tor has been shown to be released upon stimulation

of muscarinic receptors [76] . Moreover, functional

nicotinic ACh receptors (nAChRs) recently were

identified in the rat bladder urothelium [78] ( Fig. 2.3 ).

Two opposing nicotinic signaling pathways appear

to exist: an inhibitory one mediated by type α

7

nAChRs and an excitatory one mediated by type

α

3 nAChRs. It was proposed that activation of

these pathways by ACh released by the urothelium

takes place at different phases of bladder filling,

urine storage being facilitated by activation of the

inhibitory α

7 nAChRs, while voiding is promoted

by activation of the excitatory α

3 nAChRs [78] .

In addition to TRPV1 and P2X

3 [79– 82] , the

urothelium also was found to express TRPM8 [47]

and neurotrophic factors (NGF) [83] and to release

tachykinins [84] , prostaglandins [85] , NO [86, 87] ,

and ATP [88] , further evidence for a possible inter-

action with the suburothelial nerves ( Fig. 2.3 ). The

urothelium was shown to be the main source of ATP

release in response to bladder stretch [89] ; it was

proposed that ATP released in such manner would

bind to suburothelial P2X

3 , thus initiating signal-

ing for the perception of bladder fullness [39] . In

support of this hypothesis it was shown that subu-

rothelial afferents in P2X

3 −/− mice displayed a sig-

nificant delay and increased threshold of activation

by P2X agonists [34] . A proposed nociceptive role

for ATP [90] and a significant reduction in nocic-

eptive behavioral responses noted in P2X

3 −/− mice

after injection of ATP and formalin [33] was taken

as further evidence for the presence of urothelio-

suburothelial sensory pathways. ATP release from

the urothelium appears to be partly due to vesicular

exocytosis [91] . Acetylcholine was found to interact

a

bc

Fig. 2.5. Electron micrographs of unmyelinated suburothelial nerves of the human bladder lamina propria space

containing clear and dense-cored vesicles (courtesy of Professor D.N. Landon, Institute of Neurology, University

College London). Bladder biopsies were obtained via a flexible cystoscope, fixed in 3% glutaraldehyde in 0.1 M Na

cacodylate buffer, and processed routinely for transmission electron microscopy. Ultrathin sections were obtained

from the midpoint of each biopsy specimen. ( a ) An oblique section through unmyelinated nerves containing several

axons filled with clear and dense-cored vesicles ( arrows ), in between layers of fibroblast processes. ( b ) A transverse

section through unmyelinated axon varicosities packed with clear and dense-cored vesicles ( arrows ) in close contact

with portions of fiboblasts and myofibroblasts. ( c ) An example of axonal varicosity of an unmyelinated nerve with

arrows identifying clear vesicle release sites. Scale = 1µm. in all photos

2. Neurophysiology of Micturition: What’s New? 25

with ATP, significantly increasing its release both

in normal and pathological bladder conditions [91] .

The presence of P2X

3 receptors in the urothelium

may imply an autocrine role for ATP.

A reciprocal interaction also may exist between

ATP and TRPV1. In animal experiments, TRPV1

was found to act as an initiator for urothelial

ATP release and as a mediator of hypotonically

evoked ATP release [32] . In cultured cells express-

ing TRPV1, ATP-potentiated TRPV1 responses

through activation of metabotropic P2Y1 recep-

tors via a G-protein–coupled dependent pathway

[92] . Importantly, when these cells expressed both

TRPV1 and Gq/11-coupled MACh receptors, extra-

cellular application of ACh significantly increased

the magnitude of currents evoked by either capsai-

cin or protons [92] , supporting the hypothesis that

there is involvement of G-protein–coupled signal-

ing in TRPV1 sensitization and also suggesting an

interaction between the cholinergic and the TRPV1

sensory pathway.

Further findings suggest the presence of a

urothelio-suburothelial functional syncitium with a

crucial role in bladder pathophysiology ( Fig. 2.3 ).

An increased basal urothelial release of ACh dur-

ing bladder filling has been proposed as exciting

afferent nerves in the suburothelium and within

the detrusor, increasing detrusor smooth muscle

tone, and contributing to detrusor overactivity [77] .

It was suggested, therefore, that anticholinergics

mainly act during the storage phase to produce

an increase in bladder capacity and decrease in

urgency [93] . Distension-evoked (?co-) release of

ACh from the urothelium was found to increase

significantly with age, providing a possible expla-

nation for the increased rate of DO in the elderly

[77] . In addition, continuing studies in human IDO

bladders show that the muscarinically mediated

inhibitory influence of the urothelium on the detru-

sor that was recently identified in health is sup-

pressed in these patients [76] . Finally, ATP release

from the urothelium during stretch was found to

be significantly increased in conditions of spinal

NDO [94, 95] .

TRVP1 urothelial levels have been shown to

be increased in patients with NDO and to be

reduced in responders to intravesical RTX [81] .

This decrease was in parallel with a decrease in

suburothelial TRPV1; thus it was proposed that

a functional consortium exists between urothelial

and suburothelial TRPV1 that allows the percep-

tion of mechanical and irritant stimuli by the

bladder, a function mediated by the release of ATP

from the urothelium [32] . Similarly, an increase in

urothelial cell P2X

3 immunoreactivity was found

in a mixed population of NDO and IDO patients in

comparison with controls. Unexpectedly, intrade-

trusor injections of BoNT/A did not reduce urothe-

lial expression of either P2X

3 or TRPV1 despite a

dramatic decrease in suburothelial receptor levels

in patients who responded to treatment [36] . These

results indicate differences in the mechanisms of

action among various neurotoxins applied intra-

vesically and further highlight our inadequate

knowledge of the complex pathways involved in

intrinsic bladder reflexes.

Ultrastructural studies of the human bladder

suburothelium recently established the presence of

a nexus of myofibroblasts attaching to each other

and in close apposition to vesicle-packed unmyeli-

nated nerve fibers ( Fig. 2.6 ). Other investigators

identified a suburothelial network of interstitial

cells bearing some myofibroblastic morphological

characteristics, which were extensively linked by

connexin 43-containing gap junctions [96] or were

immunoreactive for c-kit, TRPV channels, and

nNOS [97] .

Electrophysiological experiments have shown

that a subpopulation of human bladder subu-

rothelial cells possessing some myofibroblastic

morphological and immunohistochemical charac-

teristics have high membrane capacitance, show

spontaneous spikes of electrical activity, and

respond to ATP by an increase in intracellular

Ca

2+ sufficient to activate contractile proteins

and generation of an inward current [98] . Such

characteristics together with the presence of the

connexin 43-containing gap junctions support

the hypothesis that the myofibroblasts/interstitial

cells and their closely associated axonal varicosi-

ties could function collectively as a bladder stretch

receptor [99] . Intracellular electrical signaling

could pass from cell to cell enabled by their high

membrane capacitance, while contraction of that

cell layer could exert stretch-dependent activation

of the sensory nerves [98] . Similarly, guinea pig

suburothelial vimentin-positive cells, thought to

be myofibroblasts, were shown to respond to ATP

in a manner similar to the activation of ATP-gated

P2Y receptors [100] . Subsequently, it was shown

26 A. Apostolidis and C.J. Fowler

in single-cell immunohistochemical experiments

that these cells may express a variety of purinergic

receptors, including P2X

3 , P2Y 2 , and P2Y

4 , but

mainly the P2Y

6 subtype [100] ( Fig. 2.3 ). Further

electrophysiological findings from guinea pig

suburothelial “myofibroblasts” show that cell pair

formation greatly enhances their functional prop-

erties, such as the inward current generated in

response to exogenous ATP (C. Fry, personal com-

munication). However, our ultrastructural study of

the guinea pig bladder suburothelium reveals that

only a small proportion (1.2%) of suburothelial

cells possess human myofibroblastic character-

istics (A. Pullen, personal communication), sug-

gesting that the guinea pig bladder may not be an

entirely appropriate model for the study of human

myofibroblasts. Nevertheless, the properties of

this strategically positioned cell layer ( Fig. 2.3 )

constitute an exciting novel area of research; their

role in human bladder physiology and disease

states warrants further investigation.

Neurophysiological Basis

of the Painful Bladder

There is increasing evidence for a role of abnormal

afferent activity in the pathophysiology of the pain-

ful bladder syndrome [(PBS) previously interstitial

cystitis (IC)]. Bladder afferents in cats with feline

IC showed increased firing in response to various

levels of intravesical pressure compared to normal

cats, suggesting increased mechanoreceptor sensi-

tivity in this condition [101] . In addition, the pres-

ence of an abnormally permeable urothelium [102]

has been proposed, exposing suburothelial afferents

to the chemical irritants of urine. In support of this

hypothesis, high concentrations of intravesical KCl

almost could abolish afferent neural activity in cats

with feline IC [101] , whereas lower concentrations

of KCl are thought to cause bladder pain via depo-

larization of suburothelial afferents [103] .

Stretch-evoked ATP release from urothelial cells

is increased in patients with IC compared to con-

trols [104] . In addition, P2X

3 expression was upreg-

ulated in the urothelium of IC patients [105] and

stretch of cultured urothelial cells from IC bladders

resulted in higher P2X

3 expression compared to

stretch of “normal” cells [106] . Increased numbers

of SP-immunoreactive fibers have been found in the

suburothelium of IC patients in comparison to con-

trols [107] , while SP receptor-encoding mRNA was

found to be increased within the vascular endothe-

lium of IC bladders [108] . Women with IC have

increased mean urine concentration of SP compared

to age-matched controls, which correlated signifi-

cantly with urinary frequency and urgency in those

treated with dimethylsulfoxide (DMSO) [56] . Also,

decrease in urine SP levels after epidural anesthesia

was accompanied by successful pain control in IC

Fig. 2.6 . Electron micrograph of the lamina propria

space of the human bladder presenting an example of a

myofibroblast (MF) adjacent to an unmyelinated axonal

varicosity rich in clear and dense-cored vesicles (cour-

tesy of Professor D.N. Landon, Institute of Neurology,

University College London). Bladder biopsies were

obtained via a flexible cystoscope, fixed in 3% glutar-

aldehyde in 0.1 M Na cacodylate buffer, and processed

routinely for transmission electron microscopy. Ultrathin

sections were obtained from the midpoint of each biopsy

specimen. Scale = 1µm

2. Neurophysiology of Micturition: What’s New? 27

patients [57] . In support of neuroplastic changes in

IC bladders, NGF immunoassay levels were found

to be increased in such bladders, with increased

NGF immunoreactivity localizing in the bladder

urothelium, but not in the muscular component of

the biopsies [83] . Moreover, significant attenuation

of pain and urgency in IC patients treated with intra-

vesical instillation of alkalinized lidocaine, which is

known to have an inhibitory effect on neurite regen-

eration and synapse formation [109] , suggested

modulation of bladder afferents [110] .

Furthermore, in patients with urgency-frequency

due to increased bladder sensation (previously

“bladder hypersensitivity”), a condition thought

by some to be a precursor of PBS/IC, a short-lived

decrease in pain was noted following treatment

with intravesical RTX, suggesting a pathophysi-

ological role for TRPV1-expressing suburothelial

afferents [111, 112] . Indeed, a recent study of

patients with PBS/IC showed increased suburothe-

lial TRPV1-positive nerve density in comparison

with controls, which correlated significantly with

pain scores in these patients [113] . However,

a multicenter placebo-controlled trial of various

doses of intravesical RTX in patients with PBS/

IC showed no additional benefit on pain above the

placebo effect [114] , suggesting more complex

pathophysiological mechanisms involved in PBS/

IC or yet unidentified gaps between basic research

findings and clinical applications.

PBS/IC also is characterized by evidence of

long-standing inflammation. Increased urinary lev-

els of mast cell mediators have been found in

these patients [115] and mast cells often are found

in close apposition to nerve fibers. These can be

activated by SP and carbachol [116] , suggesting

a neuroimmunomodulatory role. Increased mast

cell count in the urothelium/suburothelium has

been reported in PBS/IC, although not consistently

[117] . Detrusor mastocytosis now is proposed as

a diagnostic criterion for IC [118] . Interestingly,

novel findings demonstrate that detrusor smooth

muscle cells from patients with PBS/IC express

and release a variety of factors that are involved

in the regulation of the development, function,

and signaling of mast cells [119] . A constitutive and

cytokine-induced production of chemokines and

cytokines from such detrusor smooth muscle cells

now has been shown [120] . Together these find-

ings suggest that in PBS/IC the detrusor may play

a significant role in the inflammatory process by

contributing to the infiltration of mast cells into the

bladder interstitium.

The sensory bladder pathways involved in PBS/

IC are being extensively investigated. Recently,

M2AChR immunoreactivity was reported to be

increased in suburothelial myofibroblastlike cells

in patients with PBS [72] , a finding that may

be associated with the local anesthetic action

attributed to certain anticholinergics. Increased

expression of the bradykinin B1 receptor was

found in cultured urothelial cells of a rat model of

cyclophosphamide-induced cystitis. Activation of

the receptor resulted in initiation of the micturi-

tion pathway, a response that was attenuated by

P2 receptor antagonists, implying involvement

of purinergic signaling pathways in bradykinin-

induced micturition [121] .

Neurophysiological Basis

of Urgency

Urinary urgency is a pathological sensation, distinct

from the normal sensation of even strong desire to

void and is the defining symptom of the overac-

tive bladder syndrome [122] . The pathophysiology

of urgency is not fully understood but is assumed

to be due to aberrant afferent activity; peripheral

afferent neuromodulation has been used success-

fully to suppress the sensation of urgency and urge

incontinence [22, 24] . When urgency occurs in the

context of DO, it is thought that pathologically sen-

sitive bladder stretch-sensing receptors may give

rise to afferent activity, which causes both reflex

detrusor contractions and— provided the spinal

cord is sufficiently preserved— ascends as a bar-

rage to consciousness, perceived as “urgency.”

Understanding urgency now is seen as a central

goal for reaching an effective treatment of DO.

Several reports suggested a role of the afferents

in the pathophysiology of human DO-associated

urgency and incontinence [22, 123, 124] . In this

respect, at a cellular level a recent study showed

an association between suburothelial P2X

3 and, to

a lesser degree, TRPV1 and the pathological sen-

sation of urgency: in patients with intractable DO

who were successfully treated with intradetrusor

injections of botulinum toxin type A (BoNT/A),

posttreatment changes in quantified sensation of

28 A. Apostolidis and C.J. Fowler

urgency from their bladder diaries correlated sig-

nificantly with respective changes in P2X

3 receptor

levels in suburothelial nerve fibers. A trend for cor-

relation was found for changes in TRPV1 receptor

levels [36] .

In a further study of the natural history of the

decline of urgency following BoNT/A bladder

injections, we found that urgency and associated

incontinence were markedly improved as soon as

day 2 postinjection, whereas a significant reduction

in frequency only occurred on day 4, suggesting

different pathophysiological mechanisms regulat-

ing these symptoms [125] . In support of such a

hypothesis, TRPM8 receptor levels in suburothe-

lial, presumably afferent, nerve fibers did not cor-

relate with urgency scores in either IDO or PBS/

IC patients, while a significant positive correlation

was seen with frequency scores [47] .

In a mixed population of patients with IDO or

PBS/IC, M2AChR and M3AChR immunoreactiv-

ity in a population of suburothelial cells was found

to correlate significantly with urgency scores [72] ,

the latter measured with a recently designed pel-

vic pain/urgency/frequency (PUF) questionnaire

[126] . However, DO-associated urgency may be

fundamentally different to the urgency seen in

PBS/IC. Nevertheless, this finding appears to be in

keeping with the proposed mechanism of action of

anticholinergics in the decrease of urgency in the

overactive bladder [127] .

As urgency now is identified as the most bother-

some of the symptoms of the overactive bladder

syndrome with significant effect on patients’ qual-

ity of life, it has understandably become a prime

target for the pharmaceutical industry.

Acknowldgments . Funding. A. Apostolidis: Pfizer

Inc Independent Research Grant; C.J. Fowler:

Pfizer Inc Independent Research Grant, Allergan

Ltd Unrestricted Educational Health Grant, and

Multiple Sclerosis Society of Great Britain and

Northern Ireland Research Grant.

References

1. de Groat WC , Booth AM , Yoshimura N . Neuro-

physiology of micturition and its modification in ani-

mal models of human disease. In : Maggi CA , ed. The

autonomic nervous system, Vol. 3, Nervous control of

the urogenital system . London : Harwood Academic

Publishers , 1993 : 227 – 290 .

2. Chai TC , Steers WD . Neurophysiology of mic-

turition and continence . Urol Clin North Am

1996 ; 23 : 221 – 236 .

3. Yoshimura N , de Groat WC . Neural control of the

lower urinary tract . Int J Urol 1997 ; 4 : 111 – 125 .

4. de Groat WC . Integrative control of the lower uri-

nary tract: Preclinical perspective . Br J Pharmacol

2006 ; 147 ( Suppl 2 ): S25 – 40 .

5. Blok BF , Holstege G . Direct projections from the

periaqueductal grey to the pontine micturition centre

(M-region). An antegrade and retrograde tracing

study in the cat . Neurosci Lett 1994 ; 166 : 93 – 96 .

6. Blok BF , de Weerd H , Holstege G . Ultrastructural

evidence for a paucity of projections from lumbosac-

ral cord to the pontine micturition centre or M-region

in the cat: A new concept for the organization of the

micturition reflex with the periaqueductal grey as

central relay . J Comp Neurol 1995 ; 359 : 300 – 309 .

7. Blok BF , Willemsen AT , Holstege G . A PET study

on brain control of micturition in humans . Brain

1997 ; 120 (Pt 1) : 111 – 121 .

8. Blok BF , Sturms LM , Holstege G . Brain activation

during micturition in women . Brain 1998 ; 121 (Pt

11) : 2033 – 2042 .

9. Nour S , Svarer C , Kristensen JK , et al. Cerebral

activation during micturition in normal men . Brain

2000 ; 123 (Pt 4) : 781 – 789 .

10. Athwal BS , Berkley KJ , Hussain I , et al. Brain

responses to changes in bladder volume and urge

to void in healthy men . Brain 2001 ; 124 (Pt 2) : 369 –

377 .

11. Matsuura S , Kakizaki H , Mitsui T , et al. Human

brain region response to distention or cold stimula-

tion of the bladder: A positron emission tomography

study . J Urol 2002 ; 168 (5) : 2035 – 2039 .

12. Dasgupta R , Critchley HD , Dolan RJ , Fowler

CJ . Changes in brain activity following sac-

ral neuromodulation for urinary retention . J Urol

2005 ; 174 (6) : 2268 – 2272 .

13. Zhang H , Reitz A , Kollias S , et al. An fMRI study

of the role of suprapontine brain structures in the

voluntary voiding control induced by pelvic floor

contraction . Neuroimage 2005 ; 24 (1) : 174 – 180 .

14. Kavia RB , Dasgupta R , Fowler CJ . Functional imag-

ing and the central control of the bladder . J Comp

Neurol 2005 ; 493 (1) : 27 – 32 .

15. Griffiths D , Derbyshire S , Stenger A , Resnick N .

Brain control of normal and overactive bladder .

J Urol 2005 ; 174 (5) : 1862 – 1867 .

16. Blok B , Groen J , Veltman D , Bosch R . Brain plastic-

ity and urge incontinence: PET studies during the

first hours of sacral neuromodulation . Neurourol

Urodyn 2003 ; 22 : 490 .

2. Neurophysiology of Micturition: What’s New? 29

17. Rauch SL , Savage CR , Alpert NM , et al. Probing

striatal function in obsessive-compulsive disor-

der: A PET study of implicit sequence learning .

J Neuropsychiatry Clin Neurosci 1997 ; 9 (4) : 568 – 573 .

18. Valet M , Sprenger T , Boecker H , et al. Distraction

modulates connectivity of the cingulo-frontal cortex

and the midbrain during pain—An fMRI analysis .

Pain 2004 ; 109 (3) : 399 – 408 .

19. Yoshimura N . Bladder afferent pathway and spinal cord

injury: Possible mechanisms inducing hyperreflexia of

the urinary bladder . Prog Neurobiol 1999 ; 57 : 583 – 606 .

20. Morrison J , Birder L , Craggs M , et al. Neural con-

trol. In : Abrams P , Cardozo L , Khoury S , Wein A ,

eds. Incontinence . New Jersey : Health Publications ;

2005 : 363 – 422 .

21. Leng WW , Chancellor MB . How sacral nerve stimu-

lation neuromodulation works . Urol Clin North Am

2005 ; 32 (1) : 11 – 18 .

22. Oliver S , Fowler CJ , Mundy A , Craggs M . Measuring

the sensations of urge and bladder filling during

cystometry in urge incontinence and the effects of

neuromodulation . Neurourol Urodyn 2003 ; 22 : 7 – 16 .

23. Aguirre OA . Acute pudendal nerve stimulation

improves cystometric volumes in urge incontinent

patients . Int Urogynecol J Pelvic Floor Dysfunct

2006 ; 17 (Suppl. 2) : S125 (Abstract 13) .

24. Congregado RB , Pena OXM , Campoy MP , et al.

Peripheral afferent nerve stimulation for treatment

of lower urinary tract irritative symptoms . Eur Urol

2004 ; 45 : 65 – 69 .

25. Dasgupta R , Wiseman OJ , Kitchen N , Fowler

CJ . Long-term results of sacral neuromodula-

tion for women with urinary retention . BJU Int

2004 ; 94 (3) : 335 – 337 .

26. Michel MC , Oelke M . Duloxetine in the treatment

of stress urinary incontinence . Women’s Health

2005 ; 1 (3) : 345 – 358 .

27. de Groat WC , Kawatani M , Hisamitsu T , et al.

Mechanisms underlying the recovery of urinary

bladder function following spinal cord injury . J Auton

Nerv Syst 1990 ; 30 (Suppl) : S71 – 77 .

28. Brady CM , Apostolidis A , Harper M , et al. Parallel

changes in bladder suburothelial vanilloid receptor

TRPV1 (VR1) and pan-neuronal marker PGP9.5

immunoreactivity in patients with neurogenic detru-

sor overactivity (NDO) following intravesical resin-

iferatoxin treatment . BJU Int 2004 ; 93 : 770 – 776 .

29. Dasgupta P , Chandiramani VA , Beckett A , et al. The

effect of intravesical capsaicin on the suburothelial

innervation in patients with detrusor hyper-reflexia .

BJU Int 2000 ; 85 (3) : 238 – 245 .

30. Fowler CJ , Harper M , Fry CH . Voiding and the

sacral reflex arc: Lessons from capsaicin instillation .

Scand J Urol Nephrol 2002 ; Suppl 210 : 46 – 50 .

31. Apostolidis A , Dasgupta P , Fowler CJ . Proposed

mechanism for the efficacy of injected botulinum

toxin in the treatment of human detrusor overactiv-

ity . Eur Urol 2006 ; 49 (4) : 644 – 650 .

32. Birder LA , Nakamura Y , Kiss S , et al. Altered uri-

nary bladder function in mice lacking the vanilloid

receptor TRPV1 . Nat Neurosci 2002 ; 5 (9) : 856 – 860 .

33. Cockayne DA , Hamilton SG , Zhu Q-M , et al.

Urinary bladder hyporeflexia and reduced pain-

related behaviour in P2X3-deficient mice . Nature

2000 ; 407 : 1011 – 1015 .

34. Vlaskovska M , Kasakov L , Rong W , et al. P2X3

knock-out mice reveal a major sensory role for urotheli-

ally released ATP . J Neurosci 2000 ; 21 (15) : 5670 – 5677 .

35. Brady C , Apostolidis A , Yiangou Y , et al. P2X3-

immunoreactive nerve fibres in neurogenic detrusor

overactivity and the effect of intravesical resinifera-

toxin (RTX) . Eur Urol 2004 ; 46 : 247 – 253 .

36. Apostolidis A , Popat R , Yiangou Y , et al. Decreased

sensory receptors P2X3 and TRPV1 in suburothelial

nerve fibres following intra-detrusor injections of

botulinum toxin for human detrusor overactivity .

J Urol 2005 ; 174 : 977 – 83 .

37. Silva C , Ribeiro MJ , Cruz F . The effect of intravesi-

cal resiniferatoxin in patients with idiopathic detru-

sor instability suggests that involuntary detrusor

contractions are triggered by C-fiber input . J Urol

2002 ; 168 (2) : 575 – 579 .

38. Morenilla-Palao C , Planells-Cases R , Garcia-Sanz N ,

Ferrer-Montiel A . Regulated exocytosis contributes

to protein kinase C potentiation of vanilloid receptor

activity . J Biol Chem 2004 ; 279 : 25665 – 25672 .

39. Burnstock G . Purine-mediated signalling in pain

and visceral perception . Trends Pharmacol Sci

2001 ; 22 : 182 – 188 .

40. Guo A , Vulchanova L , Wang J , et al. Immuno-

cytochemical localization of the vanilloid receptor 1

(VR1): Relationship to neuropeptides, the P2X3

purinoceptor and IB4 binding sites . Eur J Neurosci

1999 ; 11 (3) : 946 – 958 .

41. Montell C . Physiology, phylogeny, and functions of

the TRP superfamily of cation channels . Sci STKE

2001 ; 2001 (90) : RE1 .

42. Geirsson G . Evidence of cold receptors in the human

bladder: Effect of menthol on the bladder cooling

reflex . J Urol 1993 ; 150 (2 Pt 1) : 427 – 430 .

43. Lindstrom S , Mazieres L . Effect of menthol on the

bladder cooling reflex in the cat . Acta Physiol Scand

1991 ; 141 (1) : 1 – 10 .

44. Fall M , Lindstrom S , Mazieres L . A bladder-to-bladder

cooling reflex in the cat . J Physiol 1990 ; 427 : 281 – 300 .

45. Peier AM , Moqrich A , Hergarden AC , et al. A TRP

channel that senses cold stimuli and menthol . Cell

2002 ; 108 (5) : 705 – 715 .

30 A. Apostolidis and C.J. Fowler

46. McKemy DD , Neuhausser WM , Julius D .

Identification of a cold receptor reveals a general

role for TRP channels in thermosensation . Nature

2002 ; 416 (6876) : 52 – 58 .

47. Mukerji G , Yiangou Y , Corcoran SL , et al. Cool and

menthol receptor TRPM8 in human urinary blad-

der disorders and clinical correlations . BMC Urol

2006 ; 6 : 6 .

48. Wakabayashi Y , Tomoyoshi T , Fujimiua M , et al.

Substance P-containing axon terminals in the mucosa

of the human urinary bladder: Pre-embedding immu-

nohistochemistry using cryostat sections for electron

microscopy . Histochemistry 1993 ; 100 : 401 – 407 .

49. Smet PJ , Moore KH , Jonavicius J . Distribution and

colocalization of calcitonin gene-related peptide,

tachykinins, and vasoactive intestinal peptide in nor-

mal and idiopathic unstable human urinary bladder .

Lab Invest 1997 ; 77 : 37 – 49 .

50. De Biasi S , Rustioni A . Glutamate and substance P

coexist in primary afferent terminals in the superfi-

cial laminae of spinal cord . Proc Natl Acad Sci USA

1988 ; 85 : 7820 – 7824 .

51. Cruz F . Vanilloid receptor and detrusor instability .

Urology 2002 ; 59 (5 Suppl 1) : 51 – 60 .

52. Avelino A , Cruz F . Peptide immunoreactivity and

ultrastructure of rat urinary bladder nerve fibers after

topical desensitization by capsaicin or resinifera-

toxin . Auton Neurosci 2000 ; 86 (1–2) : 37 – 46 .

53. Maggi CA , Gepetti P , Santicioli P , et al. The correla-

tion between sensory-efferent functions mediated

by the capsaicin-sensitive neurons and substance P

content of the urinary bladder of the rat . Neurosci

Lett 1987 ; 76 : 351 – 356 .

54. Shaker HS , Tu LM , Kalfopoulos M , et al.

Hyperreflexia of the urinary bladder: Possible role

of the efferent function of the capsaicin sensitive pri-

mary afferents . J Urol 1998 ; 160 (6 Pt 1) : 2232 – 2239 .

55. Crowe R , Moss HE , Chapple CR , et al. Patients with

lower motor spinal cord lesion: A decrease of vasoac-

tive intestinal polypeptide, calcitonin gene-related

peptide and substance P, but not neuropeptide Y and

somatostatin-immunoreactive nerves in the detrusor

muscle of the bladder . J Urol 1991 ; 145 : 600 – 604 .

56. Kushner L , Chiu PY , Brettschneider N , et al. Urinary

substance P concentration correlates with urinary

frequency and urgency in interstitial cystitis patients

treated with intravesical dimethyl sulfoxide and not

intravesical anesthetic cocktail . Urology 2001 ; 57

(6 Suppl 1) : 129 .

57. Sukiennik A , Carr DB , Bonney I , et al. The effect

of short-term epidural local anesthetic blockade on

urinary levels of substance P in interstitial cystitis .

Anesth Analg 2004 ; 98 : 846 – 850 .

58. Priestley JV , Michael GJ , Averill S , et al. Regulation

of nociceptive neurons by nerve growth factor and

glial cell line derived neurotrophic factor . Can J

Physiol Pharmacol 2002 ; 80 : 495 – 505 .

59. Donnerer J , Amann R , Schuligoi R , Skofitsch

G . Complete recovery by nerve growth factor of

neuropeptide content and function in capsaicin-

impaired sensory neurons . Brain Res 1996 ; 741 (1–

2) : 103 – 108 .

60. Burbach GJ , Kim KH , Zivony AS , et al. The neu-

rosensory tachykinins substance P and neurokinin

A directly induce keratinocyte nerve growth factor .

J Invest Dermatol 2001 ; 117 : 1075 – 1082 .

61. Oh EJ , Gover TD , Cordoba-Rodriguez R , Weinreich

D . Substance P evokes cation currents through

TRP channels in HEK293 cells . J Neurophysiol

2003 ; 90 : 2069 – 2073 .

62. Ito K , Rome C , Bouleau Y , Dulon D . Substance P

mobilizes intracellular calcium and activates a non-

selective cation conductance in rat spiral ganglion

neurons . Eur J Neurosci 2002 ; 16 : 2095 – 2102 .

63. Huang H , Wu X , Nicol GD , et al. ATP augments

peptide release from rat sensory neurons in culture

through activation of P2Y receptors . J Pharmacol

Exp Ther 2003 ; 306 (3) : 1137 – 1144 .

64. Paukert M , Osteroth R , Geisler HS , et al.

Inflammatory mediators potentiate ATP-gated chan-

nels through the P2X(3) subunit . J Biol Chem

2001 ; 276 (24) : 21077 – 21082 .

65. Persson K , Johansson K , Alm P , et al. Morphological

and functional evidence against a sensory and sym-

pathetic origin of nitric oxide synthase-containing

nerves in the rat lower urinary tract . Neuroscience

1997 ; 77 (1) : 271 – 281 .

66. Gulbenkian S , Merighi A , Wharton J , et al.

Ultrastructural evidence for the coexistence of calci-

tonin gene-related peptide and substance P in secre-

tory vesicles of peripheral nerves in the guinea pig . J

Neurocytol 1986 ; 15 (4) : 535 – 542 .

67. Burnstock G . The changing face of autonomic neuro-

transmission . Acta Physiol Scand 1986 ; 126 (1) : 67 – 91 .

68. Parsons SM , Prior C , Marshall IG . Acetylcholine

transport, storage, and release . Int Rev Neurobiol

1993 ; 35 : 279 – 390 .

69. Gabella G . Structure of the intramural nerves

of the rat bladder . J Neurocytol 1999 ; 28 (8) :

615 – 637 .

70 . Gabella G . The structural relations between nerve

fibres and muscle cells in the urinary bladder of the

rat . J Neurocytol 1995 ; 24 (3) : 159 – 187 .

71. Hoyle CH , Burnstock G . Postganglionic efferent

transmission in the bladder and urethra. In : Maggi

CA , ed. Nervous control of the urogenital system.

Chur , Switzerland : Harwood Academic Publishers ,

1993 : 349 – 381 .

72. Mukerji G , Yiangou Y , Grogono J , et al. Localization

of M2 and M3 muscarinic receptors in human bladder

2. Neurophysiology of Micturition: What’s New? 31

disorders and their clinical correlations . J Urol

2006 ; 176 (1) : 367 – 373 .

73. Pontari MA , Braverman AS , Ruggieri MR , Sr . The

M2 muscarinic receptor mediates in vitro bladder

contractions from patients with neurogenic blad-

der dysfunction . Am J Physiol Regul Integr Comp

Physiol 2004 ; 286 (5) : R874 – 880 .

74. Chess-Williams R , Chapple CR , Yamanishi T , et al.

The minor population of M3-receptors mediate

contraction of human detrusor muscle in vitro . J

Auton Pharmacol 2001 ; 21 (5–6) : 243 – 248 .

75. Somogyi GT , Zernova GV , Yoshiyama M , et al.

Frequency dependence of muscarinic facilitation

of transmitter release in urinary bladder strips from

neurally intact or chronic spinal cord transected rats .

Br J Pharmacol 1998 ; 125 : 241 – 246 .

76. Chess-Williams R . Muscarinic receptors of the uri-

nary bladder: Detrusor, urothelial and prejunctional .

Auton Autacoid Pharmacol 2002 ; 22 : 133 – 145 .

77. Yoshida M , Miyamae K , Iwashita H , et al.

Management of detrusor dysfunction in the elderly:

Changes in acetylcholine and adenosine triphos-

phate release during aging . Urology 2004 ; 63 (Suppl

3A) : 17 – 23 .

78. Beckel JM , Kanai A , Lee SJ , et al. Expression of

functional nicotinic acetylcholine receptors in rat

urinary bladder epithelial cells . Am J Physiol Renal

Physiol 2006 ; 290 (1) : F103 – 110 .

79. Birder LA , Kanai AJ , de Groat WC , et al. Vanilloid

receptor expression suggests a sensory role for

urinary bladder epithelial cells . Proc Natl Acad Sci

USA 2001 ; 98 (23) : 13396 – 13401 .

80. Lazzeri M , Vannucchi G , Zardo C , et al.

Immunohistochemical evidence of vanilloid recep-

tor 1 in normal human urinary bladder urothelium .

Eur Urol 2004 ; 46 : 792 – 799 .

81. Apostolidis A , Brady CM , Yiangou Y , et al. Capsaicin

receptor TRPV1 in the urothelium of neurogenic

human bladders and the effect of intravesical resinif-

eratoxin . Urology 2005 ; 65 : 400 – 405 .

82. Elneil S , Skepper JN , Kidd EJ , et al. Distribution of

P2X(1) and P2X(3) receptors in the rat and human

urinary bladder . Pharmacology 2001 ; 63 (2) : 120 – 128 .

83. Lowe EM , Anand P , Terenghi G , et al. Increased

nerve growth factor levels in the urinary bladder of

women with idiopathic sensory urgency and intersti-

tial cystitis . Br J Urol 1997 ; 79 : 572 – 577 .

84. Lecci A , Maggi CA . Tachykinins as modulators of

the micturition reflex in the central and peripheral

nervous sytem . Regul Pept 2001 ; 101 : 1 – 18 .

85. Badawi AF , Habib SL , Mohammed MA , et al.

Influence of cigarette smoking on prostaglandin

synthesis and cyclooxygenase-2 gene expression

in human urinary bladder cancer . Cancer Invest

2002 ; 20 (5–6) : 651 – 656 .

86. Birder LA , Apodaca G , De Groat WC , Kanai AJ .

Adrenergic- and capsaicin-evoked nitric oxide

release from urothelium and afferent nerves in

urinary bladder . Am J Physiol 1998 ; 275 (2 Pt 2) :

F226 – 229 .

87. Moon A . Influence of nitric oxide signalling path-

ways on pre-contracted human detrusor smooth

muscle in vitro . BJU Int 2002 ; 89 : 942 – 949 .

88. Ferguson DR , Kennedy I , Burton T . ATP is

released from rabbit urinary bladder epithelial cells

by hydrostatic pressure changes – a possible sen-

sory mechanism ? J Physiol 1997 ; 505 : 503 – 511 .

89. Kumar V , Chapple CR , Chess-Williams R .

Characteristics of adenosine triphosphate release

from porcine and human normal bladder . J Urol

2004 ; 172 : 744 – 747 .

90. Kennedy C , Leff P . Painful connection for ATP .

Nature 1995 ; 377 : 385 – 386 .

91. Birder LA , Barrick SR , Roppolo JR , et al. Feline

interstitial cystitis results in mechanical hyper-

sensitivity and altered ATP release from blad-

der urothelium . Am J Physiol Renal Physiol

2003 ; 285 (3) : F423 – 429 .

92. Tominaga M , Wada M , Masu M . Potentiation of

capsaicin receptor activity by metabotropic ATP

receptors as a possible mechanism for ATP-evoked

pain and hyperalgesia . Proc Natl Acad Sci USA

2001 ; 98 (12) : 6951 – 6956 .

93. Andersson KE . Antimuscarinics for treatment of

overactive bladder . Lancet Neurol 2004 ; 3 : 47 – 53 .

94. Khera M , Somogyi GT , Kiss S , et al. Botulinum

toxin A inhibits ATP release from bladder urothe-

lium after chronic spinal cord injury . Neurochem

Int 2004 ; 45 : 987 – 993 .

95. Yoshida M , Inadome A , Masunaga K , et al. Non-

neuronal acetylcholine and ATP releases from

isolated normal and neurogenic human blad-

der . Neurourol Urodyn 2004 ; 23 (5/6) : 503 – 504

(A73) .

96. Sui GP , Rothery S , Dupont E , et al. Gap junctions

and connexin expression in human suburothelial

interstitial cells . BJU Int 2002 ; 90 : 118 – 129 .

97. Ost D , Roskams T , Van Der Aa F , deRidder D .

Topography of the vanilloid receptor in the human

bladder: More than just the nerve fibers . J Urol

2002 ; 168 : 293 – 297 .

98. Sui GP , Wu C , Fry CH . Electrical characteristics of

suburothelial cells isolated from the human blad-

der . J Urol 2004 ; 171 (2 Pt 1) : 938 – 943 .

99. Wiseman OJ , Fowler CJ , Landon DN . The role of

the human bladder lamina propria myofibroblast .

BJU Int 2003 ; 91 : 89 – 93 .

100. Wu C , Sui GP , Fry CH . Purinergic regulation of

guinea pig suburothelial myofibroblasts . J Physiol

2004 ; 559 (Pt 1) : 231 – 243 .

32 A. Apostolidis and C.J. Fowler

101. Roppolo JR , Tai C , Booth AM , et al. Bladder

Adelta afferent nerve activity in normal cats

and cats with feline interstitial cystitis . J Urol

2005 ; 173 (3) : 1011 – 1015 .

102. Keay S , Zhang CO , Shoenfelt JL , Chai TC .

Decreased in vitro proliferation of bladder epi-

thelial cells from patients with interstitial cystitis .

Urology 2003 ; 61 (6) : 1278 – 1284 .

103. Parsons CL , Stein PC , Bidair M , Lebow D .

Abnormal sensitivity to intravesical potassium in

interstitial cystitis and radiation cystitis . Neurourol

Urodyn 1994 ; 13 (5) : 515 – 520 .

104. Sun Y , Keay S , De Deyne PG , Chai TC . Augmented

stretch activated adenosine triphosphate release from

bladder uroepithelial cells in patients with interstitial

cystitis . J Urol 2001 ; 166 (5) : 1951 – 1956 .

105. Tempest HV , Dixon AK , Turner WH , et al. P2X2

and P2X3 receptor expression in human bladder

urothelium and changes in interstitial cystitis . BJU

Int 2004 ; 93 : 1344 – 1348 .

106. Sun Y , Chai TC . Up-regulation of P2X3 recep-

tor during stretch of bladder urothelial cells

from patients with interstitial cystitis . J Urol

2004 ; 171 : 448 – 452 .

107. Pang X , Marchand J , Sant GR , et al. Increased

number of substance P positive nerve fibres in

interstitial cystitis . Br J Urol 1995 ; 75 (6) : 744 – 750 .

108. Marchand JE , Sant GR , Kream RM . Increased

expression of substance P receptor-encoding

mRNA in bladder biopsies from patients with

interstitial cystitis . Br J Urol 1998 ; 81 (2) : 224 – 228 .

109. Onizuka S , Takasaki M , Syed NI . Long-term

exposure to local but not inhalation anesthet-

ics affects neurite regeneration and synapse for-

mation between identified lymnaea neurons .

Anesthesiology 2005 ; 102 (2) : 353 – 363 .

110. Parsons CL . Successful downregulation of bladder

sensory nerves with combination of heparin and

alkalinized lidocaine in patients with interstitial

cystitis . Urology 2005 ; 65 (1) : 45 – 48 .

111. Lazzeri M , Beneforti P , Spinelli M , et al. Intravesical

resiniferatoxin for the treatment of hypersensitive

disorder: A randomized placebo controlled study . J

Urol 2000 ; 164 (3 Pt 1) : 676 – 679 .

112. Apostolidis A, Gonzales GE, Fowler CJ. Effect of

intravesical resiniferatoxin (RTX) on lower urinary

tract symptoms, urodynamic parameters, and qual-

ity of life of patients with urodynamic increased

bladder sensation. Eur Urol 2006.

113. Mukerji G , Yiangou Y , Agarwal SK , Anand P .

Transient receptor potential vanilloid receptor sub-

type 1 in painful bladder syndrome and its correla-

tion with pain . J Urol 2006 ; 176 (2) : 797 – 801 .

114. Payne CK , Mosbaugh PG , Forrest JB , et al.

Intravesical resiniferatoxin for the treatment of inter-

stitial cystitis: A randomized, double-blind, placebo

controlled trial . J Urol 2005 ; 173 (5) : 1590 – 1594 .

115. Sant GR , Theoharides TC . The role of the mast

cell in interstitial cystitis . Urol Clin North Am

1994 ; 21 (1) : 41 – 53 .

116. Spanos C , el-Mansoury M , Letourneau R , et al.

Carbachol-induced bladder mast cell activation:

Augmentation by estradiol and implications for

interstitial cystitis . Urology 1996 ; 48 (5) : 809 – 816 .

117. Theoharides TC , Kempuraj D , Sant GR . Mast

cell involvement in interstitial cystitis: A review

of human and experimental evidence . Urology

2001 ; 57 (6 Suppl 1) : 47 – 55 .

118 . Nordling J , Anjum FH , Bade JJ , et al. Primary

evaluation of patients suspected of having intersti-

tial cystitis (IC) . Eur Urol 2004 ; 45 (5) : 662 – 669 .

119. Bouchelouche K , Andresen L , Alvarez S , et al.

Interleukin-4 and -13 induce the expression and

release of monocyte chemoattractant protein 1,

interleukin-6 and stem cell factor from human

detrusor smooth muscle cells: Synergy with inter-

leukin-1beta and tumor necrosis factor-alpha .

J Urol 2006 ; 175 (2) : 760 – 765 .

120. Bouchelouche K , Alvarez S , Horn T , et al. Human

detrusor smooth muscle cells release interleukin-6,

interleukin-8, and RANTES in response to proin-

flammatory cytokines interleukin-1beta and tumor

necrosis factor-alpha . Urology 2006 ; 67 (1) : 214 – 219 .

121. Chopra B , Barrick SR , Meyers S , et al. Expression

and function of bradykinin B1 and B2 receptors in

normal and inflamed rat urinary bladder urothe-

lium . J Physiol 2005 ; 562 (Pt 3) : 859 – 871 .

122. Abrams P , Cardozo L , Fall M , et al. The stand-

ardisation of terminology of lower urinary tract

function: Report from the Standardisation Sub-

committee of the International Continence Society .

Neurourol Urodyn 2002 ; 21 : 167 – 178 .

123. Everaert K , De Ridder D , Baert L , et al. Patient

satisfaction and complications following sacral

nerve stimulation for urinary retention, urge incon-

tinence and perineal pain: A multicenter evalu-

ation . Int Urogynecol J Pelvic Floor Dysfunct

2000 ; 11 (4) : 231 – 235 ; discussion 236 .

124. Silva C , Silva J , Ribeiro MJ , et al. Urodynamic

effect of intravesical resiniferatoxin in patients

with neurogenic detrusor overactivity of spinal ori-

gin: Results of a double-blind randomized placebo-

controlled trial . Eur Urol 2005 ; 48 (4) : 650 – 655 .

125. Kalsi V , Apostolidis A , Gonzales G , et al. The

decline of urgency following intradetrusor botu-

linum neurotoxin type A (BoNT/A) injections for

detrusor overactivity (DO): Preliminary results .

Eur Urol 2006 ; 49 (Suppl. 1) : A798 .

126. Parsons CL , Dell J , Stanford EJ , et al. Increased preva-

lence of interstitial cystitis: Previously unrecognized

2. Neurophysiology of Micturition: What’s New? 33

urologic and gynecologic cases identified using a

new symptom questionnaire and intravesical potas-

sium sensitivity . Urology 2002 ; 60 (4) : 573 – 578 .

127. Andersson KE , Yoshida M . Antimuscarinics and

the overactive detrusor – which is the main mechanism

of action ? Eur Urol 2003 ; 43 (1) : 1 – 5 .

35

Introduction

Urinary incontinence is a common medical and

social problem of women of all age groups. Up

to 28% of women younger than 60 years of age

and up to 35% older than 60 years suffer from

urinary incontinence [1, 2] . Of all incontinence

types, women are predominantly afflicted by stress

urinary incontinence, with an estimated propor-

tion of about 60% [2] . Women with stress urinary

incontinence report about a varying amount of

urinary leakage during physical activity, coughing,

sneezing, laughing, or straining. Basically, urinary

incontinence occurs when the intravesical pressure

rises above the urethral pressure. In stress urinary

incontinence, intra-abdominal pressure is transmit-

ted to the bladder and exceeds urethral pressure,

which leads to passive urinary leakage through the

urethra. Therefore, urethral closure insufficiency

is responsible for stress urinary incontinence.

Understanding the continence mechanisms and the

underlying causes of urethral closure insufficiency

helps to restore continence.

Strategies for the treatment of stress urinary

incontinence have been established, and later,

concepts have been developed to explain the suc-

cessful outcome. However, much of the discussion

is speculation, theory, and hypothesis [3] . The effi-

cacy of the chosen treatment seems to support the

individual theory. Today, two concepts are widely

accepted and used in clinical practice. However,

these concepts seem to compete with each other.

The key question in the discussion of the concepts

is related to the part of the urethra that is assumed

to be responsible for urethral closure and conti-

nence: is it the bladder neck or midurethra?

Anatomy of the Female Lower

Urinary Tract and Continence

Mechanisms

The urinary bladder is located in the pelvis at the

caudal site of the abdominal cavity and surrounded

by fatty tissue. The urethra has a total length

of about 4–5 cm and reaches from the bladder

neck to the external meatus. The bladder neck is

located above the level of the inferior margin of

the symphysis and lies on the endopelvic fascia.

The endopelvic fascia is attached to the levator ani

muscle at both sides of the urethra and contraction

of the levator ani muscle leads to simultaneous

elevation of the bladder neck [4] . The urethral

wall consists of a mucosal lining, underneath a

submucosal cushion of blood vessels embedded

in connective tissue and elastic fibers, and a lon-

gitudinal and circular layer of smooth muscle cells

[5] . The urethra runs nearly parallel to the axis of

the anterior vaginal wall and is closely attached to

the surrounding vaginal tissue. The posterior wall

of the urethra is supported by the fibromuscular

vaginal tissue, which is connected to the pelvic

bones via the pubovaginal portion of the levator

ani muscle and the longitudinal muscle of the anus.

The urethra is attached to the posterior site of the

symphysis by the pubourethral ligaments.

Chapter 3

Continence: Bladder Neck versus

Mid-Urethra

Matthias Oelke and Jan-Paul Roovers

36 M. Oelke and J.-P. Roovers

Accumulations of muscle cells exist around the

urethra. The bladder neck is densely surrounded

by smooth muscle cells (internal urethral sphincter,

0–15th percentile of the urethra) that are innervated

by sympathetic nerve fibers coming from the level

Th11–L2 of the spinal cord [3, 4] . The distal part

of the proximal and midurethra is surrounded by

striated muscle cells (20–60th percentile of the ure-

thra); this rhabdomyosphincter (external urethral

sphincter) is innervated by the pudendal nerves,

which leave the spinal cord at the level S2–S4.

The following mechanisms are believed to con-

tribute to female urinary continence (“stress conti-

nence control system” [4] ):

1. Smooth and striated muscle cells in and around

the urethra close the urethral lumen (active

sphincteric system).

2. The length of the urethra and urethral wall ten-

sion (collagen and elastic fibers, mucosa and

submucosal cushion of blood vessels in the

urethral wall) guarantee additional positive pres-

sure in the urethra in the resting position (passive

sphincteric system or urethral wall factor) [6] .

3. Pressure transmission from the abdominal cav-

ity to the proximal urethra (passive pressure

transmission) [7] .

4. Activation of the coughing reflex via the puden-

dal nerve leads to a fast contraction of the

urethral rhabdomyosphincter and pelvic floor

before and during vesical pressure increase

(active pressure transmission) [7, 8] .

5. Posterior urethral wall support by fibromuscular

tissue of the anterior vaginal wall and the tendinous

arch of the pelvic fascia (hammock system) [9] .

6. Ventral kinking of the urethra during contrac-

tion of the levator ani muscle, longitudinal

muscle of the anus, and the hammock muscle

pulls the vagina and bladder base back- and

downward and presses the urethra against the

pubic bone (integral theory) [10] .

Bladder Neck: Intrinsic Sphincter

Deficiency, Urethral Hypermobility,

and the “Hammock Hypothesis”

The active and passive sphincteric systems, active

and passive pressure transmissions, as well as the

“hammock hypothesis” (points 1–5, above) support

the concept that the bladder neck and proximal

urethra are responsible for urinary continence.

Sphincters guarantee that the urethral lumen is

watertightly closed in the filling phase of the blad-

der and, together with the surrounding tissue, give

structural support to keep the proximal urethra

from moving during abdominal pressure increase.

Anatomical or functional damage of the sphincteric

systems may cause an insufficient approximation

of the urethral lumen. Two causes were identified

for sphincteric insufficiency:

• In intrinsic sphincter deficiency (ISD), the ure-

thral sphincters are too weak to close the urethral

lumen. Urinary leakage may be associated with

a minimal increase in intravesical pressure or

even may be gravitational. Patients with this type

of incontinence have a low leak point pressure

during coughing or straining (<60 cm H

2 O) and

a low urethral closure pressure at rest in urethral

pressure profilometry (<20 cm H

2 O) [11, 12] .

During video-urodynamic investigation, the blad-

der neck and proximal urethra, regardless of the

anatomic position, are open at rest.

• In urethral hypermobility, the sphincters remain

strong in the resting position but become insuf-

ficient during stress situations. Patients with this

type of incontinence have a pathological cotton

swab (Q-tip) test (difference of the urethrovesical

angle from the horizontal plane >30°), whereas

the leak point pressure (>60 cm H

2 O) and the ure-

thral closure pressure at rest remain high (>20 cm

H

2 O) [13, 14] . A loss of the anchoring system of

the bladder neck and proximal urethra is believed

to cause urethral hypermobility, leading to insuf-

ficiency of pressure transmission to the proximal

urethra. During video-urodynamic investigation,

the bladder neck and proximal urethra are closed

at rest but open and descend during stress.

Based on these two distinct findings, a classifica-

tion system of stress urinary incontinence consist-

ing of five subtypes has been established ( Table 3.1 )

[15– 17] . Types 0 – IIb refer to urethral hypermobil-

ity and type III refers to ISD. Ultrasound investiga-

tions demonstrated that the rhabdomyosphincter is

significantly thicker in continent than incontinent

women and significantly thicker in women with

urethral hypermobility than ISD [18] .

The hammock system is a supportive anatomical

structure that can explain closure of the bladder

3. Continence: Bladder Neck versus Mid-Urethra 37

neck and proximal urethra during abdominal pres-

sure increase [9] . According to this hypothesis, the

bladder neck and proximal urethra lie in a position

where they can be compressed against a backboard

and sealed during abdominal pressure increase. The

hammock consists of the anterior vaginal wall and

the surrounding connective tissue that are connected

with the pelvic bones via the pubovaginal portion of

the levator ani muscle and the tendinous arch of the

pelvic fascia. If the hammock system is intact but

in a more caudal position, continence still may be

maintained. The stability of the supporting layers

and muscles therefore are responsible for conti-

nence during stress situations. Laxity of the ham-

mock would give less resistance during abdominal

pressure increase and lead to urinary incontinence.

DeLancey described this system like a water hose:

stepping on the hose would stop the water flow if

the hose would lie on a firm, noncompliant ground

[4, 9] . The results after anterior colporrhaphy sup-

port this hypothesis. In a prospective randomized

trial comparing the outcome of three different

operation techniques 37% of women reported to be

dry 5 years after colporraphy [19] .

Midurethra: The Integral Theory

The integral theory (6) supports the concept

that the midurethra is responsible for urinary

continence. The integral theory is a complex

musculoelastic concept whereby muscle forces

pull on the vaginal tissue to open and close the

urethra [10, 20] . This theory adds a dynamic

extrinsic mechanism – contractions of specific

pelvic floor muscles – to the concept of urethral

closure. Closure of the urethra occurs when

three muscle forces interact together, pulling

the vagina simultaneously to the dorsal, caudal,

and ventral direction. The levator ani muscle

contracts and pulls the vagina and the attached

bladder base and urethra to the dorsal direction,

the longitudinal muscle of the anus contracts and

pulls the vagina to a caudal direction, and the

so-called “hammock muscle” contracts and pulls

the vagina to the ventral direction. As a result of

the muscle contractions, the upper urethra moves

to a horizontal and the lower urethra to a verti-

cal position, causing kinking of the midurethra

and closure of the urethral lumen. Mechanical

obstruction of the urethral lumen occurs only

during muscle contraction; this effect was named

“dynamic mid-urethral knee angulation” or “iris

effect” [21, 22] . Possible mechanisms of dam-

age of this system during childbirth with regard

to urinary incontinence, prolapse, and voiding

disorders were described [23] . Laxity of any of

the involved muscles or ligaments prevents the

urethra, vagina, and bladder base from stretch-

ing, and therefore weakens the transmission of

muscular forces, leading to urinary incontinence.

Application of a forceps on one side of the

Table 3.1. Classification of stress urinary incontinence based on the concept of urethral hypermobility and intrin-

sic sphincter deficiency .

Incontinence type Description

Type O The patient has a typical history of stress incontinence, which, however, cannot be reproduced dur-

ing clinical or urodynamic investigation. The bladder neck and proximal urethra are closed at

rest and situated at or above the inferior end of the symphysis. The bladder neck and proximal

urethra descend and open during stress. Failure to demonstrate urinary incontinence may be due

to momentary voluntary contraction of the external urethral sphincter during the examination

Type I The bladder neck is closed at rest and located above the inferior margin of the symphysis. The

bladder neck and proximal urethra open and descend less than 2 cm during stress, and urinary

incontinence is apparent during periods of increased abdominal pressure. There is a small or no

cystocele

Type IIa The bladder neck is closed at rest and located above the inferior margin of the symphysis. The

bladder neck and proximal urethra open during stress and a rotational descent is observed (cys-

tourethrocele)

Type IIb The bladder neck is closed at rest and situated at or below the inferior margin of the symphysis.

During stress, there may or may not be further descent but the proximal urethra opens and urinary

leakage occurs

Type III The bladder neck and proximal urethra are open at rest. The proximal urethra does not function as

a sphincter anymore

38 M. Oelke and J.-P. Roovers

vagina at the midurethral area can control supine

urine loss while coughing by preventing abnor-

mal descent and funneling of the bladder base

(midurethral one-sided Bonney test) [20] .

Efficacy of Surgical Therapies

Superiority of one continence concept could be

proved by direct comparison of the efficacy of

operations that are based on the individual theory.

Treatment of urethral hypermobility is possible

with suspension operations such as the retropubic

urethropexy (Burch operation) [24] . During the

Burch operation, the lateral parts of the anterior

vaginal wall are connected with the ipsilateral

Cooper’s ligament using nonresorbable sutures

[25] . Suspension operations aim to elevate and fix

the bladder neck in order to avoid (excessive) move-

ment [24, 26] . Restoration of pubourethral liga-

ment support and treatment of insufficient urethral

kinking is possible with the tension-free vaginal

tape (TVT) operation [27] . During the operation,

a polypropylene tape is implanted via an anterior

colpotomy at the level of the midurethra, causing

stabilization of the posterior urethral wall, kinking

of the urethra during abdominal pressure increase,

and intermittent mechanical compression of the

urethra between implant and symphysis [22, 27] .

Until August 2006, five randomized studies have

been published that compared the results of the Burch

urethropexy with the TVT operation ( Table 3.2 ).

Even though the studies have a limited follow up

and continence results might change after a longer

period, no significant differences with regard to

efficacy have been found. Differences of continence

results of one operation technique are caused by

using different continence definitions.

Conclusions

Concepts aim to explain the mechanisms of urinary

continence. The bladder neck and midurethra have

become the center of interest. Clinical, urodynamic,

and radiological signs seem to support the individual

theory. However, many women have risk factors for

urinary incontinence (e.g., overweight, childbirth,

hysterectomy, advanced age), urethral hypermobility,

a low urethral closure pressure, laxity of the ante-

rior vaginal wall, or cystourethrocele without being

incontinent [14, 33] . Furthermore, no strict relation-

ship exists between the degree of urethral hypermo-

bility and the severity of stress incontinence [33, 34] .

Additionally, urethral hypermobility or ISD after

midurethral operations and urethral closure pressure

after bladder neck operations remain unchanged;

nevertheless, these women become continent [21,

35– 37] . Obviously, insufficiency of one mechanism

can be compensated for by others. Therefore, conti-

nence seems to be produced by several mechanisms.

However, damage of one part of the continence sys-

tem may be more severe than damage of other parts.

Randomized studies demonstrated that operation

techniques (suspension operations vs. TVT) are

equally effective in restoring continence in 65–90%

of patients. Surgical restoration of one part of the

continence mechanism at the level of the bladder

Table 3.2. Prospective randomized trials comparing the efficacy of the bladder neck suspension (Burch ure-

thropexy) and midurethral operation [tension-free vaginal tape (TVT)]

.

Publication Follow up (months) Patients ( n ) Continence (%) p -Value between operations

Ward and Hilton [28] 6 Burch: 128 65 0.83

TVT: 150 73

Bai et al. [29] 12 Burch: 33 88 >0.05

TVT: 31 87

Wang and Chen [30] 12–36 (median 22) Burch: 41 88 1.0

TVT: 49 90

Liapis et al. [31] 24 Burch: 35 86 >0.05

TVT: 36 84

Ward and Hilton [32] 24 Burch: 175 87 0.64

TVT: 169 85

No Significant differences with regard to the Continence results were found

3. Continence: Bladder Neck versus Mid-Urethra 39

neck or midurethra compensates for the existing

loss of urethral support and functions by creating

new areas for urethral compression. However,

some women remain incontinent after the opera-

tion, indicating that reconstruction of the individual

system was wrong or not sufficient enough to

restore continence [38, 39] . Consequently, it is

hypothesized to choose an operation based on the

other continence concept after failed primary sur-

gery. This strategy is clinical reality; however, it

remains to be proved in randomized studies.

References

1 . Thom D. Variation in estimates of urinary incon-

tinence prevalence in the community: Effects of

differences in definition, population character-

istics, and study type . J Am Geriatr Soc 1998 ;

46 : 473480 .

2 . Hunskaar S , Burgio K , Diokno A et al. Epidemiology

and natural history of urinary incontinence in women .

Urology 2003 ; 62 (Suppl 4A) : 1623 .

3 . DeLancey JO . Stress urinary incontinence: Where

are we now, where should we go? Am J Obstet

Gynecol 1996 ; 175 : 311319 .

4 . DeLancey JO , Ashton-Miller JA . Pathophysiology

of adult urinary incontinence . Gastroenterology

2004 ; 126 (Suppl 1) : S23 – S32 .

5 . Strohbehn K , Quint LE , Prince MR , et al. Magnetic

resonance imaging anatomy of the female urethra:

A direct histologic comparison . Obstet Gynecol

1996 ; 88 : 750756 .

6 . Zinner NR , Sterling AM , Ritter RC . Role of inner

urethral softness and urinary continence . Urology

1980 ; 16 : 115 – 117 .

7 . Enhörning G . Simultaneous recording of intravesical

and intraurethral pressure . Acta Chir Scand 1961 ;

276 (Suppl) : 168 .

8 . Kamo I , Cannon TW , Conway DA , et al. The role

of bladder-to-urethral reflexes in urinary continence

mechanisms in rats . Am J Physiol Renal Physiol

2004 ; 287 : F434 – F441 .

9 . DeLancey JO . Structural support of the urethra as it

relates to stress urinary incontinence: The hammock

hypothesis . Am J Obstet Gynecol 1994 ; 170 : 1713 –

1720 .

10 . Petros PE , Ulmsten UI . An integral theory of female

urinary incontinence. Experimental and clinical con-

siderations . Acta Obstet Gynecol Scand Suppl 1990 ;

153 : 731 .

11 . McGuire EJ , Fitzpatrick CC , Wan J , et al. Clinical

assessment of urethral sphincter function . J Urol

1993 ; 150 : 1452 – 1454 .

12 . Summitt RL , Bent AE , Ostergard DR , et al. Stress

incontinence and low urethral closure pressure.

Correlation of preoperative urethral hypermobil-

ity with successful suburethral sling procedures .

J Reprod Med 1990 ; 35 : 877 – 880 .

13 . Crystle CD , Charm LS , Copeland WE . Q-tip test in

stress urinary incontinence . Obstet Gynecol 1972 ;

38 : 313315 .

14 . Bergman A , McCarthy TA , Ballard CA , et al. Role

of the Q-tip test in evaluating stress urinary inconti-

nence . J Reprod Med 1987 ; 32 : 273275 .

15 . Green TH . The problem of stress urinary inconti-

nence in female: An appraisal of its current status .

Obstet Gynecol Surv 1968 ; 23 : 603634 .

16 . McGuire EJ , Lytton B , Pepe V , et al. Stress urinary

incontinence . Obstet Gynecol 1976 ; 47 : 255264 .

17 . Blaivas JG , Olsson CA . Stress incontinence:

Classification and surgical approach . J Urol 1988 ;

139 : 727731 .

18 . Kondo Y , Homma Y , Takahashi S , et al. Transvaginal

ultrasound of urethral sphincter at the midurethra

in continent and incontinent women . J Urol 2001 ;

165 : 149152 .

19 . Bergman A , Elia G . Three surgical procedures for

genuine stress incontinence: Five-year follow-up

of a prospective randomized study . Am J Obstet

Gynecol 1995 ; 173 : 6671 .

20 . Petros PE , Ulmsten UI . An integral theory and its

method for the diagnosis and management of female

urinary incontinence . Scand J Urol Nephrol Suppl

1993 ; 153 : 193 .

21 . Lo TS , Wang AC , Horng SG , et al. Ultrasonograhic

and urodynamic evaluation after tension free vagina

tape procedure (TVT) . Acta Obstet Gynecol Scand

2001 ; 80 : 6570 .

22 . Dietz HP , Wilson PD . The ”iris effect”: How two-

dimensional and three-dimensional ultrasound can

help us understand anti-incontinence procedures.

Ultrasound Obstet Gynecol 2004 ; 23 : 267271 .

23 . Petros PP , Ulmsten U . An anatomical classification.

A new paradigm for management of female lower

urinary tract dysfunction . Eur J Obstet Gynecol

Reprod Biol 1998 ; 80 : 8794 .

24 . Creighton SM , Clark A , Pearce JM , et al. Perineal

bladder neck ultrasound: Appearances before and

after continence surgery . Ultrasound Obstet Gynecol

1994 ; 4 : 428433 .

25 . Burch JC . Urethrovaginal fixation to Cooper“s liga-

ment for the correction of stress incontinence,

cystocele and prolapse . Am J Obstet Gynecol 1961 ;

81 : 281290 .

26 . Viereck V , Bader W , Krauss T , et al. Intra-operative

introital ultrasound in Burch colposuspension

reduces post-operative complications . BJOG 2005 ;

112 : 791796 .

40 M. Oelke and J.-P. Roovers

27 . Ulmsten U , Henriksson L , Johnson P , et al. An

ambulatory surgical procedure under local anesthe-

sia for treatment of female urinary incontinence . Int

Urogynecol J Pelvic Floor Dysfunct 1996 ; 7 : 8185 .

28 . Ward K , Hilton P . Prospective multicentre ran-

domised trial of tension-free vaginal tape and

colposuspension as primary treatment for stress

incontinence . BMJ 2002 ; 325 : 6770 .

29 . Bai SW , Sohn WH , Chung DJ , et al. Comparison of

the efficacy of Burch colposuspension, pubovaginal

sling, and tension-free vaginal tape for stress urinary

incontinence. Int J Gynaecol Obstet 2005 ; 91 : 246251 .

30 . Wang AC , Chen MC . Comparison of tension-free

vaginal taping versus modified Burch colposuspen-

sion on urethral obstruction: A randomized control-

led study . Neurourol Urodyn 2003 ; 22 : 185190 .

31 . Liapis A , Bakas P , Creatsas G . Burch colposuspen-

sion and tension-free vaginal tape in the manage-

ment of stress urinary incontinence in women . Eur

Urol 2002 ; 41 : 469473 .

32 . Ward KL , Hilton P . A prospective multicenter

randomized trial of tension-free vaginal tape and

colposuspension for primary urodynamic stress

incontinence: Two-year follow-up . Am J Obstet

Gynecol 2004 ; 190 : 324331 .

33 . Fleischmann N , Flisser AJ , Blaivas JG , et al.

Sphincteric urinary incontinence: Relationship of

vesical leak point pressure, urethral mobility and

severity of incontinence . J Urol 2003 ; 169 : 9991002 .

34 . Cross CA , Cespedes RD , McGuire EJ . Treatment

results using pubovaginal slings in patients with

large cystoceles and stress incontinence . J Urol

1997 ; 158 : 431 – 434 .

35 . Atherton MJ , Stanton SL . A comparison of the blad-

der neck movement and elevation after TVT and

colposuspension . BJOG 2000 ; 107 : 13661370 .

36 . Klutke JJ , Carlin BI , Klutke CG . The tension-free

vaginal tape procedure: Correction of stress incon-

tinence with minimal alteration in proximal urethral

mobility . Urology 2000 ; 55 : 512514 .

37 . Lukacz ES , Luber KM , Nager CW . The effects

of the tension-free vaginal tape on proximal ure-

thral position: A prospective, longitudinal observa-

tion . Int Urogynecol J Pelvic Floor Dysfunct 2003 ;

14 : 179184 .

38 . Paick JS , Ku JH , Shin JW , et al. Tension-free

vaginal tape procedure for urinary incontinence

with low Valsalva leak point pressure . J Urol 2004 ;

172 : 13701373 .

39 . O“Connor RC , Nanigian DK , Lyon MB , et al.

Early outcomes of mid-urethral slings for female

stress incontinence stratified by Valsalva leak

point pressure . Neurourol Urodyn 2006 ; 25 :

685 – 688 .

41

Introduction

For many surgeons, the anatomy of the pelvic floor

has been the foundation for the advancement of

novel techniques in the treatment of incontinence

and prolapse of the pelvic organs. From the early

descriptions of pelvic floor dysfunction (Ebers

Papyrus, 1550 BC) to present-day medical lit-

erature, the techniques are founded on the basic

understand of three-dimensional pelvic anatomy.

This chapter will serve as the basis to understand,

treat, and develop new techniques in the ongoing

efforts to treat these disease processes.

In a historical prospective on female prolapse,

Legendre and Bistien (1858) first investigated

the tendency of prolapse of the uterus by apply-

ing traction. Mengert repeated their initial studies

in an attempt to further determine which of the

pelvic ligaments provided the primary support to

the uterus. By applying 1 kg weight to the uterus,

the pelvic ligaments were systematically cut. He

reported that when the parametrial and paravaginal

tissues were cut and the round ligaments were left

intact, the cervix easily prolapsed.

Bony Pelvis

The bony pelvis consists of sacrum, coccyx, and

paired bones of the pubis, ischium, and the ilium.

The pelvis is divided into the true (below the

arcuate line) and the false pelvis. The pelvis is

the foundation from which the pelvic support is

derived (Fig. 4.1 ). The sciatic foramen is formed

medially by the sacrum, laterally by the ischium,

superiorly by the ilium, and is divided into the

greater and lesser sciatic foramen by the sacros-

pinous ligament. The internal pudendal vessels

and nerve traverses the greater and lesser sciatic

foramen in close proximity (inferior) to the ischial

spine. The pudendal canal is bound medially by the

fascia of the obturator internus and laterally by its

corresponding muscle, and lines the lateral wall of

the ischioanal fossa.

Obturator Foramen

The obturator foramen (OF) is the result of the

fusion of the pubic bone and the ischium. The

anatomy of the OF allows surgeons to approach the

female urethra from the lateral aspect, as opposed

to the traditional suprapubic approach. The OF is

traversed by the obturator nerve artery and vein,

all at the most inferiolateral aspect, via the obtu-

rator canal (Figs. 4.2 – 4.4 ). The OF is covered

medially and laterally by the obturator internus/

externus, respectively. Using cadaveric dissections,

the transobturator needle was an average of 2.3 cm

inferior-medial to the obturator canal. The needle

was passed through the gracilis, adductor brevis,

obturator externus, and obturator membrane, and

beneath or through the obturator internus muscle

and periurethral endopelvic connective tissue [1] .

Chapter 4

Pelvic Floor: Three-Dimensional

Surgical Anatomy

Ardeshir R. Rastinehad and Gopal H. Badlani

42 A.R. Rastinehad and G.H. Badlani

Soft Tissues of the Pelvis

The tendinous arch (arcus tendineus) is a condensa-

tion of the medial fascia of the obturator internus

muscle, spanning from the posterior aspect of the

pubic ramus to the ischial spine (Fig. 4.5 ). The

arcus tendineus is the origin of the pelvic diaphragm

(levator ani and coccygeus muscle (Fig. 4.6 ). The

levator ani is considered to be the true muscular

floor of the pelvis and is composed of the pubococ-

cygeus, ischiococcygeus, and puborectalis muscles.

The levator ani muscle forms a U-shaped hiatus

through which the urethra, rectum, and in the female

the vagina traverse (Fig. 4.7 ). The coccygeus and

piriformis muscles are the remaining paired muscles

that complete the pelvic floor.

Fig. 4.1. Bony pelvis

Fig. 4.2. Anatomical dissection of the path of the transobturator sling. Published by Whiteside and Walters (repro-

duced with permission) [1]

4. Pelvic Floor: Three-Dimensional Surgical Anatomy 43

The levator ani muscles have a baseline resting

tone, similar to other postural muscles [2] . They

are composed of type I and type II fibers [3] . The

contraction of the levator ani closes the urogenital

hiatus by compressing the vagina, rectum, and

urethra, displacing the pelvic contents in a cepha-

lad direction. This shifts the strain of the pelvic

contents to the muscles from the ligamentous sup-

ports and also eliminates potential spaces through

which pelvic contents could herniate [2] .

Endopelvic Fascia

Endopelvic fascia is an extension of the transver-

salis fascia [4] , which drapes on the pelvic floor.

The endopelvic fascia is the result of the ingrowth

of splanchnic mesoderm. The endopelvic fascia,

which lies immediately beneath the peritoneum,

is a viscerofascial layer that interconnects vari-

ous pelvic organs [4] . DeCaro et al. analyzed the

pelvic viscera of cadaveric females, describing the

traditional subdivisions of the endopelvic fascia

Fig. 4.3. Cadaveric dissection of the endopelvic fascia and right lateral pelvic fossa, including the obturator foramen.

The scalpel handle measures the distance from the obturator foramen to the path of the transobturator needle

Fig. 4.4. Lateral view of the hemipelvis

44 A.R. Rastinehad and G.H. Badlani

(cardinal, uterosacral, urethropelvic, and puboure-

thral ligaments) as one continuous condensation

(3D network) of areolar tissue, with smooth mus-

cle cells surrounding pelvic neurovasculature and

no true demarcation between the “ligaments” [5] .

Therefore, the strength provided by the endopelvic

fascia is due to the entire fascia, not the individual

ligaments appreciated during surgical dissection

(Figs. 4.8 and 4.9 ) .

Cardinal ligaments give support to the uterus,

cervix, and upper vagina by attaching to the pelvic

side wall. As described previously, the “ligaments”

contain divisions of the hypogastric vessels, which

supply the uterus and upper vagina. In conjunction

with the uterosacral ligaments, they maintain the

position of the cervix and vagina over the levator

plate by restricting the downward and outward

movements [4] . Uterosacral ligaments are formed

by the medial aspect of the endopelvic fascia,

spanning from the cervix and upper vagina to the

sacrum. The combined uterosacral and cardinal

ligaments are the paracolpium, which attach to

the vagina, and the parametrium, which attach to

the uterus. Urethropelvic ligaments are an anterior

medial condensation of the endopelvic fascia,

which combines with fibers from the pubococ-

cygeus muscle to span the area from the anterior

aspect of the tendinous arc to the anterior vaginal

wall, bladder neck, and proximal urethra [4] . This

portion of the pelvic floor is the main musculofas-

cial support for the bladder, neck, and proximal

urethra. The pubourethral ligament attaches the

Fig. 4.5 . Four-layer artistic interpretation of the pelvis, from the bony ligamentous structures progressing through the

deep and superficial musculature

Fig. 4.6. Three-dimensional rotation of the pelvis, anteriorly denoting the path of transobturator needle

4. Pelvic Floor: Three-Dimensional Surgical Anatomy 45

F ig. 4.7. Vaginal view of ( a ) levator ani muscle and bony pelvis with ( b ) MRI correlation

Fig. 4.8. Lateral pelvic view of endopelvic fascia and associated structures

46 A.R. Rastinehad and G.H. Badlani

mid-urethra to the inferior surface of the pubic

symphysis. The pubourethral ligaments are analo-

gous to the puboprostatic ligaments in the male.

The pubourethral ligaments, in conjunction with

the pubourethralis muscle, prevent the rotational

decent of the proximal urethra [2] .

The fascia of the bladder has two divisions:

the perivesical fascia on the vaginal side and the

endopelvic fascia on the abdominal side. This

provides the posterior support to the bladder and

bladder neck. DeLancey described the pelvic fas-

cial support in three distinct functional levels.

Level I, upper portion, consists of long sheets

endopelvic fascia attaching the vagina to the pelvic

wall. Level II, paracolpium, attaches the vagina

laterally and more directly to the pelvic walls

and stretches the vagina between the bladder and

the rectum. The pubocervical fascia is composed

of the anterior vaginal wall and directly supports

the bladder. Posteriorly, the vaginal wall and the

endopelvic fascia form the restraining layer that

prevents the formation of a rectocele. Level III,

the distal vagina, the walls are directly anchored to

the surrounding structures without any intervening

paracolpium (Figs. 4.10 and 4.11 ) [7] .

The bladder is a hollow viscus organ used for the

temporary storage of urine. While empty, the blad-

der resides within the true pelvis; during filling,

the bladder is displaced anteriorly and superiorly

into the preperitoneal space. The bladder neck is

located ~3cm posterior to the pubic symphysis

Fig. 4.9. A diagram representing the corresponding fas-

cial support of the bladder, urethra, and uterus. Adapted

from four-defect repair of grade 4 cystocele [6]

Fig. 4.10. Artist’s rendition of DeLancey’s classic description of the three levels of pelvic support [8]

Ischial spine &

sacrospinous

ligament

I

II

III

Levator ani

Pubocervical fascia

Rectovaginal fascia

Level I

Level II

III

4. Pelvic Floor: Three-Dimensional Surgical Anatomy 47

and is supported by the endopelvic fascia. The

urachus anchors the bladder dome to the anterior

abdominal wall.

Yucel and Baskin proposed a three-component

mechanism to male/female continence: the detrusor,

trigone, and urethral muscles. These components

were of a distinctly different muscular origin. Also,

the levator ani muscles do not converge ventrally

to the urethra; therefore, their role in continence is

questioned [9] . This contrasts the previous theories

relating to urethral sphincter development, which

postulated a continuation of the trigone and bladder

musculature in the formation of the urethral sphinc-

ter [10] . The smooth muscle of the urethra, sur-

rounding rhabdosphincter, and periurethral striated

muscle of the levator ani are the distinct components

of the continence mechanism (Fig. 4.12 ).

Using three-dimensional imaging techniques,

combined with immunohistochemical staining,

complete reconstructions of the male and female

urethra were completed. The bladder neck is ori-

ented in an oblique angle with the ventral aspect of

the bladder neck in a cranial position. The muscle

layers of the trigone and the rest of the bladder

were different in morphology. Below the ureteral

orifices, the trigonal muscle narrowed and then

broadened and thickened dorsally to the blad-

der and proximal urethra. The outer longitudinal

muscle layer of the ventral bladder wall continued

in a ventrolateral direction at the bladder neck

to envelope the ventral circular muscle fibers of

the proximal urethra. The dorsal division did not

extend to the proximal urethra. The inner proximal

urethra muscle layer could be traced to the internal

meatus, where the detrusor inner muscle begins.

The inner muscle layer of the urethra continues to

the distal urethra [9] .

The external urethra sphincter begins in the

bladder neck and continues to the distal urethra.

Cranially, the external urethral sphincter starts as

horseshoe-shaped, only covering the ventral and

lateral faces of the proximal and midurethra. The

external urethral sphincter at the distal portion

remains horseshoe-shaped, yet has a longer exten-

sion that covers the distal vagina [9] .

The rectovaginal muscle, external urinary sphinc-

ter muscle, levator ani muscles, and bulbospon-

giosis muscle all converged on the median fibrous

Fig. 4.11. Artist’s rendition of the vagina and supportive structures which have been extirpated, including the bladder,

which was removed above the bladder neck. The paracolpium extends along the lateral aspects of the vagina [8]

Paracolpium

Obturator internus muscle

Arcus tendineus

levator ani

Vesical neck

Levator ani

Arcus tendineus fasciae pelvis

Ischial spine

Vagina

48 A.R. Rastinehad and G.H. Badlani

raphe. The origins of Denonvilliers’ fascia have

been debated since the first description in 1836.

Currently, taking into account the embryological

origins, Denonvilliers’ fascia is a condensation of

the peritoneal cul-de-sac, resulting in a single layer.

Denonvilliers’ fascia then fuses with the posterior

vaginal wall [11] . The illustration outlines the

international pelvic organ prolapse; note that at

point D, there is a fusion of the Denonvilliers’ fas-

cia and the peritoneum (Fig. 4.13 ). Perineal body

relaxation characteristically is associated with an

increase in the diameter of the vaginal opening.

The female pelvis can be divided into two trian-

gles by drawing a line between the ischial tuberosi-

ties. The line passes directly through the perineal

body (Fig. 4.14 ).

Fig. 4.12 . Vaginal view of the pubourethral ligaments, rhabdosphincter, and compressor urethrae [2]

Compressor urethra

Urethrovaginal sphincter

Urethral rhabdosphincter

Pubic symphysis

Trigonal ring

Detrusor loop

Distal

urethral

sphincter

Urinary trigone

Vagina

Fig. 4.13. POP classification of prolapse

C

D

Bp

Ap

Aa

3 cm Ba

tvl

pb

gh

4. Pelvic Floor: Three-Dimensional Surgical Anatomy 49

Vaginal Anatomy

Vagina

The vaginal wall is 2–3 mm thick and consists of

an inner mucous coat, an outer fibrous sheath, and

a muscular layer in between. The muscular coat

is made of smooth muscle cell bundles, arranged

in a spiral system, which allows for distention

with tearing [4] . The vaginal depth and axis are

maintained, as described by DeLancey in his three-

tiered system (Fig. 4.10 ). The rectovaginal fascia

attaches to the posterior vaginal wall, contributing

to the overall support system of the vaginal vault

[13] . (Fig. 4.15 ) .

Tissue Planes of the Pelvis

The connective tissue planes of the pelvis allow

for independent function of the uterus, bladder,

and rectum. These connective tissue planes create

potential spaces to allow for dissection during uro-

logic and gynecologic procedures and also impede

the spread of infection among adjacent organs/

spaces. The septa dividing these areas envelope

neurovascular and lymphatic structures supplying

each organ (Fig. 4.16 ).

Vesicovaginal Space

The vesicovaginal space traverses the area poste-

rior to the adventia of the bladder and anterior to

the vagina. The lateral borders consist of the blad-

der septa containing the ureter and efferent veins,

which attaches laterally inferiorly at the lateral

portion of the bladder and extends up to the lateral

portion of the cardinal ligaments. The vesicovagi-

nal space fuses closed between the adventia of the

bladder and uterus, forming the vesicovaginal sep-

tum, which progresses as the vesicocervical space.

Fig. 4.14. Anterior and posterior pelvic triangles with superficial muscles [12]

Pubic symphysis

Ischiocavernosus

Bulbospongiosus

Urethral orifice

Vaginal orifice

Transversus perinei

superficialis

Levator ani

Gluteus maximus

Sphincter ani externus

Perineal body

Sacrotuberous

ligament

Greater vestibular

gland

Inferior fascia of

urogenital diaphragm

Bulb of the vestibule

Ramus of ischium

Obturator foramen

Crus of clitoris

Body of clitoris

Body of pubis

Fig. 4.16. Superficial and deep pelvis (anterior view) with potential dissecting planes

Fig. 4.15. ( a ) Vaginal axis – lower two thirds (vesical) and upper one third (almost horizontal with poster tilt).

( b ) Loss of axis post hysterectomy. ( c ) Apical and anterior compartment prolapse secondary to loss of axis

a

bc

4. Pelvic Floor: Three-Dimensional Surgical Anatomy 51

Space of Retzius (Retropubic Space)

The prevesical space of Retzius extends from the

posterior aspect of the pubis, anteriorly to the

bladder, and then extends cephalad between the

medial umbilical ligaments. It offers the space to

approach the endopelvic fascia and arcus tendineus

for suprapubic approach in continence procedures,

as well as the space that needles traverse.

Paravesical Space

The paravesical spaces, which are preformed fat-

filled spaces, are bilaterally bound, superiorly by

the lateral umbilical ligaments and medially by the

bladder separating the space. This lies superior to

the cardinal ligaments. The lateral boundary con-

sists of the fascia from the levator ani muscles and

the obturator internus. The so-called paravaginal

tear at the endopelvic fascia and its attachment to

the arcus tendineus are described as a cause of lat-

eral cystocele and urethral hypermobility.

Pararectal Space

The pararectal space is inferior to the cardinal liga-

ments, extends from the anteriolateral boundaries

of the sacrum, and spans the area to the lateral

borders of the rectum and the levator ani muscles.

Superiorly, the rectum is contained within a single

circular pararectal space, which is a confluence of

the two inferior pararectal spaces.

Rectovaginal Space

The superior portion of the rectovaginal space is

bound by the rectouterine pouch (Douglas) and

inferiorly by the perineal body. The pelvic floor

muscle (levator ani) inserts on the perineal body.

The detachment of the endopelvic prerectal fascia

from the perineal body results in a rectocele.

Pelvic organ prolapse is divided into three major

categories (anterior, middle, and posterior). Anterior

vaginal wall prolapse consists of two subtypes: lat-

eral and central or posterior cystoceles. The lateral

Fig. 4.17. Neurovascular anatomy of the pelvis (lateral review) [15]

Ureter

Internal pudendal artery

Uterine artery

Vagina

Rectal artery

Connecting band

sacrospinous

ligament and S3 root

USL

Internal iliac

artery and vein

Superior gluteal

artery and vein

S1 root

Inferior gluteal

artery and vein

Sacrospinous

ligament

Rectum

52 A.R. Rastinehad and G.H. Badlani

cystocele is associated with a hypermobility of the

bladder neck, which includes the urethra. This condi-

tion results from the attenuation of the lateral supports

(pubourethral and endopelvic fascia). In contrast to

the central variant (bladder), this is secondary to lax-

ity of the vesicopelvic fascia.

Vaginal vault prolapse is secondary to the loss

of support from the sacrouterine and cardinal liga-

ments. Also, midline defects included enteroceles,

which are most commonly associated with a laxity

between the vagina and the rectum, and the length

of the posterior vaginal wall is preserved [13] .

There is a 75% incidence of enteroceles associated

with vault eversion [14] .

Posterior compartmental prolapse (rectocele)

can be secondary to attenuation of the distal pos-

terior wall, perineal membrane, and perineal body.

The rectum has numerous attachments contribut-

ing to its overall support, including the Waldeyer’s

fascia, perineal body (anterior), ATFP (laterally),

and rectovaginal fascial attachment to uterosacral

ligaments (superior) [13] .

Neurovascular Anatomy

The neurovascular anatomy of the pelvis is com-

plex due to the venous and neural plexus widely

spread through the entire pelvis. Presacral, retro-

trigonal, and pararectal nerve dissection leads to

functional impairment and violation of the prevesi-

cal spaces, resulting in significant bleeding. The

arterial anatomy is more predictable with branches

of the internal iliac supply of the pelvic organ.

Vascular grafts for labia majora (Martius flap) can

be anteriorly or posteriorly based.

The location of the neurovascular bundle, 1–2 cm

medial to the ischial spine over the sacrospinalis

ligament, is well recognized. Similarly, venous

plexus in presacral space can be a cause of signifi-

cant bleeding in the repair (Fig. 4.17 ).

References

1 . Whiteside J , Walters M . Anatomy of the obtura-

tor region: Relations to a trans-obturator sling . Int

Urogynecol J 2004 ; 15 : 223 – 226 .

2. Plzak L , Staskin D . Genuine stress incontinence:

Theories of etiology and surgical correction . Urol

Clin North Am 2002 ; 29 : 527 – 535.

3 . Gosling J , Dixon J , Crichely H , Thompson S. A

comparative study of the human external sphincter

and periurethral levator ani muscles . Br J Urol 1981 ;

53 (1) : 35 – 41 .

4 . Klutke C , Siegel C . Functional female pelvic anat-

omy . Urol Clin North Am 1995 ; 22 (3) : 487 – 498 .

5 . DeCaro R , Aragona F , Herms A , Guidolin D .

Morphometric analysis of the fibroadipose tissue of

the female pelvis . J Urol 1998 ; 160 : 707 – 713 .

6 . Safir MH , Gousse AE , Rovner ES , . 4-Defect repair

of grade 4 cystocele . J Urol 1999 ; 161 : 587 – 594 .

7 . DeLancey J . Anatomy and biomechanics of genital

prolapse . Clin Obstet Gynecol 1993 ; 36 (4) : 897 –

909 .

8 . DeLancey JOL . Anatomic aspects of vaginal ever-

sion after hysterectomy . Am J Obstet Gynecol 1992 ;

166 : 1717 – 1728 .

9 . Yucel S , Baskin L . An anatomical description of the

male and female urethral sphincter complex. J Urol

2004 ; 171 : 1890 – 1897 .

10 . Delancy J . Structural aspects of urethrovesical

junction in the female . Neurourol Urodyn 1988 ;

7 : 509 .

11 . Cesoedes RD . The treatment of posterior compartment

vaginal defects . Atlas Urol Clin 2004 ; 12 : 233 – 241 .

12. From Williams PL, Warwick R. Gray’s anat-

omy, 35th British ed. Philadelphia, WB Saunders,

1973:1364.

13 . Zhu H , Kluthke JJ , Lutke CG . MR imaging find-

ings with female prolapse . Atlas Urol Clin 2003 ; 11 :

101 – 112 .

14 Nichols DH, Randall CL. Vaginal surgery, 4th ed.

Baltimore, Williams and Wilkins.

15 . Chesson RR , Shobeiri SA . Uterosacral suspen-

sion of the vaginal vault . Atlas Urol Clin 2003 ;

11 : 113 – 127 .

53

Introduction

Pelvic floor prolapse or pelvic organ prolapse (POP)

( Fig. 5.1 ) is a common but poorly understood con-

dition affecting millions of women worldwide. In

the United States, the lifetime risk of undergoing

surgery for POP or urinary incontinence is estimated

to be 11%, and nearly 30% of these patients require

another operation for recurrence [1] . The Women’s

Health Initiative (WHI) data revealed that approxi-

mately 40% of women had some form of POP [2] .

This difference in rates of prolapse between surgical

patients and patients being seen for routine gyneco-

logic examinations reflects the often asymptomatic

presentation of prolapse [3] . Understanding the

progression of this disease may allow clinicians

to apply more appropriate treatment to patients

depending on the etiology of their prolapse and their

symptoms. Despite the prevalence of POP, little is

known regarding the mechanism for development

and natural history of the disease. Much of this

stems from the lack of a clear and standardized defi-

nition for POP, which limits our ability to study its

etiologies. A conference on terminology assembled

by the National Institutes of Health (NIH) recently

focused on developing clear definitions for POP to

foster more epidemiological research into the disease

[4] . These studies are forthcoming, but with a 45%

increase over 30 years in demand for services related

to pelvic floor dysfunction, our understanding of its

development will become important in meeting the

treatment needs of the future [5] . Successful treat-

ment will require the identification and management

of risk factors that could potentially be involved in

the development of POP.

In order to recognize risk factors for POP, a thor-

ough understanding of pelvic anatomy is needed.

As the female pelvis evolved from quadruped

ambulation to bipedalism, supportive structures

adapted to support pelvic viscera and enable partu-

rition (see Chapter 4, Three-Dimensional surgical

anatomy). Activities and events that are shaped by

a bipedal lifestyle can contribute to failures in the

supportive structure of the pelvis that can lead to

POP. Maintaining or rehabilitating levator muscle

bulk and strength may be the key to preventing

many cases of pelvic organ prolapse [6] . Just as

humans evolve, so too do the signs and symptoms

of POP. Research into the evolution of POP should

focus on the anatomical disruptions predisposed

to by specific risk factors and physical insults to

the female pelvis. It is not uncommon for urinary

incontinence, fecal incontinence, and POP to coex-

ist because of their anatomical relationships and

common risk factors ( Fig. 5.2 ) . In this chapter we

will focus specifically on the cause and effect of

pelvic organ prolapse.

Causes

There are many postulated risk factors for POP,

including genetics, race, pregnancy, vaginal child-

birth, prior surgery, neuropathy, obesity, smoking,

chronically increased intra-abdominal pressure, cer-

tain recreational or occupational activities, aging,

Chapter 5

Pelvic Floor Prolapse: Cause and Effect

Matthew A. Barker and Mickey M. Karram

54 M.A. Barker and M. M. Karram

and menopause. In reality, the etiology most likely

is multifactorial and reflects a combination of some

if not all of these risk factors [3] . Individuals will

develop POP based on the combination of these

risk factors. Bump and Norton described a useful

approach to understanding the development of POP

by considering the risk factors as predisposing,

inciting, promoting, and decompensating events

[7] ( Table 5.1 ).

Predisposing Events

Predisposing factors such as race and genetics

may increase an individual’s risk for developing

POP. Unfortunately, many of the studies looking

at the etiology of POP included predominately

Caucasians. Data from the WHI showed African-

Americans had a lower rate of POP compared to

Caucasians, whereas Hispanics had a higher risk of

developing uterine and anterior wall prolapse [2] .

These differences may be related to differences in

the bony pelvis and muscle mass or it may reflect

a paucity of data regarding racial differences with

pelvic floor dysfunction. Many ethnic and racial

studies have small sample sizes that limit us from

Fig. 5.1. Picture of pelvic organ prolapse

Fig. 5.2. Anatomy of the pelvic floor. (From: Anson BJ. An atlas of human anatomy. Philadelphia: WB Saunders,

1950, with permission.)

5. Pelvic Floor Prolapse: Cause and Effect 55

drawing any statistically meaningful inferences.

These studies may actually harm certain racial

demographics by minimizing the need to assess

certain ethnic groups or by providing inappropriate

therapy [8] . Studies are limited and data often are

contradictory in regard to racial differences in the

incidence of pelvic organ prolapse, and it is impos-

sible to draw any firm conclusions [9] . Further

population-based studies are needed to decipher

whether racial differences exist for POP so that

appropriate care and counseling can be given.

Although no study exists that identifies indi-

viduals who are destined to develop POP, there

are certain risk factors that may predispose women

to POP. Just as race is inherited, so too are other

familial traits such as the shape of bony pelvis.

There have been studies showing that women are at

greater risk for developing prolapse if their moth-

ers or sisters reported the condition [10– 13] . This

association among relatives may have to do with

similar collagen make up. Defective connective tis-

sue such as that associated with joint hypermobility

and diseases like Ehlers–Danlos syndrome may

contribute to POP through defects in the underlin-

ing collagen of the pelvic floor [14] . The connec-

tive tissue that supports and suspends the pelvic

organs can become structurally or biochemically

defective, leading to POP. Women undergoing

surgery for POP have a decrease in fibroblasts and

an increase in abnormal collagen [15] . Other stud-

ies reaffirmed this imbalance of collagen, meaning

that there was an increase in type III collagen,

which is weaker and its overabundance may lead

to POP [16] . It yet has to be determined whether

this change in collagen is related to age, hypoestro-

genic states, or remodeling secondary to an already

present POP.

Just as breakdown in support can occur and

lead to POP, pelvic neuropathies can cause similar

effects. The resting tone of the levator ani helps

support the pelvic floor and prevent prolapse;

any disruption to this innervation can predispose

a women to POP. Occult spina bifida has been

correlated with the development of POP, and 80%

of newborn females and nulliparous women with

spina bifida have uterine prolapse [17 , 18] . Other

conditions that affect the spinal cord pathway and

pelvic nerve roots result in flaccid paralysis of the

pelvic floor muscles and POP [19] . It is the loss of

support, whether structural, biochemical, or dener-

vation to pelvic tissues, that predisposes women to

POP. This concept of loss of support at many levels

is important when looking at other insults to the

pelvic floor and its effects.

Inciting Events

The factors that may incite POP are related to

events that lead to damage to the pelvic floor.

This may include vaginal birth, nerve and muscle

damage, and pelvic surgery. Parity is a risk factor

often associated with POP and increasing parity is

associated with advancing prolapse [20] . In data

from the WHI the first birth doubled the risk of

uterine prolapse as well as anterior and posterior

wall prolapse; each additional birth increased the

risk by 10–21% [2] . The Oxford Family Planning

Study showed that women with two deliveries were

8.4 times more likely to have surgery for prolapse

compared to nulliparous women ( Fig. 5.3 ) [21] .

Even though vaginal delivery is associated with

POP, other obstetric risk factors exist that may

contribute to POP. Operative deliveries, prolonged

second stage, macrosomia, episiotomies, epidur-

als, and oxytocin have been implicated in causing

prolapse [3] .

The labor and delivery process may cause direct

injury to the nerves and muscles and possible tis-

sue disruption, all of which can cause pelvic floor

dysfunction. Increased pressure on the pelvic floor

may stretch and tear maternal tissues during deliv-

ery. Forceps and episiotomies are risk factors for

Table 5.1. Potential risk factors for pelvic organ prolapse.

Predispose Incite Promote Decompensate

Genetics Pregnancy Obesity Aging

Race Delivery Smoking Menopause

Pelvic surgery Pulmonary disease Myopathy

Myopathy Constipation Neuropathy

Neuropathy Heavy lifting Debilitation

56 M.A. Barker and M. M. Karram

pelvic floor dysfunction. Many argue for elective

cesarean sections to prevent these injures to the pel-

vic floor [22 – 24] . Because there is no evidence that

elective episiotomy and operative vaginal delivery

are beneficial and the potential harm is great, some

feel that the routine use of these procedures should

be avoided [3] . Data relating vaginal delivery to

the development of POP are confusing because

most pelvic floor dysfunction occurs long after

the vaginal birth, and most women who experi-

ence childbirth do not develop POP [7] . In a recent

cross-sectional study comparing women who had

undergone one or more vaginal deliveries com-

pared to women who had only cesarean sections,

the vaginal delivery cohort showed a significantly

greater risk of developing symptomatic POP, after

adjusting for age, parity, and obesity [25] . This

study suggests that it is the labor process more so

than the pregnancy that contributes to pelvic floor

dysfunction. Yet, other studies exist that contradict

these findings, and the problem that still persists

is that pregnancy is a risk factor in itself; further

data are needed to evaluate which has the greatest

impact on pelvic floor dysfunction [20 , 21] .

The debate is ongoing about elective cesarean sec-

tions, but it seems reasonable to offer women with

preexisting pelvic floor dysfunction or prior injury

an elective cesarean section to prevent further wors-

ening of their disease. Recently, the NIH held a

conference on cesarean delivery and it was concluded

that more research was needed before promoting

elective operative deliveries [26] . What is interest-

ing about the consensus group is that it still left

open the possibility for planned cesarean deliveries,

but thought it should be made on an individual

basis. This is exactly how we should approach

women with risk factors for POP: individualize

their care based on risk stratification and orient their

treatment to their specific risk factors or causes of

their POP. Ideally, physician’s efforts should be aimed

at identifying which women are at risk and which risk

factors in the birthing process can be modified.

In addition to childbirth, pelvic surgery is an

identifiable inciting factor for pelvic floor dysfunc-

tion. During radical pelvic surgery muscles and

supportive tissues often are transected, predisposing

women to POP. Hysterectomy alone is thought to

double the risk of severe POP and prior surgery for

pelvic organ prolapse is a risk factor for recurrence

as well [27] . In the Oxford Family Planning Study,

the incidence of surgery for POP was higher in

women with a prior hysterectomy for reasons other

than prolapse and substantially higher in women

who had a hysterectomy for prolapse [21] . This

may reflect surgical techniques that have resulted

in high failure rates for surgical correction of POP

or the disruption to the pelvic muscles, nerves, and

tissues that occur during surgery. One study looked

at the risk of developing POP after vaginal hyster-

ectomy and found that a prophylactic McCall-type

culdoplasty at the time of vaginal hysterectomy

may prevent the development of posterior wall pro-

lapse [28] . There is potential to modify our surgical

techniques in order to improve clinical outcomes,

decrease recurrence rates, and counsel patients who

may be at risk for later POP development.

Promoting Events

The area that holds the greatest benefit to prevent-

ing the development of POP is modifying the

behaviors and activities that are known risk factors

for POP. We have discussed risk factors that predis-

pose and incite POP, but there are many factors that

promote the development of POP. Risk factors such

as obesity, smoking, chronic coughing, constipa-

tion, and heavy lifting can be modified to prevent

the cause-and- effect relationship we see with them

and the development of POP.

Obesity is one of the few modifiable risk factors

for POP identified so far [2, 21] . Data from the WHI

showed that body mass index greater that 30 kg m

−2

conferred a 40–75% increased risk of POP [2] . The

data revealed that “apple” body-shaped women had

a 17% increase of anterior and posterior vaginal

wall prolapse. This supports the theory that chronic

Fig. 5.3. Adjusted effects of parity on inpatient admis-

sion rates for genital prolapse. (From Mant J, Painter R,

Vesse M. Epidemiology of genital prolapse: observations

from the Oxford Family Planning Association Study. Br

J Obstet Gynaecol 1997;104:579, with permission.)

5. Pelvic Floor Prolapse: Cause and Effect 57

increases in intra-abdominal pressure lead to POP.

There are limited data on the results of weight

reduction and resolution of pelvic floor disorders.

The prevalence of urinary and anal incontinence in

the obese population is high, and weight loss may

be able to reverse some of these symptoms [29] .

The effects of increased weight and intra-abdominal

pressure on the pelvic floor cause a mixture of pelvic

floor dysfunction, with POP being a symptom of

this. There is potential to possibly reverse urinary

and defecatory symptoms with weight loss, and

further data are needed to evaluate the potential to

reverse the symptoms of POP.

The theory behind the development of POP from

chronically increased intra-abdominal pressure is

supported by many associations. Obesity, chronic

constipation, chronic coughing and repetitive heavy

lifting have been associated with the development

of POP. The chronic straining associated with con-

stipation is thought to lead to progressive pelvic

neuropathy and dysfunction due to stretching of

the pudendal nerve [30] . Women with a history of

constipation and straining during bowel movements

before the onset of pelvic floor dysfunction had an

increased risk of developing both POP and urinary

incontinence compared to women who did not have

pelvic floor dysfunction [31] . Similar repetitive

forceful straining also can occur with coughing usu-

ally associated with cigarette smoking and chronic

obstructive pulmonary disease (COPD).

The data around smoking as a cause of POP are

mixed, and one study suggests it may be protective

[1, 2, 10, 20, 21, 32] . Interestingly, data analyzing

COPD and its association with POP failed to show

a correlation [1, 24] . Studies looking at urinary

incontinence revealed an increase in stress urinary

incontinence with smokers [33] . It was thought

that smokers’ more chronic and stronger coughing

contributed to their incontinence. Again, POP is

intuitively thought to be influenced by a similar

mechanism, but data showing an association with

COPD are lacking.

Activities that increase intra-abdominal pressure

such as repetitive manual lifting are associated

with POP. Nursing assistants who were exposed

to repetitive heavy lifting were at increased risk

of undergoing surgery for POP [34] . In a clinic-

based study of Nepalese women with POP, their

POP was associated with heavy lifting especially

during the postpartum period [35] . Another report

implicated the stress of airborne training in female

paratroopers as a risk factor for the development

of POP and urinary incontinence [36] . A survey

of Olympic athletes in high-impact sporting events

did not have any greater risk for the development

of urinary incontinence years later compared with

athletes competing in low-impact events [37] . This

study did not look at prolapse and there is limited

data showing an association of high impact forces

on the pelvic floor and the development of POP.

A clear cause-and-effect relationship with

increased intra-abdominal pressure and the devel-

opment of POP has yet to be validated with large

prospective studies. This is an area where research

is clearly needed and could possibly help identify

women at risk and possibly contribute to the preven-

tion of POP. It also could potentially decrease the

risk of POP recurrence, which is as high as 30%

following pelvic surgery [1] . In a study looking

at certain activities and intra-abdominal pressure

measurements, there were wide variations in pres-

sures generated, and many of the activities surgeons

recommend patients avoid after surgery did not

generate pressures greater than simply getting out of

a chair [38] . A better understanding of the mecha-

nisms that abdominal forces play on the pelvic floor

is needed to help guide our understanding of the

causes of POP and help us educate our patients bet-

ter in terms of avoiding these promoting factors.

Decompensating Events

The normal pelvic floor anatomy of the female

evolved to withstand the shift in abdominal forces

from the anterior abdominal wall to the pelvis,

stress from childbirth, and permit urinary and fecal

evacuation. It often is affected by the direct strain

these changes place on it, but it also is susceptible

to factors extrinsic to the pelvic floor. Age, estro-

gen status, and comorbid diseases contribute to the

development of POP, but studies are limited that

show a direct relationship of these individual fac-

tors on the pelvic floor.

Advancing age is probably the greatest risk fac-

tor for POP. Prior studies have evaluated age as

a risk factor for POP; utilizing multiple logistic

regression analysis, the menopausal status becomes

nonsignificant and age more than estrogen levels

places a woman at risk for prolapse [2, 10, 20,

24] . Estrogen receptors are found throughout the

vagina, but little is known about the potential inde-

pendent effects of menopause or estrogen status on

58 M.A. Barker and M. M. Karram

POP. Dermatologic studies have shown that estro-

gen increases total skin collagen content and vagi-

nal estrogen is routinely recommended to correct

POP [39] . One study looking at selective estrogen

receptor modulator (SERM) for osteoporosis was

stopped before completion secondary to adverse

affects including increased urinary incontinence

and twofold increase in progression of prolapse

[40] . In contrast to this study there is one case-

controlled study showing a decreased risk of POP

in postmenopausal women using hormone replace-

ment therapy (HRT) for greater than 5 years [41] . It

is not clear if HRT is truly protective, but other than

in a SERM study HRT does not appear to have a

negative effect on POP. The common use of topical

vaginal estrogen cream in postmenopausal women

with POP hopefully will generate future studies

that examine estrogen status as an independent risk

factor for prolapse.

Age and postmenopausal status are associated

with many other medical illnesses. Medical dis-

eases that lead to microvasculature damage and

peripheral neuropathies potentially can cause POP.

In one large study of the etiologies of POP the

presence of any chronic illness was not associated

with POP, but in another study hypertension was a

risk factor [20, 24] . Large epidemiological studies

evaluating women with POP are needed to exam-

ine and assess the impact diseases like diabetes,

hypertension, and other chronic illnesses have on

the pelvic floor.

Effects

The grouping of risk factors established by Bump

and Norton enable clinicians to organize their

thoughts about the development and progression

of POP, but it does not enable them to predict

who will be symptomatic from their POP or what

type of pelvic floor dysfunction they will suffer

[7] . The risk factors that lead to causes of POP

usually manifest as symptoms perceived by an

individual. The suggested definition of POP by the

NIH conference to standardize the terminology of

pelvic floor disorders relied on physical findings

alone to define POP, but in clinical practice it is the

patient’s symptoms that lead them to seek treat-

ment; there are limited data regarding the signifi-

cance of asymptomatic POP [4] . The effects that

POP have on individuals vary in severity in terms

of the impact on their quality of life. Symptoms

that individuals with POP traditionally describe

can be broken down into anatomic, functional,

or sexual symptoms. Because of the anatomical

relationships of the urinary, reproductive, and

digestive systems, much overlap often exists in

symptoms associated with POP. These symptoms

include vaginal bulging, pelvic pressure, voiding

dysfunction, defecatory dysfunction, and sexual

dysfunction ( Table 5.2 ). Our understanding of the

relationship between prolapse and pelvic floor

symptoms have improved with the implementation

of validated self-administered questionnaires that

enable researchers to assess the impact different

symptoms have on individuals and which correlate

with POP [42] .

Anatomic Symptoms

The failure of normal pelvic floor support leads to

symptoms of POP. The protusion of the cervix or

herniations of vaginal tissue through the vaginal

introitus cause symptoms which patients describe

as a “bulge,” protrusion, pelvic or low back pain,

or just pressure. The levator ani muscles and con-

nective tissue attachments to the pelvic viscera

provide the normal support to pelvic organs and

their surrounding tissue ( Fig. 5.4 ). The levator ani

muscles have a normally contracted basal tone that

Table 5.2. Symptoms of pelvic floor prolapse .

Anatomic Functional (urinary) Functional (bowel) Sexual

Sense “bulge” Incontinence (stress and/or urge) Incontinence (fecal/flatal) Dyspareunia

Visualize “bulge” Frequency and urgency Urgency Interference of POP during

intercourse

Pressure/fullness Incomplete bladder emptying Incomplete rectal emptying

Hesitancy Straining

Splinting to void Splinting to defecate

5. Pelvic Floor Prolapse: Cause and Effect 59

keeps the urogenital hiatus closed, but also can

contract reflexively in response to certain actions

that increase intra-abdominal pressure [43] . If there

is damage or weakening of the levator ani muscles,

the connective tissue around the pelvic organs will

provide support until the load becomes too great

[43] . The genital hiatus then will open with the

loss of levator ani contraction and failure of the

connective tissue allows for the pelvic organs and/

or tissues to prolapse [43] . It is this failure of the

normal anatomy caused by previously described

risk factors that leads to the development of POP.

The varying complaints that patients report have

led clinicians to investigate whether the extent of

prolapse correlates with symptoms. In one study, the

symptoms of POP increased when the leading edge

of the prolapse was beyond the hymenal remnants

[44] . The concept that symptoms worsen with stage

of POP is important, but it does not explain why

patients with similar degrees of POP present with

different and multiple symptoms. Ellerkmann et al.

found a correlation between patients being able to

visualize a bulge and worsening stage of POP, but

symptoms did not necessarily correlate with com-

partment-specific defects [45] . Also, they did not

show a strong correlation between the stage of POP

and other symptoms related to urinary and defeca-

tory dysfunction. Other studies have confirmed that

the typical symptom that is anatomically associated

with POP is a “bulging” sensation and that other

symptoms do not correlate with the severity of POP

[46 , 47] . The inability to correlate stage of prolapse

with voiding and defecatory symptoms with stage

of POP may imply that a different mechanism may

be involved in the development of functional com-

plaints in women with POP.

Functional Symptoms

The loss of normal urinary and bowel function in

an individual can be very debilitating to an indi-

vidual’s quality of life. POP often is associated

with different complaints that relate to the urinary

and bowel function controlled by the pelvic floor.

Individuals with POP often complain of urinary

stress incontinence, urgency and or frequency, hes-

itancy, incomplete emptying, and splinting (digit-

ally reducing prolapse) to fully evacuate urine. The

bowel symptoms in individuals with POP consist

of straining to defecate, incontinence of flatus and

stool, incomplete rectal emptying, and splinting

to complete defecation. All these symptoms can

impact an individual’s life in a negative way. It is

important to question regarding these symptoms in

anyone with any stage of POP because symptoms

do not always correlate with stage of POP and

these symptoms can be debilitating and need to be

addressed [45– 47] .

The typical urinary symptoms that develop in

women with POP are variable. Stress incontinence

Fig. 5.4. Levator ani muscle and connective tissue supportive function of the pelvic floor. (From DeLancey JOL.

Anatomy and biomechanics of genital prolapse. Clin Obstet Gynecol 1993;36:906, with permission.)

60 M.A. Barker and M. M. Karram

often is encountered in women with a hypermobile

urethra, often seen in patients with anterior vaginal

wall prolapse [42] . The symptom of stress incon-

tinence can resolve as a prolapse worsens or even

develop into obstructive urinary symptoms depend-

ing on the stage of the prolapse [45 , 46, 48] . Often

women with POP beyond the hymen have less

stress incontinence symptoms, but have to splint

(digitally reduce the prolapse) in order to urinate

[46] . The reason patients with advanced stage

prolapse are often continent of urine is because

the urethra is kinked and urinary retention devel-

ops as the anterior vaginal wall prolapse worsens

[42] . This becomes important in the evaluation of

women considering both conservative management

with a pessary or surgical correction because each

can unmask occult stress urinary incontinence.

Symptoms of defecatory dysfunction are just as

variable as that of urinary incontinence in women

with POP. The defecatory symptom that seems to

correlate most greatly with POP of the posterior

compartment is the need to splint the vagina or

perineum to defecate [42, 45 , 46] . Unfortunately,

the exam and extent of prolapse do not always

correlate with symptoms, and factors involved in

defecactory dysfunction usually benefit from an

extensive workup looking at other causes than

just POP [49] . Because symptoms of POP such

as constipation and straining may contribute to

POP, it is difficult to elicit whether the symptoms

are the cause or effect or POP [30, 31, 42] . Other

defecatory symptoms may have different etiolo-

gies, but are present in association with POP. Fecal

incontinence is seen in 7–31% of women with POP

[50 – 51] . Fecal incontinence typically is associated

with rectal prolapse rather than POP, but the two

disorders share similar risk factors including neu-

ropathic and muscular injury to the pelvic floor [7,

42, 51] . Variation in symptoms may be related to

the degree of insult to the pelvic floor, which may

explain why people with more symptoms may have

a greater degree of injury to the pelvic floor.

Sexual Symptoms

Female sexual dysfunction is characterized by

problems with sexual desire, arousal, orgasm,

or dyspareunia that cause personal distress [52] .

Women with POP and urinary incontinence tradi-

tionally have been considered to have similar rates

of sexual activity to those of aged-matched individ-

uals without POP and urinary incontinence [53] .

Age more than POP and incontinence seems to

contribute to sexual dysfunction. As POP increases

in stage, women report more interference with

sexual activity, but data are mixed on whether this

limits their sexual activity or negatively affects

their sexual satisfaction [45, 53, 54] . In another

study looking at pelvic floor dysfunction and

sexual function, POP did not reveal an association

with sexual complaints, but this study did not use

questionnaires designed for women with pelvic

floor disorders [55] . Our understanding of the

effects of POP rely on our ability to adequately

study and measure these effects. In a study looking

at patients presenting to a urogynecology office,

only 10% of patients who were not sexually active

reported that their POP was contributing to sexual

dysfunction [56] . Clearly the overlap of disorders

and symptoms in women with pelvic floor dysfunc-

tion contributes to their sexual function and further

studies using validated measuring techniques are

needed to further understand the effects of POP on

sexual function.

Sexual dysfunction also includes pain symp-

toms, which are often frequent complaints in indi-

viduals with POP. Patients with POP often attribute

their back pain or pelvic pain to their prolapse. Heit

et al. examined women with POP and found no

association between low back pain or pelvic pain

[57] . Similar results were found in another study

that did not show any pain association with severity

of POP [44] . Just as sexual dysfunction is influ-

enced by other factors, so too are pain symptoms.

Individuals caring for women with POP who have

pain symptoms should evaluate this further instead

of just equating it with their other POP symptoms.

Conclusions

Pelvic organ prolapse is caused by multiple fac-

tors that lead to variable effects on the pelvic

floor. There is as yet no large epidemiological

study evaluating the natural history of women with

asymptomatic POP or the type and frequency of

symptoms in women with symptomatic POP [4] .

Much of the difficulty in designing a large study

lies in the fact that multiple factors are involved

in the development of this condition and there is a

5. Pelvic Floor Prolapse: Cause and Effect 61

lack of a standard definition. The future of under-

standing the etiology of POP will rest in our ability

to design studies to look at individual factors that

contribute to POP. Ideally, a model needs to be

created to test these factors in controlled environ-

ments so that their individual effects on the pelvic

floor can be studied. Recently computer- generated

models have been developed based on radiological

imaging and muscle morphology to study pelvic

anatomy and the effect of vaginal birth on the

pelvic floor muscles [58– 60] . This advancement in

the comprehension of pelvic anatomy and use of

technology will lead to the development of a vali-

dated model to study the causes and effects of POP.

Further understanding of the etiology and natural

history of POP will enable clinicians to intervene

and prevent disease progression in patients with

recognized risk factors.

References

1 . Olsen AL , Smith VJ , Bergstrom JO , et al. Epidemiology

of surgically managed pelvic organ prolapse and uri-

nary incontinence . Obstet Gynecol 1997 ; 89 : 501 – 506 .

2 . Hendrix SL , Clark A , Nygaard I , et al. Pelvic organ

prolapse in the Women’s Health Initiative: Gravity and

gravidity . Am J Obstet Gynecol 2002 ; 186 : 1160 – 1166 .

3 . Schaffer JI , Wai CY , Boreham MK . Etiology

of pelvic organ prolapse . Clin Obstet Gynecol

2005 ; 48 : 639 – 647 .

4 . Weber AM , Abrams P , Brubaker L , et al. The standard-

ization of terminology for researchers in female pelvic

floor disorders . Int Urogynecol J 2001 ; 12 : 178 – 186 .

5 . Luber KM , Boreo S , Choe JY . The demographics of

pelvic floor disorders current observations and future

projections . Am J Obstet Gynecol 2001 ; 184 : 1496 –

1503 .

6 . Schimpf M , Tulikangas P . Evolution of the female

pelvis and relationships to pelvic organ prolapse . Int

Urogynecol J 2005 ; 16 : 315 – 320 .

7 . Bump RC , Norton PA . Epidemiology and natural

history of pelvic floor dysfunction . Obstet Gynecol

Clin North Am 1998 ; 25 : 723 – 746 .

8 . Mallett VT , Bump RC . The epidemiology of female

pelvic floor dysfunction . Curr Opin Obstet Gynecol

1994 ; 6 : 308 – 312 .

9 . Kim S , Harvey MA , Johnston S . A review of the

epidemiology and pathophysiology of pelvic floor

dysfunction: Do racial differences matter? J Obstet

Gynaecol Can 2005 ; 27 : 251 – 259 .

10 . Chiaffarino F , Chatenoud L , Dindelli M , et al.

Reproductive factors, family history, occupation and

risk of urogenital prolapse . Eur J Obstet Gynecol

Reprod Biol 1999 ; 82 : 63 – 67 .

11 . Buchsbaum G , Kerr L , Guzick D . Pelvic relaxation in

nulliparous postmenopausal women and their parous

sisters . Neurourol Urodyn 2003 ; 22 : 508 – 509 .

12 . Buchbaum GM , Duecy EE , Kerr LA , et al. Pelvic

organ prolapse in mulliparous women and their

parous sisters . Obstet Gynecol 2006 ; 108 : 1388 – 1393 .

13 . Jack GS , Nikolova G , Vilain E , et al. Familial trans-

mission of genitovaginal prolapse . Int Urogynecol J

Pelvic Floor Dysfunct 2005 ; 17 : 498 – 501 .

14 . Norton P , Baker J , Sharp HC , et al. Genitourinary

prolapse and joint hypermobiity in women . Obstet

Gynecol 1995 ; 85 : 225 – 228 .

15 . Makinen J , Soderstrom KO , Kiilhoma P , et al.

Histological changes in the vaginal connective tissue

of patients with and without uterine prolapse . Arch

Gynecol 1986 ; 239 : 17 – 20 .

16 . Norton P , Boyd C , Deak S . Abnormal collagen ratios

in women with genitourinary prolapse . Neurourol

Urodyn 1992 ; 11 : 2 – 4 .

17 . Fidas A , MacDonald HL , Elton RA , et al. Prevalence

of spina bifida occulta in patients with functional

disorders of the lower urinary tract and its relation

to urodynamic and neurophysiologic measurements .

BMJ 1989 ; 298 : 357 – 359 .

18 . Findley P . Prolapse of the uterus in nulliparous

women . Am J Obstet Dis Women 1917 ; 75 : 12 .

19 . DeMola JRL , Carpenter SE . Management of genital

prolapse in neonates and young women . Obstet

Gynecol Surv 1996 ; 51 : 253 – 260 .

20 . Swift S , Woddman P , O’Boyle A , et al. Pelvic organ

support study (POSST): The distribution, clinical

definition and epidemiology of pelvic organ support

defects . Am J Obstet Gynecol 2005 ; 192 : 795 – 806 .

21 . Mant J , Painter R , Vessey M . Epidemiology of geni-

tal prolapse: Observations from the Oxford Family

Planning Association study . Br J Obstet Gynaecol

1997 ; 104 : 579 – 585 .

22 . Klein MC , Gauthier RJ , Robbins JM , et al.

Relationship of episiotomy to perineal trauma and

morbidity, sexual function, and pelvic floor relaxa-

tion . Am J Obstet Gynecol 1994 ; 171 : 591 – 598 .

23 . Sultan AH , Kamm MA , Hudson CH , et al. Anal-

sphincter disruption during vaginal delivery . N Engl

J Med 1993 ; 329 : 1905 – 1911 .

24 . Sultan AH , Kamm MA , Hudson CH , et al. Third

degree obstetric anal sphincter tears: Risk factors and

outcome of primary repair . BMJ 1994 ; 308 : 887 – 891 .

25 . Lukacz ES , Lawrence JM , Contreras R , et al. Parity,

mode of delivery, and pelvic floor disorders . Obstet

Gynecol 2006 ; 107 : 1253 – 1260 .

26 . National Institutes of Health state-of-the-science con-

ference statement: Cesarean delivery on maternal

62 M.A. Barker and M. M. Karram

request March 27–29, 2006. Obstet Gynecol

2006;107:1386-1397.

27 . Swift SE , Pound T , Dias JE . Case-control study of

the etiology of severe pelvic organ prolapse . Int

Urogynecol J 2001 ; 12 : 187 – 192 .

28 . Cruikshank SH , Kovak SR . Randomized comparison

of three surgical methods used at the time of vaginal

hysterectomy to prevent posterior enterocele . Am J

Obstet Gynecol 1999 ; 180 : 859 – 865 .

29 . Richter HE , Burgio KL , Clements RH , et al. Urinary

and anal incontinence in morbidly obese women

considering weight loss surgery . Obstet Gynecol

2005 ; 106 : 1272 – 1277 .

30 . Lubowski DZ , Swash M , Nichols RJ , et al. Increases

in pudendal nerve terminal motor latency with def-

ecation straining . Br J Surg 1988 ; 75 : 1095 – 1097 .

31 . Spence-Jones C , Kamm MA , Henry MM , et al.

Bowel dysfunction: A pathogenic factor in uterov-

aginal prolapse and urinary stress incontinence . Br J

Obstet Gynaecol 1994 ; 101 : 147 – 152 .

32 . Samuelsson EU , Victor FTA , Tibblin G , et al. Signs

of genital prolapse in a Swedish population of

women 20–59 years of age and possible related fac-

tors . Am J Obstet Gynecol 1999 ; 180 : 299 – 305 .

33 . Bump RC , McClish DK . Cigarette smoking and uri-

nary incontinence in women . Am J Obstet Gynecol

1992 ; 167 : 1213 – 1218 .

34 . Jorgensen S , Hein HO , Gyntelberg F . Heavy lifting

at work and risk of genital prolapse and herni-

ated lumbar disk is assistant nurses . Occup Med

1994 ; 44 : 47 – 49 .

35 . Bonetti TR , Erpelding A , Pathak LR . Listening to

“felt needs”: Investigating genital prolapse in west-

ern Nepal . Reprod Health Matters 2004 ; 12 : 166 –

175 .

36 . Davis GD , Goodman M . Stress urinary incontinence

in nulliparous female soldiers in airborne infantry

training . J Pelvic Surg 1996 ; 2 : 68 – 71 .

37 . Nygaard IE . Does prolonged high-impact activ-

ity cause urinary incontinence? A retrospective

cohort study of female Olympians . Obstet Gynecol

1997 ; 90 : 718 – 722 .

38 . Weir LF , Nygaard IE , Wilken J , et al. Postoperative

activity restrictions: Any evidence ? Obstet Gynecol

2006 ; 107 : 305 – 309 .

39 . Brincat M , Versi E , Moniz CF , et al. Skin collagen

changes in postmenopausal women receiving differ-

ent regimens of estrogen therapy . Obstet Gynecol

1987 ; 70 : 123 – 127 .

40 . Goldstein SR , Nanavati N . Adverse events that are

associated with selective estrogen receptor mod-

ulator levormeloxifene in an aborted phase III

osteoporosis study treatment study . Am J Obstet

Gynecol 2002 ; 187 : 521 – 527 .

41 . Moalli PA , Ivy SJ , Meyn LA , et al. Risk fac-

tors associated with pelvic floor disorders in

women undergoing surgical repair . Obstet Gynecol

2003 ; 101 : 869 – 874 .

42 . Barber MD . Symptoms and outcome measures

of pelvic organ prolapse . Clin Obstet Gynecol

2005 ; 48 : 648 – 661 .

43 . DeLancey JOL . Anatomy and biomechanics of geni-

tal prolapse . Clin Obstet Gynecol 1993 ; 36 : 897 – 909 .

44 . Swift SE, Tate SB, Nicholas J . Correlation of

symptoms with degree of pelvic organ support in a

general population of women: What is pelvic organ

prolapse? Am J Obstet Gynecol 2003 ; 189 : 372 – 377 .

45 . Ellerkmann MR , Cundiff GW , Melick CF , et al.

Correlation of symptoms with location and sever-

ity of pelvic organ prolapse . Am J Obstet Gynecol

2001 ; 185 : 1332 – 1337 .

46 . Burrows LJ , Meyn LA , Walters MD , et al. Pelvic

symptoms in women with pelvic organ prolapse .

Obstet Gynecol 2004 ; 104 : 982 – 988 .

47 . Ghetti C , Gregory WT , Edwards SR , et al. Pelvic

organ descent and symptoms of pelvic floor disor-

ders . Am J Obstet Gynecol 2005 ; 193 : 53 – 57 .

48 . Romanzi LJ , Chaikin DC , Blaivas JG . The effect of

genital prolapse on voiding . J Urol 1999 ; 161 : 581 – 586 .

49 . Cundiff GW , Fenner D . Evaluation and treatment

of women with rectocele: Focus on associated

defecatory and sexual dysfunction . Obstet Gynecol

2004 ; 104 : 1403 – 1421 .

50 . Jackson SL , Weber AM , Hull TL , et al. Fecal inconti-

nence in women with urinary incontinence and pelvic

organ prolapse . Obstet Gynecol 1997 ; 89 : 423 – 427 .

51 . Nichols CM , Gill EJ , Nguyen T , et al. Anal sphinc-

ter injury in women with pelvic floor disorders .

Obstet Gynecol 2004 ; 104 : 690 – 696 .

52 . Basson R , Berman J , Burnett A , et al. Report of the

international consensus development conference on

female sexual dysfunction: Definitions and classifi-

cations . J Urol 2000 : 183 : 888 – 893 .

53 . Barber MD , Visco AG , Wyman JF , et al. Sexual func-

tion in women with urinary incontinence and pelvic

organ prolapse . Obstet Gynecol 2002 ; 1999 : 281 – 289 .

54 . Weber AM , Walters MD , Schover LR , et al. Sexual

function in women with uterovaginal prolapse and

urinary incontinence . Obstet Gynecol 1995 ; 85 :

483 – 487 .

55 . Handa VL , Harvey L , Cundiff GW , et al. Sexual

dysfunction among women with urinary incon-

tinence and pelvic organ prolapse . Am J Obstet

Gynecol 2004 ; 191 : 751 – 756 .

56 . Pauls RN , Segal JL , Silva WA , et al. Sexual function

in patients presenting to a urogynecology practice .

Int Urogynecol J Pelvic Floor Dysfucnt 2006 ; 17 :

576 – 580 .

5. Pelvic Floor Prolapse: Cause and Effect 63

57 . Heit M, Culligan P, Rosenquist C, et al . Is pelvic

organ prolapse a cause of pelvic or low back pain?

Obstet Gynecol 2002 ; 99 : 23 – 28 .

58. Hoyte L, Schierlitz L, Zou K, et al. Two- and 3-dimen-

sional MRI comparison of levator ani structure, vol-

ume, and integrity in women with stress incontinence

and prolapse . Am J Obstet Gynecol 2001;185:11–29.

59 . Janda S , va der Helm FCT , deBlok SB . Measuring

morphological parameters of the pelvic floor for

finite element modeling purposes . J Biomech

2003 ; 36 : 749 – 757 .

60 . Lien KC , Mooney B , DeLancey JOL , et al. Levator

ani muscle stretch induced by simulated vaginal

birth . Obstet Gynecol 2004 ; 103 : 31 – 40 .

65

Introduction

The female genital and lower urinary tract share

a common embryological origin, arising from the

urogenital sinus ( Fig. 6.1 ). Both are sensitive to the

effects of female sex steroid hormones. Estrogen is

known to have an important role in the function of

the lower urinary tract throughout adult life with

estrogen and progesterone receptors demonstrated

in the vagina, urethra, bladder, and pelvic floor

musculature [1– 4] . This is supported by the fact that

estrogen deficiency occurring following the meno-

pause is known to cause atrophic changes within the

urogenital tract [5] and is associated with urinary

symptoms such as frequency, urgency, nocturia,

incontinence, and recurrent infection. These also

may coexist with symptoms of vaginal atrophy such

as dyspareunia, itching, burning, and dryness.

This chapter will review the role of estrogens

in lower urinary tract function and dysfunction as

well as the role of estrogen replacement therapy in

the management of urogenital atrophy.

Estrogen Receptors and Hormonal

Factors

The effects of the steroid hormone 17 β -estradiol

are mediated by ligand-activated transcription fac-

tors known as estrogen receptors. These share com-

mon features with both androgen and progesterone

receptors and can be divided into several functional

domains [6] . The classic estrogen receptor (ER α )

was first discovered by Elwood Jensen in 1958 and

cloned from uterine tissue in 1986 [7] , although it

was not until 1996 that the second estrogen recep-

tor (ER β ) was identified [8] . The precise role of the

two different receptors remains to be elucidated,

although ER α appears to play a major role in the

regulation of reproduction while ER β has a more

minor role [9] .

Estrogen receptors have been demonstrated

throughout the female lower urinary tract and are

expressed in the squamous epithelium of the proxi-

mal and distal urethra, vagina, and trigone of the

bladder [3, 10] , although not in the dome of the

bladder, reflecting its different embryological origin.

Pubococcygeus and the musculature of the pelvic

floor also have been shown to be estrogen sensitive

[11, 12] , although estrogen receptors have not yet

been identified in the levator ani muscles [13] .

The distribution of estrogen receptors through-

out the urogenital tract also has been studied with

both α and β receptors being found in the vaginal

walls and uterosacral ligaments of premenopausal

women, although the latter were absent in the

vaginal walls of postmenopausal women [14] . In

addition, α receptors are localized in the urethral

sphincter and when sensitized by estrogens are

thought to help maintain muscular tone [15] .

In addition to estrogen receptors both androgen

and progesterone receptors are expressed in the

lower urinary tract, although their role is less clear.

Progesterone receptors are expressed inconsist-

ently, having been reported in the bladder, trigone,

and vagina. Their presence may be dependent on

Chapter 6

Hormonal Influences on Continence

Dudley Robinson and Linda Cardozo

66 D. Robinson and L. Cardozo

estrogen status [5] . While androgen receptors are

present in both the bladder and urethra, their role

has not yet been defined [16] . Interestingly, estro-

gen receptors also have been identified in mast

cells in women with interstitial cystitis [17, 18] and

in the male lower urinary tract [19] .

The incidence of both estrogen and progesterone

expression has been examined throughout the lower

urinary tract in 90 women undergoing gynecologic

surgery; 33 were premenopausal, 26 postmenopau-

sal without hormone replacement therapy, and 31

postmenopausal and taking hormone replacement

therapy [20] . Biopsies were taken from the blad-

der dome, trigone, proximal urethra, distal urethra,

vagina, and vesicovaginal fascia adjacent to the

bladder neck. Estrogen receptors were found to be

consistently expressed in the squamous epithelia,

although they were absent in the urothelial tissues

of the lower urinary tract of all women, irrespective

of estrogen status. Progesterone receptor expres-

sion, however, showed more variability, being

mostly subepithelial, and it was significantly lower

in postmenopausal women not taking estrogen

replacement therapy.

Fig. 6.1. Embryological origin of the female genital and lower urinary tract

6. Hormonal Influences on Continence 67

Hormonal Influences on Lower

Urinary Tract Symptoms

In order to maintain continence the urethral pressure

must remain higher than the intravesical pressure at all

times except during micturition [21] . Estrogens play

an important role in the continence mechanism with

bladder and urethral function becoming less efficient

with age [22] . Elderly women have been found to

have a reduced flow rate, increased urinary residuals,

higher filling pressures, reduced bladder capacity, and

lower maximum voiding pressures [23] . Estrogens

may affect continence by increasing urethral resist-

ance, raising the sensory threshold of the bladder, or

by increasing α adrenoreceptor sensitivity in the ure-

thral smooth muscle [24, 25] . In addition, exogenous

estrogens have been shown to increase the number of

intermediate and superficial cells in the vagina of post-

menopausal women [26] . These changes also have

been demonstrated in the bladder and urethra [27] .

More recently a prospective observational study

has been performed to assess cell proliferation rates

throughout the tissues of the lower urinary tract [28] .

Fifty-nine women were studied of whom 23 were

premenopausal, 20 were postmenopausal and not

taking hormone replacement therapy, and 20 were

postmenopausal and taking hormone replacement

therapy. Biopsies were taken from the bladder dome,

trigone, proximal urethra, distal urethra, vagina, and

vesicovaginal fascia adjacent to the bladder neck. The

squamous epithelium of estrogen-replete women was

shown to exhibit greater levels of cellular proliferation

than in those women who were estrogen deficient.

Cyclical variations in the levels of both estrogen

and progesterone during the menstrual cycle have

been shown to lead to changes in urodynamic vari-

ables and lower urinary tract symptoms with 37% of

women noticing a deterioration in symptoms prior to

menstruation [29] . Measurement of the urethral pres-

sure profile in nulliparous premenopausal women

shows there is an increase in functional urethral

length midcycle and early in the luteal phase cor-

responding to an increase in plasma estradiol [30] .

Furthermore, progestogens have been associated

with an increase in irritative bladder symptoms [31,

32] and urinary incontinence in those women taking

combined hormone replacement therapy [33] . The

incidence of detrusor overactivity in the luteal phase

of the menstrual cycle may be associated with raised

plasma progesterone following ovulation and proges-

terone has been shown to antagonize the inhibitory

effect of estradiol on rat detrusor contractions [34] .

This may help to explain the increased prevalence of

detrusor overactivity found in pregnancy [35] .

The role of estrogen therapy in the manage-

ment of women with fecal incontinence also has

been investigated in a prospective observational

study using symptom questionnaires and anorectal

physiological testing before and after 6 months of

estrogen replacement therapy. At follow up 25% of

women were asypmtomatic and a further 65% were

improved in terms of flatus control, urgency, and

fecal staining. In addition, anal resting pressures

and voluntary squeeze increments were significantly

increased following estrogen therapy, although there

were no changes in pudendal nerve terminal latency.

The authors conclude that estrogen replacement

therapy may have a beneficial effect, although larger

studies are needed to confirm these findings [36] .

Hormonal Influences on Urinary

Tract Infection

Urinary tract infection also is a common cause of

urinary symptoms in women of all ages. This is a

particular problem in the elderly, with a reported

incidence of 20% in the community and over 50% in

institutionalized patients [37, 38] . Pathophysiological

changes such as impairment of bladder emptying,

poor perineal hygiene, and both fecal and urinary

incontinence partly may account for the high preva-

lence observed. In addition, changes in the vaginal

flora due to estrogen depletion lead to colonization

with gram-negative bacilli, which in addition to caus-

ing local irritive symptoms also act as uropathogens.

These microbiological changes may be reversed

with estrogen replacement following the menopause,

offering a rationale for treatment and prophylaxis.

Hormonal Influences on Lower

Urinary Tract Function

Neurological Control

Sex hormones are known to influence the central neu-

rological control of micturition, although their exact

role in the micturition pathway has yet to be eluci-

dated. Estrogen receptors have been demonstrated in

the cerebral cortex, limbic system, hippocampus, and

68 D. Robinson and L. Cardozo

cerebellum [39, 40] , while androgen receptors have

been demonstrated in the pontine micturition center

and the preoptic area of the hypothalamus [41] .

Bladder Function

Estrogen receptors, although absent in the transitional

epithelium at the dome of the bladder, are present in

the areas of the trigone which have undergone squa-

mous metaplasia [10] . Estrogen is known to have a

direct effect on detrusor function through modifica-

tions in muscarinic receptors [42, 43] and by inhibi-

tion of movement of extracellular calcium ions into

muscle cells [44] . Consequently, estradiol has been

shown to reduce the amplitude and frequency of

spontaneous rhythmic detrusor contractions [45] and

there also is evidence that it may increase the sensory

threshold of the bladder in some women [46] .

Urethra

Estrogen receptors have been demonstrated in the

squamous epithelium of both the proximal and

distal urethra [10] and estrogen has been shown to

improve the maturation index of urethral squamous

epithelium [47] . It has been suggested that estrogen

increases urethral closure pressure and improves

pressure transmission to the proximal urethra,

promoting continence [48– 51] . Additionally, estro-

gens have been shown to cause vasodilatation in

the systemic and cerebral circulation, and these

changes also are seen in the urethra [52– 54] .

The vascular pulsations seen on urethral pres-

sure profilometry secondary to blood flow in the

urethral submucosa and urethral sphincter have

been shown to increase in size following estrogen

administration [55] , while the effect is lost follow-

ing estrogen withdrawal at the menopause. The

urethral vascular bed is thought to account for

around a third of the urethral closure pressure and

estrogen replacement therapy in postmenopausal

women with stress incontinence has been shown to

increase the number of periurethral vessels [56] .

Collagen

Estrogens are known to have an effect on collagen

synthesis and they have been shown to have a direct

effect on collagen metabolism in the lower genital

tract [57] . Changes found in women with urogenital

atrophy may represent an alteration in systemic col-

lagenase activity [58] and urodynamic stress incon-

tinence, and urogenital prolapse has been associated

with a reduction in both vaginal and periurethral col-

lagen [59– 61] . Furthermore, there is a reduction in

skin collagen content following the menopause [62]

with rectus muscle fascia being shown to become

less elastic with increasing age, resulting in a lower

energy requirement to cause irreversible damage

[63] . Changes in collagen content also have been

identified, the hydroxyproline content in connective

tissue from women with stress incontinence being

40% lower than in continent controls [64] .

Lower Urinary Tract Symptoms

Urinary Incontinence

The prevalence of urinary incontinence is known

to increase with age, affecting 15–35% of commu-

nity-dwelling women over the age of 60 years [65]

and other studies reporting a prevalence of 49%

in women over 65 years [66] . In addition, rates of

50% have been reported in elderly nursing home

residents [67] . A recent cross-sectional population

prevalence survey of 146 women aged 15–97 years

found that 46% experienced symptoms of pelvic

floor dysfunction defined as stress or urge incon-

tinence, flatus, or fecal incontinence, symptomatic

prolapse, or previous pelvic floor surgery [68] .

Little work has been done to examine the

incidence of urinary incontinence, although a

study in New Zealand of women over the age of

65 years found 10% of the originally continent

developed urinary incontinence in the 3-year

study period [69] .

Epidemiological studies have implicated estro-

gen deficiency in the etiology of lower urinary

tract symptoms, with 70% of women relating the

onset of urinary incontinence to their final men-

strual period [5] . Lower urinary tract symptoms

have been shown to be common in postmenopausal

women attending a menopause clinic, with 20%

complaining of severe urgency and almost 50%

complaining of stress incontinence [70] . Urge

incontinence in particular is more prevalent fol-

lowing the menopause and the prevalence would

appear to rise with increasing years of estrogen

deficiency [71] . There is, however, conflicting

6. Hormonal Influences on Continence 69

evidence regarding the role of estrogen withdrawal

at the time of the menopause. Some studies have

shown a peak incidence in perimenopausal women

[72, 73] , while other evidence suggests that many

women develop incontinence at least 10 years prior

to the cessation of menstruation, with significantly

more premenopausal women than postmenopausal

women being affected [74] .

Urogenital Atrophy

Urogenital atrophy is a manifestation of estrogen

withdrawal following the menopause and symptoms

may appear for the first time more than 10 years after

the last menstrual period [75] . In addition, increas-

ing life expectancy has led to an increasingly elderly

population and it is now common for women to

spend a third of their lives in the estrogen-deficient

postmenopausal state [76] , with the average age of

the menopause being 50 years [77] .

Postmenopausal women comprise 15% of the

population in industrialized countries,with a pre-

dicted growth rate of 1.5% over the next 20 years.

Overall, in the developed world 8% of the total

population have been estimated to have urogenital

symptoms [78] ; this represents 200 million women

in the United States alone.

It has been estimated that 10–40% of all post-

menopausal women are symptomatic [79] , although

only 25% are thought to seek medical help ( Table

6.1 ). In addition, two out of three women report

vaginal symptoms associated with urogenital atro-

phy by the age of 75 years [80] . However, the

prevalence of symptomatic urogenital atrophy is

difficult to estimate, since many women accept

the changes as being an inevitable consequence of

the ageing process, and thus do not seek help; this

leads to considerable underreporting ( Table 6.2 ) .

A study assessing the prevalence of urogenital

symptoms in 2,157 Dutch women recently has

been reported [81] . Overall, 27% of women com-

plained of vaginal dryness, soreness, and dyspareu-

nia, while the prevalence of urinary symptoms such

as leakage and recurrent infections was 36%. When

considering severity, almost 50% reported moder-

ate to severe discomfort, although only a third

had received medical intervention. Interestingly,

women who previously had had a hysterectomy

reported moderate to severe complaints more often

than those who had not.

The prevalence of urogenital atrophy and uro-

genital prolapse also has been examined in a popu-

lation of 285 women attending a menopause clinic

[82] . Overall, 51% of women were found to have

anterior vaginal wall prolapse, 27% posterior vagi-

nal prolapse, and 20% apical prolapse. In addition,

34% of women were noted to have urogenital atro-

phy and 40 % complained of dyspareunia. While

urogenital atrophy and symptoms of dyspareunia

were related to menopausal age, the prevalence of

prolapse showed no association.

However, while urogenital atrophy is an inevi-

table consequence of the menopause, women

may not always be symptomatic. A recent study

of 69 women attending a gynecology clinic

were asked to fill out a symptom questionnaire

prior to examination and vaginal cytology [83] .

Urogenital symptoms were found to be relatively

low and were poorly correlated with age and

physical examination findings, although not with

vaginal cytological maturation index ( Fig. 6.2 ).

Women who were taking estrogen replacement

therapy had higher symptom scores and physical

examination scores.

In order to clinically grade and quantify the

changes associated with urogenital atrophy a scoring

system has been developed based on a five-point scale

[84] ( Table 6.3 ). From this evidence it would appear

that urogenital atrophy is a universal consequence of

the menopause, although often elderly women may

be minimally symptomatic. Hence, treatment should

not be the only indication for replacement therapy.

Table 6.2. Signs of urogenital atrophy.

Pallor/inflammation

Petechiae

Epithelial or mucosal thinning

Decreased elasticity

Urogenital prolapse

Table 6.1. Symptoms of urogenital atrophy .

Vaginal dryness

Dyspareunia

Vaginal burning

Pruritis

Urinary symptoms: urgency, frequency, nocturia, dysuria,

recurrent infection

Prolapse

70 D. Robinson and L. Cardozo

Management of Lower Urinary

Dysfunction

Estrogens in the Management

of Incontinence

Estrogen preparations have been used for many

years in the treatment of urinary incontinence [85,

86] , although their precise role remains contro-

versial. Many of the studies performed have been

uncontrolled observational series examining the

use of a wide range of different preparations, doses,

and routes of administration. The inconsistent use

of progestogens to provide endometrial protection

is a further confounding factor making interpreta-

tion of the results difficult.

In order to clarify the situation a meta-analysis

from the Hormones and Urogenital Therapy (HUT)

Committee has been reported [87] . Of 166 articles

identified that were published in English between

1969 and 1992, only six were controlled trials and

17 were uncontrolled series. Meta-analysis found

an overall significant effect of estrogen therapy

on subjective improvement in all subjects and

for subjects with urodynamic stress incontinence

alone. Subjective improvement rates with estrogen

therapy in randomized controlled trials ranged

from 64 to 75%, although placebo groups also

reported an improvement of 10–56%. In uncon-

trolled series subjective improvement rates were

8–89%, with subjects with urodynamic stress

incontinence showing improvement of 3–73%.

However, when assessing objective fluid loss there

was no significant effect. Maximum urethral clo-

sure pressure was found to increase significantly

with estrogen therapy, although this outcome was

influenced by a single study showing a large effect

[88] ( Table 6.4 ).

A further meta-analysis performed in Italy has

analyzed the results of randomized controlled

clinical trials on the efficacy of local and systemic

estrogen treatment in postmenopausal women with

urinary incontinence [89] . A search of the literature

(1965–1996) revealed 72 articles of which only

four were considered to meet the meta-analysis

criteria. There was a statistically significant differ-

ence in subjective outcome between estrogen and

placebo, although there was no such difference

in objective or urodynamic outcome. The authors

conclude that this difference could be relevant,

although the studies may have lacked objective

sensitivity to detect this.

Overall elasticity

Fluid secretion (type and consistency)

pH

Epithelial integrity

Moisture

Table 6.3. The vaginal health index.

F ig. 6.2 . Vaginal cytology in ( a ) a healthy premenopausal woman and ( b ) following the menopause in a woman with

symptomatic vaginal atrophy

6. Hormonal Influences on Continence 71

The most recent meta-analysis of the effect of

estrogen therapy on the lower urinary tract has been

performed by the Cochrane group [90] . Overall, 28

trials were identified, including 2,926 women. In

the 15 trials comparing estrogen to placebo there

was a higher subjective impression of improvement

rate in those women taking estrogen, and this was

the case for all types of incontinence (RR for cure

1.61; 95% CI 1.04–2.49). Equally, when subjective

cure and improvement were taken together there

was a statistically higher cure and improvement

rate for both urge (57% vs. 28%) and stress (43%

vs. 27%) incontinence. In those women with urge

incontinence the chance of improvement was 25%

higher than in women with stress incontinence;

overall, about 50% of women treated with estro-

gen were cured or improved compared to 25% on

placebo. The authors conclude that estrogens can

improve or cure incontinence and that the effect

may be most useful in women complaining of urge

incontinence.

Systemic HRT and Urinary Incontinence

Several large-scale systemic HRT studies recently

have been reported that have led to greater con-

troversy regarding the role of oral estrogens on

the lower urinary tract. The role of estrogen

replacement therapy in the prevention of ischemic

heart disease has been assessed in a 4-year ran-

domized trial: the Heart and Estrogen/progestin

Replacement Study (HERS) [91] , involving 2,763

postmenopausal women younger than 80 years

with intact uteri and ischemic heart disease. In the

study, 55% of women reported at least one episode

of urinary incontinence each week and were ran-

domly assigned to oral conjugated estrogen plus

medroxyprogesterone acetate (MPA) or placebo

daily. Incontinence improved in 26% of women

assigned to placebo compared to 21% receiving

HRT, while 27% of the placebo group complained

of worsening symptoms compared with 39% in the

HRT group ( P = 0.001). The incidence of incon-

tinent episodes per week increased an average of

0.7 in the HRT group and decreased by 0.1 in the

placebo group ( P < 0.001). Overall, combined

hormone replacement therapy was associated with

worsening stress and urge urinary incontinence,

although there was no significant difference in

daytime frequency, nocturia, or number of urinary

tract infections.

These findings also have been confirmed in the

Nurse’s Health Study, which followed 39,436 post-

menopausal women aged 50–75 years over a 4-year

period. The risk of incontinence was found to be

elevated in those women taking HRT compared

to those who had never taken HRT. There was an

increased risk in women taking oral estrogen (RR

1.54; 95% CI 1.44–1.65), transdermal estrogen

(RR 1.68; 95% CI 1.41–2.00), oral estrogen and

progesterone (RR 1.34; 95% CI 1.24–1.34), and

transdermal estrogen and progesterone (RR 1.46; CI

1.16–1.84). In addition, while there was a small risk

that remained after the cessation of HRT (RR 1.14;

95% CI 1.06–1.23), by 10 years the risk was identi-

cal (RR 1.02; 95% 0.91–1.41) and was identical to

those women who had never taken HRT [92] .

In addition, the effects of oral estrogens and

progestogens on the lower urinary tract have been

assessed in 32 female nursing home residents [93]

Table 6.4. Summary of randomized controlled trials assessing the use of estrogens in the management of urinary

incontinence.

Study Year Type of incontinence Estrogen Route

Henalla et al. [88] 1989 Stress incontinence Conjugated estrogen Vaginal

Hilton et al. [103] 1990 Stress incontinence Conjugated estrogen Vaginal

Beisland et al. [102] 1984 Stress incontinence Estriol Vaginal

Judge [138] 1969 Mixed incontinence Quinestradol Oral

Kinn and Lindskog [25] 1988 Stress incontinence Estriol Oral

Samsioe et al. [106] 1985 Mixed incontinence Estriol Oral

Walter et al. [98] 1978 Urge incontinence Estradiol and estriol Oral

Walter et al. [139] 1990 Stress incontinence Estriol Oral

Wilson et al. [97] 1987 Stress incontinence Piperazine estrone sulfate Oral

72 D. Robinson and L. Cardozo

with an average age of 88 years. Subjects were

randomized to oral estrogen and progesterone

or placebo for 6 months. At follow-up there was

no difference between severity of incontinence,

prevalence of bacteriuria, or the results of vaginal

cultures, although there was an improvement in

atrophic vaginitis in the placebo group.

The most recent paper to be reported by the

Women’s Health Initiative (WHI) writing group

also studied the effect of estrogens, with and with-

out progestogens, on urinary incontinence [94] .

This paper represents another subanalysis of the

data, although it should be remembered that the

study was not designed to assess urinary inconti-

nence, and thus may lack the appropriate power to

do so conclusively.

In this study 27,347 postmenopausal women

aged 50–79 years were assessed in a multicenter,

double-blind, placebo-controlled trial. Of these,

23,296 were known to complain of lower urinary

tract symptoms at baseline and at1-year follow-up.

Women were randomized based on hysterectomy

status to active treatment or placebo in either the

estrogen and progestogen or estrogen-only tri-

als. The estrogen was conjugated equine estrogen

(CEE), while the progestogen was MPA. The main

outcome measure was the incidence of urinary

incontinence at 1 year among women who were

continent at baseline and the severity of urinary

incontinence at 1 year in those who were inconti-

nent at baseline.

Overall, HRT was found to increase the inci-

dence of all types of urinary incontinence at 1 year

in those women continent at baseline. The risk was

highest for stress incontinence [CEE + MPA; RR

1.87 (1.61–2.18); CEE alone; RR 2.15 (1.77–2.62)]

followed by mixed incontinence [CEE + MPA;

RR 1.49 (1.10–2.01); CEE alone; RR 1.79 (1.26–

2.53)]. However, the effect on urge urinary incon-

tinence was not uniform – [CEE + MPA; RR 1.15

(0.99–1.34); CEE alone; RR 1.32 (1.10–1.58)].

When considering those women who were

symptomatic at baseline, urinary frequency was

found to increase in both arms [CEE + MPA; RR

1.38 (1.28–1.49); CEE alone; RR 1.47 (1.35–1.61)]

and the incidence of urinary incontinence was

seen to increase at 1 year [CEE + MPA; RR 1.20

(1.06–1.36); CEE alone; RR 1.59 (1.39–1.82)].

In addition, while no formal quality of life (QoL)

assessment was reported, women receiving HRT

were more likely to report that urinary inconti-

nence limited their daily activities and bothered

and disturbed them.

These results, while supportive of the previously

reported HERS study and Nurse Health study,

would certainly seem to contradict much of the

previous work assessing the use of estrogens in

the management of lower urinary tract symptoms.

There are several possible explanations why these

findings may differ.

First, this trial was not designed specifically to

assess urinary symptoms and the questionnaires

used may have lacked the sensitivity to correctly

identify incontinent women. The question, “Have

you ever leaked even a very small amount of

urine involuntarily and you couldn’t control it,”

may have overestimated the actual prevalence of

urinary incontinence in this population, and this is

supported by the findings that over 45% of 60 to

69-year-old women in the study were found to be

incontinent.

In addition to a possible overestimation of the

population the relatively large age range of this

trial (50–79 years) and considerable comorbidi-

ties of participants may not accurately reflect the

current clinical use of HRT. Since the majority of

women receive hormone replacement for sympto-

matic relief in the perimenopausal period, it may be

more appropriate to stratify the results with respect

to age, as this may more accurately reflect current

clinical practice.

Furthermore, the treatment regimens themselves

also may not be representative of current clinical

practice, and certainly in Europe there has been a

move away from the use of CEEs to favor the use

of estradiol. It also is important to remember that

this trial has only examined the use of oral systemic

replacement therapy, while local topical estrogens

have been shown to be effective in the management

of troublesome lower urinary tract symptoms and

have minimal systemic effect.

Neither menopausal symptoms nor urinary incon-

tinence are life-threatening conditions, although

both have a significant effect on QoL. The cur-

rent evidence from all trials suggests that estrogen

replacement therapy may have a minor role in lower

urinary tract dysfunction and the findings of the

WHI studies should not prevent its use in women

who complain of troublesome menopausal symp-

toms after appropriate counseling and discussion.

6. Hormonal Influences on Continence 73

Estrogens in the Management of Stress

Incontinence

In addition to the studies included in the HUT

meta-analysis, several authors also have investi-

gated the role of estrogen therapy in the manage-

ment of urodynamic stress incontinence only.

Oral estrogens have been reported to increase the

maximum urethral pressures and lead to symp-

tomatic improvement in 65–70% of women [95,

96] , although other work has not confirmed this

[97, 98] . More recently, two placebo-controlled

studies have been performed examining the use

of oral estrogens in the treatment of urodynamic

stress incontinence in postmenopausal women.

Neither CEEs and medroxyprogesterone [99] , or

unopposed estradiol valerate [100] showed a sig-

nificant difference in either subjective or objective

outcomes. Furthermore, a review of 8 controlled

and 14 uncontrolled prospective trials concluded

that estrogen therapy was not an efficacious treat-

ment for stress incontinence but may be useful for

symptoms of urgency and frequency [101] .

From the available evidence estrogen does not

appear to be an effective treatment for stress incon-

tinence, although it may have a synergistic role

in combination therapy. Two placebo-controlled

studies have examined the use of oral and vaginal

estrogens with the α -adrenergic agonist, phenyl-

propanolamine, used separately and in combina-

tion. Both studies found that combination therapy

was superior to either drug given alone, although

while there was subjective improvement in all

groups [102] , there was only objective improve-

ment in the combination therapy group [103] . This

may offer an alternative conservative treatment for

women who have mild urodynamic stress incon-

tinence, although because of its pressor effects

phenylpropanolamine now has been withdrawn in

the United States [104] .

A recently reported meta-analysis has helped

determine the role of estrogen replacement in

women with stress incontinence [105] . Of the papers

reviewed, 14 were nonrandomized studies, 6 were

randomized trials (of which 4 were placebo control-

led), and 2 were meta-analyses. Interestingly, there

was only a symptomatic or clinical improvement

noted in the nonrandomized studies, while there

was no such effect noted in the randomized trials.

The authors concluded that currently the evidence

would not support the use of estrogen replacement

alone in the management of stress incontinence.

Estrogens in the Management of Urge

Incontinence

Estrogens have been used in the treatment of

urinary urgency and urge incontinence for many

years, although there have been few control-

led trials to confirm their efficacy. A double-

blind, placebo-controlled crossover study using

oral estriol in 34 postmenopausal women produced

subjective improvement in 8 women with mixed

incontinence and 12 with urge incontinence [106] .

However, a double-blind, multicenter study of the

use of estriol (3 mg d

−1 ) in postmenopausal women

complaining of urgency has failed to confirm

these findings [107] , showing both subjective and

objective improvement but not significantly better

than placebo. Estriol is a naturally occurring weak

estrogen that has little effect on the endometrium

and does not prevent osteoporosis, although it has

been used in the treatment of urogenital atrophy.

Consequently, it is possible that the dosage or route

of administration in this study was not appropriate

in the treatment of urinary symptoms and higher

systemic levels may be required.

The use of sustained-release 17 β -estradiol vagi-

nal tablets (Vagifem, Novo Nordisk) also has been

examined in postmenopausal women with urgency

and urge incontinence or a urodynamic diagno-

sis of sensory urgency or detrusor overactivity.

These vaginal tablets have been shown to be well

absorbed from the vagina and to induce matura-

tion of the vaginal epithelium within 14 days

[108] . However, following a 6-month course of

treatment the only significant difference between

active and placebo groups was an improvement

in the symptom of urgency in those women with

a urodynamic diagnosis of sensory urgency [109] .

A further double-blind, randomized, placebo-con-

trolled trial of vaginal 17 β -estradiol vaginal tablets

has shown lower urinary tract symptoms of fre-

quency, urgency, and urge and stress incontinence

to be significantly improved, although there was no

objective urodynamic assessment performed [110] .

In both of these studies the subjective improvement

in symptoms may simply represent local estrogenic

effects reversing urogenital atrophy rather than a

direct effect on bladder function.

74 D. Robinson and L. Cardozo

More recently a randomized, parallel group, con-

trolled trial has been reported comparing the estra-

diol-releasing vaginal ring (Estring, Pharmacia,

Uppsala, Sweden) with estriol vaginal pessaries

in the treatment of postmenopausal women with

bothersome lower urinary tract symptoms [111] .

Low-dose vaginally administered estradiol and

estriol were found to be equally efficacious in

alleviating lower urinary tract symptoms of urge

incontinence (58% vs. 58%), stress incontinence

(53% vs. 59%), and nocturia (51% vs. 54%),

although the vaginal ring was found to have

greater patient acceptability.

To try and clarify the role of estrogen therapy

in the management of women with urge incon-

tinence a meta-analysis of the use of estrogen in

women with symptoms of “overactive bladder”

has been reported by the HUT Committee [112] .

In a review of ten randomized placebo-controlled

trials estrogen was found to be superior to placebo

when considering symptoms of urge incontinence,

frequency, and nocturia, although vaginal estrogen

administration was found to be superior for symp-

toms of urgency. In those taking estrogens there

also was a significant increase in first sensation and

bladder capacity compared to placebo.

Estrogens in the Management

of Recurrent Urinary Tract Infection

Estrogen therapy has been shown to increase vagi-

nal pH and reverse the microbiological changes

that occur in the vagina following the menopause

[113] . Initial small uncontrolled studies using oral

or vaginal estrogens in the treatment of recurrent

urinary tract infection appeared to give promising

results [114, 115] , although unfortunately this has

not been supported by larger randomized trials.

Several studies have been performed examining the

use of oral and vaginal estrogens, although these

have had mixed results ( Table 6.5 ) .

Kjaergaard and colleagues [116] compared vagi-

nal estriol tablets with placebo in 21 postmenopausal

women over a 5-month period and found no signifi-

cant difference between the two groups. However,

a subsequent randomized, double-blind, placebo-

controlled study assessing the use of estriol vaginal

cream in 93 postmenopausal women during an

8-month period did reveal a significant effect [117] .

Kirkengen randomized 40 postmenopausal

women to receive either placebo or oral estriol

and found that although initially both groups had

a significantly decreased incidence of recurrent

infections, after 12 weeks estriol was shown to be

significantly more effective [118] . These findings,

however, were not confirmed subsequently in a trial

of 72 women postmenopausal women with recur-

rent urinary tract infections randomized to oral

estriol or placebo. Following a 6-month treatment

period and a further 6-month follow-up estriol was

found to be no more effective than placebo [119] .

The role of vaginal estriol cream also has been

assessed in 93 postmenopausal women with a his-

tory of recurrent urinary tract infections in a rand-

omized double-blind, placebo-controlled trial [120] .

Overall the incidence of urinary tract infection in

the estriol group was lower than the placebo group

(0.5 vs. 5.9 episodes per patient year; P < 0.001) and

more of the women in the estriol group remained

infection free. In addition, lactobacilli were absent in

all vaginal cultures before treatment and reappeared

after 1 month in 61% of estriol-treated women but in

none of the placebo group ( P < 0.001), and the rate

of vaginal colonization with Enterobacteriaceae fell

from 67 to 31% in the treatment group compared to

67 to –63% in the placebo arm.

More recently a randomized, open, parallel-group

study assessing the use of an estradiol-releasing

silicone vaginal ring (Estring; Pharmacia, Uppsala,

Sweden) in postmenopausal women with recur-

rent infections has been performed that showed

the cumulative likelihood of remaining infection

free was 45% in the active group and 20% in the

placebo group [121] . Estring also was shown to

decrease the number of recurrences per year and to

prolong the interval between infection episodes.

Estrogens in the Management

of Urogenital Atrophy

Symptoms of urogenital atrophy do not occur until

the levels of endogenous estrogen are lower than that

required to promote endometrial proliferation [122] .

Consequently, it is possible to use a low dose of estro-

gen replacement therapy in order to alleviate urogeni-

tal symptoms while avoiding the risk of endometrial

proliferation and removing the necessity of providing

endometrial protection with progestogens [123] .

6. Hormonal Influences on Continence 75

Study Study group

Type of

estrogen

Route of

delivery Duration of therapy Results

Kjaergaard

et al. 1990

[116]

21 postmenopausal women with

recurrent cystitis

10 active group 11 placebo

Estradiol

Vaginal tablets

5 months

Number of positive cultures not statistically different

between the two groups

Kirkengen

et al. 1992

[118]

40 postmenopausal women with

recurrent UTIs

20 active group 20 placebo

Estriol

Oral

12 weeks

Both estriol and placebo significantly reduced the

incidence of UTI’s ( p < 0.05)

After 12 weeks estriol was significantly more effective

than placebo ( p < 0.05)

Raz and Stamm

1993 [120]

93 postmenopausal women with

recurrent UTIs 50 active group

43 placebo

Estriol Vaginal cream 8 months Significant reduction in the incidence of UTI’s in the

group given estriol compared to placebo ( p < 0.001)

Cardozo et al.

1998 [119]

72 postmenopausal women with

recurrent UTIs 36 active group

36 placebo

Estriol Oral 6 month treatment period with

a further 6 months follow-up

Reduction in urinary symptoms and incidence of UTI’s

in both groups. Estriol no better than placebo

Eriksen 1999

[120]

108 women with recurrent UTIs

53 active group 55 no treatment

Estradiol Estring 36 weeks for the active group

36 weeks or until first

recurrence for the controls

Cumulative likelihood of remaining free of infection

was 45% in active group and 20% in control group

( p = 0.008)

Table 6.5. Summary of randomized controlled trials assessing the use of estrogens in the management of recurrent lower urinary tract.

76 D. Robinson and L. Cardozo

Vaginal Estrogens

The dose of estradiol commonly used in sys-

temic estrogen replacement is usually 25–100 µ g,

although studies investigating the use of estrogens

in the management of urogenital symptoms have

shown that 8–10 µ g of vaginal estradiol is effective

[124] . Thus only 10–30% of the dose used to treat

vasomotor symptoms may be effective in the man-

agement of urogenital symptoms. Since 10–25% of

women receiving systemic hormone replacement

therapy still experience the symptoms of urogenital

atrophy [125] , low-dose local preparations may

have an additional beneficial effect ( Table 6.6 ) .

The addition of local vaginal estrogen replace-

ment as an adjunct to systemic therapy has been

assessed in a randomized, double-blind, placebo-

controlled study of 27 women with menopausal

symptoms and atrophic vaginitis [126] . In addition

to systemic therapy with transdermal 17 β -estradiol

and oral MPA, women were randomized to adjuvant

0.5-mg vaginal estriol or placebo. When consider-

ing the results overall there were no differences

between the two groups in terms of symptoms or

cytological changes, although those women taking

additional vaginal estrogens exhibited a shorter

latency period for urinary symptoms. While this

small short-term study would not appear to support

the use of adjuvant vaginal estrogen replacement,

this may be explained by the fact that estriol is a

relatively weak estrogen, and thus the dose may

have been too low.

The efficacy and safety of vaginally adminis-

tered low-dose 25-µg 17 β -estradiol (Vagifem,

NovoNordisk) has been reported in a multicenter

double-blind, placebo-controlled study in 1,612

women [127] . Patients were randomized to 25- µg

estradiol or placebo once daily for 2 weeks and twice

weekly thereafter. Overall there was a significant

improvement in symptoms of urogenital atrophy

in the treatment arm compared to placebo (85.5%

vs. 41.4%) and also an improvement in cystometric

capacity, first desire to void, and strong desire to void

on urodynamic testing. Reassuringly there appeared

to be no effect on serum estrogen levels and there

were no cases of endometrial proliferation.

These findings are supported by a 12-week

observational study assessing the safety and effi-

cacy of low-dose, 25-µg 17 β -estradiol (Vagifem,

NovoNordisk) in 91 symptomatic postmenopau-

sal women [128] . Overall there was a signifi-

cant improvement in the symptoms of vaginal

dryness, vaginal itching, and dyspareunia. When

considering safety, despite a significant increase in

serum estradiol in relation to baseline ( P < 0.001)

and decrease in FSH levels (47.4–45.5 mIU ml

−1 ;

P < 0.003), these levels remained within the normal

range for postmenopausal women.

Two studies also have assessed the efficacy of

using ultra-low-dose vaginal estrogens. The first

was a single-blind, single-arm study to determine

the effects of de-escalating doses of vaginal estro-

gens on symptoms of urogenital atrophy, vaginal

pH, and vaginal and urethral cytology [129] .

Overall, 10-µg vaginal estradiol was found to have

an 82% clinical response in symptoms as well

as causing a statistical improvement in vaginal

cytology, urethral cytology, and vaginal pH. The

endometrium remained atrophic and serum estra-

diol remained within the normal postmenopausal

range. The second study evaluated the effects of

25- and 10-µg 17 β -estradiol in 58 symptomatic

postmenopausal women in a double-blind, rand-

omized, parallel-group study [130] . After 12 weeks

of therapy the area under the curve, maximal, and

average over 24 hr, estradiol concentration was

higher in the 25-µg arm (563 pg hr ml

−1 , 49 and

23 pg ml

−1 ) than the 10-µg (264 pg hr ml

−1 , 22 and

11 pg ml

−1 ). Overall, 74% in the 25-µg group and

96% in the 10-µg group had low systemic absorp-

tion of estradiol (<500 pg ml

−1 ), absorption patterns

remained consistent, and there was no evidence of

accumulation. These two studies thus would sug-

gest that ultra-low-dose vaginal estradiol may be

safe and efficacious in the treatment of urogenital

symptoms in postmenopausal women.

Vaginal estradiol also has been compared to vagi-

nal CEEs in the management of urogenital atrophy.

A multicenter, open-label, randomized, parallel-

group study compared 25-µg 17 β -estradiol with

1.25 mg CEE vaginal cream in 159 menopausal

Table 6.6. Vaginal estrogen preparations .

Type of estrogen Mode of administration

Estriol Cream: Ovestin

Pessary: Orthogynest

Estradiol Tablets: Vagifem

Ring: Estring

Conjugated Cream: Premarin

6. Hormonal Influences on Continence 77

women over 24 weeks [131] . While both treatment

regimens provided relief of the symptoms associ-

ated with atrophic vaginitis, increases in serum

estradiol and suppression of follicle-stimulating

hormone (FSH) were found to be significantly

higher in those women using CEEs compared to

vaginal estradiol tablets ( P < 0.001). In addition,

fewer patients who were using the vaginal tablets

experienced endometrial proliferation or hyper-

plasia. In terms of satisfaction, significantly more

women favored vaginal tablets and they also were

associated with lower rates of withdrawal (10%

vs. 32%). These findings have been confirmed by

a further study of 53 women randomized to 25 µg

estradiol or 1 gm conjugated estrogen cream for

12 weeks [132] . Both groups showed improvement

in urogenital symptoms, vaginal health index, and

vaginal cytology after 4 weeks of therapy, although

the vaginal cream was found to be superior in terms

of vaginal dryness and dyspareunia.

The use of the continuous low-dose estradiol-

releasing silicone vaginal ring (Estring; Pfizer)

releasing estradiol 5–10 µ g/24 h also has been

investigated in postmenopausal women with symp-

tomatic urogenital atrophy [112] . There was a

significant effect on symptoms of vaginal dryness,

pruritis vulvae, dyspareunia, and urinary urgency

with improvement being reported in over 90% of

women in an uncontrolled study, while the matura-

tion of vaginal epithelium also was significantly

improved. The patient acceptability was high, and

while the maturation of vaginal epithelium ( Fig. 6.3 )

was significantly improved, there was no effect on

endometrial proliferation.

These findings were supported by a 1-year

multicenter study of Estring in postmenopausal

women with urogenital atrophy, which found

subjective and objective improvement in 90% of

patients up to 1 year. However, there was a 20%

withdrawal rate with 7% of women reporting vagi-

nal irritation – two having vaginal ulceration and

three complaining of vaginal bleeding – although

there were no cases of endometrial proliferation

[133] . Long-term safety has been confirmed by

a 10-year review of the use of the estradiol ring

delivery system, which has found its safety, effi-

cacy, and acceptability to be comparable to other

forms of vaginal administration [134] . A compara-

tive study of safety and efficacy of Estring with

CEE vaginal cream in 194 postmenopausal women

complaining of urogenital atrophy found no signif-

icant difference in vaginal dryness, dyspareunia,

and resolution of atrophic signs between the two

treatment groups. Furthermore, there was a similar

improvement in the vaginal mucosal maturation

index and a reduction in pH in both groups with

the vaginal ring being found to be preferable to

the cream [135] .

In order to clarify the situation a review of estro-

gen therapy in the management of urogenital atro-

phy has been performed by the HUT Committee

[136] . Ten randomized trials and 54 uncontrolled

series were examined from 1969 to 1995 assessing

24 different treatment regimens. Meta-analysis of

ten placebo-controlled trials confirmed the sig-

nificant effect of estrogens in the management of

urogenital atrophy.

The route of administration was assessed and oral,

vaginal, and parenteral (transcutaneous patches and

subcutaneous implants) were compared. Overall,

Fig. 6.3. Topical vaginal estrogen replacement increases

the number of intermediate and superficial cells in the

vaginal mucosa; ( a ) prior to treatment and ( b ) following

treatment

78 D. Robinson and L. Cardozo

the vaginal route of administration was found

to correlate with better symptom relief, greater

improvement in cytological findings, and higher

serum estradiol levels.

With regard to the type of estrogen preparation

estradiol was found to be most effective in reducing

patient symptoms, although conjugated estrogens

produced the most cytological change and the

greatest increase in serum levels of estradiol and

estrone.

Finally, the effect of different dosages was exam-

ined. Low-dose vaginal estradiol was found to be

the most efficacious according to symptom relief,

although oral estriol also was effective. Estriol had

no effect on the serum levels of estradiol or estrone,

while vaginal estriol had minimal effect. Vaginal

estradiol was found to have a small effect on serum

estrogen, although not as great as systemic prepara-

tions. In conclusion it would appear that estrogen

is efficacious in the treatment of urogenital atrophy

and low-dose vaginal preparations are as effective

as systemic therapy.

A more recent meta-analysis of the use of

estrogens in the management of urogenital atro-

phy has been reported by the Cochrane group

[137] . Overall, 16 trials with 2,129 women were

included in the meta-analysis. When comparing

the efficacy of estrogen-containing preparations

there were significant differences favoring creams,

tablets, and the estradiol ring compared to placebo

and nonhormonal gel. Fourteen trials assessed

safety; four examined endometrial hyperplasia,

four endometrial stimulation, and six adverse

effects. One trial found a significant increase in

adverse effects (uterine bleeding, breast pain, and

perineal pain) associated with CEE cream com-

pared to estradiol tablets (1 RCT; OR 0.18, 95%

CI: 0.07–0.50). In addition, two studies showed

significant endometrial stimulation with CEE

cream compared to the estradiol ring (OR 0.29;

95% CI: 0.11–0.78). While not significant, there

was a 2% incidence of simple hyperplasia in the

estradiol ring group compared to CEE cream and

a 4% incidence of endometrial hyperplasia (one

simple, one complex) in the conjugated estrogen

cream group compared to the estradiol vaginal

tablets. Acceptability was assessed in nine stud-

ies, and overall found a significant preference for

the estradiol-releasing ring.

Conclusions

Estrogens are known to have an important physi-

ological effect on the female lower genital tract

throughout adult life, leading to symptomatic,

histological, and functional changes. Urogenital

atrophy is the manifestation of estrogen withdrawal

following the menopause, presenting with vaginal

and/or urinary symptoms. The use of estrogen

replacement therapy has been examined in the man-

agement of lower urinary tract symptoms as well as

in the treatment of urogenital atrophy, although

only recently has it been subjected to randomized

placebo-controlled trials and meta-analysis.

Estrogen therapy alone has been shown to have

little effect in the management of urodynamic stress

incontinence. At present there are no data regard-

ing the synergistic use of estrogens and duloxetine,

a combined serotonin and noradrenaline reuptake

inhibitor, and the only drug to be licensed for the

treatment of stress urinary incontinence.

When considering the irritive symptoms of

urinary urgency, frequency, and urge incon-

tinence estrogen therapy may be of benefit,

although this may simply represent reversal of

urogenital atrophy rather than a direct effect

on the lower urinary tract. The role of systemic

estrogen replacement therapy in the management

of women with recurrent lower urinary tract

infection remains to be determined, although

there is now good evidence that vaginal admin-

istration may be efficacious. While low-dose

vaginal estrogens have been shown to be have

an important role in the treatment of urogenital

atrophy in postmenopausal women and would

appear to be as effective as systemic prepara-

tions, at present the role of adjuvant vaginal

estrogen remains uncertain.

References

1 . Cardozo LD . Role of oestrogens in the treatment

of female urinary incontinence . J Am Geriatr Soc

1990 ; 38 : 326 – 328 .

2 . Iosif S , Batra S , Ek A , Astedt B . Oestrogens recep-

tors in the human female lower urinary tract . Am J

Obstet Gynaecol 1981 ; 141 : 817 – 820 .

3 . Batra SC , Fossil CS . Female urethra, a target for

oestrogen action . J Urol 1983 ; 129 : 418 – 420 .

6. Hormonal Influences on Continence 79

4 . Batra SC , Iosif LS . Progesterone receptors in the

female urinary tract . J Urol 1987 ; 138 : 130 – 134 .

5 . Iosif C , Bekassy Z . Prevalence of genitourinary

symptoms in the late menopause . Acta Obstet

Gynaecol Scan 1984 ; 63 : 257 – 260 .

6 Beato M , Herrich P , Schutz G . Steroid hormone

receptors: Many actors in search of a plot . Cell

1995 ; 83 : 851 – 857 .

7 . Green S , Walter P , Kumar V , et al. Human oestrogen

receptor cDNA: Sequence, expression and homol-

ogy to v-erbA . Nature 1986 ; 320 : 134 – 139 .

8 . Kuiper G , Enmark E , Pelto-Huikko M , et al.

Cloning of a novel oestrogen receptor expressed

in rat prostate and ovary . Proc Natl Acad Sci USA

1996 ; 93 : 5925 – 5930 .

9 . Warner M , Nilsson S , Gustafsson JA . The oestrogen

receptor family . Curr Opin Obstet Gynecol 1999 ;

11 : 249 – 254 .

10 . Blakeman PJ , Hilton P , Bulmer JN . Mapping oes-

trogen and progesterone receptors throughout the

female lower urinary tract . Neurourol Urodyn 1996 ;

15 : 324 – 325 .

11 . Ingelman-Sundberg A , Rosen J , Gustafsson SA .

Cytosol oestrogen receptors in urogenital tissues

in stress incontinent women . Acta Obstet Gynecol

Scand 1981 ; 60 : 585 – 586 .

12 . Smith P. Oestrogens and the urogenital tract. Acta

Obstet Gynaecol Scand 1993; 72(Suppl): 1–26.

13 . Bernstein IT . The pelvic floor muscles: Muscle

thickness in healthy and urinary-incontinent women

measured by perineal ultasonography with refer-

ence to the effect of pelvic floor training. Oestrogen

receptor studies . Neurourol Urodyn 1997 ; 16 (4) :

237 – 275 .

14 . Chen GD , Oliver RH , Leung BS , et al. Oestrogen

receptor α and β expression in the vaginal walls

and uterosacral ligaments of premenopausal and

postmenopausal women . Fertil Steril 1999 ; 71 (6) :

1099 – 1102 .

15 . Screiter F , Fuchs P , Stockamp K . Oestrogenic sen-

sitivity of α receptors in the urethral musculature .

Urol Int 1976 ; 31 : 13 – 19 .

16 . Blakeman PJ , Hilton P , Bulmer JN . Androgen

receptors in the female lower urinary tract . Int

Urogynaecol J 1997 ; 8 : S54 .

17 . Pang X , Cotreau-Bibbo MM , Sant GR , Theoharides

TC . Bladder mast cell expression of high affinity

oestrogen receptors in receptors in patients with

interstitial cystitis . Br J Urol 1995 ; 75 : 154 – 161 .

18 . Letourneau R , Pang X , Sant GR , Theoharides TC .

Intragranular activation of bladder mast cells and

their association with nerve processes in interstitial

cystitis . Br J Urol 1996 ; 77 : 41 – 54 .

19 . Bodker A , Balsev E , Juul BR , et al. Oestrogen

receptors in the human male bladder, prostatic

urethra and prostate . Scan J Urol Nephrol 1995 ;

29 : 161 – 165 .

20 . Blakeman PJ , Hilton P , Bulmer JN . Oestrogen and

progesterone receptor expression in the female

lower urinary tract, with reference to oestrogen

status . BJU Int 2000 ; 86 : 32 – 38 .

21 . Abrams P , Blaivas JG , Stanton SL , et al. The

standardisation of terminology of lower urinary

tract dysfunction . Br J Obstet Gynaecol 1990 ; 97 :

1 – 16 .

22 . Rud T , Anderson KE , Asmussen M , et al. Factors

maintaining the urethral pressure in women . Invest

Urol 1980 ; 17 : 343 – 347 .

23 . Malone-Lee J. Urodynamic measurement and urinary

incontinence in the elderly. In: Brocklehurst JC, ed.

Managing and measuring incontinence. Proceedings

of the Geriatric Workshop on Incontinence, July

1988 (Geriatric Medicine).

24 . Versi E , Cardozo LD . Oestrogens and lower urinary

tract function. In : Studd JWW, Whitehead MI,

eds. The menopause . Oxford : Blackwell Scientific

Publications , 1988 : 76 – 84 .

25 . Kinn AC , Lindskog M . Oestrogens and phenylpro-

panolamine in combination for stress incontinence .

Urology 1988 ; 32 : 273 – 280 .

26 . Smith PJB . The effect of oestrogens on bladder

function in the female. In : Campbell S, ed. The man-

agement of the menopause and postmenopausal

years . Carnforth : MTP 1976 : 291 – 298 .

27 . Samsioe G , Jansson I , Mellstrom , D , Svandborg A .

Occurrence, nature and treatment of urinary inconti-

nence in a 70 year old female population . Maturitas

1985 ; 7 : 335 – 342 .

28 . Blakeman PJ , Hilton P , Bulmer JN . Cellular pro-

liferation in the female lower urinary tract with

reference to oestrogen status . Br J Obstet Gynaecol

2001 ; 8 : 813 – 816

29 . Hextall A , Bidmead J , Cardozo L , Hooper R .

Hormonal influences on the human female lower

urinary tract: A prospective evaluation of the effects

of the menstrual cycle on symptomatology and

the results of urodynamic investigation . Neurourol

Urodyn 1999 ; 18 (4) : 282 – 283 .

30 . Van Geelen JM , Doesburg WH , Thomas CMG .

Urodynamic studies in the normal menstrual cycle:

The relationship between hormonal changes during

the menstrual cycle and the urethral pressure pro-

file . Am J Obstet Gynaecol 1981 ; 141 : 384 – 392 .

31 . Burton G , Cardozo LD , Abdalla H , et al. The

hormonal effects on the lower urinary tract in 282

women with premature ovarian failure . Neurourol

Urodyn 1992 ; 10 : 318 – 319 .

32 . Cutner A , Burton G , Cardozo LD , et al. Does proges-

terone cause an irritable bladder? Int Urogynaecol J

1993 ; 4 : 259 – 261 .

80 D. Robinson and L. Cardozo

33 . Benness C , Gangar K , Cardozo LD , Cutner A .

Do progestogens exacerbate urinary incontinence

in women on HRT? Neurourol Urodyn 1991 ; 10 :

316 – 318 .

34 . Elliot RA , Castleden CM . Effect of progestogens

and oestrogens on the contractile response of rat

detrusor muscle to electrical field stimulation . Clin

Sci 1994 ; 87 : 342 .

35 . Cutner A. The urinary tract in pregnancy. MD

Thesis, 1993, University of London.

36 . Donnelly V , O’Connell PR , O’Herlihy C . The

influence of hormonal replacement on faecal incon-

tinence in post menopausal women . Br J Obstet

Gynaecol 1997 ; 104 : 311 – 315 .

37 . Sandford JP . Urinary tract symptoms and infection .

Annu Rev Med 1975 ; 26 : 485 – 505 .

38 . Boscia JA , Kaye D . Asymptomatic bacteria in the

elderly . Infect Dis Clin North Am 1987 ; 1 : 893 – 903 .

39 . Maggi A , Perez J . Role of female gonadal hor-

mones in the CNS . Life Sci 1985 ; 37 : 893 – 906 .

40 . Smith SS , Berg G , Hammar M , eds. The modern

management of the menopause. Hormones, mood

and neurobiology – a summary . Carnforth, UK :

Parthenon Publishing; 1993 : 204 .

41 . Blok EFM , Holstege G . Androgen receptor immu-

noreactive neurones in the hypothalamic preoptic

area project to the pontine micturition centre in the

male cat . Neurourol Urodyn 1998 ; 17 (4) : 404 – 405 .

42 . Shapiro E . Effect of oestrogens on the weight and

muscarinic receptor density of the rabbit bladder

and urethra . J Urol 1986 ; 135 : 1084 – 1087 .

43 . Batra S , Anderson KE . Oestrogen induced changes

in muscarinic receptor density and contractile

responses in the female rat urinary bladder . Acta

Physiol Scand 1989 ; 137 : 135 – 141 .

44 . Elliott RA , Castleden CM , Miodrag A , Kirwan P .

The direct effects of diethylstilboestrol and nifed-

ipine on the contractile responses of isolated human

and rat detrusor muscles . Eur J Clin Pharmacol

1992 ; 43 : 149 – 155 .

45 . Shenfield OZ , Blackmore PF , Morgan CW , et al.

Rapid effects of oestriol and progesterone on tone

and spontaneous rhythmic contractions of the rabbit

bladder . Neurourol Urodyn 1998 ; 17 (4) : 408 – 409 .

46 . Fantl JA , Wyman JF , Anderson RL , et al. Post men-

opausal urinary incontinence: Comparison between

non-oestrogen and oestrogen supplemented women .

Obstet Gynaecol 1988 ; 71 : 823 – 828 .

47 . Bergman A , Karram MM , Bhatia NN . Changes in

urethral cytology following oestrogen administra-

tion . Gynaecol Obstet Invest 1990 ; 29 : 211 – 213 .

48 . Rud T . The effects of oestrogens and gestogens on

the urethral pressure profile in urinary continent and

stress incontinent women . Acta Obstet Gynaecol

Scand 1980 ; 59 : 365 – 270 .

49 . Hilton P , Stanton SL . The use of intravaginal oes-

trogen cream in genuine stress incontinence . Br

J Obstet Gynaecol 1983 ; 90 : 940 – 944 .

50 . Bhatia NN , Bergman A , Karram MM , et al. Effects

of oestrogen on urethral function in women with

urinary incontinence . Am J Obstet Gynaecol 1989 ;

160 : 176 – 180 .

51 . Karram MM , Yeko TR , Sauer MV , et al. Urodynamic

changes following hormone replacement therapy in

women with premature ovarian failure . Obstet

Gynaecol 1989 ; 74 : 208 – 211 .

52 . Ganger KF , Vyas S , Whitehead RW , et al. Pulsitility

index in the internal carotid artery in relation to

transdermal oestradiol and time since the meno-

pause . Lancet 1991 ; 338 : 839 – 842 .

53 . Jackson S , Vyas S . A double blind, placebo control-

led study of postmenopausal oestrogen replacement

therapy and carotid artery pulsatility index . Br

J Obstet Gynaecol 1998 ; 105 (4) : 408 – 412 .

54 . Penotti M , Farina M , Sironi L , et al. Long term

effects of postmenopausal hormone replacement

therapy on pulsatility index of the internal carotid

and middle cerebral arteries . Menopause J North

Am Menopause Soc 1997 ; 4 (2) : 101 – 104 .

55 . Versi E , Cardozo LD . Urethral instability: Diagnosis

based on variations in the maximum urethral pres-

sure in normal climateric women . Neurourol Urodyn

1986 ; 5 : 535 – 541 .

56 . Girao MJ , Jarmy-Di Bella ZI , Sartori MG , et al.

Doppler velocimetry parameters of periurethral

vessels in postmenopausal incontinent women

receiving oestrogen replacement . Int Urogynaecol

2001 ; 12 : 241 – 246 .

57 . Falconer C , Ekman-Ordeberg G , Ulmsten U , et al.

Changes in paraurethral connective tissue at meno-

pause are counteracted by oestrogen . Mauturitas

1996 ; 24 : 197 – 204 .

58 . Kushner L , Chen Y , Desautel M , et al. Collagenase

activity is elevated in conditioned media from

fibroblasts of women with pelvic floor weakening .

Int Urogynaecol 1999 ; 10 (S1) : 34 .

59 . Jackson S , Avery N , Shepherd A , et al. The effect

of oestradiol on vaginal collagen in postmenopausal

women with stress urinary incontinence . Neurourol

Urodyn 1996 ; 15 : 327 – 328 .

60 . James M , Avery N , Jackson S , et al. The pathophys-

iological changes of vaginal skin tissue in women

with stress urinary incontinence: A controlled trial .

Int Urogynaecol 1999 ; 10 (S1) : 35 .

61 . James M , Avery N , Jackson S , et al. The biochemi-

cal profile of vaginal tissue in women with geni-

tourinary prolapse: A controlled trial . Neurourol

Urodyn 1999 ; 18 (4) : 284 – 285 .

62 . Brincat M , Moniz CF , Studd JWW . Long term

effects of the menopause and sex hormones on

6. Hormonal Influences on Continence 81

skin thickness . Br J Obstet Gynaecol 1985 ; 92 :

256 – 259 .

63 . Landon CR , Smith ARB , Crofts CE , Trowbridge

EA . Biochemical properties of connective tissue in

women with stress incontinence of urine . Neurourol

Urodyn 1989 ; 8 : 369 – 370 .

64 . Ulmsten U , Ekman G , Giertz G . Different bio-

chemical composition of connective tissue in con-

tinent and stress incontinent women . Acta Obstet

Gynaecol Scand 1987 ; 66 : 455 .

65 . Diokno AC , Brook BM , Brown MB . Prevalence of

urinary incontinence and other urological symp-

toms in the non-institutionalised elderly . J Urol

1986 ; 136 : 1022 .

66 . Yarnell J , Voyle G , Richards C , Stephenson T . The

prevalence and severity of urinary incontinence in

women . J Epidemiol Commun Health 1981 ; 35 :

71 – 74 .

67 . Ouslander JG . Urinary incontinence in nursing

homes . JAGS 1990 ; 38 : 289 – 291 .

68 . MacLennan AH , Taylor AW , Wilson AW , Wilson

D . The prevalence of pelvic floor disorders and

their relationship to gender, age, parity, and mode

of delivery . Br J Obstet Gynaecol 2000 ; 107 :

1460 – 1470 .

69 . Kok AL , Voorhorst FJ , Burger CW , et al. Urinary

and faecal incontinence in community residing

elderly women . Age Ageing 1992 ; 21 : 211 .

70 . Cardozo LD , Tapp A , Versi E , eds. The lower

urinary tract in peri- and postmenopausal women.

In: The urogenital deficiency syndrome . Bagsverd,

Denmark : Novo Industri AS , 1987 : 10 – 17 .

71 . Kondo A , Kato K , Saito M , et al. Prevalence of

hand washing incontinence in females in compari-

son with stress and urge incontinence . Neurourol

Urodyn 1990 ; 9 : 330 – 331 .

72 . Thomas TM , Plymat KR , Blannin J , et al. Prevalence

of urinary incontinence . Br Med J 1980 ; 281 : 1243 –

1245 .

73 . Jolleys JV . Reported prevalence of urinary incon-

tinence in a general practice . Br Med J 1988 ; 296 :

1300 – 1302 .

74 . Burgio KL , Matthews KA , Engel B . Prevalence,

incidence and correlates of urinary incontinence

in healthy, middle aged women . J Urol 1991 ; 146 :

1255 – 1259 .

75 . Iosif CS . Effects of protracted administration of

oestriol on the lower genitourinary tract in post-

menopausal women . Acta Obstet Gynaecol Scand

1992 ; 251 : 115 – 120 .

76 . American National Institute of Health Population

Figures. US Treasury Department. NIH, 1991.

77 . Research on the menopause in the 1990’s. Report

or a WHO Scientific Group. In: WHO Technical

Report Series 866 Geneva, Switzerland, 1994.

78 . Barlow D , Samsioe G , van Geelan H . Prevalence of

urinary problems in European countries . Maturitas

1997 ; 27 : 239 – 248 .

79 . Greendale GA , Judd JL . The menopause: Health

implications and clinical management . J Am Geriatr

Soc 1993 ; 41 : 426 – 436 .

80 . Samsioe G , Jansson I , Mellstrom D , Svanborg A .

The occurrence, nature and treatment of urinary

incontinence in a 70 year old population . Mauturitas

1985 ; 7 : 335 – 343 .

81 . Van Geelen JM , Van de Weijer PH , Arnolds HT .

Urogenital symptoms and resulting discomfort in

non-institutionalised Dutch women aged 50–75

years . Int Urogynecol J Pelvic Floor Dysfunct

2000 ; 11 (1) : 9 – 14

82 . Versi E , Harvey MA , Cardozo L , et al. Urogenital

prolapse and atrophy at menopause: A prevalence

study . Int Urogynaecol J Pelvic Dysfunct 2001 ;

12 (2) : 107 – 110

83 . Davila GW , Karapanagiotou I , Woodhouse S , et al.

Are women with urogenital atrophy symptomatic?

Obstet Gynaecol 2001 ; 97 (4 Suppl 1) : S48 .

84 . Bachman GA . Urogenital aging: An old problem

newly recognised . Maturitas 1995 ; 22 : S1 – S5 .

85 . Salmon UL , Walter RI , Gast SH . The use of oes-

trogen in the treatment of dysuria and incontinence

in postmenopausal women . Am J Obstet Gynaecol

1941 ; 14 : 23 – 31 .

86 . Youngblood VH , Tomlin EM , Davis JB . Senile

urethritis in women . J Urol 1957 ; 78 : 150 – 152 .

87 . Fantl JA , Cardozo LD , McClish DK , the Hormones

and Urogenital Therapy Committee. Oestrogen

therapy in the management of incontinence in

postmenopausal women: A meta-analysis. First

report of the Hormones and Urogenital Therapy

Committee . Obstet Gynaecol 1994 ; 83 : 12 – 18 .

88 . Henalla SM , Hutchins CJ , Robinson P , Macivar J .

Nonoperative methods in the treatment of female

genuine stress incontinence of urine . Br J Obstet

Gynaecol 1989 ; 9 : 222 – 225 .

89 . Zullo MA , Oliva C , Falconi G , et al. Efficacy

of oestrogen therapy in urinary incontinence. A

meta-analytic study . Minerva Gynecol 1998 ; 50 (5) :

199 – 205 .

90 . Moehrer B, Hextall A, Jackson S. Oestrogens for

urinary incontinence in women. Cochrane Database

Syst Rev 2003; (2): CD001405.

91 . Grady D , Brown JS , Vittinghoff E , et al.

Postmenopausal hormones and incontinence: The

Heart and Estrogen/Progestin Replacement Study .

Obstet Gynaecol 2001 ; 97 : 116 – 120 .

92 . Grodstein F , Lifford K , Resnick NM , Curhan GC .

Postmenopausal hormone therapy and risk of devel-

oping urinary incontinence . Obstet Gynaecol 2004 ;

103 : 254 – 260 .

82 D. Robinson and L. Cardozo

93 . Ouslander JG , Greendale GA , Uman G , et al.

Effects of oral oestrogen and progestin on the lower

urinary tract among female nursing home residents .

Am Geriatr Soc 2001 ; 49 (6) : 803 – 807 .

94 . Hendrix SL , Cochrane BR , Nygaard IE , et al. Effects

of estrogen with and without progestin on urinary

incontinence . JAMA 2005 ; 293 (8) : 935 – 948 .

95 . Caine M, Raz S. The role of female hormones in

stress incontinence. In: Proceedings of the 16th

Congress of the International Society of Urology,

Amsterdam, The Netherlands.

96 . Rud T . The effects of oestrogens and gestogens on

the urethral pressure profile in urinary continent and

stress incontinent women . Acta Obstet Gynaecol

Scand 1980 ; 59 : 265 – 270 .

97 . Wilson PD , Faragher B , Butler B , et al. Treatment

with oral piperazine oestrone sulphate for genuine

stress incontinence in postmenopausal women . Br J

Obstet Gynaecol 1987 ; 94 : 568 – 574 .

98 . Walter S , Wolf H , Barlebo H , Jansen H . Urinary

incontinence in postmenopausal women treated

with oestrogens: A double-blind clinical trial . J

Urol 1978 ; 33 : 135 – 143 .

99 . Fantl JA , Bump RC , Robinson D , et al. Efficacy of

oestrogen supplementation in the treatment of urinary

incontinence . Obstet Gynaecol 1996 ; 88 : 745 – 749 .

100 . Jackson S , Shepherd A , Brookes S , Abrams P . The

effect of oestrogen supplementation on post-meno-

pausal urinary stress incontinence: A double-blind,

placebo controlled trial . Br J Obstet Gynaecol 1999 ;

106 : 711 – 718 .

101 . Sultana CJ , Walters MD . Oestrogen and urinary incon-

tinence in women . Maturitas 1995 ; 20 : 129 – 138 .

102 . Beisland HO , Fossberg E , Moer A , et al. Urethral

insufficiency in post-menopausal females: Treatment

with phenylpropanolamine and oestriol separately

and in combination . Urol Int 1984 ; 39 : 211 – 216 .

103 . Hilton P , Tweddel AL , Mayne C . Oral and intravag-

inal oestrogens alone and in combination with alpha

adrenergic stimulation in genuine stress inconti-

nence . Int Urogynecol J 1990 ; 12 : 80 – 86 .

104 . Horwitz RI, Brass LM, Kernan WN, Viscoli

CM. Phenylpropanolamine and risk of hemorrhagic

stroke: Final report of the Hemorrhagic Stroke

Project, May 10, 2000.

105 . Ahmed Al-Badr , Ross S , Soroka D , Drutz HP . What

is the available evidence for hormone replacement

therapy in women with stress urinary incontinence?

J Obstet Gynaecol Can 2003 ; 25 (7) : 567 – 574 .

106 . Samsicoe G , Jansson I , Mellstrom D , Svanberg A .

Urinary incontinence in 75 year old women . Effects of

oestriol. Acta Obstet Gynaecol Scand 1985 ; 93 : 57 .

107 . Cardozo LD , Rekers H , Tapp A , et al. Oestriol in

the treatment of postmenopausal urgency: A multi-

centre study . Maturitas 1993 ; 18 : 47 – 53 .

108 . Nilsson K , Heimer G . Low dose oestradiol in the

treatment of urogenital oestrogen defiiciency –

A pharmacokinetic and pharmacodynamic study .

Maturitas 1992 ; 15 : 121 – 127 .

109 . Benness C , Wise BG , Cutner A , Cardozo LD .

Does low dose vaginal oestradiol improve fre-

quency and urgency in postmenopausal women . Int

Urogynaecol J 1992 ; 3 (2) : 281 .

110 . Eriksen PS , Rasmussen H . Low dose 17 β -oestradiol

vaginal tablets in the treatment of atrophic vaginitis:

A double-blind placebo controlled study . Eur J

Obstet Gynaecol Reprod Biol 1992 ; 44 : 137 – 144 .

111 . Lose G , Englev E . Oestradiol-releasing vaginal ring

versus oestriol vaginal pessaries in the treatment

of bothersome lower urinary tract symptoms . Br J

Obstet Gynaecol 2000 ; 107 : 1029 – 1034 .

112 . Cardozo L , Lose G , McClish D , Versi E . Estrogen

treatment for symptoms of an overactive bladder,

results of a meta-analysis . Int J Urogynaecol 2001 ;

12 (3) : V .

113 . Brandberg A , Mellstrom D , Samsioe G . Low dose

oral oestriol treatment in elderly women with uro-

genital infections . Acta Obstet Gynaecol Scand

1987 ; 140 : 33 – 38 .

114 . Parsons CL , Schmidt JD . Control of recurrent uri-

nary tract infections in postmenopausal women . J

Urol 1982 ; 128 : 1224 – 1226 .

115 . Privette M , Cade R , Peterson J , et al. Prevention of

recurrent urinary tract infections in postmenopausal

women . Nephron 1988 ; 50 : 24 – 27 .

116 . Kjaergaard B , Walter S , Knudsen A , et al. Treatment

with low dose vaginal oestradiol in postmenopausal

women. A double blind controlled trial . Ugeskr

Laeger 1990 ; 152 : 658 – 659 .

117 . Raz R , Stamm WE . A controlled trial of intravagi-

nal oestriol in postmenopausal women with recur-

rent urinary tract infections . New Engl J Med 1993 ;

329 : 753 – 756 .

118 . Kirkengen AL , Anderson P , Gjersoe E , et al.

Oestriol in the prophylactic treatment of recurrent

urinary tract infections in postmenopausal women .

Scand J Prim Health Care 1992 ; 10 : 142 .

119 . Cardozo LD , Benness C , Abbott D . Low dose

oestrogen prophylaxis for recurrent urinary tract

infections in elderly women . Br J Obstet Gynaecol

1998 ; 105 : 403 – 407.

120 . Raz R , Stamm WE . A controlled trial of intravagi-

nal oestriol in postmenopausal women with recur-

rent urinary tract infections . New Engl. J Med 1993 ;

329 : 753 – 756 .

121 . Eriksen B . A randomised, open, parallel-group

study on the preventitive effect of an oestradiol-

releasing vaginal ring (Estring) on recurrent urinary

tract infections in postmenopausal women . Am J

Obstet Gynaecol 1999 ; 180 : 1072 – 1079 .

6. Hormonal Influences on Continence 83

122 . Samicoe G . Urogenital ageing – A hidden problem .

Am J Obstet Gynaecol 1998 ; 178 (5) : S245 – S249 .

123 . Mettler L , Olsen PG . Long term treatment of

atrophic vaginitis with low dose oestradiol vaginal

tablets . Maturitas 1991 ; 14 : 23 – 31 .

124 . Smith P , Heimer G , Lindskog, Ulmsten U .

Oestradiol releasing vaginal ring for treatment

of postmenopausal urogenital atrophy . Maturitas

1993 ; 16 : 145 – 154 .

125 . Smith RJN , Studd JWW . Recent advances in hor-

mone replacement therapy . Br J Hosp Med 1993 ;

49 : 799 – 809 .

126 . Palacios S , Castelo-Branco C , Cancelo MJ , Vazquez

F . Low dose vaginally administered oestrogens may

enhance local benefits of systemic therapy in the

treatment of urogenital atrophy in postmenopausal

women on hormone replacement therapy . Maturitas

2005 ; 50 : 98 – 104 .

127 . Simunic V , Banovic I , Ciglar S , et al. Local oestro-

gen treatment in patients with urogenital symptoms .

Int J Gynaecol Obstet 2003 ; 82 : 187 – 197 .

128 . Akrivis Ch , Varras M , Thodos A , et al. Action of

25 mcg 17 β oestradiol vaginal tablets in the treat-

ment of vaginal atrophy in Greek postmenopausal

women; clinical study . Clin Exp Obstet Gynaecol

2003 ; 30 : 229 – 234 .

129 . Santen RJ , Pinkerton JV , Conaway M , et al. Treatment

of urogenital atrophy with low dose oestradiol:

Preliminary results . Menopause 2002 ; 9 : 179 – 187 .

130 . Notelovitz M , Funk S , Nanavati N , Mazzeo M .

Oestradiol absorption from vaginal tablets in postmen-

opausal women . Obstet Gynaecol 2002 ; 99 : 556 – 562 .

131 . Rioux JE , Devlin C , Gelfend MM , et al. 17 β

Oestradiol vaginal tablet versus conjugated equine

oestrogen vaginal cream to relieve menopausal

atrophic vaginitis . Menopause 2000 ; 7 : 156 – 161 .

132 . Manonai J , Theppisai U , Suthutvoravut S , et al. The

effect of oestradiol vaginal tablet and conjugated

oestrogen cream on urogenital symptoms in post-

menopausal women: A comparative study . J Obstet

Gynaecol Res 2001 ; 27 : 255 – 260 .

133 . Henriksson L , Stjernquist M , Boquist L , et al. A

one-year multicentre study of efficacy and safety

of a continuous, low dose, oestradiol-releasing

vaginal ring (Estring) in postmenopausal women

with symptoms and signs of urogenital aging . Am J

Obstet Gynaecol 1996 ; 174 : 85 – 92 .

134 . Bachmann G . Oestradiol-releasing vaginal ring

delivery system for urogenital atrophy. Experience

over the last decade . J Reprod Med 1998 ; 43 :

991 – 998.

135 . Ayton RA , Darling GM , Murkies AL , et al. A com-

parative study of safety and efficacy of low dose

oestradiol released from a vaginal ring compared

with conjugated equine oestrogen vaginal cream in

the treatment of postmenopausal vaginal atrophy .

Br J Obstet Gynaecol 1996 ; 103 : 351 – 358 .

136 . Cardozo LD , Bachmann G , McClish D , et al. Meta-

analysis of oestrogen therapy in the management

of urogenital atrophy in postmenopausal women:

Second report of the Hormones and Urogenital

Therapy Committee . Obstet Gynaecol 1998 ; 92 :

722 – 727 .

137 . Suckling J, Lethaby A, Kennedy R. Local oes-

trogen for vaginal atrophy in postmenopausal

women. Cochrane Database Syst Rev 2003; (4):

CD001500.

138 . Judge TG . The use of quinestradol in elderly incon-

tinent women: A preliminary report . Gerontol Clin

1969 ; 11 : 159 – 164 .

139 . Walter S , Kjaergaard B , Lose G , et al. Stress urinary

incontinence in postmenopausal women treated

with oral oestrogen (oestriol) and an α -adrenocep-

tor stimulating agent (phenylpropanolamine): A

randomised double-blind placebo-controlled study .

Int. Urogynaecol. J . 1990 ; 1 : 74 – 79 .

Part III

Management of Stress Urinary

Incontinence

87

Introduction

In 1948, Kegel [1] was the first to report pelvic

floor muscle training (PFMT) to be effective in

treatment of female urinary incontinence. In spite

of his reports of cure rates of >84%, surgery soon

became the first choice of treatment, and not until

the 1980s was there renewed interest for conserva-

tive treatment. This new interest for conservative

treatment may have developed because of higher

awareness among women on incontinence and

health and fitness activities, cost of surgery, and

morbidity, complications, and relapses reported

after surgical procedures.

Today several consensus statements based on

systematic reviews have recommended conserva-

tive treatment and especially PFMT as the first

choice of treatment for stress urinary inconti-

nence (SUI) [2– 5] . However, many physicians

seem to be skeptical about PFMT. This skepti-

cism may be based on inadequate knowledge of

exercise science and physical therapy, and beliefs

that there is insufficient evidence for the effec-

tiveness of PFMT, that evidence for long-term

effects is lacking or poor, and that women are

not motivated to regularly perform PFMT. In this

chapter the focus will be to report evidence-based

knowledge on the above-mentioned points related

to PFMT for SUI.

Methods

This review is limited to the effect of physical

therapy on patients with a history of or urodynamic

SUI. Only outcomes from randomized controlled

trials (RCT) are included. Computerized search

on the PubMed, studies, data, and conclusions

from the two latest International Consultations on

Incontinence (ICI) [2, 5] , and the Cochrane Library

of systematic reviews [3, 4] have been used as

background sources. This overview will comprise

rehabilitation with PFMT with or without biofeed-

back or cones in addition to the use of electrical

stimulation.

Is PFMT Effective in Treatment

of Female SUI?

The gold standard research design to evaluate the

effect of an intervention (surgery, pharmaceutical,

training) is RCT. However, there are high- and low-

quality RCTs. High methodology quality is judged

on concealment of treatment allocation, blinding of

assessors, sufficient sample size (based on power

calculation if possible), use of reproducible and

valid outcome measurements, and handling of drop-

outs and low adherence (intention to treat analysis).

Chapter 7

Pelvic Floor Rehabilitation

Kari Bø

88 K . B ø

Equally important, but less written about in text-

books of statistics and research methodology, is

the quality of the intervention, e.g., surgery in the

hands of well-experienced surgeons or research-

based and high-quality conducted PFMT. A lot of

ineffective or even harmful treatments can be put

into a RCT of high-methodology quality. Herbert

and Bø [6] found that by adding studies with high

sample size but low training dosage and nonsu-

pervised training to smaller studies with adequate

training dosage in a meta-analysis, the effect size

may change dramatically in disfavor of high-qual-

ity smaller studies.

For PFMT studies there is an additional prob-

lem. Several research groups have shown that

>30% of women are not able to voluntarily contract

the pelvic floor muscles at their first consultation

even after thorough individual instruction [7– 10] .

Hay-Smith et al. [3] reported that only in 15 of

43 RCTs on the effect of PFMT for SUI, urge and

mixed incontinence, ability to contract was checked

before training started. A common mistake is to

strain instead of squeeze and lift. If women are

straining instead of performing a correct contrac-

tion, the training may harm and not improve pelvic

floor muscles (PFM) function.

The numerous reports by Kegel with >80%

cure rate comprised uncontrolled studies with the

inclusion of a variety of incontinence types and no

measurement of urinary leakage before and after

treatment. However, since then, several RCTs have

demonstrated that PFMT is more effective than

no treatment to treat SUI [11– 15] . In addition, a

number of RCTs have compared PFMT alone with

either the use of vaginal resistance devices, bio-

feedback, or vaginal cones [4] . Only one study did

not show any significant effect of PFMT on urinary

leakage [3] . Interestingly, in this study there was no

check of the women’s ability to contract, adherence

to the training protocol was poor, and the placebo

group contracted gluteal muscles and external

rotators of the hips; activities that may give co-

contractions of the PFM [16, 17] .

Improvement Rates

As for surgery [18] and pharmacology studies

[19] , a combination of cure and improvement

measures often is reported. To date there is no

consensus on what outcome measure to choose as

the gold standard for cure [urodynamic diagnosis,

no leakage episodes, ≤ 2 g of leakage on pad test

(tests with standardized bladder volume, 1, 24, and

48 h?), women’s report, etc.] [20] . Subjective cure/

improvement rates of PFMT including studies of

both SUI and mixed incontinence reported in RCTs

varies between 56 and 70% [3, 21] .

Cure Rates

It often is reported that PFMT is more commonly

associated with improvement of symptoms rather

than a total cure. However, in several RCTs cure

has been reported. In a study by Bø et al. [22]

cure rate was defined as conversion of negative to

positive closure pressure during cough and a cure

rate of 60% was found. This corresponded with

the number of women reporting to be continent or

almost continent. In newer RCTs short-term cure

rates of 44–70% defined as <2 g of leakage on

different pad tests has been found after PFMT [11,

13, 14, 23– 26] . The highest cure rate from PFMT

alone was shown in a single-blind RCT where the

female subjects had thorough individual instruc-

tion by a trained physical therapist (PT), combined

training with biofeedback, and close follow-up

once and every second week. The training period

lasted 6 months. Adherence was high and dropout

was low [25] . The third ICI meeting concludes

that PFMT should be offered as first-line therapy

to all women with stress, urge, or mixed urinary

incontinence [5] .

The Most Effective PFMT Program

Because of use of different outcome measures and

instruments to measure PFM function and strength,

it is impossible to combine results among studies

and it is difficult to conclude which training regi-

men is the more effective. Also the exercise dosage

(type of exercise, frequency, duration, and inten-

sity) varies significantly between studies [3, 5] .

Several research groups have found that either

more intensive training, more frequent training,

or supervised training is more effective than lower

dosage of training [22, 23, 27, 28] . Bø et al. com-

bined individual assessment and teaching of cor-

rect contraction with strength training in groups in

a 6-month training program [11, 22] . The women

were randomized to either an (1) intensive training

7. Pelvic Floor Rehabilitation 89

program consisting of seven individual sessions

with a PT, combined with 45 min weekly PFMT

classes, and three sets of 8–12 contractions per

day at home or (2) the same program without the

weekly intensive exercise classes ( Figs. 7.1 and

7.2 ). The results showed a much better improve-

ment in both muscle strength and urinary leak-

age in the intensive exercise group. Sixty percent

reported to be continent/almost continent in the

intensive exercise group compared to 17% in the

less intensive group. A significant reduction of

urinary leakage, measured by pad test with stand-

ardized bladder volume, was demonstrated only in

the intensive exercise group.

This study demonstrated that a huge differ-

ence in outcome can be expected according to the

intensity and follow-up of the training program

and very little effect can be expected after training

without close follow-up. It is worth noting that the

significantly less effective group in this study had

seven visits with a skilled PT and that adherence to

the home-training program was high. Nevertheless,

the effect was only 17%. There is a dose–response

issue in all sorts of training regimens [29] . Hence,

one reason for disappointing effects shown in some

clinical practices or research studies may be due to

insufficient training stimulus and low dosage [30] .

Furthermore, if low-dosage programs are chosen

as one arm in a RCT comparing PFMT with other

methods, PFMT is bound to be less effective. The

third ICI recommends that clinicians should pro-

vide the most intensively supervised PFMT pro-

gram possible within service constraints [5] .

PFMT with Biofeedback

Biofeedback has been defined as “a group of

experimental procedures where an external sensor

is used to give an indication on bodily processes,

usually in the purpose of changing the measured

quality” [31] . Biofeedback equipment has been

developed within the area of psychology, mainly

for measurement of sweating, heart rate, and blood

pressure during different forms of stress. Kegel

[1] always based his training protocol on thorough

instruction of correct contraction using vaginal

palpation and clinical observation. He combined

PFMT with use of vaginal squeeze pressure meas-

urement as biofeedback during exercise. Today, a

variety of biofeedback apparatuses are commonly

used in clinical practice to assist with PFMT.

In urology or urogynecology textbooks the term

“biofeedback” often is used to classify a method

different from PFMT. However, biofeedback is not

a treatment by itself. It is an adjunct to training,

measuring the response from a single PFM con-

traction. For PFMT, both vaginal and anal surface

electromyograms (EMG) and urethral and vaginal

squeeze pressure measurements have been used to

help make the patients more aware of muscle func-

tion and to enhance and motivate patients’ effort

during training [3] .

Since Kegel first presented his results, several

RCTs have shown that PFMT without biofeedback

is more effective than no treatment for SUI [3, 5] . In

women with stress or mixed incontinence, all but one

of RCTs have failed to show any additional effects

of adding biofeedback to the training protocol.

Fig. 7.1. Individual assessment of ability to contract

the pelvic floor muscles correctly is necessary to assure

effective training. Vaginal palpation is used to give direct

feedback to the patient about muscle performance

90 K . B ø

In the study of Glavind et al. [23] a positive effect

was demonstrated. However, this study was con-

founded by a difference in training frequency, and

the effect might be due to double-training dosage,

the use of biofeedback, or both. Hence, the results of

the above-mentioned study support the studies that

conclude there is a dose–response issue in PFMT

[22, 27, 28] .

Since PFMT is effective without biofeedback,

a large sample size may be needed to show any

beneficial effect of adding biofeedback to an effec-

tive training protocol. In most of the published

studies the sample sizes are small, and type II error

may have been the reason for negative findings.

However, in the two largest RCTs published, no

additional effects were demonstrated [3, 25] .

Many women may not like to undress, lock the

room, and insert a vaginal or rectal device in order

to exercise [32] . On the other hand, some women

find it motivating to use biofeedback to control and

enhance the strength of the contractions when train-

ing. Any factor that may stimulate high adherence

and intensive training should be recommended to

enhance the effect of a training program. Hence,

there is a place for biofeedback in PFMT.

PFMT with Vaginal Cones

Vaginal cones are weights that are put into the

vagina above the levator plate [4] . The theory

behind the use of cones in strength training is that

the PFM are contracted reflexively or voluntary

when the cone is perceived to slip out. The weight

of the cone is supposed to give a training stimulus

and make the women contract harder with progres-

sive weight ( Fig. 7.3 ). It has been concluded that

Fig. 7.2 . After individual instruction and assurance of ability to contract the pelvic floor muscles correctly, regular

strength training of the muscles can be done in groups. This may be more fun, motivating, and less time-consuming

for both the patients and the physical therapists. In between the pelvic floor muscle strength training, focus is on

other muscle groups such as the abdominals, back, arm, and thigh muscles. The program also comprises relaxation

and breathing exercise and practice on correct lifting techniques and ergonomics [11, 22]

Fig. 7.3. Vaginal weighted cones comes in different sizes

and shapes

7. Pelvic Floor Rehabilitation 91

training with vaginal cones is more effective than

no treatment [4] . Several RCTs have been found

comparing PFMT with and without vaginal cones

for SUI [11, 33– 36] . Bø et al. [11] found that

PFMT was significantly more effective than train-

ing with cones both to improve muscle strength and

to reduce urinary leakage. In the three other studies

there was no difference between PFMT with and

without cones [33– 35] . Cammu and Van Nylen

[34] reported very low compliance, and therefore

did not recommend use of cones. Bø et al. [11]

reported that women in the cones group reported

great motivational problems and Laycock et al.

[35] had a total dropout rate in their study of 33%.

The use of cones can be questioned from an

exercise science perspective. Holding the cone

for as long as 15–20 min as recommended might

cause decreased blood supply, decreased oxygen

consumption, muscle fatigue and pain, and recruit

contraction of other muscles instead of the PFM.

In addition, many women report that they dislike

using cones [34] . On the other hand, the cones may

add benefit to the training protocol if used in a dif-

ferent way. Arvonen et al. [36] used “vaginal balls”

and followed general strength training principles

with dynamic contractions. They found that train-

ing with the balls was significantly more effective

in reducing urinary leakage than regular PFMT.

Electrical Stimulation

The aim of electrical stimulation for SUI is to

strengthen the PFM mirroring voluntary contrac-

tions. Several consensus reports have concluded

that strength training is more effective than elec-

trical stimulation to increase muscle strength for

other skeletal muscles [37, 38] . In most physical

therapy practices, electrical stimulation has been

used for partially paralyzed muscles and to stimu-

late to activity when the patients were not able

to contract. As soon as the patient can contract

voluntarily, most PTs would stop using electri-

cal stimulation and continue with regular muscle

training. Surprisingly, in the area of PFM reha-

bilitation, there has been a great interest especially

among gynecologists and general practitioners to

treat urinary incontinence with electrical stimula-

tion alone. In one of the first studies in this area,

Eriksen et al. [39] used long-term stimulation (8 h a

day, usually during sleep, with 10 Hz) and showed

significant improvement in urodynamic parameters

and urinary leakage. However, the study design

was uncontrolled and unblinded.

Today there are several RCTs on the effect of

electrical stimulation on female SUI [5] . A number

of different currents, apparatus, and stimulation

regimens have been used. For SUI, short-term

stimulation applying 35–50 Hz has been used in

most of the studies. Electrical stimulation was

compared with sham or untreated control in six

studies for SUI. Henalla et al. [14] , Sand et al. [40] ,

and Yamanishi et al. [41] found a significant effect

compared to control or sham stimulation, while

Luber and Wolde Tsadik [42] , Brubaker et al. [43] ,

and Bø et al. [11] did not find significant effect. It

has been concluded that more studies are needed to

clarify whether electrical stimulation is effective in

treatment of female SUI [5] .

PFMT or Electrical Stimulation?

Hennalla et al. [14] and Bø et al. [11] found

that PFMT was significantly better than electrical

stimulation to treat SUI. Laycock and Jerwood [44]

and Hahn et al. [45] found no difference, and Smith

[46] found that electrical stimulation was signifi-

cantly better. In addition, several research groups

have found no effect of adding electrical stimula-

tion to PFMT [28, 47, 48] . Many of these studies

are flawed by small numbers of subjects, and future

RCTs with better methodological quality should be

repeated [5] . However, electrical stimulation has

shown to have side effects [40] and to be less toler-

able to women than PFMT [11] . In addition, Bø

and Talseth [49] found that voluntary PFM contrac-

tion increases urethral pressure significantly more

than electrical stimulation.

Adverse Effects of PFM Rehabilitation

Methods

Few, if any, adverse effects have been found after

PFMT [5] . The only reported adverse effect is from

Lagro-Jansson [50] where one woman reported

pain with exercise and three had an uncomfortable

feeling during the exercises. In other studies no

side effects have been found [11] .

Reported adverse effects after electrical stimula-

tion have been pain, discomfort, vaginal irritations

or infections, urinary tract infections, and diarrhea

[11, 40, 51] . In a Norwegian study of 3,100 women

who had used electrical stimulation 51% reported

92 K . B ø

one or more side effect [51] . The most common

side effects were soreness/local irritation (26%),

pain (20%), and psychological distress. Most of

the cases were mild. Reported adverse effects of

cones have been abdominal pain, vaginities, and

bleeding [11] .

Two Concepts of How and Why PFMT May

Work in Treatment of SUI

There are two main concepts of explaining how

PFMT may work for SUI [21] :

1 . Use of conscious cocontraction of the PFM with

increase in abdominal pressure . Precontractions

before increases in intra-abdominal pressures

have been part of PFMT in many physical

therapy practices for years [52] . Miller et al. [15]

showed that teaching women how to contract

and encourage them to contract before cough-

ing significantly reduced urinary leakage within

a week. They named the precontraction “the

Knack,” and there is evidence that the conscious

contraction can clamp the urethra [21] . However,

Bump et al. [10] showed that only 49% of

women were able to contract the PFM in a way

that effectively closed the urethra, and we do not

know the amount of strength necessary to close

the urethra.

2 . Strength training . Kegel [1] described his train-

ing program as a tightening up of the pelvic floor.

Strength training of the pelvic floor aims to build

up a permanently better structural support for

the bladder and urethra by lifting the anatomical

location of the pelvic floor to a higher position,

hypertrophying the muscle fibers, increasing

stiffness in the muscles and connective tissue,

and closing the levator hiatus. A strong structural

support (stiff pelvic floor) may prevent descent

of the bladder neck and urethra and close the ure-

thra during abrupt increase in intra-abdominal

pressure. There is some evidence in the litera-

ture showing such morphological changes after

PFMT, put so far only from noncontrolled trials

[21] .

The theoretical rationale will decide how the

therapist teaches PFMT. The literature shows that

only one research group has used the Knack only,

and very few researchers report the use of a com-

bination of strength training and the Knack. Most

of the protocols describe regular strength training

only. In continent subjects, the PFM contraction is

an automatic response without conscious voluntary

contraction before activity. In addition, conscious

precontractions are only possible before single

bouts of physical exertion (for instance, cough-

ing and sneezing). Nobody can run or dance over

a longer period of time and contract the PFM

voluntarily all the time. Therefore, the main goal

of PFMT is to build the muscles to improve stiff-

ness of the pelvic floor to avoid the occurrence

of descent. The following recommendations on

effective training to increase strength and muscle

volume is given by the American College of Sport

Sciences (ACSM) [53] :

1. Initial training: 8–12 repetition maximum (RM)

(close to maximum effort) 2–3 times a week.

2. Intermediate to advanced training: 1–12 RM in a

periodized fashion with heavy loading 4–5 times

a week.

Typically higher intensity (close to maximum

contraction) is recommended for maximizing

hypertrophy [53] . However, the authors state that

the recommendations should be viewed in the

context of the individual’s target goals, physical

capacity, and training status. Hence, optimally

PFMT should be based on a thorough evaluation of

the function of the PFM ( Fig. 7.4 .). In all RCTs on

PFMT to treat SUI the women have been encour-

aged to do everyday exercise.

Long-Term Effects of PFMT

Long-term effects of any exercise program cannot

be expected if the persons stop exercising. Several

studies have reported long-term effects of PFMT

[3] . However, usually women in the nontreat-

ment or less effective intervention groups have

gone on to receive treatment after cessation of the

study period. Follow-up data therefore usually are

reported for either all women or for only the group

with best effects. As for surgery [54] , there are

only a few long-term studies that include clinical

examination [55– 57] . Klarskov et al. [55] assessed

only a few of the women originally participating

in the study. Lagro-Janssen et al. [56] evaluated

88 out of 110 women with stress, urge, or mixed

incontinence 5 years after cessation of training,

and found that 67% remained satisfied with the

7. Pelvic Floor Rehabilitation 93

condition. Only 7of 110 had been treated with

surgery. Moreover, satisfaction was closely related

to adherence to training and type of incontinence,

with mixed incontinent women being more likely

to lose the effect. SUI women had the best long-

term effect, but only 39% of them were exercising

daily or “when needed.”

Cammu et al. [58] sent postal questionnaires and

evaluated medical files of 52 women who had par-

ticipated in an individual course of PFMT for uro-

dynamic SUI. Eighty-seven percent were suitable

for analysis. Thirty-three percent had had surgery

after 10 years. However, only 8% had undergone

surgery in the group originally being successful after

training, whereas 62% had undergone surgery in the

group initially dissatisfied with training. Successful

results were maintained after 10 years in two thirds

of the patients originally classified as successful.

In a 5-year follow-up, Bø and Talseth [57] found

that urinary leakage was significantly increased

after cessation of organized training. Three of

23 had been treated with surgery. Two of these

women who had not been cured after the initial

training, were satisfied with their surgery, and had

no leakage on pad test. The third women had been

cured after initial PFMT. However, after 1 year

she stopped training because of personal problems

connected to the death of her husband. Her incon-

tinence problems returned and she had surgery 2

years before the 5-year follow-up. She was not

satisfied with the outcome after surgery and had

visible leakage on cough test and 17 g of leakage

on the pad test. Fifty-six percent of the women

had a positive closure pressure during cough and

70% had no visible leakage during cough at 5-year

follow-up. Seventy percent of the patients were

still satisfied with the results and did not want

other treatment options. However, following up the

same patients with questionnaires 15 years after

cessation of organized training, the short-term sig-

nificant effect of intensive training was no longer

present [59] . Fifty percent from both groups had

interval surgery for SUI; however, more women in

the less intensive training group had surgery within

the first 5 years after ending the training program.

At 15 years follow-up there were no differences in

reported frequency or amount of leakage between

nonoperated and operated women, but women who

had surgery reported significantly more severe

leakage and to be more bothered by urinary incon-

tinence during daily activities than those who did

not have surgery.

The general recommendations for maintaining

muscle strength are one set of 8–12 contractions

Fig. 7.4. Measurement of pelvic floor muscle function is important when teaching pelvic floor muscle training. There

are different apparatuses available commercially. Ideally, all apparatuses should be tested for responsiveness, reliabil-

ity, and validity before use. The picture shows Camtech squeezemeter (Camtech AS, Sandvika, Norway)

94 K . B ø

twice a week [60] . The intensity of the contrac-

tion seems to be more important than frequency

of training. So far, no studies have evaluated how

many contractions subjects have to perform to

maintain PFM strength after cessation of organized

training. In the study of Bø and Talseth [57] PFM

strength was maintained 5 years after cessation of

organized training, with 70% exercising more than

once a week. However, number and intensity of

exercises varied considerably among successful

women [61] . One series of 8–12 contractions easily

could be taught in aerobic dance classes or recom-

mended as part of women’s general strength train-

ing programs. On the other hand, we do not know

how a voluntary precontraction before increase in

intra-abdominal pressure will maintain or increase

muscle strength. In the study of Cammu et al. [58]

the long-term effect of PFMT appeared to be attrib-

uted to the precontraction before sudden increases

in intra-abdominal pressure and not so much to

regular strength training. Unfortunately, muscle

strength was not measured in their study.

PFMT in Prevention of SUI

Only a few RCTs have been found to prevent

urinary incontinence and in some of the studies

women with symptoms or diagnoses of SUI, urge,

and mixed incontinence have been included. As far

as this author has ascertained there are no primary

prevention studies in the general population using

PFMT for nonsymptomatic women to avoid the

occurrence of SUI sometime in the future [5] . The

focus of most of the prevention studies has been

to evaluate the effect of PFMT during pregnancy

and after childbirth. Four RCTs have been found

that assess the effect of PFMT during pregnancy

( Fig. 7.5 ). Sampselle et al. [62] found significantly

less incontinence symptoms in the PFMT group

at 6 weeks and 6 months postpartum. However,

the effect was no longer present at 12 months

postpartum. Huges et al. [63] did not find any

effect of only one session of physical therapy to

prevent urinary leakage during pregnancy. On the

other hand, Reilly et al. [64] found a significant

reduction in the prevalence of urinary leakage in

a group of primigravida women with bladder neck

mobility, and Mørkved et al. [65] found significant

reduction in the prevalence of urinary leakage after

18 weeks of supervised group training combined

with home exercise.

Three RCTs and one matched controlled trial

have been found that evaluate the effect of postpar-

tum PFMT. Sleep and Grant [66] did not find any

effect of midwives counseling postpartum women

to perform PFMT. However, Mørkved and Bø [67] ,

Meyer et al. [68] , and Chiarelli and Cochburn [69]

found significant reduction of urinary incontinence

in favor of PFMT. In the matched controlled trial

of Mørkved and Bø [67] a 50% reduction in preva-

lence was found in the training group. Hence, there

is evidence from high-quality RCTs to recommend

PFMT both antenatally and postpartum.

Fig. 7.5. Since randomized controlled trials have dem-

onstrated effects on reducing and preventing urinary

incontinence during pregnancy and after childbirth,

strength training of the pelvic floor muscles should start

antenatally. Much important general information about

health issues during pregnancy and after childbirth can

be discussed in the class

7. Pelvic Floor Rehabilitation 95

Motivation

Some women may find the exercises difficult to

conduct on a regular basis [70] . However, when

analyzing results of RCTs, adherence to the exer-

cise program is generally high and dropout rate is

low [3, 5] . In a few studies low adherence and high

dropout rates have been reported [35, 71] . The

PTs knowledge about behavioral sciences such as

pedagogy and health psychology and their ability

to explain and motivate patients may be a crucial

factor to enhance adherence and minimize drop-

outs from training. In some studies such strategies

have been followed, and high adherence has been

achieved [70, 72] . In other studies specific strate-

gies have not been reported, but much emphasis

has been put on creating a positive, enjoyable, and

supportive training environment. Group training

after thorough individual instruction may be a good

concept if led by a skilled and motivating therapist

[11, 22] . PFMT concepts with 0 dropouts [73] and

adherence >90% [11] are possible. In a study by

Alewijnse [70] most women followed the adviceto

train four to six times a week 1 year after cessation

of the training program. The following factors pre-

dicted adherence with 50%: positive intention to

adhere, high short-term adherence levels, positive

self-efficacy expectations, and frequent weekly

episodes of leakage before and after initial therapy.

Patients do not comply with treatment for a wide variety

of reasons: long-lasting and time-consuming treat-

ments, requirement of lifestyle changes, poor client/

patient interaction, cultural and health beliefs, poor

social support, inconvenience, lack of time, motiva-

tional problems, and travel time to clinics have been

listed as important factors [74] .

In a Japanize study, Sugaya et al. [75] used a com-

puterized pocket-size device that emits a sound three

times a day to remind the person to perform PFMT.

To stop the sound the person needed to push a but-

ton, and by pushing the button for each contraction,

adherence was registered. Forty-six women were

randomly assigned to either instruction to contract

the PFM following a pamphlet or the same pam-

phlet together with the sound device and instruction

in how to use the device. Interestingly, the results

showed a significant improvement in daily inconti-

nence episodes and pad test only in the device group.

Forty-eight percent were satisfied in the device group

compared to 15% in the control group.

In most countries patients receive physical ther-

apy on physicians’ referrals only. This means that

the motivation of the general practitioner, gynecolo-

gist, or urologist for PFMT and conservative treat-

ment is extremely important. If these professions

are not updated on the effect of PFMT, do not know

any trained PTs in their area, or think PFMT is bor-

ing and a big demand, the patients may not even be

introduced to the option of training. PFMT can be

put forward either as a “boring demanding task you

need to do the rest of your life” or it can be intro-

duced as a method that is “easy, at a low cost and

with no side effects. It may take less than 10 min per

day to build up strength if it is conducted correctly

(three sets of 8–12 contractions a day), and it takes

even less to maintain it.” The number of PTs spe-

cializing in women’s health and pelvic floor issues

vary among countries. In order to recruit more PTs

into the area, it may be important to advocate for a

mandatory curriculum on pelvic floor dysfunction

and treatment at undergraduate education level, add

courses on postgraduate level, and stimulate urolo-

gists to participate in the teaching of PTs.

Is PFMT Effective only for the Young

and Those with Minor Leakage?

Several researchers have looked into factors affect-

ing outcome of PFMT on urinary incontinence

[5] . No single factor has been shown to predict

outcome, and it has been concluded that many fac-

tors traditionally supposed to affect outcomes such

as age and severity of incontinence may be less

crucial than previously thought. Factors that appear

to be most associated with positive outcome are

thorough teaching of correct contraction, motiva-

tion, adherence with the intervention, and intensity

of the program [5] .

Conclusion

RCT and systematic reviews have shown that

PFMT with or without biofeedback or cones has

proved to be effective in the treatment of female

SUI. There is increasing evidence that PFMT

can prevent urinary incontinence when performed

antenatally and postpartum. Compared to surgery

PFMT has no known side effects and is relatively

inexpensive, and women should be motivated to

96 K . B ø

intensively perform PFMT as first-line treatment.

However, more than 30% do not contract correctly

at their first consultation, and thorough individual

instruction is needed. Manual techniques and elec-

trical stimulation may be used to teach how to

contract. Three sets of 8–12 close to maximum

contractions every day or every second day is

recommended based on general strength training

theory and results of high-quality RCTs. In addi-

tion, the women should learn to precontract before

increase in intra-abdominal pressure.

Most women need motivation and encourage-

ment to perform regular strength training. This

can be achieved in individual training sessions or

in specifically designed PFMT classes. When suf-

ficient function has been achieved, PFM strength

has to be maintained by ongoing training but with

lower frequency. More research is needed to find

out how much exercise is needed to improve and

maintain optimal PFM function and whether the

effect is attributed to a conscious precontraction,

the building up of a firm structural support giving

automatic cocontractions, or a combination. There

is a need for better collaboration between physi-

cians and PTs to organize a better health service

for SUI patients and for planning of future high-

quality clinical trials.

References

1 . Kegel AH . Progressive resistance exercise in the

functional restoration of the perineal muscles . Am J

Obstet Gynecol 1948 ; 56 : 238 – 249 .

2 . Wilson PD , Bø KH-SJ , Nygaard I , et-al. Conservative

treatment in women. In: Abrams P , Cardozo L ,

Khoury S , Wein A , eds . Incontinence . Plymouth :

Plymbridge, Health Publication, 2002 : 571 – 624 .

3 . Hay-Smith E , Bø K , Berghmans L , et al. Pelvic floor

muscle training for urinary incontinence in women

(Cochrane review).[3] . Oxford, UK : The Cochrane

Library , 2001.

4 . Herbison P , Plevnik S , Mantle J . Weighted vaginal

cones for urinary incontinence . Oxford, UK : The

Cochrane Library , 2000 ; 1 – 24 .

5 . Wilson PD , Berghmans B , Hagen S , et al. Adult conserv-

ative management. In: Abrams P , Cardozo L , Khoury S ,

Wein A , eds. Incontinence, Vol 2, Management . Paris :

Health Publications 2005 : 855 – 964

6 . Herbert RD , Bø K . Analysis of quality of interventions

in systematic reviews. BMJ 2005 ; 331 : 507 – 509 .

7 . Kegel AH . Stress incontinence and genital relaxa-

tion . Ciba Clin Symp 1952 ; 2 : 35 – 51 .

8 . Benvenuti F , Caputo GM , Bandinelli S , et al.

Reeducative treatment of female genuine stress

incontinence. Am J Phys Med 1987 ; 66 (4) : 155 – 168 .

9 . Bø K , Larsen S , Oseid S , et al. Knowledge about

and ability to correct pelvic floor muscle exercises in

women with urinary stress incontinence . Neurourol

Urodyn 1988 ; 7 (3) : 261 – 262 .

10 . Bump R , Hurt WG , Fantl JA , et al. Assessment of

Kegel exercise performance after brief verbal instruc-

tion . Am J Obstet Gynecol 1991 ; 165 : 322 – 329 .

11 . Bø K , Talseth T , Holme I . Single blind, randomised

controlled trial of pelvic floor exercises, electrical

stimulation, vaginal cones, and no treatment in man-

agement of genuine stress incontinence in women .

BMJ 1999 ; 318 : 487 – 493 .

12 . Lagro-Janssen TLM , Debruyne FMJ , Smits AJA ,

et al. Controlled trial of pelvic exercises in the treat-

ment of urinary stress incontinence in general prac-

tice . Br J Gen Pract 1991 ; 41 : 445 – 449 .

13 . Henalla S , Millar D , Wallace K . Surgical versus con-

servative management for post-menopausal genuine

stress incontinence of urine . Neurourol Urodyn

1990 ; 9 (4) : 436 – 437 .

14 . Henalla SM , Hutchins CJ , Robinson P , et al. Non-

operative methods in the treatment of female genuine

stress incontinence of urine . J Obstet Gynaecol 1989 ;

9 : 222 – 225 .

15 . Miller JM , Ashton-Miller JA , DeLancey J . A pel-

vic muscle precontraction can reduce cough-related

urine loss in selected women with mild SUI . J Am

Geriatr Soc 1998 ; 46 : 870 – 874 .

16 . Bø K , Kvarstein B , Hagen R , et al. Pelvic floor mus-

cle exercise for the treatment of female stress urinary

incontinence: II. Validity of vaginal pressure measure-

ments of pelvic floor muscle strength and the neces-

sity of supplementary methods for control of correct

contraction. Neurourol Urodyn 1990 ; 9 : 479 – 487.

17 . Peschers U , Gingelmaier A , Jundt K , et al. Evaluation

of pelvic floor muscle strength using four different

techniques . Int Urogynecol J 2001 ; 12 : 27 – 30 .

18 . Smith T , Daneshgari F , Dmochowski R , et al. Surgical

treatment of incontinence in women. In : Abrams P ,

Cardozo L , Khoury S , Wein A , eds. Incontinence .

Plymouth, UK : Plymbridge Distributors , 2002 :

823 – 863 .

19 . Andersson K , Appell R , Awad S , et al. Pharmacological

treatment of urinary incontinence. In: Abrams P ,

Cardozo L , Khoury S , Wein A , eds. Incontinence .

Plymouth : Plymbridge Distributors , 2002 : 479 – 511 .

20 . Blaivas JG , Appell RA , Fantl JA , et al. Standards

of efficacy for evaluation of treatment outcomes in

7. Pelvic Floor Rehabilitation 97

urinary incontinence: Recommendations of the urody-

namic society . Neurourol Urodyn 1997 ; 16 (145) : 147 .

21 . Bø K . Pelvic floor muscle training is effective in treat-

ment of female stress urinary incontinence, but how

does it work? Int Urogynecol J 2004 ; 15 : 76 – 84 .

22 . Bø K , Hagen RH , Kvarstein B , et al. Pelvic floor

muscle exercise for the treatment of female stress

urinary incontinence: III. Effects of two different

degrees of pelvic floor muscle exercise. Neurourol

Urodyn 1990 ; 9 : 489 – 502.

23 . Glavind K , Laursen B , Jaquet A . Efficacy of biofeed-

back in the treatment of urinary stress incontinence .

Int Urogyn J 1998 ; 9 : 151 – 153 .

24 . Wong K , Fung B , Fung , et al. Pelvic floor exercises

in the treatment of stress urinary incontinence in

Hong Kong chinese women. Papers to be read by

title, ICS 27th annual Meeting, Yokohama , Japan ,

1997 : 62 – 63 .

25 . Mørkved S , Bø K , Fjørtoft T . Is there any additional

effect of adding biofeedback to pelvic floor muscle

training? A single-blind randomized controlled trial .

Obstet Gynecol 2002 ; 100 (4) : 730 – 739 .

26 . Dumoulin C , Lemieux M , Bourbonnais D , et al.

Physiotherapy for persistent postnatal stress urinary

incontinence: A randomized controlled trial . Obstet

Gynecol 2004 ; 104 : 504 – 510 .

27 . Wilson PD , Samarrai TAL , Deakin M , et al. An

objective assessment of physiotherapy for female

genuine stress incontinence . Br J Obstet Gynaecol

1987 ; 94 : 575 – 582 .

28 . Goode PS , Burgio KL , Locher JL , et al. Effect of

behavioral training with or without pelvic floor elec-

trical stimulation on stress incontinence in women .

JAMA 2003 ; 290 (3) : 345 – 352 .

29 . Bouchard C , Shephard RJ , Stephens T . Physical

activity, fitness, and health. International procedings

and consensus statement . 1st ed . Champaign : Human

Kinetics Publishers , 1994 .

30 . Bø K . Pelvic floor muscle exercise for the treatment

of stress urinary incontinence. An exercise physiol-

ogy perspective . Int Urogynecol J 1995 ; 6 : 282 – 291.

31 . Schwartz G , Beatty J . Biofeedback: Theory and

research . New York : Academic Press , 1977 .

32 . Prashar S , Simons A , Bryant C , et al. Attitudes to

vaginal touching and device placement in women with

urinary incontinence . Int Urogynecol J 2000 ; 11 : 4 – 8 .

33 . Pieber D , Zivkovic F , Tamussino K . Beckenbod-

engymnastik allein oder mit Vaginalkonen bei pra-

menopausalen Frauen mit milder und massiger

Stressharninkontinenz . Gynecol Geburtshilfliche

Rundsch 1994 ; 34 : 32 – 33 .

34 . Cammu H , Van Nylen M . Pelvic floor exercises ver-

sus vaginal weight cones in genuine stress incon-

tinence . Eur J Obstet Gynecol Reprod Biol 1998 ;

77 : 89 – 93 .

35 . Laycock J , Brown J , Cusack C , et al. Pelvic floor

reeducation for stress incontinence: Comparing three

methods . Br J Commun Nurs 2001 ; 6 (5) : 230 – 237 .

36 . Arvonen T , Fianu-Jonasson A , Tyni-Lenne R .

Effectiveness of two conservative modes of physical

therapy in women with urinary stress incontinence .

Neurourol Urodyn 2001 ; 20 : 591 – 599 .

37 . Dudley GA , Harris RT . Use of electrical stimula-

tion in strength and power training. In: Komi PV ,

ed. Strength and power in sport. Oxford : Blackwell

Scientific Publications , 1992 : 329 – 337 .

38 . Vuori I , Wilmore JH . Physical activity, fitness, and

health: Status and determinants. In: Bouchard C ,

Shephard RJ , Stephens T , eds. Physical activity, fit-

ness and health. Consensus statement. Champaign :

Human Kinetics Publishers , 1993 : 33 – 40 .

39 . Eriksen B , Eik-Nes SH . Long-term electrostimula-

tion of the pelvic floor: Primary therapy in female

stress incontinence? Urol Int 1989 ; 44 : 90 – 95 .

40 . Sand PK , Richardson DR , Staskin SE , et al. Pelvic

floor stimulation in the treatment of genuine stress

incontinence: A multicenter placebo-controlled trial .

Am J Obstet Gynecol 1995 ; 173 : 72 – 79 .

41 . Yamanishi T , Yasuda K , Sakakibara R . Pelvic floor

electrical stimulation in the treatment of stress inconti-

nence: An investigational study and a placebo control-

led double-blind trial . J Urol 1997 ; 158 : 2127 – 2131 .

42 . Luber KM , Wolde-Tsadik G . Efficacy of func-

tional electrical stimulation in treating genuine stress

incontinence: A randomized clinical trial . Neurourol

Urodyn 1997 ; 16 : 543 – 551 .

43 . Brubaker L , Benson JT , Bent A , et al. Transvaginal

electrical stimulation for female urinary inconti-

nence . Am J Obstet Gynecol 1997 ; 177 : 536 – 540 .

44 . Laycock J , Jerwood D . Does pre-modulated inter-

ferential therapy cure genuine stress incontinence?

Physiotherapy 1996 ; 79 (8) : 553 – 560 .

45 . Hahn I , Sommar S , Fall M . A comparative study of

pelvic floor training and electrical stimulation for

treatment of genuine female stress urinary inconti-

nence . Neurourol Urodyn 1991 ; 10 : 545 – 554 .

46 . Smith JJ . Intravaginal stimulation randomized trial .

J Urol 1996 ; 155 : 127 – 130 .

47 . Knight S , Laycock J , Naylor D . Evaluation of neu-

romuscular electrical stimulation in the treatment of

genuine stress incontinence . Physiotherapy 1998 ;

84 (2) : 61 – 71 .

48 . Bidmead J , Mantle J , Cardozo L , et al. Home electri-

cal stimulation in addition to pelvic floor exercises .

A useful adjunct or expensive distraction? Neurourol

Urodyn 2002 ; 21 (4) : 372 – 373

98 K . B ø

49 . Bo K , Talseth T . Change in urethral pressure during

voluntary pelvic floor muscle contraction and vagi-

nal electrical stimulation . Int Urogyn J 1997 ; 8 : 3 – 7 .

50 . Lagro-Janssen A , Debruyne F , Smiths A , et al. The

effects of treatment of urinary incontinence in gen-

eral practice . Fam Pract 1992 ; 9 (3) : 284 – 289 .

51 . Indrekvam S , Hunskaar S . Side-effects, feasabil-

ity, and adherence to treatment during home-man-

aged electrical stimulation for urinary incontinence:

A Norwegian national cohort of 3198 women .

Neurourol Urodyn 2002 ; 21 : 546 – 552 .

52 . Mantle J . Physiotherapy for incontinence. In: Cardozo

L , Staskin D , eds. Textbook of female urology and

urogynecology. London : Isis Medical Media , 2001 :

351 – 358.

53 . Kraemer J , Adams , K , Cafarelli E , et al. Progression

models in resistance training for healthy adults.

American College of Sport Medicine. Position Stand.

Med Sci Sports Exerc 2002 ; 34 (2) : 364 – 380 .

54 . Black NA , Downs SH . The effectiveness of surgery

for stress incontinence in women: A systematic

review . Br J Urol 1996 ; 78 (497) : 510 .

55 . Klarskov P , Nielsen KK , Kromann-Andersen B ,

Maegaard E . Long-term results of pelvic floor

training for female genuine stress incontinence . Int

Urogynecol J 1991 ; 2 : 132 – 135 .

56 . Lagro-Janssen T , van Weel C . Long-term effect of

treatment of female incontinence in general practice .

Br J Gen Pract 1998 ; 48 : 1735 – 1738 .

57 . Bø K , Talseth T . Long term effect of pelvic floor

muscle exercise five years after cessation of organ-

ized training . Obstet Gynecol 1996 ; 87 (2) : 261 – 265 .

58 . Cammu H , Van Nylen M , Amy J . A ten-year

follow-up after Kegel pelvic floor muscle exercises

for genuine stress incontinence . BJU Int 2000 ;

85 : 655 – 658 .

59 . Bø K , Kvarstein B , Nygaard I . Lower urinary tract

symptoms and pelvic floor muscle exercise adher-

ence after 15 years . Obstet Gynecol 2005 , 105 : 999 –

1005.

60 . Pollock ML , Gaesser GA , Butcher JD , et al. The

recommeneded quantity and quality of exercise for

developing and maintaining cardiorespiratory and

muscular fitness, and flexibility in healthy adults .

Med Sci Sports Exerc 1998 ; 30 (6) : 975 – 991 .

61 . Bø K . Adherence to pelvic floor muscle exercise and

long term effect on stress urinary incontinence. A

five year follow up. Scand J Med Sci Sports 1995 ;

5 : 36 – 39 .

62 . Sampselle CM , Miller JM , Mims BL , et al. Effect of

pelvic muscle exercise on transient incontinence dur-

ing pregnancy and after birth . Obstet Gynecol 1998 ;

91 (3) : 406 – 412 .

63 . Hughes P , Jackson S , Smith P , et al. Can antenatal

pelvic floor exercises prevent postnatal incontinence .

Neurourol Urodyn 2001 ; 20 (4) : 447 – 448 .

64 . Reilly E , Freeman R , Waterfield M , et al. Prevention

of postpartum stress incontinence in primigravidae

with increased bladder neck mobility: A randomised

controlled trial of antenatal pelvic floor exercises .

BJOG 2002 ; 109 : 68 – 76 .

65 . Mørkved S , Bø K , Schei B , et al. Pelvic floor muscle

training during pregnancy to prevent urinary incon-

tinence: A single blind randomized controlled trial .

Obstet Gynecol 2003 ; 101 : 313 – 319 .

66 . Sleep J , Grant A . Pelvic floor exercises in postnatal

care . Midwifery 1987 ; 3 : 158 – 164 .

67 . Mørkved S , Bø K . The effect of postpartum pelvic

floor muscle exercise in the prevention and treat-

ment of urinary incontinence . Int Urogynecol J 1997 ;

8 : 217 – 222 .

68 . Meyer S , Hohlfield P , Achtari C , et al. Pelvic floor

education after vaginal delivery . Obstet Gynecol

2001 ; 97 : 673 – 677 .

69. Chiarelli P, Cockburn J. Promoting urinary conti-

nence in women after delivery: Randomised control-

led tiral. BMJ 2002; (324):1241–1246.

70. Alewijnse D. Urinary incontinence in women. Long

term outcome of pelvic floor muscle exercise therapy.

Maastricht Health Research Institute for Prevention

and Care/Department of Health Education and Health

Promotion. Doctoral thesis, 2002.

71 . Ramsey IN , Thou M . A randomized, double blind,

placebo controlled trial of pelvic floor exercise in the

treatment of genuine stress incontinence . Neurourol

Urodyn 1990 ; 9 (4) : 398 – 399 .

72. Chiarelli P, Cockburn J. Promoting urinary conti-

nence in women after delivery: Randomised control-

led trial. BMJ 2002, (324):1241.

73 . Berghmans LCM , Frederiks CMA , deBie RA , et al.

Efficacy of biofeedback, when included with pelvic

floor muscle exercise treatment, for genuine stress

incontinence . Neurourol Urodyn 1997 ; 15 : 37 – 52 .

74 . Paddison K . Complying with pelvic floor exercises:

A literature review . Nurs Stand 2002 ; 16 (39) : 33 – 38 .

75. Sugaya K , Owan T , Hatano T , et al. 2003 Device to

promote pelvic floor muscle training for stress incon-

tinence. Int J Urol 10 : 416 – 422.

99

Introduction

Stress urinary incontinence (SUI) is a very common

condition that affects an average of 49% (24–75%)

of incontinent women between 18 and 90 years of

age [1] . SUI incontinence is much less common in

men than in women by a 1:2 ratio, ranging from 2

to 39% with advancing age [2] .

Although it is not a life-threatening condition, SUI

may produce a considerable impact on female qual-

ity of life. Treatment of SUI is indicated if it begins

to affect the sufferer’s quality of life and if the symp-

tom cannot be properly managed by an increase of

voluntary micturition or reduction of physical activ-

ity. Possible therapies range from absorbent pads

and pelvic floor muscles training (PFMT) to several

drugs, devices, and surgical procedures. Various

drugs, including estrogens, α -adrenoceptor agonists,

β -adrenoceptor agonists, and tricyclic antidepres-

sants have been used off label. With the advent of

new targets and drugs with a different mechanism

of action, pharmacological treatment of SUI is cur-

rently regaining interest.

There are several factors involved in the patho-

genesis of SUI including the urethral support, the

bladder neck function, and the function of the mus-

cles of the urethra and pelvic floor [3] . As women

with SUI have lower resting urethral pressures than

age-matched continent women [4, 5] , it appears

likely that there is a reduced urethral closure pres-

sure in most women with SUI. Consequently,

it seems logical to increase urethral pressure in

order to improve continence. Urethral closure is

the result of several contributing factors, including

tone of urethral smooth and striated muscle and

passive properties of the vasculature of urethral

lamina propria. Although the relative contribution

of each of these factors to intraurethral pressure is

not fully understood, there is ample pharmacologi-

cal evidence that a substantial part of urethral tone

is mediated through stimulation of a -adrenoceptors

in the urethral smooth muscle by release of nore-

pinephrine. Lack of estrogens, mainly in elderly

women, may be another contributing factor pro-

moting a lack of mucosal function [6] .

Pharmacotherapies for SUI aim to increase intra-

urethral closure forces by increasing tone in the

urethral smooth and striated muscles. Several drugs

may contribute to achievement of this goal, but

limited efficacy or side effects often have limited

their clinical use.

Hormonal Therapy

In postmenopausal women, hormone replacement

therapy (HRT) is thought to increase the urethral

closure pressure, to raise the sensory threshold of

the bladder and urethra, and to increase the number

of epithelial cells lining the bladder and urethra [7] .

It also has been observed that estrogens increase

the response to α -adrenoceptor agonists by increas-

ing the number of α -adrenoceptors in an animal

model [8, 9] . A symptomatic or clinical improve-

ment has been observed in nonrandomized studies,

but the actual role of HRT in the management of

Chapter 8

Pharmacotherapy of Stress Urinary

Incontinence

David Castro-Diaz and Sergio Fumero

100 D. Castro-Diaz and S. Fumero

SUI has not been established. There is a lack of

well-designed, randomized placebo-controlled tri-

als documenting a benefit of HRT therapy among

women with SUI. In a recent analysis of 28 clinical

trials including 2,926 women with SUI or urge uri-

nary incontinence (UUI) using varying combina-

tion of estrogens, dosages, duration of treatments,

and length of follow-up, little benefit of estrogens

for SUI was found [10] .

In the 4-year follow-up of the Heart and Estrogen/

Progestin Replacement Study, 1,525 postmenopausal

women were randomized to either daily oral estrogen

plus progestogen therapy or placebo. Overall, daily

doses of oral estrogen plus progestogen therapy were

associated with worsening urinary incontinence. The

authors suggested that the beneficial effect of estro-

gen-only is negated by the addition of progestogens

to the regimen [11] . In addition, there is new evidence

suggesting that long-term estrogen/progestogen

increases the risk of stroke, heart attack, and ovarian

cancer, making this therapeutic modality much less

attractive [12] . At the International Consultation on

Incontinence it was agreed to recommend estrogens

as an optional therapy (grade of recommendation:

C) as there was no evidence of good quality that

showed a benefit for the treatment of SUI [6] . A

recent multicenter double-blind, placebo-controlled,

randomized clinical trial of menopausal hormone

therapy, which included 27,347 women, showed that

the use of estrogens alone or in combination with

progestin was associated with an increased risk for

urinary incontinence among continent women and

worsening of characteristics of urinary incontinence

among symptomatic women. The authors concluded

that estrogens alone or in combination with progestin

should not be prescribed for the prevention or relief

of urinary incontinence [13] . In spite of their known

effects on urethral pressure in the animal model

and those trophic effects on the urethral epithelium,

estrogens play little, if any, role in the treatment of

SUI. Estrogen therapy may be more effective in

improving irritative symptoms of urinary urgency,

frequency, and urgency incontinence.

α -Adrenoceptor Agonists

α -Adrenoceptor agonists have been widely used

for SUI treatment because they effectively increase

bladder outlet resistance during bladder filling in

animal models [14] . They have been found to be

effective for SUI in both open-label and controlled

clinical trials [15– 17] . These drugs also have been

used in combination with estrogens and conserva-

tive therapies such as pelvic floor exercises and

electrical stimulation; nevertheless, there is a lack

of long-term, randomized controlled clinical trials

[18] . Phenylpropanolamine was withdrawn from

the US market by the FDA because of the risk of

hemorrhagic stroke in women [19] . Furthermore,

α -adrenoceptor agonists lack exclusive selectiv-

ity for urethral α -adrenoceptors and may cause

elevated blood pressure, sleep disturbances, nau-

sea, dry mouth, headache, tremor, palpitations, and

exacerbation of abnormal cardiac rhythms [20] .

Midodrine is another a -adrenoceptor agonist

prescribed mainly for orthostatic hypotension,

which has been used for the treatment of SUI in

some countries. However, in a randomized, double-

blind, placebo-controlled multicenter study in 80

women with SUI, midodrine did not significantly

improve urodynamic measures [21] . Methoxamine

is a similar α -adrenoceptor agonist that was studied

in a placebo-controlled crossover trial. No signifi-

cant increases in maximum urethral pressure com-

pared with placebo were observed. Furthermore,

all patients experienced systemic adverse effects,

including piloerection, headache, and cold extremi-

ties. The investigators suggested that the clinical

usefulness of direct, peripherally acting selective

α 1 -adrenoceptor agonists in the treatment of SUI

may be limited by adverse effects [22] .

Ro 115–1240 is a new selective α 1A/1L -adren-

oceptor partial antagonist known to produce a

maximal increase in urethral tension at doses that

had no effect on blood pressure [23] . In a rand-

omized, crossover study in women with SUI, Ro

115–1240 was associated with a significantly lower

mean weekly number of SUI episodes than placebo

(8.4 vs. 6.0: P = 0.0079), a 28% relative improve-

ment over placebo. There also was a significantly

lower mean number of pads used and wet pads

changed/week with Ro 115–240 than with placebo

( P = 0.0055 and 0.0066, respectively). Treatment-

emergent adverse events were transient and mild to

moderate in intensity. There were no cardiovascu-

lar effects or clinically significant changes in elec-

trocardiograms or laboratory tests [24] . However,

another phase II trial did not achieve the same level

as seen in the earlier study; furthermore, studies on

8. Pharmacotherapy of Stress Urinary Incontinence 101

the rat showed some carcinogenic effects. For these

reasons the manufacturing company decided to dis-

continue the development of this compound [25] .

β -Adrenoceptor Antagonists

The theoretical basis for the use of β -adrenoceptor

antagonists in the treatment of SUI is that blockade

of urethral β -adrenoceptors may enhance the effects

of norepinephrine on urethral β -adrenoceptors.

Although it has been suggested that propranolol

might promote some improvement in patients with

SUI [26] , there are no randomized controlled trials

demonstrating such effect. In addition, although

it has been suggested that the use of these com-

pounds might be an alternative to a -adrenoceptor

agonists in hypertensive patients with SUI, these

agents have major potential cardiac and pulmonary

side effects that limit their utility [6] .

β -Adrenoceptor Agonists

β -Adrenoceptor agonists are indicated as bron-

chodilators in the treatment of asthma. It has been

suggested that β 2 -adrenoceptor agonists, such as

clenbuterol, which initially was developed as a

bronchodilator, may increase the contractility of

the urethral striated sphincter by releasing acetyl-

choline at the neuromuscular junction [27] . In a

placebo-controlled, double-blind trial, clenbuterol

produced clinically significant improvement and

an increase in mean maximal urethral closure pres-

sure in 165 women with SUI [28] . Seventy-three

percent of women in the clenbuterol arm showed

significant improvement versus 55% of significant

improvement in the placebo arm. In a 12-week

randomized trial, clenbuterol was compared with

pelvic floor exercises and a combination of both in

61 female patients with SUI [27] . The frequency of

SUI episodes, the volume of each leakage, and the

patient’s own impression were the outcome vari-

ables. Clenbuterol alone improved incontinence in

76.9% of patients, pelvic floor exercises in 52.6%,

and the combination of both therapies improved

incontinence in 89.5% of patients. Adverse effects

of clenbuterol included tremors, tachycardia, and

headache. In spite of these promising results, to

date, there have no been good studies documenting

the effects of clenbuterol as a potential treatment

for SUI. Consequently, there is a need of well-

designed, randomized placebo-controlled trials in

order to study the actual applicability of these

agents for the treatment of SUI (level of evidence

2, grade of recommendation C) [6] .

Tricyclic Antidepressants

Tricyclic antidepressants (TCA) are indicated for

depressive disorders and have been reported to

produce beneficial effects in patients with urinary

incontinence. Imipramine is the main tricyclic antide-

pressant that has been used in the treatment of urinary

incontinence, mainly in nocturnal enuresis in children

but also in patients with SUI [29] . The mechanism of

action is not fully understood. If adequately dosed, all

TCA inhibit the reuptake of norepinephrine and sero-

tonin into nerve endings. Moreover, some TCA such

as imipramine have a marked anticholinergic action.

At the urethral level, the effects on amine uptake

can be expected to enhance the contractile effects of

norepinephrine on smooth muscle, which also may

influence the striated muscles in the urethra and pel-

vic floor by effects at the spinal cord level [20] . In an

open-label study, Gilja et al. reported that imipramine

produced subjective continence in 70% of patients

and also increased the urethral closure pressure [30] .

In a prospective study in 40 women with SUI, Lin

et al. found that imipramine improved SUI in 60%

of patients [31] . However, imipramine has not been

studied in good-quality, randomized controlled clini-

cal trials. Furthermore, imipramine has troublesome

adverse effects including dry mouth, blurred vision,

constipation, orthostatic hypotension, sedation, drow-

siness, and heart rhythm abnormalities [32] . At the

last International Consultation on Incontinence imi-

pramine was considered to have level of evidence 3

(case-control studies, case series) and was granted a

grade of recommendation D (evidence inadequate/

conflicting) [6] ( Table 8.1 ).

Serotonin and Norepinephrine

Reuptake Inhibitors: Duloxetine

In the last decade, in vivo animal studies have

demonstrated that serotonin and norepinephrine

have a role in the neural control of the micturition

102 D. Castro-Diaz and S. Fumero

cycle. Studies in the anesthetized cat model have

demonstrated that serotonin 5-HT receptor ago-

nists suppress parasympathetic activity and enhance

sympathetic and somatic activity in the bladder.

These effects promote urine storage by relax-

ing the bladder and increasing urethral resistance.

Duloxetine hydrochloride is a balanced dual sero-

tonin and norepinephrine reuptake inhibitor, which

has affinity for binding to these neurotransmitters

uptake sites. In an acetic acid-induced model of

irritated bladder in the cat, duloxetine significantly

increased bladder capacity and sphincteric muscle

activity, presumably by acting at the central level

via both motor and sensory afferent modulation

[33] . These effects were not reproduced by a com-

bination of two separate single reuptake inhibitors

[34] . Duloxetine is believed to affect SUI by block-

ing the reuptake of serotonin and norepinephrine

and causing accumulation of serotonin and nore-

pinephrine at the synapses in Onuf’s nucleus, an

area in the sacral spinal cord that has a high density

of 5-HT and norepinephrine receptors. Pudendal

motor neurons located in Onuf’s nucleus regulate

the urethral striated muscle sphincter. Serotonin and

norepinephrine stimulate these neurons, increasing

the strength of urethral sphincter contractions [32– 36]

( Fig. 8.1 ). Phase I safety studies showed that

duloxetine is well tolerated in healthy volunteers

[18] . In a phase II dose-finding clinical trial con-

ducted in 48 centers in the United States, duloxetine

was associated with a significant reduction in SUI

episodes. Five hundred thirty-three women aged

18–65 years, with at least four incontinence episodes

per week, were randomized to 12 weeks of treat-

ment with placebo or duloxetine at one of three

doses (20, 40, or 80 mg/day). Duloxetine was asso-

ciated with significant dose-dependent decreases in

incontinence episode frequency (IEF). This decrease

paralleled improvements in the Patient Global

Impression of Improvement (PGI-I) scale and the

Incontinence Quality of Life (I-QOL) question-

naire. The median IEF decrease with placebo was

41% compared with 54% for duloxetine 20 mg/day

( P = 0.06), 59% for duloxetine 40 mg ( P = 0.002),

and 64% for duloxetine 80 mg/day ( P < 0.001)

[37] . Duloxetine was well tolerated and no adverse

events were considered to be clinically severe.

Discontinuation rates due to adverse events were

5% for placebo and 9, 12, and 15% for duloxetine

20, 40, and 80 mg/day, respectively ( P = 0.04).

Table 8.1 . Summary of characteristics and level of evidence of pharmacological agents prescribed off-label for

stress urinary incontinence.

Pharmacological agents prescribed off-label for stress urinary incontinence

Hormone replacement therapy (HRT)

Thought to increase the urethral closure pressure

Thought to increase the response of α -adrenoreceptor agonists

Clinical improvement shown in nonrandomized studies

Lack of well-designed randomized studies showing efficacy

May increase the risk for urinary incontinence among symptomatic women

Level of evidence 2, grade of recommendation D

a -Adrenoceptor agonist

Found to be effective for SUI in both open-label and controlled clinical trials

Lack of long-term randomized controlled trials

Phenylpropanolamine withdrawn by the FDA because of risk of hemorrhagic stroke in women

Level of evidence 23, grade of recommendation C–D

b -Adrenoceptors agonists: Clenbuterol

Thought to increase urethral striated sphincter activity

Lack of well-designed randomized clinical trials

Level of evidence 2, grade of recommendation C

Tricyclic antidepressants

Mechanism of action not fully understood: marked systemic anticholinergic action and weak inhibition of reuptake of nore-

pinephrine and serotonin at nerve ending

Physiologically/pharmacologically effective. Clinically widely used, but evidence from randomized studies is scarce

Know antiarrhythmic effect

Level of evidence 3, grade of recommendation D

8. Pharmacotherapy of Stress Urinary Incontinence 103

Nausea was the most common symptom that led to

discontinuation. According to these data, duloxet-

ine 80 mg/day (40 mg twice daily) was determined

to be the optimum dose in women with SUI [38] .

In a phase III clinical study conducted in North

America, which included 683 women aged 22–84

years with a weekly IEF of at least 7, duloxetine

was associated with a significant decrease in IEF

(median decrease 50% vs. 27%, P < 0.001) and

improvement in the I-QOL scores (+11 vs. + 6.8,

P < 0.001). Improvements in IEF were associated

with significant increases in voiding intervals com-

pared with placebo. At the end of the study period

10.5% of duloxetine-treated patients and 5.9%

of placebo-treated patients had no incontinence

episodes ( P < 0.05). In a subgroup of 436 patients

with severe SUI a similar significant improve-

ment in both IEF and I-QOL was observed. The

PGI-I results showed that 62% of duloxetine-treated

patients had a better bladder condition compared

with 39.6% in the placebo group. Furthermore, the

I-QOL showed significant improvements compared

with placebo in the three domains of avoidance

and limiting behavior, social embarrassment, and

psychosocial impact [38] . The effects of duloxe-

tine were confirmed in a simultaneous phase III,

placebo-controlled trial conducted in several cent-

ers in Europe and Canada. Compared with placebo,

duloxetine-treated patients showed a significant

decrease in IEF (median decrease of 50% vs. 29%,

P = 0.002) with comparable significant improve-

ments in those subjects with more severe inconti-

nence. A total of 52% of women taking duloxetine

experienced a 50–100% reduction in IEF compared

with 34% of women taking placebo ( P < 0.001).

A significant improvement in the I-QOL was

observed as well (7.3 in duloxetine group vs. 4.3

in the placebo group) [39] . In another randomized,

double-blind, placebo-controlled clinical trial con-

ducted in several geographic regions including

Argentina, Australia, Brazil, Finland, Poland, South

Africa, and Spain, 458 incontinent women were

assigned to duloxetine 40 mg twice daily (227) or

placebo (231) for 12 weeks. A significantly greater

median decrease in IEF was observed with duloxet-

ine (54%) compared with placebo (40%), and com-

parable significant improvement in quality of life

(I-QOL score increases of 10.3 vs. 6.4, P = 0.007).

Improvements with duloxetine were associated with

significantly greater increases in voiding intervals

than with placebo (20.4 vs. 8.5 min, P < 0.001). In

this study the placebo responses were higher than

those reported in the North American and European

phase III studies, which is thought to be related to

a higher number of patients being naïve for inconti-

nence management [40] .

In a randomized clinical trial conducted in women

awaiting surgery for SUI it was observed that at the

Fig. 8.1.

5-HT

5-HT5-HT

5-HT

5-HT receptors(e.g. 5-HT2)

Rhabdosphincter Motor Neuron (Pudendal Nerve)

Serotonin

terminal 5-HT reuptake

sites

5-HT5-HT

Duloxetine

block

5-HT5-HT

Duloxetine : a balanced dual

5-HT and NA reuptake inhibitor

Duloxetine is a balanced dual 5-HT and NA neuronal reuptake inhibitor

Duloxetine blocks the reuptake of 5-HT and NA and causes accumulation of 5-HT and NA

at the synapses in Onuf’s nucleus. This facilitates pudendal nerve activity and increases

rhabdosphincter contraction during the storage phase of the micturition cycle

104 D. Castro-Diaz and S. Fumero

conclusion of the study 20% of duloxetine-treated

women were no longer interested in surgery com-

pared with 0 of 45 placebo-treated women [41] .

Most common (>5%) treatment-emergent adverse

events observed in active treatment arms in clini-

cal trials with duloxetine include nausea, fatigue,

insomnia, dry mouth, constipation, dizziness. and

headache, with nausea being the most common

adverse event (23–28%) and the most common

reason for discontinuation (5.7%) [37– 41] . Nausea

tended to be mild-to-moderate, transient (lasting

1 week to 1 month), and not progressive [38– 40] .

In a recent double-blind placebo-controlled study

assessing the impact of duloxetine dose escalation

on tolerability and efficacy in the treatment of SUI,

it was found that starting duloxetine at 20 mg bid for

2 weeks before increasing to 40 mg bid significantly

improved tolerability but did not impact duloxetine

efficacy after all subjects had been on 40 mg bid for

at least 2 weeks [42] . Consequently, dose escalation

seems to be an appropriate way of reducing the risk

of nausea in patients starting with duloxetine.

Duloxetine has not been associated with car-

diovascular side effects in short-term clinical trials.

Data from a long-term study in patients with depres-

sion indicate that after 1 year of use, duloxetine was

not associated with sustained elevations in blood

pressure and did not prolong corrected QT intervals.

Duloxetine significantly increased heart rate around

two beats per minute compared with placebo [43] .

Duloxetine also has been studied in association

with pelvic floor muscle exercises. In a randomized,

controlled clinical trial of duloxetine alone, PFMT

alone, combined treatment, and no active treatment

of women with SUI, it was found that combination

therapy of duloxetine and PFMT was more effica-

cious in reducing urinary incontinence episodes

than either one alone. Combined therapy also

showed an improvement of quality of life [44] .

Duloxetine has been found to be useful in the

treatment of women with symptoms of mixed

urinary incontinence (MUI). A recent multicenter,

multinational trial compared the efficacy and safety

of duloxetine and placebo in women with symp-

toms of MUI. Overall, IEF decreases were sig-

nificantly greater with duloxetine than placebo

(mean change of 7.30 vs. 5.65 IEF/week, P < 0.05,

median percent change 60 vs. 47%, P < 0.001).

Significant benefits also were demonstrated with

duloxetine compared with placebo for changes in

I-QOL, ICIQ-SF, score as well as for PGI-I ratings

( P = 0.001) [45] .

Duloxetine also has been studied in women with

overactive bladder. In a recent double-blind, pla-

cebo-controlled study 306 women with symptoms

of overactive bladder and evidence of absence of

SUI were randomly assigned to placebo or duloxe-

tine. Patients randomized to duloxetine demon-

strated significant improvements compared with

patients randomized to placebo for decreases in

micturition and incontinence episodes and quality

of life, indicating that this drug may be an alternative

to antimuscarinics in the treatment of overactive

bladder [46] .

In healthy volunteers coadministration of duloxe-

tine and tolterodine was well tolerated and demon-

strated no significant safety findings in the studied

population [47] . Age did not influence pharma-

cokinetics of elderly healthy volunteers [48] .

The impact of demographic characteristics and

comorbidities on efficacy of duloxetine has been

studied recently using an integrated database includ-

ing data from four large randomized controlled tri-

als. Several subgroups were studied with regard

to ethnicity, age, body mass index (BMI), chronic

lung disease, hypoestrogenism, diabetes mellitus,

and depression. It was observed that the reduction

in IEF was minimal and not significantly different

between duloxetine and placebo in women with

chronic lung disease, while no differences with

regard to the rest of the subgroups. Interestingly,

the improvement in quality of life was higher in

the subgroups of patients with higher BMI. With

regard to age, reductions in IEF and increases in

I-QOL were more pronounced in women younger

than 65 years of age, suggesting that older women

may be less likely to respond to treatment directed

at the striated sphincter [49] .

Duloxetine is licensed at 40 mg twice daily

for the treatment of SUI in the European Union,

Canada, and some South-American countries but

not in the United States. However, duloxetine

has been licensed for depression and for diabetic

polyneuropathic pain in the European Union

and in the United States. There have been some

reports by the FDA of increased suicidal ideation

in adults with depression who are taking antide-

pressants, but none has been reported in clinical

trials on urinary incontinence. Communications

with the US FDA’s Division of Reproductive

8. Pharmacotherapy of Stress Urinary Incontinence 105

and Urologic Drug Products (DRUDP) led the

sponsoring companies to conclude in January

2005 that DRUDP was not prepared to grant

approval for duloxetine for the treatment of the

SUI population based on the data package sub-

mitted. This led to the withdrawal of the New

Drug Application in January 2005. The sponsor-

ing companies believe that the current overall

benefit/risk evaluation by DRUDP includes con-

siderations regarding all three elements of the

benefit/risk equation: (1) the perceived severity

and impact of SUI as a medical condition, (2) the

magnitude of the drug’s benefit in the SUI patient

population, and (3) the safety profile as it applies

to the SUI patient population [50] .

In any case, duloxetine, being the only proven

medical therapy for SUI, is being used in many

Europeans countries. According to very pre-

liminary data, indications for its use are at present

being extended to males with SUI [51] , although

definitive conclusions with regard to its use in

males can be obtained only if formal evaluation

is conducted with adequate placebo control and

standardized follow-up [52] ( Tables 8.2 and 8.3 ) .

Table 8. 2. Summarary of mechanism of action, indications, and level of evidence of duloxetine.

Serotonin and norepinephrine reuptake inhibitors: duloxetine

Duloxetine blocks the reuptake of serotonin and norepinephrine at the synapses in Onuf’s nucleus, stimulating pudendal neurons

increasing the strength of urethral sphincter contractions

Demonstrated efficacy in high quality double-blind placebo controlled trials. Level of evidence 1, grade of recommendation A

Nausea is the most common side effect. Tolerability can be improved with dose escalation starting with 20 mg 2 weeks before

increasing to 40 mg bid

Duloxetine has proven efficacy in patients with symptoms of mixed urinary incontinence and overactive bladder

Not FDA approved in the United States

Class Drug Efficacy Safety issues

Estrogen replacement Estrogens/progestogens Overall subjective improvement Breast and ovarian cancer

No significant objective effect Stroke, heart attack

β -Adrenoceptor agonists Ephedrine, phenypropa-

nolamine, phenylpropa-

nolamine pseudoephedtrine,

midodrine, methoxamine,

norfenefrine

Stimulated urethral smooth mus-

cle contraction; efficacy dem-

onstrated in

Hypertension, sleep disturbances

dry mouth, headache, tremor,

palpitations, tachycardia

β -Adrenoceptor agonists Clenbuterol It is thought to increase con-

tractility of urethral striated

sphincter

Tremors

Tachycardia

Headache

β -Adrenoceptor antagonists Propanolol Thought to increase contractil-

ity of urethral smooth mus-

cle; no controlled studies

Orthostatic hypotension

Cardiac decompensation

Tricyclic antidepressants Imipramine No controlled studies Anticholinergic symptoms

Orthostatic hypotension

Cardiac arrhythmia

Weight gain

Serotonin and norepinephrine

reuptake inhibitors

Duloxetine Increased bladder capacity,

decreased incontinence epi-

sodes, and improved quality

of life

Nausea, dry mouth, insomnia,

constipation, dizziness

Table 8. 3. Summarary of efficacy and safety issues of drugs used for stress urinary incontinence.

106 D. Castro-Diaz and S. Fumero

Conclusion

Although the female lower urinary tract is under

hormonal influences, hormonal therapy for SUI has

not proved to be efficacious. α -Adrenergic agonists

may increase urethral resistance by modifying ure-

thral pressure, but there is not a current acceptable

agent to be used for the treatment of SUI.

Duloxetine has proved to be efficacious in reduc-

ing the frequency of incontinence episodes. More

than 50% of duloxetine-treated patients experience

an improvement higher than 50%. Nausea is the

most common side effect. Dose escalation seems

to improve tolerability without any impact on

efficacy. Combination of PFMT and duloxetine is

more efficacious in reducing urinary incontinence

episodes than either one alone.

References

1 . Hunskaar S , Burgio K , Diokno , et al. Epidemiology

and natural history of urinary incontinence. In

Abrams P , Cardozo L , Khoury S , et al., eds.

Incontinence . Plymouth, UK : Health Publication

Ltd . 2002 : 165 – 201 .

2 . Hunskaar S , Burgio K , Clark A , et al. Epidemiology

of urinary (UI) and faecal (FI) incontinence and

pelvic organ prolapse. In : Abrams P , Cardozo L ,

Khoury S , Wein A eds. Incontinence, Vol. I: Basics

and evaluation . Plymouth, UK : Health Publication

Ltd . 2005 : 255 – 312 .

3 . DeLancey JOL . The pathophysiology of stress uri-

nary incontinence in women and its implications for

surgical treatment . World J Urol 1997 ; 15 (5) : 268 –

274 .

4 . Henriksson L , Anderson . K-E , Ulmsten U . The ure-

thral pressure profiles in continent and stress inconti-

nent women . Scand J Urol Nephrol 1979 ; 13 (1) : 5 – 10 .

5 . Hilton P , Stanton SL . Urethral pressure measurement

by microtransducer: The results in symptom-free

women and in those with genuine stress incontinence .

Br J Obstet Gynaecol 1983 ; 90 (10) : 919 – 933 .

6 . Anderson KE , Appell R , Caardozo L , et al.

Pharmacological treatment of urinary incontinence.

In : Abrams P , Cardozo L , Khoury S , Wein A , eds.

Incontinence: 3rd International Consultation on

Incontinence . Plymouth, UK : Health publication

Ltd . 2005 : 809 – 854 .

7 . Versi E , Cardozo L . Estrogens and the lower urinary

tract function . London : Blackwell Scientific , 1988 .

8 . Hodson BJ , Dumas S , Bolling DR , et al. Effect of

estrogen on sensitivity of rabbit bladder and urethra

to phenylephrine . Invest Urol 1978 ; 16 (1) : 67 – 69 .

9 . Larsson B , Andersson KJ , Batra S , et al. Effect of

estradiol on norepinephrine-induced contraction,

alpha adrenorecptor number and norepinephrine

content in the female rabbit uretra . J Pharmacol Exp

Ther 1984 ; 229 : 557 – 563 .

10 . Moehrer B , Hextall A , Jackson S . Oestrogens for

urinary incontinence in women (Cochrane Review).

In: The Cochrane Library , Issue 4 . Chichester, UK :

Wiley , 2003 .

11 . Grady D , Brown JS , Vittinghoff E , et al. Post-

menopausal hormones and incontinence: The Heart

and Estrogen/Progestin Replacement Study . Obstet

Gynecol 2001 ; 97 (1) : 116 – 120 .

12 . Al-Badr A . Ross A , Soroka D , et al. What is the

available evidence for hormone replacement therapy

in women stress urinary incontinence . J Obstet

Gynecol Can 2003 ; 25 (7) : 567 – 574 .

13 . Hendrix SL , Cochrane BB , Nygaard IE , et al. Effects

of estrogen with and without progestin on urinary

incontinence . JAMA 2005 ; 293 (8) : 998 – 1001 .

14 . Brune ME , O’Neill AB , Gauvin DM , et al.

Comparison of alpha 1-adrenoceptor agonists in

canine urethral pressure profilometry and abdom-

inal leak point pressure models . J Urol 2001 ;

166 (4) : 1555 – 1559 .

15 . Diokno AC , Taub M . Ephedrine in treatment of uri-

nary incontinence . Urology 1975 ; 5 (5) : 624 – 625 .

16 . Collste L , Lindskog M . Phenylpropanolamine in

treatment of female stress urinary incontinence:

Double-blind placebo controlled study in 24 patients .

Urology 1987 ; 30 (4) : 398 – 403 .

17 . Siltberg H , Larsson G , Hallen B , et al. Validation

of cough-induced leak point pressure measurement

in the evaluation of pharmacological treatment

of stress incontinence . Neurourol Urodyn 1999 ;

18 (6) : 591 – 602 .

18 . Zinner NR , Koke SC , Viktrup L . Pharmacotherapy

for stress urinary incontinence. Present and future

options . Drugs 2004 ; 64 (14) : 1503 – 1516 .

19 . Fleming G . The FDA regulation and the risk of

stroke . N Engl J Med 2000 ; 343 (25) : 1886 – 1887 .

20 . Anderson KW , Appell R , Awad S , et al.

Pharmacological treatment of urinary incontinence.

In : Abrams P , Khoury S , Wein A eds. Incontinence .

Plymouth, UK : Health Publications Ltd . 2002 :

418 – 511 .

21 . Weil EH , Eerdmans PH , Dijkman GA , et al.

Randomized double-blind placebo-controlled mul-

ticenter evaluation of efficacy and dose finding of

midodrine hydrochloride in women with mild to

moderate stress urinary incontinence: A phase II

study . Int Urogynecol J Pelvic Floor Dysfunct 1998 ;

9 (3) : 145 – 150 .

22 . Radley SC , Chapple CR , Bryan NP , et al. Effect

of methoxamine on maximum urethral pressure

8. Pharmacotherapy of Stress Urinary Incontinence 107

in women with genuine stress incontinence: A

placebo-controlled, double-blind crossover study .

Neurourol Urodyn 2001 ; 20 (1) : 43 – 52 .

23 . Blue DR . Pharmacological characteristics of Ro

115–1240, a selective a 1A/1L -adrenoceptor partial

agonist: A potential therapy for stress urinary incon-

tinence . BJU Int 2003 ; 93 : 164 – 172 .

24 . Musselman DM , Ford APDW , Gennevois DJ ,

et al. A randomized crossover study to evaluate Ro

115–1240, a selective a1A/1L-adrenoceptor partial

agonist in women with stress urinary incontinence .

BJU Int . 2004 ; 93 (1) : 78 – 83 ).

25. Script. World Pharmaceutical News. April 28th,

2004. No. 2947.

26 . Kaisary AV . Beta adrenoceptor blockade in the treat-

ment of female urinary stress incontinence . J Urol

(Paris) 1984 ; 90 (5) : 351 – 353 .

27 . Ishiko O , Ushiroyama T , Saji F , et al. Beta 2 -

adrenergic agonists and pelvic floor exercises for

female stress incontinence . Int J Gynaecol Obstet

2000 ; 71 (1) : 39 – 44 .

28 . Yasuda K , Kawabe K , Takimoto Y , et al. A double-

blind clinical trial of a beta2-adrenergic agonist in stress

incontinence . Int Urogynecol J 1993 ; 4 : 146 – 151 .

29 . Hunsballe JM , Djurhuus JC . Clinical options for

imipramine in the management of urinary inconti-

nence . Urol Res 2001 ; 29 (2) : 118 – 125 .

30 . Gilja I , Radej M , Kovacic M , et al. Conservative

treatment of female stress incontinence with imi-

pramine . J Urol 1984 ; 132 (5) : 909 – 911 .

31 . Lin HH , Sheu BC , Lo MC , et al. Comparison of

treatment outcomes for imipramine for female genu-

ine stress incontinence . Br J Obstet Gynaecol 1999 ;

106 (10) : 1089 – 1092 .

32 . Frazer A . Pharmacology of antidepressants . J Clin

Psychopharmacol 1997 ; 17 (Suppl 1) : 2s – 18s .

33 . Thor KB , Katofiasc MA . Effects of duloxetine, a

combined serotonin and norepinephrine reuptake

inhibitor, on central neural control of lower urinary

tract function in the chloralose-anesthesized female

cat . J Pharmacol Exp Ther 1995 ; 274 : 1014 – 1024 .

34 . Katofiasc MA , Nissen J , Audia JE , Thor KB .

Comparison of the effects of serotonin selective,

norpepinephrine selective, and dual serotonin and

norepinephrine reuptake inhibitors on lower urinary

tract function in cats . Life Sci 2002 ; 71 : 1227 – 1236 .

35 . Bymaster FP , Dresfield-Ahmad LJ , Threlkeld

PG , et al. Comparative affinity of duloxetine and

venlafaxine for serotonin and norpepinephrine trans-

porters in vitro and in vivo, human serotonin

receptor subtypes, and other neuronal receptors .

Neuropsychopharmacology 2001 ; 25 (6) : 871 – 880 .

36 . Michel MC , Oelke M , Duloxetine in the treatment

of stress urinary incontinence . Women’s Health

2005 ; 1 (3) : 345 – 358 .

37 . Norton PA , Zinner NR , Yalcin I , Bump RC .

Duloxetine versus placebo in the treatment of stress

urinary incontinence . Am J Obstet Gynecol 2002 ;

187 (1) : 40 – 48 .

38 . Dmochowski RR , Miklos JR , Norton PA , et al.

Duloxetine versus placebo for the treatment of non-

American women with stress urinary incontinence .

J Urol 2003 ; 170 : 1259 – 1263 .

39 . van Kerrebroeck , Abrams P , Lange R , et al.

Duloxetine vs. placebo in the treatment of European

and Canadian women with stress urinary inconti-

nence . BJOG 2004 ; 11 : 249 – 257 .

40 . Millard RJ , Moore K , Rencken R , et al. for the

Duloxetine Study Group. Duloxetine vs. placebo in the

treatment of stress urinary incontinence: A four-con-

tinent randomized clinical trial . BJUI 2004 ; 93 : 3111 –

318 .

41 . Cardozo L , Drutz HP , Baygani SK , Bump RC .

Pharmacological treatment of women awaiting sur-

gery for stress urinary incontinence . Obstet Gynecol.

2004 ; 104 (3) : 511 – 519 .

42 . Castro-Diaz D , Palma PC , Bouchard C , et al. Effect

of dose escalation on the tolerability and efficacy

of duloxetine in the treatment of women with stress

urinary incontinence . Int Urogynecol J Pelvic Floor

Disfunct 2007 ; 18 : 919 – 929 .

43 . Mallinckrodt C , Goldstein DJ , Detke MJ , et al.

Duloxetine: A long term treatment for the emotional

and physical symptoms of depression . Primary Care

Companion J Clin Psych 2003 : 5 : 19 – 28 .

44 . Ghoniem GM , Van Leeuwen JS , Elser DM , et al. A

randomized controlled trial of duloxetine alone, pel-

vic floor muscle training alone, combined treatment

and no active treatment in women with stress urinary

incontinence . J Urol 2005 ; 173 (5) : 1647 – 1653 .

45 . Bump RC , Bent AE , Gousse AE , et al. Duloxetine

treatment of women with mixed urinary incontinence

(MUI). (IUGA) [abstract No. 31] . Int Urogynecol J

2006 ; 17 (Suppl 2) : S57 – S100 .

46. Bump R, Steers W, Herschorn S, et al. Duloxetine

compared with placebo for the treatment of women

with symptoms of bladder overactivity. International

Continence Society, 36th Annual Meeting. Abstract

No. 127.

47. Hua TC, Pan A, Chan C, et al. Effect of duloxetine

on tolterodine pharmacokinetics in healthy volun-

teers. BJ Clin Pharm 57(5):652.

48 . Skinner MH , Kuan HY , Skerjanec A , et al. Effect

of age on the pharmacokinetics of duloxetine in

women . BJ Clin Pharm 2004 ; 57 (1) : 54 .

49 . Viktrup L , Yalcin I . Duloxetine treatment of stress

urinary incontinence in women: Effects of demo-

graphics, obesity, chronic lung disease, hypoestrogen-

ism, diabetes mellitus and depression on efficacy . Eur

J Obstet Gynecol Reprod Biol. 2007 ; 133 : 105 – 113 .

108 D. Castro-Diaz and S. Fumero

50 . Castro-Diaz D , Pascual MA . Pharmacotherapy for

stress urinary incontinence . Curr Opin Urol 2005 ;

15 (4) : 227 – 230 .

51 . Schlenker B , Gratzke C , Reich O , et al. Preliminary

results of the off-label use of duloxetine for

the treatment of stress incontinence after radi-

cal prostatectomy or cystectomy . Eur Urol 2006 ;

49 : 1075 – 1078 .

52 . Chapple CR . Duloxetine for male stress inconti-

nence . Eur Urol 2006 ; 49 : 958 – 960 .

109

Introduction

The demographics of stress incontinence sug-

gest that a significant percentage of the female

population is affected by this condition and that

the number of women who report discomfort

due to stress incontinence is increasing [1– 4] .

Stress incontinence is associated with quality

of life aberrations that, while often managed by

changes in physical activity, lead to treatment-

seeking behavior on the part of the sufferer in

order to regain normal physical function. Cure

of stress incontinence is the ultimate goal of

any intervention aimed at this symptom; how-

ever, complete symptom resolution often is not

attained with therapy. Yet, it is now becoming

evident from evolving outcomes analysis research

that symptom improvement, when attained after

intervention, is viewed as a significant and posi-

tive aspect of intervention, even if absolute cure

is not obtained [5] . When compared to the well-

defined prevalence of stress incontinence, the

actual number of surgical procedures (colposus-

pensions and slings) performed for this condition

reveal a significant disparity in absolute numbers

of women who actually undergo surgical interven-

tion. This numeric difference implies that women

may be reluctant to undergo operative interven-

tions due to concerns about morbidity, recovery

times, or other perceived risk/lifestyle issues [2, 6, 7] .

Nonsurgical modalities, despite the associated

noninvasive nature of these options, are plagued

by durability and efficacy concerns [8, 9] .

Radio frequency (RF) energy application to the

endopelvic fascia has been proposed recently as

an option for the treatment of women with less

bothersome stress incontinence as a less invasive,

initial surgical procedure. RF tissue remodeling

has been used for other indications such as fecal

incontinence [10] and gastroesophageal reflux dis-

ease [11] in which luminal contents pass through

a poorly functional anatomic and/or physiological

barrier. The goal of the RF energy procedure is

to correct the laxity and elasticity of the fascial

“hammock” that underlies the proximal urethra and

bladder neck and which is thought to contribute

to anatomic stress incontinence [12] by creating

thermally induced tissue shrinkage and contrac-

tion [13] . Focal RF application produces heating

of the endopelvic fascia, which denatures collagen

fibers, resulting in acute contraction (shrinkage) of

the target area and which then results in a chronic

fibrotic response [14] . Within 4–6 weeks, collagen

ingrowth and fibrosis further shrink and stabi-

lize the endopelvic fascia. These dynamic tissue

changes result in a decreased compliance to intra-

abdominal pressure increases and produce stabili-

zation of the position of the bladder neck [15] . The

theory of RF effect subsequently will be reviewed

in light of clinical experience.

Chapter 9

Radio Frequency Therapy

for the Treatment of Female

Stress Urinary Incontinence

Roger R. Dmochowski and Emily Cole

110 R. R. Dmochowski and E. Cole

Theory of Radio Frequency Tissue

Interaction and Treatment of the

Endopelvic Fascia for the Treatment

of Stress Urinary Incontinence

Several factors are thought to contribute to the

pathophysiology of stress urinary incontinence in

women: (1) damage or loss of the intrinsic closure

mechanism (“seal”) of the proximal urethra; (2)

loss of active and passive support of the urethra

from tissue stretching and loss of stability; and (3)

disruption of the neurological control of the pelvic

floor and urethra [12, 16– 18] . Loss of urethral

support results in urethral hypermobility, which

contributes to poor urethral compression during

periods of increased abdominal pressure and pro-

duces urinary incontinence [19– 21] . Endopelvic

support defects may be compounded by urethral

displacement, which results in the unequal distribu-

tion of intra-abdominal pressure changes, further

compounding urinary loss due to unequal pressure

transmission to the bladder and urethra.

It has been hypothesized that RF application to

the collagen-rich endopelvic fascia would produce

collagenous ultrastructural changes mimicking a

“tightening” or contraction of the fascia, which

then would stabilize the tissue during increased

abdominal pressure events. The ultimate goal

would approximate a resuspension of the proximal

urethral mechanism. Based on surgical experi-

ences from other specialties, this technology also

was envisioned as being accomplished with mini-

mally invasive techniques with minimal morbidity.

Ideally, a method to perform this intervention with-

out an incision would provide the optimal form of

intervention delivery.

Thermally induced contraction of collagen is

dependent on several unique characteristics of the

collagen molecule. Collagen exists in vivo as a

fibrillar structure that has a triple helix configura-

tion. The helical configuration is maintained by

cross-linking hydrogen bonds, which are unstable

when subjected to heat. The fibrillar structure is

maintained by thermally stable bonds, and therefore

is more resistant to deformation when subjected to

thermal stress. Thermal energy in the range of

60–80°C will cause unwinding of the helix, due to

disruption of the intramolecular cross-links, yet the

heat-stable fibrillar structure remains intact. The

overall effect is shrinkage of the molecule along

the longitudinal axis associated with distortion

(swelling) of the individual fibrils [13] .

RF energy has been used clinically to achieve

tissue shrinkage via collagen denaturation for

numerous indications including ophthalmologic,

orthopedic, and dermatologic [13, 22– 25] . RF

energy is imparted to the tissue via direct applica-

tion (contact) to the target area using electrodes.

During this energy application, tissue heating

ensues due in large part to tissue resistance to the

flow of the RF energy. A three-dimensional ther-

mal effect is created as heat spreads from areas of

high to low temperature. Overall thermal effects

vary according to the electrode configuration, the

actual amount of RF energy delivered, and inherent

tissue resistance that may be affected by intrinsic as

well external factors (such as excess free fluid in

the energy delivery area).

Several basic and clinical studies have substan-

tiated the theoretic effect of RF energy-induced

collagenous changes. While evaluating the use of

monopolar RF energy to treat bovine joint capsular

tissue in vivo, Hecht et al. noted that the application

of RF energy produced acute tissue inflammatory

reaction with associated degradation of collagen.

Subsequently, new collagen developed over a

12-week period, which produced a remodeling of

the articular capsular tissue. They noted that the

primary treatment effect was collagen denaturation

produced by the thermal application with attendant

tissue shrinkage (loss of three-dimensional vol-

ume). These effects were noted to maximally occur

at 60–80°C. Histological evaluation of the treated

tissue demonstrated that the thermal effects were

very localized to the specific area of energy appli-

cation with little or no changes being seen beyond

the area of thermal effect (7–10 mm). At 3 months

posttreatment, further histological study showed

fibroblast proliferation and capillary ingrowth pro-

ducing complete tissue healing [13] . Other types of

dense collagenous structures also have been stud-

ied to assess RF thermal effects. Fresh bovine heart

tendons were mounted in a tension-free device, RF

energy was imparted to the tissue, and tissue volume

changes (degree of shrinkage) were measured as a

function of time and temperature variables associ-

ated with thermal delivery [26] . Threshold values

9. Radio Frequency Therapy for the Treatment of Female Stress Urinary Incontinence 111

for time and temperature were noted to be required

for maximal tissue shrinkage (volume loss) to

occur. Interestingly, the optimal temperature to

effect near-maximal shrinkage when applied for a

minimum of 30 s was 70°C. Less effective shrink-

age was noted to occur with temperatures below

70°C. This finding was found to be independent of

the duration of energy delivery.

Given these reproducible effects, RF energy deliv-

ery was evaluated for potential salubrious effects in

the treatment of stress incontinence in women. It

was postulated that thermal energy application to the

endopelvic fascia could produce a “resuspension” of

the proximal urethra, decreasing hypermobility and

reducing or curing urinary incontinence. Clinical

studies were undertaken to assess this effect.

Technique

The first commercially available RF bladder neck

suspension procedure was known as the SURx

transvaginal system (SURx System, Cooper

Surgical, Inc. Trumbull, CT). The device is com-

posed of an applicator and a RF generator (see

Fig. 9.1 ). The generator produces bipolar radio

frequency, while monitoring tissue temperature and

resistance. The sterile, single-use applicator is com-

posed of a handle, with a triggering mechanism and

a 270°-rotational tip with microbipolar electrodes

and a saline drip at the distal end of the probe.

Accurate monitoring of treatment tissue tempera-

tures is performed by a thermistor that is located in

the applicator tip between the electrodes.

The RF procedure may be performed either

laparoscopically or transvaginally, with thermal

energy being applied to the endopelvic fascia at

least 1 cm lateral to the midurethra on each side of

midline. RF energy produces a similar treatment

effect when applied either to the superior or infe-

rior surface of the endopelvic fascia depending on

the surgical approach.

Patients considered to be candidates for the

RF procedure as performed by the SURx system

should be evaluated carefully prior to surgery

with a history and physical (demonstrating proxi-

mal urethral hypermobility of greater than 30°

associated with objective urinary incontinence

associated with either Valsalva’s effort or cough),

voiding diary, and urodynamics when indicated.

Transvaginal RF procedures may be performed

in the ambulatory setting using either general or

regional anesthesia. The thermal energy delivered

by this procedure makes local anesthesia difficult,

although the combination of sedation and local

techniques may be feasible.

For the transvaginal approach, the patient is

placed in the dorsal lithotomy position and the

bladder is drained with a Foley catheter. The

catheter is left in place and the balloon inflated

for purposes of anatomic identification of the

proximal urethra and bladder neck junction. A full

thickness vaginal incision approximately 2–3 cm

is created 1 cm lateral to the urethra at the level

mid- and proximal urethra. Hydrodissection of

the vaginal wall may be done prior to the incision

using either 20 U vasopressin in 50 ml injectable

saline or epinephrine at a 1:200,000 dilution in

injectable saline to minimize mucosal bleeding.

After the incision is performed, the vaginal mucosa

is dissected away from the underlying endopelvic

fascia laterally toward the ischium so as to expose

a 1.5 cm × 2 cm area of the inferior aspect of the

endopelvic fascia. The endopelvic fascia should

not be disrupted during the dissection. Hemostasis

is critical, as excess fluid (whether blood, serum,

or remnant hydrodissection fluid) acts as a heat-

dissipating interface and circumvents adequate

thermal delivery to the underlying tissue.

After completion of the mucosal dissection, the

applicator tip is placed in contact with the underly-

ing endopelvic fascia avoiding excess pressure (the

probe should simply touch the fascia). RF delivery

Fig. 9.1. External applicator and radiofrequency generator

112 R. R. Dmochowski and E. Cole

parameters include: minimum of 70°C to the target

tissue, a minimum of 30 s of application time,

and an absence of excess fluid in the operative

area. During RF application, a visual blanching of

the fascia occurs which is associated with tissue

volume loss (shrinkage). Tissue charring is to be

avoided as this effect also dissipates thermal deliv-

ery. Power delivered by the RF system approxi-

mates 15 W with the bipolar probe. The RF probe

is applied to the fascia with a slow, sweeping man-

ner parallel to the urethra, making sure to remain

1 cm lateral to the urethra at all times. The entire

exposed fascial surface should be treated with this

technique. During thermal application, continuous

monitoring of tissue temperature and tissue imped-

ance is accomplished by the RF generator via the

thermistor in the probe tip. When optimal resist-

ance parameters are obtained, an aural tone is

delivered by the generator indicating attainment

of optimal parameters. The same technique then is

accomplished on the contralateral side.

After the completion of RF application, the inci-

sions are closed with delayed resorbable suture

such a polydioxanone. A vaginal packing is placed

for 2–4 h, after which packing and catheter are

removed. Activity constraints include avoidance of

intercourse for 6 weeks and lifting limitations of 5

pounds for a similar period.

The laparoscopic RF technique is similar.

After insertion of laparoscopic ports (per sur-

geon preference for optimal visualization of

the pelvis), dissection exposes the intrapelvic

aspect of the endopelvic fascia. RF treatment is

delivered to the superior aspect of the endopel-

vic fascia so as to remain 1 cm lateral to the

urethra, which can be confirmed by ascertaining

the location of the urethral catheter. Similar heat

intensity and tissue impedance criteria are used

for this approach.

Therapeutic Results

Two prospective FDA investigational device (IDE)

approved clinical trials have been completed to

demonstrate the therapeutic index of the RF pro-

cedure [27, 28] . A total of 214 patients with

stress urinary incontinence were enrolled at 16 US

study sites. Of this group, 94 (44%) were treated

with a laparoscopic approach and an additional

120 (56%) underwent the transvaginal technique.

Acute and chronic safety and clinical efficacy at

6-month follow-up was assessed in both treatment

groups. All patients were primary incontinence

patients (had received no prior surgical interven-

tion for stress incontinence), without grade III or

IV anterior vaginal wall prolapse or other vaginal

support defects. Urodynamics were performed to

exclude detrusor overactivity and to assess other

vesical storage parameters. Prohibited medications

included antidepressants, a -adrenergics, and anti-

cholinergics. Per protocol, all women had had pre-

vious unsuccessful outcomes after at least 3 months

of conservative, noninvasive pelvic floor therapies

such as Kegel exercises or electrical stimulation.

Parameters for efficacy included number of incon-

tinence pads used and change in daily incontinence

episodes. Additionally, Valsalva effort also was

assessed for all patients with physical examination

and urodynamics. Also, quality of life was assessed

at baseline and at completion of follow-up.

Efficacy was defined as cured, improved, or

failed. “Cure” was defined as a negative Valsalva on

physical examination and “improved” was defined

as decreased daily incontinence episodes or pad use.

Results are shown in Table 9.1 . No reported device-

related events occurred during the study, specifically

no injury to the urethra or bladder (no identified uri-

nary tract fistulas) ( Table 9.2 ). Post hoc assessment

of study outcomes and delivered thermal parameters

Laparoscopic group Transvaginal group

Baseline 1-year Long-term Baseline 1-year Long-term

N 94 85 61 120 96 73

Neg Valsalva (%) 0 79 71 0 76 66

Pt QOL assessment (%) 88 79 74 73

Uses <1 pad per day or

none (%)

85 60 72 58

Table 9.1. Clinical efficacy .

9. Radio Frequency Therapy for the Treatment of Female Stress Urinary Incontinence 113

revealed two treatment parameters that significantly

impacted efficacy: (1) early and persistent increases

of impedance due to excessive fluid in the surgical

field which causes energy dissipation and result-

ant superficial, insufficient treatment; and (2) lack

of continuity of thermal delivery to the treatment

area (intermittent energy applications resulting from

multiple “on/off” cycles which produces inadequate

thermal delivery to the targeted tissues).

Using these additional criteria, the original

patient cohort was assessed using the same out-

come criteria at longer follow-up. The average

follow-up times were 38 ± 3.51 months in the

laparoscopic group and 30 ± 3.29 months in the

transvaginal group. Using an actuarial survival

analysis of objective and subjective outcomes from

the initial evaluation, results projected to 30 ± 3.3

months demonstrated relative stability [29] .

Future Directions

Transurethral delivery of RF energy recently has been

described. Appell et al. [30] have used a system intro-

duced by Novasys (Novasys Medical, Inc., Newark,

CA) that is composed of a 21-French transurethral

RF microremodeling probe mated to an RF generator.

This system is monopolar and uses a standard return

electrode (“grounding pad”), which is placed on

the patient and connected to the RF generator. The

urethral mucosa is continuously irrigated to avoid

injury from heat application, with a tubing line carry-

ing sterile, room-temperature water routed through a

pump on the RF generator to the probe.

The technique does not require cystoscopic visu-

alization. The RF probe is placed into the bladder

lumen and a retention balloon on the end of the

probe is insufflated and then palpably anchored

within the bladder outlet, identical to positioning

a Foley catheter. Immediately below the reten-

tion balloon, four 23-gauge needle electrodes are

located within the probe. After probe localization,

the needles are simultaneously deployed, and

the needle tips are deployed through the urethral

mucosa into the submucosa. Four separate sub-

mucosal tissue targets are treated with the needles,

microremodeling requiring 60 s of current delivery

at each site. Subsequently, a series of rotational

maneuvers between periods of RF delivery result

in the four needles residing in nine different posi-

tions (a total of 9 min of RF delivery). The goal of

treatment is microremodeling of 36 microscopic,

submucosal, circumferential targets ranging from

the proximal urethra to the bladder neck.

In the pilot study, 110 women were randomized

to the RF treatment group and 63 patients to

a sham treatment group (probe insertion only).

Subjective outcomes included the rate of ≥ 10

point Incontinence Quality of Life (I-QOL) score

improvement and magnitude of perceived improve-

ment based on patient satisfaction with treatment.

Objective outcomes assessed included the change in

mean leak-point pressure (LPP), and the number of

women with ≥ 25% reduction in both incontinence

episode frequency and pad weight during stress test-

ing. Adverse events were noted for both groups.

The 12-month safety profile was identical

between the two groups ( Table 9.3 ). Of the women

with moderate to severe stress incontinence, 74%

experienced ³ 10 point I-QOL score improvement

at 12 months following RF remodeling versus

Table 9.2. Summary of reported complications.

Laparoscopic

group

Transvaginal

group

Bladder (%) 2 0

Cardiovascular (%) 0 0

Pulmonary (%) 0 0

Additional surgery (%) 0 0

Transfusion (%) 0 0

Retention > 4 weeks (%) 0 0

UT infection (%) 2 0

Sexual dysfunction (%) 0 0

Postop urgency (%) 1 1

Table 9.3. Self explanatory .

Adverse event

Sham arm

( n = 63)

RF arm

( n = 110)

P

Value

Urinary retention 0% 0.9% (1) 1.0

Urinary tract

infection

4.8% (3) 4.5% (5) 1.0

Hematuria 0% 0.9% (1) 1.0

Dysuria 1.6% (1) 9.1% (10) 0.06

Hesitancy 1.6% (1) 0% 0.4

Asymptomatic detrusor

overactivity

6.3% (4) 1.8% (2) 0.2

Dry overactive bladder 3.2% (2) 7.3% (8) 0.3

Wet overactive bladder 9.5% (6) 10% (11) 1.0

From [30]

114 R. R. Dmochowski and E. Cole

50% of women who underwent sham treatment

( P = 0.03). Of the women with mild inconti-

nence, 22% of women who received RF treatment

reported improvement versus 35% of women who

received sham treatment ( P = 0.2). Changes in the

LPP between the two groups were noted. Although

a high degree of variability was noted [RF treat-

ment group demonstrated an increase in mean LPP

at 12 months (13.2 ± 39.2 cm H

2 O)], women in the

sham treatment group demonstrated a reduction

in mean LPP at 12 months [−2.0 ± 33.8 cm H

2 O

( P = 0.02)].

Summary

RF-induced tissue responses are well-defined and

reproducible [12, 13] . Immediate effects reflect a

denaturation of collagen fibers, with resultant loss

in collagen fibril integrity. After 1 week, general-

ized granulation response is seen with resolution of

acute inflammatory infiltrate. At 3 weeks, fibrosis

and initial collagen remodeling are predominant.

At 6 weeks posttreatment, continued resolution

of inflammatory components has occurred, with

further progression of the expected fibrotic heal-

ing response [15] . The final histological result is

replacement of the elastic fascia by fibrotic tissue.

The overall structural result is shortening, stiffen-

ing, and thickening of the fascia, which results in

increased support of the bladder neck and proxi-

mal urethra and a decrease in hypermobility of

these structures. These reproducible RF thermal

tissue effects have been used in dermatology, in

orthopedics, and for treatment of varicose veins

[28] . The contractile response to RF energy also

has been applied to the treatment of tendinous and

ligamentous attachments within joints to shorten

and strengthen these structures [27] .

Loss of integrity of the endopelvic fascia gener-

ally is thought to be caused by pregnancy and child-

birth [31, 32] . However, fascial support defects also

may occur in other women such as athletes and those

possibly at risk due to familial propensity, resulting

in stress incontinence [33] . Hypermobility of the

proximal urethra and bladder neck now are felt to

be contributory but not causative to the develop-

ment of stress urinary incontinence. Hypermobility

of these structures is considered to be resultant

from increased elasticity of the surrounding fascial

tissues. Clinical studies performed thus far indicate

that the RF procedure offers a safe and effective

modality to impart thermal energy to the endopel-

vic fascia, replacing elastic tissue with inelastic

fibrotic scar. Stabilization of the proximal urethra

and bladder neck, which recapitulates support of

the suburethral tissue, results from these changes,

producing improvement and in some cases cure of

stress urinary incontinence.

Overall, efficacy results must be balanced against

any adverse events or safety issues resulting from

an intended intervention, and both these considera-

tions must be taken in the context of patient expec-

tations for therapy [31– 33] . For women with mild

to moderate incontinence, continued evaluation of

new therapies is ongoing in an effort to best balance

risks and benefits of these therapies as opposed to

those associated with more invasive procedures.

Such considerations as voiding dysfunction after

surgery requiring short- or long-term urethral cath-

eterization, restrictions on future pregnancy that

are inherent to sling and suspension procedures,

and concerns regarding the use of biomaterials and

possible adverse events resulting from these mate-

rials including erosion and poor tissue healing can

impact patient preference for intervention. Given

these issues, new therapies that potentially may

decrease adverse events yet maintain relatively

significant degrees of efficacy as compared to more

invasive procedures are intriguing.

The RF approach does not rely on the use of

implanted materials for structural support, thereby

eliminating the concerns of voiding dysfunction

resulting from sling placement and the potential for

foreign material erosion. The minimal invasiveness

of the procedure resulting from either the small

incision and dissection used in the SURx tech-

nique or the probe insertion used in the Novasys

procedure provides a therapeutic option for stress

incontinence without the potential for injury to the

lower urinary tract, bowel, and major vessels.

Inherent weaknesses exist, however, regard-

ing the evidence extant for RF interventions for

stress urinary incontinence. Longer-term follow-up

analysis is necessary to determine the ultimate

efficacy of RF interventions, as is the necessity

for more uniform outcomes reporting using both

objective and subjective criteria. Whether or not

9. Radio Frequency Therapy for the Treatment of Female Stress Urinary Incontinence 115

these procedures will be generally adopted also

will depend on the overall comparative therapeutic

index for RF therapy as compared to midurethral

sling or bulking interventions. Ideally, RF thermal

delivery could be carried out under local anesthesia

as an ambulatory intervention. The SURx device

is not as amenable to this technique, but possible

further device evolution may allow this considera-

tion. The Novasys system is much more applicable

to the ambulatory, minimal anesthesia setting and

further data may indeed support its use under these

circumstances.

References

1 . Hannestad YS , Rortveit G , Sandvik H , et al. A

community based epidemiological survey of female

urinary incontinence: The Norwegian EPINCONT

study . J Clin Epidemiol , 53 : 1150 – 1157 , 2000 .

2 . Luber KM . The definition, prevalence, and rick

factors for stress urinary incontinence . Rev Urol ,

6 (Suppl 3) : S3 – S9 , 2004 .

3 . Luber KM , Boero S , Choe JY . The demographics

of pelvic floor disorders: Current observations and

future projections . Am J Obstet Gynecol , 184 : 1496 –

1501 , 2001 .

4 . Hampel C , Weinhold N , Eggersmann C , et al.

Definition of overactive bladder and epidemiology

of urinary incontinence . Urology , 50 (Suppl 6A) : 4 –

14 , 1997 .

5 . Elkadry EA , Kenton KS , Fitzgerald MP , et al.

Patient selected goals: A new perspective on surgi-

cal outcome . Am J Obstet Gynecol , 189 : 1551 – 1558 ,

2003 .

6 . Kinchen KS , Burgio K , Diokno AC , et al. Factors

associated with women’s decisions to seek treat-

ment for urinary incontinence . J Women’s Health ,

12 : 687 – 698 , 2003 .

7 . Norton PA , MacDonald LD , Sedgwick PM , et al.

Distress and delay associated with urinary incon-

tinence, frequency, and urgency in women . BMJ ,

297 : 1187 – 1189 , 1988 .

8 . Cammu H , Van Nylen M , Amy JJ . A 10-year follow-

up after Kegel pelvic floor muscle exercises for genu-

ine stress incontinence . BJU Int , 85 : 655 – 658 ., 2000 .

9 . Goode PS , Burgio KL , Locher JL , et al. Effect of

behavioral training with or without pelvic floor

electrical stimulation on stress incontinence in

women: A randomized controlled trial . JAMA ,

290 : 345 – 352 , 2003 .

10 . Takahashi T , Garcia-Osogobio S , Valdovinos MA ,

et al. Extended two-year results of radio-frequency

energy delivery for the treatment of fecal inconti-

nence (the Secca Procedure) . Dis Colon Rectum ,

46 : 711 – 715 , 2003 .

11 . Fanelli RD , Gersin KS , Bakhsh A . The Stretta pro-

cedure: Effective endoluminal therapy for GERD .

Surg Technol Int , 11 : 129 – 134 , 2003 .

12 . DeLancey JO . Structural support of the urethra as it

relates to stress urinary incontinence: The hammock

hypothesis . Am J Obstet Gynecol , 170 : 1713 – 1720 ,

1994 .

13 . Hecht P , Hayashi K , Lu Y , et al. Monopolar radi-

ofrequency energy effects on joint capsular tissue:

Potential treatment for joint instability. An in-vivo

mechanical, morphological, and biochemical study

using an ovine model . Am J Sports Med , 27 : 761 –

771 , 1999 .

14 . Galen DL . Histologic results of a new treatment

for stress urinary incontinence without implantable

materials . Obstet Gynecol , 95 : 530 – 533 , 2000 .

15 . Fulmer BR , Sakamoto K , Turk TM , et al. Acute and

long-term outcomes of RF BNS . J Urol , 167 : 141 –

144 , 2002 .

16 . Smith A , Hosker GL , Warrell DW . The role of par-

tial denervation of the pelvic floor in the aetiology

of genito-urinary prolapse and stress incontinence of

urine. A neurophysical study . Br J Obstet Gynaecol ,

96 : 24 – 28 , 1989 .

17 . Allen R , Hosker GL , Smith AR , et al. Pelvic floor

damage and childbirth: A neurophysiologic study .

Br J Obstet Gyaecol , 97 : 770 – 779 , 1990 .

18 . Keane DP , Sims TJ , Abrams P , et al. Analysis

of collagen status in premenopausal nulliparous

women with genuine stress incontinence . Br J

Obstet Gynaecol , 104 : 994 – 998 , 1997 .

19 . Norton P . Pelvic floor disorders: The role of fascia and

ligaments . Clin Obstet Gynecol , 36 : 929 – 939 , 1993 .

20 . Aronson M , Bates SM , Jacoby AF , et al. Periurethral

and paravaginal anatomy: An endovaginal magnetic

resonance imaging study . Am J Obstet Gynecol ,

173 : 1702 – 1710 , 1995 .

21 . Richardson , A . Cystocele. Paravaginal repair. In :

Female pelvic floor disorders . Benson J , ed. New

York : Norton Medical Books , 1992 : 280 .

22 . Osmond C , Hecht P , Hayashi K , et al. Comparative

effects of laser and radio frequency energy on joint

capsule . Clin Orthoped , 286 : 299 , 2000 .

23 . Hecht P , Hayashi K , Cooley AJ , et al. The thermal

effect of monopolar radio frequency energy on the

properties of joint capsule. An in-vivo histologic

study using a sheep model . Am J Sports Med ,

26 : 808 , 1998 .

24 . Lopez MJ , Hayashi K , Fanton GS , et al. The effect

of radio frequency energy on the ultrastructure

116 R. R. Dmochowski and E. Cole

of joint capsular collagen . Arthroscopy , 14 : 495 ,

1998 .

25 . Allain JC , Le Lous M , Cohen S , et al. Isometric ten-

sions developed during the hydrothermal swelling of

rat skin . Connect Tissue Res , 7 : 127 – 132 , 1980 .

26 . Chen SS , Wright NT , Humphrey JD . J Biomech

Eng , 119 : 372 – 378 , 1997 .

28 . Ross J , Galen D , Abbott K , et al. A prospective

multisite study of radiofrequency biopolar energy

for treatment of genuine stress incontinence . J Am

Assoc Gynecol Laparosc , 9 : 493 – 499 , 2002 .

29. Dmochowski RR, Ross JW, Levy BS, et al. Three-

year cure and improvement rates of a transvaginal

radio frequency procedure for genuine stress incon-

tinence. Unpublished data, 2005.

30 . Appell RA , Juma S , Wells WG , et al. Transurethral

radiofrequency energy collagen micro-remodeling

for the treatment of female stress urinary inconti-

nence . Neurourol Urodyn , 25 (4) : 331 – 336 , 2006 .

31 . Tincello DG , Alfirevic Z . Important clinical out-

comes in urogynecology: Views of patients, nurses

and medical staff . Int Urogynecol J Pelvic Floor

Dysfunct , 13 : 96 – 98 , 2002 .

32 . Hullfish KL , Bovbjerg VE , Gibson J , et al. Patient-

centered goals for pelvic floor dysfunction surgery:

What is success, and is it achieved? Am J Obstet

Gynecol , 187 : 88 – 92 , 2002 .

33 . Robinson D , Anders K , Cardozo L , et al. What

women want – their interpretation of the concept of

cure . Neurourol Urodyn , 21 : 429 – 430 , 2002 .

117

Why a historical survey of surgery for stress incon-

tinence? There are several reasons. First, there is

much to learn from the mistakes of the past. In the

words of Miguel de Santayana, “Those who fail to

heed the lessons of history are doomed to repeat

it.” There was a time, for example, when surgeons

were taught that to be effective, slings needed to be

tied tightly enough to compress the urethra. That

resulted in some disastrous complications and we

do not do that any more. Second, as pointed out

by Issac Newton, the accumulated experience of

those who have gone before forms the substrate on

which we formulate the innovations of the future.

Relating to his own work, he said, “If I have seen

further, it is by standing on the shoulders of giants.”

Relating to stress incontinence, the history of pro-

posed pathophysiology and classification serves as

a cogent example of this concept.

In Hinman’s textbook of urology, published in

1935, fewer than 2 of 1,111 pages were devoted

to incontinence. It was classified as (1) true incon-

tinence, (2) false incontinence, (3) paradoxical

(overflow) incontinence, and (4) essential inconti-

nence. True incontinence was defined as “constant

urinary leakage….resulting from a permanent dys-

function of the urinary reservoir or its sphincteral

apparatus.” No real distinction was made between

the two. In 1961, Green proposed the first formal

classification system for stress incontinence based

on the radiographic appearance of the bladder

neck and urethra during increases in abdominal

pressure. He described two types. In type 1 SUI

there was loss of the posterior urethrovesical angle,

whereas in type 2 there was in addition a rotational

descent of the urethra [1] . This remained the only

classification until 1980, when McGuire defined

type 3 SUI [later termed intrinsic sphincter defi-

ciency (ISD)], as a low urethral closure pressure

associated with an open vesical neck at rest [2] .

McGuire’s classification was based on his own

astute clinical observations. He noticed that there

was an unusually high failure rate among women

who underwent retropubic urethropexy after prior

unsuccessful anti-incontinence surgery. He sought

to find the reason why using newly refined uro-

dynamic techniques. He found that those who

had what he termed type 3 stress incontinence

were the ones with the high failure rates, and he

subsequently found that those patients fared better

after autologous fascial sling surgery instead of

urethropexy.

Until that time urodynamic studies were not used

very often for women with stress incontinence;

rather, they were reserved mostly for patients with

neurogenic bladder. McGuire’s contribution in uti-

lizing urodynamics in women cannot be overstated.

Using videourodynamic techniques, Blaivas and

Olson (1988) further refined this Green/McGuire

classification by adding type 0 stress incontinence

[3] . Type 0 SUI was defined as a woman who com-

plains of stress incontinence, but is not incontinent

during the urodynamic study, yet has the substrate

for type 2stress incontinence (rotational descent

of the urethra and opening of the vesical neck and

proximal urethra). They further observed that some

patients with apparent hypermobility, the bladder

Chapter 10

Surgery for Stress Urinary Incontinence:

Historical Review

Matthew P. Rutman and Jerry G. Blaivas*

118 M.P. Rutman and J.G. Blaivas

neck and proximal urethra were not hypermobile

at all; rather, they were scarred (from previous sur-

gery) in a low-lying position. They called this type

2B SUI. The implications for surgical treatment of

type 2B SUI is that a urethrolysis was necessary at

the time of sling procedure.

Thereafter, the Green/McGuire/Blaivas classi-

fication of SUI became an important clinical tool

for helping to determine which anti-incontinence

procedure to choose in an effort to minimize

surgical failures [2, 3] . Subsequently, it has been

documented over and over that sling procedures

have good efficacy in treating type 3 SUI, whereas,

retropubic urethropexy and transvaginal suspension

do not fare as well. This fact, and the decreased

morbidity associated with vaginal approaches, has

led to widespread use of sling procedures as a first-

line option to treat SUI.

The Green/McGuire/Blaivas classification is

still widely utilized today, but as urodynamic

techniques became more sophisticated and more

widely used in clinical research, it became appar-

ent that deficient anatomy was only part of the

pathophysiology of sphincteric incontinence. Until

McGuire’s reported observation in 1980, it was

thought that urethral hypermobility was the only

cause of sphincteric incontinence and that surgi-

cal treatment should be aimed at restoring the

proximal urethra to its normal “high retropubic

position [1, 4] .

Based on these observations, during the decade

of the 1990s, it became fashionable to classify

sphincteric incontinence into two distinct catego-

ries: urethral hypermobility and intrinsic sphincter

deficiency based on the leak point pressure [5, 6] .

The need for this classification was fortified when

in the United States Medicare regulations required

that in order to receive payment for periurethral

injection of collagen, the leak point pressure must

be less than 60 cm H

2 0, i.e., intrinsic sphincter

deficiency. At the time it was widely believed

that women with urethral hypermobility should

be treated with bladder neck suspensions and

those with ISD should undergo a sling procedure.

However, further studies revealed that these two

conditions can (and often do) coexist in the same

patient and that the expected inverse relationship

between leak point pressure and urethral hypermo-

bility does not exist [7, 8] . Accordingly, we (the

authors) no longer classify SUI according to any

of these schemas; rather, we simply characterize it

by the leak point pressure (a measure of sphincter

strength) and the degree of urethral hypermobility

(Q-tip angle).

Of course, the linchpin of all of these classifica-

tions systems is the underlying pathophysiology.

For most of the twentieth century, until the inno-

vative work of Petros and Ulmsten, it was widely

believed that the bladder neck is the primary

mechanism of continence [9, 10] . Reinforced by

a number of basic science and clinical studies, it

was postulated that increased abdominal pressure

normally is transmitted equally to both bladder

and urethra. When the proximal urethra descends

too far, increases in abdominal pressure become

unequally transmitted, and when vesical pressure

exceeds urethral pressure, stress urinary inconti-

nence ensues [11– 15] .

However, further studies unexpectantly showed

that many women with significant urethral hyper-

mobility remain continent, suggesting that urethral

hypermobility is not the sole cause [16] . In fact,

in McGuire’s original description of type 3 SUI,

he noted that it denoted an intrinsic malfunction

of the urethral sphincter independent of urethral

mobility. Further, as early as 1981, Constantinou

demonstrated that pressure changes during stress

are highest in the midurethra in continent woman

and that this is lost in women with stress incon-

tinence [12] . Subsequently, Petros and Ulmsten

proposed that the midurethra, supported anteriorly

by the pubourethral ligaments, is the primary

continence mechanism, and from their worked

emerged the midurethral sling procedures surgical

procedures that have become the current rage [9,

10, 12, 17– 21] .

Petros and Ulmsten further expounded on the

pathophysiology of incontinence with their “inte-

gral theory.” The integral theory posits that stress

and urge incontinence have a common etiology [9] .

It states that support of the anterior vaginal wall is

provided by three separate, but synergistic mecha-

nisms: (1) the anterior pubococcygeus muscle lifts

the anterior vaginal wall to compress the urethra,

(2) the bladder neck is closed by traction of the

underlying vaginal wall in a backward and down-

ward fashion, and, (3) the pelvic floor muscula-

ture, under voluntary control, draws the hammock

upward, closing the bladder neck. Overall laxity

of the anterior vaginal wall causes a dissipation of

10. Surgery for SUI: Historical Review 119

all of these forces, resulting in stress incontinence.

They further suggested that laxity of the anterior

vaginal wall causes activation of stretch receptors

in the bladder neck and proximal urethra, which can

trigger an inappropriate micturition reflex, resulting

in detrusor overactivity. Based on this theoretical

work, they devised an operation: the tension-free

vaginal tape (TVT) placed at the midurethra rather

than the bladder neck. Subsequently, this and other

midurethral operations have been shown to be suc-

cessful in treating stress incontinence, at least in

the short term [22– 26] .

In the 1990s a group of investigators at Johns

Hopkins, using fast scan MRI and real-time perineal

ultrasound, proposed that another mechanism caus-

ing SUI is unequal movement of the anterior and

posterior walls of the bladder neck and proximal

urethra during stress; the urethral lumen is liter-

ally pulled open as the posterior wall moves away

from the anterior wall [27, 28] . According to this

theory, it is the relative strength of the anterior and

posterior urethral attachments that determine conti-

nence. If both are equally strong (or weak), the ure-

thral walls will either not move at all or will move

equally and continence will be maintained. If the

anterior attachments are stronger than the posterior

ones when there is sufficient force to cause move-

ment, the posterior wall will be pulled open and

incontinence will ensue. These investigators also

demonstrated that the common denominator in

SUI is opening of the bladder neck (funneling), not

urethral hypermobility.

In 1995, John DeLancey proposed the hammock

theory of urethral support [29] . He postulated that

continence is maintained when the urethra is com-

pressed against the hammocklike musculofascial

structures on which the bladder and urethra rest. In

this model, it is not the degree of urethral mobil-

ity, but the weakness of the supporting layers that

cause sphincteric incontinence.

Upon first reflection, the preceding discussion

might appear to be one of semantics, just splitting

hairs. In fact, though, it is the understanding of

pathophysiology and the mechanisms by which

treatments affect pathophysiology that provides the

requisite knowledge base for innovation. Based on

this understanding (or misunderstanding), the sur-

gical treatment of SUI has evolved from compres-

sion of the urethra to restoring the bladder neck to

a high retropubic position to preventing descent to

creating a backboard against which the urethra can

be compressed. Additionally, the focus of attention

has turned from the bladder neck to the midurethra.

In fact some of the most popular procedures for the

treatment of stress incontinence do not change the

position of the urethra or even correct hypermobility

[30– 32] . Just as the current treatments have evolved

from those of the past, future treatments will evolve

from those of the present. Exploring the century-

long history of retropubic suspensions and slings

provides a critical background and comprehension

of where we are currently and hopefully what the

future has in store for the treatment of SUI.

Surgical Procedures for SUI

The surgical treatment of SUI has evolved along

three different lines: retropubic suspensions, trans-

vaginal placations, and pubovaginal slings. The

latest iteration of the former is the laparoscopic

and robotic Burch colposuspension and trans-

vaginal bladder neck suspension and the latter is

the midurethral sling. The latest, of course, is not

necessarily the best!

Transvaginal Plication

In 1914, Kelly first reported plication of the “lat-

eral tissues” of the bladder neck under the urethra

in “women without manifest injury to the bladder”

[33] . His initial report revealed an 80% short-term

success rate in 20 patients. Kennedy, nearly a quar-

ter of a century later, described his modification

to the Kelly procedure to include dissection of the

urethra from the vaginal wall with plication of the

injured sphincter muscle at the urethrovesical junc-

tion. The procedure became commonly known as

the Kelly-Kennedy plication [34] . Although both

of these procedures had relatively poor long-term

success rates, they remained very popular because

of their simplicity, lack of significant complica-

tions, and the ease with which they could be per-

formed at the time of prolapse surgery [35] . The

Ball–Burch procedure used a combined approach,

performing a transabdominal Burch procedure with

transvaginal imbrication of the urethra. Compared

with the Burch or Kelly plication alone, the Ball–

Burch procedure had improved continence rates in

120 M.P. Rutman and J.G. Blaivas

women with SUI and low urethral pressures [36,

37] . However, in a meta-analysis of the English

language literature, Leach et al. concluded that the

overall success rate of the Kelly–Kennedy proce-

dure was only about 60% compared to over 85%

for slings and retropubic operations [35] .

Retropubic Suspensions

The retropubic suspensions or urethropexy proce-

dures use existing tissues to reinforce, reposition,

and stabilize the bladder neck into a high retropubic

position. This procedure was first described in the

United States by George White in 1909, as part of

a retropubic paravaginal repair done for a cystocele

repair [38] . The abdominal paravaginal repair was

later popularized by Richardson in the early 1980s

[39] . The paravaginal repair reattaches the endopel-

vic fascia that has pulled away form its attachment

to the arcus tendinous fascia pelvis. It was reported

to result in the cure of SUI; however, there was a

paucity of literature demonstrating good efficacy.

A recent prospective evaluation comparing the

paravaginal defect repair to the Burch procedure

showed a much higher failure rate in those under-

going the former [40] . At the present time, most

surgeons who perform paravaginal repair combine

it with a Marshall–Marchetti–Krantz (MMK) or a

Burch colposuspension in order to treat SUI [41] .

The original MMK procedure was first reported

in 1949 [42] . The rationale for the MMK was

based on observations made in men who presented

with urinary retention after abdominoperineal (AP)

resection of the rectum : “…Most of the patients…

had mobility and marked sagging of the vesical

base and outlet…lack of elevation and fixation…In

some cases firm upward pressure on the perineum

with a fist or harness would provide temporary

elevation and fixation and these patients could

thereby void satisfactorily.” The first MMK was

actually performed on a man who developed uri-

nary retention after AP resection: “Two transure-

thral resections resulted in total incontinence even

though the external urethral sphincter had not been

damaged. Perineal pressure would provide good

control. Simple suprapubic suspension of the vesi-

cal outlet by suturing to the pubis immediately and

completely corrected his urinary control which has

remained normal for a period of 46 months. By

analogy, the knowledge gained from the study of

these rectal cases was applied to the problem of

the common stress incontinence of females.” The

first operation on a woman was performed on June

8, 1944.

In the original description of the MMK proce-

dure, two sutures were placed on either side of the

periurethral tissues and anchored to the periosteum

of the pubic symphysis. The operation resulted

in “a simple elevation and immobilization of the

vesical neck and urethra by suturing them to the

pubis and rectus muscles” [43] . In a large review

of 56 articles, the overall complication rate was

21.1% with a 5% wound complication rate and

a 2.5% incidence of osteitis pubis [44] . In some

instances, osteitis pubis resulted in severe and

prolonged pubic pain with significant discomfort

and disability [45] . Subsequently, to avoid these

problems, sutures were placed in the cartilage of

the symphysis.

In a further modification, Burch, in 1958,

described the operation that now bears his name.

Three sutures of 2–0 chromic were placed bilater-

ally, attaching the periurethral tissue directly to the

ileopectineal ligament of Cooper [46] . Tanagho

reported his modification of the original Burch

procedure in 1976 at the Western Section of the

American Urological Association meeting [47] .

His adjustments included placement of more lateral

sutures and emphasizing the avoidance of excess

tension between Cooper’s ligament and the anterior

vaginal wall. Tanagho was the first to suggest the

concept of avoiding overelevation of the vaginal

wall during urethropexy surgery in an effort to

limit prolonged voiding dysfunction. The retro-

pubic urethropexy remains an important part of

the choices available to the surgeon and the Burch

colposuspension is its gold standard. Cure rates

have been reported to range from 69 to 93.7% in

long-term (10–15 year) follow-up [48– 50] .

Laparoscopic Retropubic

Urethropexy

Laparoscopic approaches to retropubic urethropexy

were introduced to address the morbidity associ-

ated with open procedures, but the overall success

rate has been disappointing. It was first described

10. Surgery for SUI: Historical Review 121

in 1991, using a transperitoneal approach [51] .

Currently, most laparoscopic urethropexy surgery

uses an extraperitoneal approach mimicking the

open procedure. Both Burch and MMK procedures

have been reported using laparoscopic techniques,

but reported cure rates have been lower than the

open technique (80% vs. 96% at minimum 1-year

follow-up) [52] . Techniques for suture placement

have varied from instrument suturing (duplicating

the open procedure) to stapling and tacking devices

that attach mesh to Cooper’s ligament. Recent

publications have revealed an increase in the use

of laparoscopy and robotic-assisted laparoscopy

for vaginal prolapse surgery, which may lead to

an increase in the number of concomitant laparo-

scopic urethropexies. Theoretically, performing the

procedure laparoscopically in an identical manner

to the open approach should reveal equivalent out-

comes with potentially less morbidity, but theory is

far from practice.

Transvaginal Needle Suspensions

Transvaginal needle suspension procedures evolved

in an effort to provide a simpler and less morbid

treatment option, yet preserve the excellent results

of retropubic urethropexy. The initial goal of these

operations was to elevate the bladder neck and

proximal urethra in that high retropubic position

with the use of nonabsorbable suture. Armand

Pereyra introduced the first transvaginal needle

suspension in 1959, because of his observational

failures with the MMK procedure. The Peyera

operation used a ligature carrier to suspend the

“pericervical” fascia from the rectus fascia with

stainless steel sutures [53] . He later modified the

procedure to include chromic suture material for

helical passes through the pubourethral endopel-

vic fascia. Further multiple modifications were

developed under the generic name of “modified

Pereyra procedures.” In 1973, Thomas Stamey fur-

ther modified the procedure by passing the suture

through a polyester buttress (Dacron pledgets) that

was placed superficial to the endopelvic fascia

in an attempt to prevent the observed high rate

of suture pull-through with the modified Pereyra

procedure. He also recommended performing cys-

toscopy to identify the position of the bladder neck

and aid in placing the sutures in a more accurate

manner and to recognize inadvertent passage of the

suture through the bladder or urethra [54] . Stamey

devised a single-holed ligature carrier (Stamey nee-

dle) that was the forerunner of the instruments used

to pass sutures from the abdomen to the vagina.

The Stamey procedure, as it was known, became

very popular and remained so until the mid 1980s

when it was supplanted by a further modification

reported by Shlomo Raz. In 1981, Raz further

modified the modified Pereyra by including the

vaginal wall (beneath the epithelium) and the

pubocervical fascia (which he later called the ure-

thropelvic ligament) within the helical suture [55] .

Raz reported a greater than 90% success rate, but

this was not reproducible by other surgeons. In

1987, Ruben Gittes and Kevin Loughlin reported

yet another modification, which they called the

“incisionless suspension.” They passed the helical

sutures through the vaginal wall without any inci-

sion and used stab puncture wounds suprapubically

with blind passage of a needle ligature passer [56] .

This operation also gained some popularity for a

while and became known as the Gittes procedure.

All these operations were reported to have excel-

lent short-term results (without, of course, any

meaningful or validated outcome measures), but

longer follow-up revealed a high rate of recurrent

incontinence attributed to pull through of the

sutures from their vaginal attachments. Further,

many complications went unreported (suture gran-

ulomas, erosions, ureteral injuries). Transvaginal

needle suspensions were evaluated by the American

Urological Association Female Stress Urinary

Incontinence Clinical Guidelines Panel and their

recommendation for these procedures was “low”

or “marginal” due to low long-term cure rates [35] ,

and these operations fell into disfavor. The lessons

learned from all these operations, though, paved

the way for the next generation of operations: ante-

rior vaginal wall suspensions, vaginal wall slings,

and bone anchor suspensions. All these operations

were intended to improve on the rate of suture pull-

through by incorporating stronger fixation points in

the repair.

In 1989, Raz described the “four-corner suspen-

sion,” a transvaginal needle suspension operation

that repaired anterior vaginal wall prolapse in addi-

tion to its anti-incontinence mechanism. He accom-

plished this by placing a second set of sutures at the

cystocele base. The four sutures were transferred

122 M.P. Rutman and J.G. Blaivas

suprapubically by a ligature carrier and secured

to the anterior rectus fascia. He reported subjec-

tive cure rates of 94 and 98% for incontinence

and cystocele, respectively. Longer-term follow-up

revealed significant cystocele recurrences [57] .

Using a rabbit model, Bruskewitz and colleagues

compared different anchoring materials and suture

pull-through rates, reporting that loops of suture

and greater cross-sectional area of the anchor would

lead to lower pull-through rates and higher success

rates [58] . Based on that research, Leach and

Zimmern modified the Raz procedure by obtaining

a broader anterior vaginal wall anchor to decrease

the rate of suture tissue pull-through. They referred

to this procedure as the “anterior vaginal wall sus-

pension” [59] . This procedure is still advocated by

some due to its technical ease, low morbidity, and

reproducibility, particularly in patients with a small

to moderate cystocele and urethral hypermobility,

but in our judgment has the same high failure rate

accorded the other procedures.

Pubovaginal Sling

The pubovaginal sling originally was described

nearly a century ago. Urologists and gynecologists

used the sling procedure in an attempt to replace

the sphincter mechanism due to anatomic sphincter

defects. It has undergone numerous modifications

and advances, and what once was an operation

considered only for severe and refractory SUI, it

has now become the most commonly performed

and efficacious procedure for treating SUI. While

the autologous rectus fascial sling remains the gold

standard for treating SUI, synthetic midurethral

slings are gaining momentum and are the most

commonly performed operations in the industrial-

ized world today.

In 1907, Von Giordano described the first rudi-

mentary pubovaginal sling, where via an abdomi-

nal approach he wrapped a gracilis muscle graft

around the urethra [60] . Three years later, Goebell

performed a sling constructed from pyrimidalis

muscle, tunneling the muscle flaps through the ret-

ropubic space and suturing them together under the

bladder neck [61] . In 1914, Frangenheim modified

Goebell’s technique, incorporating the overlying

rectus fascia in the flap to allow for a longer sling

[62] . Three years later, Stoeckl further modified

the technique by adding a combined abdominal

and vaginal approach to plicate the bladder neck

[63] . This later became known as the Goebell–

Frangenheim–Stoeckel technique and was the first

to use a combined abdominal–vaginal approach. In

1923, Thompson sutured rectus muscle and fascia

around the urethra [64] . Martius, in 1929, described

the interposition of bulbocavernosus muscle and

the labial fat pad between the vaginal wall and

urethra [65] . While novel in concept and impor-

tant historically, each of these procedures caused

urethral compression and obstruction, resulting in

high rates of urethral sloughing, fistula occurrence,

and recurrent cystitis.

In 1933, Price became the first to report using

autologous fascia lata, which he passed beneath

the urethra from an antegrade approach. The ends

of the fascia then were secured to the rectus mus-

cle [66] . In 1942, Aldridge, in a single case report,

described the use of rectus fascia as a fascial sling

placed through the retropubic space under the ure-

thra. He detached strips of rectus fascia and external

oblique aponeurosis laterally, leaving them attached

medially. He was the first to suggest that the sling

resulted in urethral compression during times of

increased intra-abdominal pressure. Aldridge also

identified the periurethral fascia and described the

bloodless plane that permitted entry into the space

of Retzius (retropubic space) [67] . The anatomic

drawings of surgical technique that accompanied

the original paper are superb and probably contrib-

uted greatly to its short-term popularity [68] . There

were, however, several significant limitations to the

Aldridge sling: (1) the attached medial edges of

rectus fascia limited the mobility of the sling, (2)

the sling length was not always long enough to pass

under the urethra, and (3) there was no method to

avoiding excess tension under the bladder neck and

proximal urethra, resulting in outlet obstruction.

As a result of these drawbacks, several modifica-

tions were made to Aldridge’s operation over the

ensuing decades in an attempt to improve mobility,

increase sling length, and avoid excess tension.

Despite these changes, multiple complications (fis-

tulas, urethral slough, obstruction, infections, and

sepsis) and poor outcomes limited the use of sling

surgery for SUI.

McGuire, in 1978, ushered in the modern era of

sling surgery when he described a modified tech-

nique using autologous rectus fascia for women

10. Surgery for SUI: Historical Review 123

with the entity that he first described: type 3 SUI

[69] . The operation was performed with a combined

vaginal and abdominal approach. A strip of rectus

fascia, 1 × 12 cm in length, was isolated leaving it

attached laterally on one side. The other end of the

fascial strip was passed through the rectus muscle

and positioned under the urethra before reattaching

it to the other side of the rectus fascia. In his initial

series of 52 women with type 3 SUI, the success

rate was 80% with 2.3 year mean follow-up. The

obvious problem with this technique was the fact

that there was no way to adjust the tension as long

as one end of the sling was left attached. To remedy

this, Blaivas reported a modification that utilized a

free graft of rectus fascia whose tension could be

adjusted [70] .

A major paradigm shift for the surgical treat-

ment of SUI occurred when Blaivas reported on the

use of autologous rectus fascial sling for all type of

SUI, not just for those with type 3 SUI or ISD. At

the time, this was a major development because it

was commonly thought that such slings should be

reserved for those with severe incontinence, since

the operation was believed to be difficult to mas-

ter and plagued by complications. Subsequently,

numerous reports have documented the safety,

efficacy, and long-term durability of the autologous

fascia pubovaginal sling with medium-term cure

rates of 73–93% [71– 74] . The complication rate

is relatively low, with risks of prolonged retention

of less than 5%, and de novo urgency incontinence

around 3% [75] . The risk of urethral erosion with

autologous fascia is miniscule. This resurrected

sling surgery and paved the way for the current era

of slings as a first-line option for women with or

without urethral hypermobility. It remains the gold

standard to which all sling procedures using new

materials and anchoring techniques are compared.

Materials

Multiple materials have been utilized in pub-

ovaginal sling surgery. These can be subdivided

into autologous, allograft, xenograft, and synthetic

sling materials.

1. Autologous fascia. Two sources of autlogous fas-

cia have been used for slings: rectus abdominis

and fascia lata. Autologous fascia lata sling

surgery initially was described by Price in 1933

[66] . After McGuire’s work reinvigorated the

pubovaginal sling, rectus fascia became the

most commonly used source, but many authors

reported the use of fascia lata to avoid the mor-

bidity of the abdominal incision employed for

harvesting of the rectus fascia. Fascia lata is

obtained from the iliotibial tract, with skin inci-

sions located between the greater trochanter and

the lateral epicondyle of the femur. Advantages

of harvested fascia lata included the quality and

length of available fascia, and the increased ten-

sile strength of nonscarred tissue. Disadvantages

included the additional time associated with

harvesting and patient repositioning, as well as

pain and cosmetic deformity at the incision site.

Autologous fascia (rectus or fascia lata) remains

the gold standard material for pubovaginal sling

surgery. Significant complications with autolo-

gous fascia are rare and are limited mostly to

urinary retention and de novo detrusor overactiv-

ity, likely the result of the sling tension and not

the material itself.

2. Allograft. Allograft tissues are those harvested

from human donors, typically cadavers, and

transplanted into human recipients. Use of these

tissues in pubovaginal sling surgery avoids the

incision and time associated with harvesting of

autologous fascia, resulting in shorter operating

room time and quicker convalescence. In addi-

tion, it avoids the potential infection and erosion

complications seen with the use of synthetic

materials. Allograft materials used in sling sur-

gery include lyophilized dura mater, fascia lata,

and acellular dermis. European urologists have

used lyophilized dura mater for many years.

It has been used in bladder augmentations,

vesicovaginal fistula repair, urethroplasty, and

surgery for Peyronie’s disease [76– 79] . Several

reports of dura in sling surgery have shown

89–92% cure rates with short- and intermediate-

term follow-up [80, 81] . Cadaveric fascia lata

(CFL) was first reported in incontinence surgery

by Handa et al. in 1996 [82] . Prior to this it was

used in orthopedic and ophthalmologic surgery

for 15 years. The allograft tissue is obtained

from a tissue bank and the process is regulated

by the American Association of Tissue Banks.

Although a thorough sterilization process is

employed, the major safety issue concerning

124 M.P. Rutman and J.G. Blaivas

the use of cadaveric allografts remains possible

disease transmission, including human immu-

nodeficiency virus (HIV) and Creutzfeldt–Jakob

disease (CJD) as well as other prion diseases.

All cadaveric tissues undergo serological screen-

ing for HIV and hepatitis B, but false-negative

results are possible. The risk of HIV transmis-

sion is estimated to between 1 in 1,667,600

and 1 in 8 million, and the risk of CJD around

1 in 3.5 million [83– 85] . There have been no

reports of disease transmission with an allograft

sling, but there have been reports of bacterial

contamination including several cases of fatal

transmission of clostridial infections in ortho-

pedic surgery [86, 87] . DNA has been detected

in solvent-dehydrated and freeze-dried CFL,

as well as acellular dermis [88, 89] . Only one

case of HIV transmission has been reported,

occurring in 1985 in a woman receiving a bone

allograft transplant [90] . One case of CJD was

reported in a nonurological procedure where a

patient received a cadaveric dura graft 12 years

earlier [91] . No cases of CJD have been reported

with the use of CFL. However, there have been

reports of fatal CJD with allograft dura and we

recommend that it no longer be used [92, 93] .

CFL is processed by one of several tech-

niques: solvent dehydration and gamma irra-

diation (Tutoplast®), freeze drying (FasLata®),

and fresh frozen. Rehydration after processing

is required for 15–30 min. Various processing

techniques and early reported allograft failures

have brought significant debate to the tensile

strength of CFL. Chaikin et al. reported the

first failure of a CFL sling in 1998, in a patient

whose SUI recurred 3 days postoperatively. At

reoperation, the edges of the graft had frayed

and sutures had pulled through [94] . Sutaria

et al. found no difference in tensile strengths

of freeze-dried CFL, solvent-dehydrated CFL,

and acellular cadaveric dermis [95] . Lemer et

al. reported freeze-dried CFL had decreased

tensile strength and tissue consistency [96] . The

early reports on CFL sling demonstrated cure

rates of 62.6–98% and were similar to those

cure rates reported with autologous fascia [85,

97– 99] . Fitzgerald et al. published their results

on 35 women who underwent a pubovaginal

sling with freeze-dried and irradiated CFL [100] .

Eight of the 35 patients (23%) failed both sub-

jectively and objectively within 6 months, of

whom 7 had been initially cured. On reexplora-

tion, the fascia had diminished to remnants or

could not be identified. Similar findings were

reported by Carbone and Raz at UCLA [101] .

Frederick and Leach recently reported durable

cystocele repair results, but noted a decrease

in continence rates with the use of cadaveric

tissues [102] . More recently, several acellular

dermal allografts have been marketed for use

in sling surgery, including Repliform®, Dermal

Allograft®, and Alloderm®. Dermal allografts

are strong, have similar mechanical properties

to autologous tissues in vitro, and integrate well

into tissue. In addition, it rehydrates in 5to 10

min, whereas CFL takes 15–30 min of hydration

prior to implantation.

3. Xenografts. Xenografts are derived from non-

human animal tissue. Zenoderm® was the first

xenograft used in pubovaginal sling surgery.

It is derived from porcine corium, treated with

proteolytic enzymes to remove the noncollagen-

ous material, and immersed in glutaraldehyde

to cros-link the collagen molecules and reduce

antigenicity. Cure rates of 78–90% have been

reported, although there were several reports

of significant wound infection rates [103– 105] .

Porcine corium also has been marketed under

the brand names Pelvicol? and DermMatrix?. In

contrast to Zenoderm®, these are cross-linked

by diisocyanate and they avoid the graft min-

eralization that may occur with glutaraldehyde.

Barrington et al. reported an 85% cure rate

in 40 patients who underwent sling surgery

with Pelvicol? with 12-month mean follow-up

[106] . Stratasis®, a graft derived from porcine

small intestinal submucosa (SIS), has been mar-

keted recently for use in vaginal sling surgery.

Rutner reported a 94% continence rate in 115

women who underwent a sling procedure, with

infrapubic bone screws and SIS, with 36-month

follow-up [107] . Bovine pericardium also has

been marketed in several preparations for sling

surgery. Using UroPatch? and infrapubic bone

screws, Pelosi reported a 95% cure rate in 22

patients with 20-month mean follow-up [108] .

4. Synthetic sling materials. Autologous fascia

remains the gold-standard of materials, but few

would deny that synthetic materials have stronger

biomechanical properties. It is hypothesized that

10. Surgery for SUI: Historical Review 125

the superior biomechanical properties will result

in greater long-term efficacy and durability. The

perfect synthetic material should have great

tensile strength, be noncarcinogenic, inexpen-

sive, nonallergenic, nonimmunogenic, and user-

friendly. Synthetic slings vary in many ways

including pore size, composition, and flexibility.

They can be absorbable or permanent. Interstices,

or interstitial pores, located in multifilament

mesh, are much smaller than standard pores.

This can prevent macrophage and immune influx

yet allow bacteria free entry. The small pore size

also can retard the fibrocollagenous ingrowth

and inhibit sling scaffolding into neighboring

tissues. Synthetic slings carry no risk of disease

transmission aside from the theoretic potential

of contamination with pathogens which has not

been reported.

Synthetic materials were first used for slings in

the 1950s in select patients (supposedly) devoid of

usable fascia. In 1951, Bracht reported using nylon

for sling construction [109] . The following year,

Anselmino described Perlon as a sling material

[110] . In 1961, Zoedler reported using nylon strips

for a suburethral sling [111] . In 1962, Williams and

TeLinde described the use of a 5-mm-wide piece

of Mersilene (Dacron) ribbon, a permanent multi-

filament synthetic, for sling surgery [112] . These

synthetic procedures were all prone to obstruction

at the bladder neck, potentially resulting in urinary

retention, suprapubic abscess formation, and ure-

thral fistula. In 1968, in an effort to decrease com-

plications, Moir utilized a wider piece of Mersilene

in a modified Aldridge sling, which was called

the “gauze hammock operation” [113] . He felt

the Aldridge sling and prior Mersilene surgeries

resulted in complications due to the narrow size of

the sling itself. His gauze hammock operation con-

sisted of a 30 cm-long piece of Mersilene which

had a center portion 2.5 cm in width placed under

the bladder neck. The two ends of the synthetic

were then secured to the rectus fascia. He reported

an 81% cured or improved rate in 71 patients with

up to 5-year follow-up. Nichols reported similar

success in 1973 [114] . Both Moir and Nichols

reported their success rates using physician assess-

ment, not patient self-assessment.

In 1970, Morgan reported the use of a Marlex

mesh for the treatment of recurrent stress urinary

incontinence [115] . Marlex is a stiff polypropylene,

permanent monofilament mesh with large pores

and is devoid of interstices. Morgan described

using a 2 cm strip of polypropylene mesh that he

anchored to Cooper’s ligament using a two-team

combined abdominal and vaginal approach. His

initial results revealed a 100% success rate. Longer

follow-up, published 15 years later, revealed this

number was closer to 80%. However, there were

significant complication rates, as with prior types

of sling surgery, including 6% rates of both urethral

erosion and chronic retention, and a 5% rate of

postoperative frequency and urgency [116] .

Many other synthetic materials have been

described in the last two decades. Stanton reported

the first use of a sling made from Silastic, a mate-

rial made from layers of silicone reinforced with

Dacron. It is a permanent multifilament mesh with

submicron pore size. This was theorized to be

advantageous due to the sheath that surrounds the

sling. In case of complications necessitating sling

removal, it was thought that the sheath would make

it easier to identify and remove the sling, while still

preserving continence. Long-term data revealed a

71% cure rate at 5 years, but again there were high

complication rates, particularly sinus formation

and rejection [117] , and subsequently the use of

Silastic was abandoned.

In 1988, Horbach described using Gore-tex as

a synthetic sling material [118] . Gore-tex is an

expanded polytetrafluoroethylene, which is nonab-

sorbable and inert, and was theorized to incorporate

with less foreign body reaction than other synthetic

materials. It is a permanent multifilament with small

pores. Initial short-term results were promising, but

longer follow-up dropped the cure rate from 86 to

61% [119] . In addition, women with Gore-tex slings

demonstrated wound infections, rejection, and ero-

sion rates of 30–35%. Norris and Staskin later

described the Gore-tex patch sling, reducing the

amount of Gore-tex sling material to decrease infec-

tion rates. Despite success rates of 88–90%, 5–7%

of patients had prolonged urinary retention and 4%

had vaginal erosions [120– 122] . Eventually, because

of the high erosion rate, Gore-tex slings were taken

off the market. The ProtoGen sling, a woven

mesh of nonabsorbable polyester impregnated with

bovine collagen matrix, gained great popularity and

was widely used before it was recalled from the

US market in 1999 due to complications including

126 M.P. Rutman and J.G. Blaivas

intractable pain and erosion rates as high as 55%

[123] ; it, too, was taken off the market.

The latest iteration of the synthetic sling is a

polypropylene nonabsorbable monofilament mesh

with large pores. It is more flexible and contains

larger pores than Marlex mesh and lacks small

interstices. It is widely considered to be the best

synthetic material for sling surgery and the mate-

rial of choice in the majority of the new generation

“midurethal” slings.

Midurethral Slings

Midurethral slings were the brainchild of Peter

Petros and Ulm Ulmsten based on their pio-

neering, innovative, and decades-long research

into the physiology and pathophysiology of stress

incontinence [9, 10] . Until their work, virtually

all operations for SUI focused on the bladder

neck. In 1994, Petros and Ulmsten were the first

to report a procedure where polypropylene mesh

was placed under the midurethra with the inten-

tion of being tension-free [124– 127] . After several

modifications, this later became known as the

tension-free vaginal tape technique (TVT) [18] .

In this technique, a wide, sharp trocar was passed

from the vagina to the abdomen. Although largely

unreported, within the first decade of its use,

there were about 15–20 deaths worldwide using

this technique due to perforation of iliac vessels

and bowel. In addition, there were innumerable,

also underreported major complications including

nonfatal vessel and bowel injuries; urethral and

vaginal erosions; vesicovaginal, urethrovaginal,

and colovescial fistulas; and even ureteral injuries.

These are listed in the MAUDE database, which

reports adverse events involving medical devices.

The data consist of voluntary reports since June

1993, user facility reports since 1991, distributor

reports since 1993, and manufacturer reports since

August 1996.

Fueled by industry, a large number of minor

modifications of the TVT were introduced under

the mantra of “midurethral sling kits.” What these

kits all have in common is that they are composed

of disposable, onetime use trocars and sling mate-

rials and sutures, although they are expensive

[18– 20, 22, 25, 128– 130] . All these procedures,

including the TVT, usually can be completed in

less than 30 min. They can be done in the out-

patient setting with local anesthesia in suitable

patients. They all pass a synthetic material beneath

the midurethra with the intention of creating a

tension-free sling. Each employs a small anterior

vaginal wall incision(s) with minimal or no dissec-

tion of the urethra. Trocars or needle passers are

passed in an antegrade or retrograde fashion and

the mesh is secured by design of the material to

anchor in the soft tissue. All rely on blind passage

of trocars and pose a risk of bladder perforation,

nerve and vascular injury, bowel injury, and even

death as discussed above.

One midurethral sling, though, is different from

the others, and in our judgment safer: the distal

urethral polypropylene sling devised by Raz [128] .

This operation requires no disposable instruments

(so it is not expensive), and because the endopelvic

fascia (urethropelvic ligament of Raz) is perforated

under direct vision, the chances of serious injury is

negligible in the hands of experienced surgeons.

Because of the known complications of blind

needle passage through the retropubic space and

in order to obtain a more anatomically correct

course for the sling, the transobturator technique

was developed. It was introduced by Delorme who

described placement of a sling material through a

vaginal incision passed out through the obturator

foramen near the medial thigh. He described an

outside to inside passage of a hooked needle [19] .

De Leval later described an inside-out transobtura-

tor urethral sling using TVT tape [129] . This was

hypothesized to decrease potential injury to the

urethra, bladder, and vagina. To date, almost all of

the midurethral slings have demonstrated accept-

able short-term results and the TVT has shown

4-year efficacy as good as the autologous rectus

fascial sling [23, 25, 26] .

Alternative Fixation Techniques

Although the composition of the sling is an impor-

tant consideration, the point of fixation is important

as well. In 1949, the MMK procedure was the

first to rely on pubic bone fixation anchoring the

periurethral tissues to the pubic symphysis. Burch

described anchoring to Cooper’s ligament. With the

introduction of transvaginal needle suspensions,

the rectus fascia became the most popular fixation

10. Surgery for SUI: Historical Review 127

point. In 1998, Leach described his bony anchor

fixation technique, where he manually attached

his suspension sutures to the pubic bone [131] . He

reported no cases of osteitis pubis or osteomyelitis

in this series. Several transvaginal bony anchoring

systems have been introduced since that rely on

an infrapubic or transvaginal approach. They drill

small screws with preattached suture directly into

the bone. The sutures then can be passed through

autologous, allogenic, or synthetic material result-

ing in a sling secured at the pubic bone. There is

only limited long-term data assessing their use in

sling surgery.

Sphincter Prosthesis

The artificial urinary sphincter (AUS) was the brain-

child of F. Brantley Scott who also developed the

inflatable penile prosthesis [132, 133] . Brantley, as

he was known, intended the sphincter prosthesis to

become a primary operation for SUI, and in fact, he

implanted many prostheses in woman. Although the

sphincter prosthesis is the mainstay of treatment for

SUI in men, it never became the operation in women

that Scott intended it to be, despite the reports of

excellent efficacy by Pierre Costa [134, 135] . Its

use in women is largely reserved for patients with

severe and refractory incontinence with low leak

point pressures who have failed other surgeries.

The prosthesis is composed of three components: a

sphincter cuff that is implanted around the bladder

neck, a fluid reservoir implanted in the retropubic

space or behind the rectus muscle, and a control

pump component implanted in the subcutaneous

tissue of the labia majora. The original prosthesis

was plagued with mechanical problems, primarily

tubing kinks and leaks, but these have been largely

eliminated by using reinforced tubing and sutureless

connectors [136, 137] .

As originally described by Scott, the opera-

tion was performed entirely through a retropubic

approach. This proved to be a particularly challeng-

ing operation from a technical standpoint, mostly

because of the difficulty creating a plane between

the anterior vaginal wall and proximal urethra. To

this end, Scott devised a special instrument that

more or less blindly cut behind the bladder neck,

resulting in the almost inevitable complications of

urethral damage, erosion, or fistula. These compli-

cations went largely unreported, but contributed to

the lack of enthusiasm among other surgeons. In an

attempt to improve on these complications, armed

with the surgical skills learned from transvaginal

urethropexies and slings, Appel reported using a

transvaginal approach for implanting the sphincter

cuff. This, too, though met with little enthusiasm.

Those who advocate the AUS over a suburethral

sling cite the ability to provide circumferential

compression around the entire urethra. The cure

rates are greater than 90% in some series [135] .

However, there remains a high revision rate that

approaches from 20 to 90% at 10 years [138] .

Additionally, there is a risk of erosion of the pump

or cuff. Nevertheless, the AUS remains a viable

treatment option in the rare patient with SUI who

has failed prior intervention. It also can be used

in patients with impaired detrusor contractility

preferentially over a suburethral sling to lessen the

chances of postoperative urinary retention.

Almost a century has passed since the initial

sling procedure was described for stress inconti-

nence. New techniques and new materials have

come and gone and there are still many questions to

be answered. Integral to the future of incontinence

surgery is an understanding of the past. The lessons

we have learned can help answer questions and

guide research efforts in the future.

References

1 . Green TH , Jr . Development of a plan for the diag-

nosis and treatment of urinary stress incontinence .

Am J Obstet Gynecol 1962 ; 83 : 632 – 648 .

2 . McGuire EJ , et al. The value of urodynamic test-

ing in stress urinary incontinence . J Urol 1980 ;

124 (2) : 256 – 258 .

3 . Blaivas JG , Olsson CA . Stress incontinence:

Classification and surgical approach . J Urol 1988 ;

139 (4) : 727 – 731 .

4 . Hodgkinson CP . Relationships of the female urethra

and bladder in urinary stress incontinence . Am J

Obstet Gynecol 1953 ; 65 (3) : 560 – 573 .

5 . McGuire EJ et al. Clinical assessment of ur ethral

sphincter function . J Urol 1993 ; 150 (5 Pt 1) : 1452 – 1454 .

6 . Horbach NS , Ostergard DR . Predicting intrin-

sic urethral sphincter dysfunction in women with

stress urinary incontinence . Obstet Gynecol 1994 ;

84 (2) : 188 – 192 .

7 . Nitti VW , Combs AJ . Correlation of Valsalva

leak point pressure with subjective degree of stress

128 M.P. Rutman and J.G. Blaivas

urinary incontinence in women . J Urol 1996 ;

155 (1) : 281 – 285 .

8 . Fleischmann N et al . Sphincteric urinary inconti-

nence: Relationship of vesical leak point pressure,

urethral mobility and severity of incontinence . J

Urol 2003 ; 169 (3) : 999 – 1002 .

9. Petros PE, Ulmsten UI. An integral theory of

female urinary incontinence. Experimental and

clinical considerations. Acta Obstet Gynecol Scand

Suppl 1990; 153:7–31.

10 . Petros PP , Ulmsten U . An anatomical classification

– a new paradigm for management of female lower

urinary tract dysfunction . Eur J Obstet Gynecol

Reprod Biol 1998 ; 80 (1) : 87 – 94 .

11 . McGuire EJ , Herlihy E . The influence of urethral

position on urinary continence . Invest Urol 1977 ;

15 (3) : 205 – 207 .

12 . Constantinou, CE , Govan DE . Contribution and

timing of transmitted and generated pressure com-

ponents in the female urethra . Prog Clin Biol Res

1981 ; 78 : 113 – 20 .

13 . Constantinou CE . Resting and stress urethral pres-

sures as a clinical guide to the mechanism of conti-

nence . Clin Obstet Gynaecol 1985 ; 12 (2) : 343 – 356 .

14 . Bump RC , Fantl JA , Hurt WG . Dynamic ure-

thral pressure profilometry pressure transmission

ratio determinations after continence surgery:

Understanding the mechanism of success, fail-

ure, and complications . Obstet Gynecol 1988 ;

72 (6) : 870 – 874 .

15 . Westby M , Asmussen M , Ulmsten U . Location of

maximum intraurethral pressure related to uro-

genital diaphragm in the female subject as studied

by simultaneous urethrocystometry and voiding

urethrocystography . Am J Obstet Gynecol 1982 ;

144 (4) : 408 – 412 .

16 . Versi E et al. Internal urinary sphincter in mainte-

nance of female continence . Br Med J (Clin Res Ed)

1986 ; 292 (6514) : 166 – 167 .

17 . Rodriguez LV , Berman J , Raz S . Polypropylene

sling for treatment of stress urinary incontinence:

An alternative to tension-free vaginal tape . Tech

Urol 2001 ; 7 (2) : 87 – 89 .

18 . Ulmsten U et al. , An ambulatory surgical procedure

under local anesthesia for treatment of female uri-

nary incontinence . Int Urogynecol J Pelvic Floor

Dysfunct 1996 ; 7 (2) : 81 – 85 ; discussion 85–86 .

19 . Delorme E . [Transobturator urethral suspension:

Mini-invasive procedure in the treatment of stress

urinary incontinence in women] . Prog Urol 2001 ;

11 (6) :1 306 – 1313 .

20 . Tash, J , Staskin DR . Artificial graft slings at the

midurethra: Physiology of continence . Curr Urol

Rep 2003 ; 4 (5) : 367 – 370 .

21 . de Leval J . Novel surgical technique for the

treatment of female stress urinary incontinence:

Transobturator vaginal tape inside-out . Eur Urol

2003 ; 44 (6) : 724 – 730 .

22 . Ulmsten U , et al. A multicenter study of tension-

free vaginal tape (TVT) for surgical treatment of

stress urinary incontinence . Int Urogynecol J Pelvic

Floor Dysfunct 1998 ; 9 (4) : 210 – 213 .

23 . Nilsson CG , et al. Long-term results of the tension-free

vaginal tape (TVT) procedure for surgical treatment of

female stress urinary incontinence . Int Urogynecol J

Pelvic Floor Dysfunct 2001 ; 12 (Suppl 2) : S5 – 8 .

24 . Olsson I , Kroon U . A three-year postoperative

evaluation of tension-free vaginal tape . Gynecol

Obstet Invest 1999 ; 48 (4) : 267 – 269 .

25 . Rezapour M , Ulmsten U . Tension-free vaginal tape

(TVT) in women with recurrent stress urinary incon-

tinence—a long-term follow up . Int Urogynecol J

Pelvic Floor Dysfunct 2001 ;; 12 (Suppl 2) : S9 – 11 .

26 . Nilsson CG . Falconer C , Rezapour M . Seven-year

follow-up of the tension-free vaginal tape proce-

dure for treatment of urinary incontinence . Obstet

Gynecol 2004 ; 104 (6) : 1259 – 1262 .

27 . Yang A et al. Pelvic floor descent in women:

Dynamic evaluation with fast MR imaging and

cinematic display . Radiology 1991 ; 179 (1) : 25 – 33 .

28 . Mostwin JL et al. Radiography, sonography, and

magnetic resonance imaging for stress inconti-

nence. Contributions, uses, and limitations . Urol

Clin North Am 1995 ; 22 (3) : 539 – 549 .

29 . DeLancey JO . Structural support of the urethra as

it relates to stress urinary incontinence: The ham-

mock hypothesis . Am J Obstet Gynecol 1994 ;

170 (6) : 1713 – 1720 ; discussion 1720–1723 .

30 . Lo TS et al. Ultrasonographic and urodynamic

evaluation after tension free vagina tape proce-

dure (TVT) . Acta Obstet Gynecol Scand 2001 ;

80 (1) : 65 – 70 .

31 . Sarlos D , Kuronen M , Schaer GN . How does ten-

sion-free vaginal tape correct stress incontinence?

Investigation by perineal ultrasound . Int Urogynecol

J Pelvic Floor Dysfunct 2003 ; 14 (6) : 395 – 398 .

32 . Minaglia S et al. Effect of transobturator tape

procedure on proximal urethral mobility . Urology

2005 ; 65 (1) : 55 – 59 .

33 . Kelly HA . Dunn W . Urinary incontinence in women

without manifest injury to the bladder . Surg Gynecol

Obstet 1914 ; 18 : 444 – 450 .

34 . Kennedy WT . Incontinence of urine in the female:

The urethral sphincter mechanism, damage of func-

tion, and restoration of control . Am J Obstet Gynecol

1937 ; 34 : 576 .

35 . Leach GE et al. Female stress urinary incontinence

clinical guidelines panel summary report on surgical

10. Surgery for SUI: Historical Review 129

management of female stress urinary incontinence.

The American Urological Association . J Urol 1997 ;

158 (3 Pt 1) : 875 – 880.

36 . Bergman A , , Koonings PP , Ballard CA . The Ball–

Burch procedure for stress incontinence with low ure-

thral pressure . J Reprod Med 1991 ; 36 (2) : 137 – 140 .

37 . Elia G , Bergman A . Genuine stress urinary inconti-

nence with low urethral pressure. Five-year follow-

up after the Ball–Burch procedure . J Reprod Med

1995 ; 40 (7) : 503 – 506 .

38 . White GR . A radical cure by suturing lateral sulci

of vagina to white line of pelvic fascia . JAMA

1909 ; 21 : 1707 – 1708 .

39 . Richardson AC . Edmonds PB , Williams NL . Treatment

of stress urinary incontinence due to paravaginal fas-

cial defect . Obstet Gynecol 1981 ; 57 (3) : 357 – 362 .

40 . Colombo M et al. A randomized comparison of

Burch colposuspension and abdominal paravaginal

defect repair for female stress urinary incontinence .

Am J Obstet Gynecol 1996 ; 175 (1) : 78 – 84 .

41 . Bruce RG , El-Galley RE , Galloway NT . Paravaginal

defect repair in the treatment of female stress uri-

nary incontinence and cystocele . Urology 1999 ;

54 (4) : 647 – 651 .

42 . Marshall VF, Krantz KE The correction of stress

incontinence by simple urethrovesical suspension .

Surg Gynecol Obstet 1949 ; 88 : 509 .

43 . Marshall VF , Marchetti AA , Krantz KE . The correc-

tion of stress incontinence by simple vesicourethral

suspension . J Urol 2002 ; 168 (4 Pt 1) : 1326 – 1331 .

44 . Mainprize TC , Drutz HP . The Marshall–Marchetti–

Krantz procedure: A critical review . Obstet Gynecol

Surv 1988 ; 43 (12) : 724 – 729 .

45 . O’Leary JA . Osteitis pubis following vesicourethral

suspension . Obstet Gynecol 1964 ; 24 : 73 – 77 .

46 . Burch J . Urethrovesical fixation to Cooper’s liga-

ment for correction of stress incontinence, cystocele,

and prolapse . Am J Obstet Gynecol 1961 ; 81 : 281 .

47 . Tanagho EA . Colpocystourethropexy: The way we

do it . J Urol 1976 ; 116 (6) : 751 – 753 .

48 . Herbertsson G , Iosif CS . Surgical results and uro-

dynamic studies 10 years after retropubic colpoure-

throcystopexy . Acta Obstet Gynecol Scand 1993 ;

72 (4) : 298 – 301 .

49 . Langer R, et al. , Long-term (10–15 years) follow-up

after Burch colposuspension for urinary stress incon-

tinence . Int Urogynecol J Pelvic Floor Dysfunct

2001 ; 12 (5) : 323 – 326 ; discussion 326–327 .

50 . Alcalay M , Monga A , Stanton SL . Burch colpo-

suspension: A 10–20 year follow up . Br J Obstet

Gynaecol 1995 ; 102 (9) : 740—745 .

51 . Vancaillie TG , Schuessler W . Laparoscopic blad-

der neck suspension . J Laparoendosc Surg 1991 ;

1 (3) : 169 – 173 .

52 . Su TH et al. Prospective comparison of laparoscopic

and traditional colposuspensions in the treatment of

genuine stress incontinence . Acta Obstet Gynecol

Scand 1997 ; 76 (6) : 576 – 582 .

53 . Pereyra AJ . A simplified surgical procedure for the

correction of stress incontinence in women . West J

Obstet Gynecol 1959 ; 67 : 223 – 226 .

54 . Stamey TA . Cystoscopic suspension of the vesical

neck for urinary incontinence . Surg Gynecol Obstet

1973 ; 136 : 547 – 554 .

55 . Raz S . Modified bladder neck suspension for female

stress incontinence . Urology 1981 ; 17 (1) : 82 – 85 .

56 . Gittes RF , Loughlin KR . No-incision pubovaginal

suspension for stress incontinence . J Urol 1987 ;

138 (3) : 568 – 570 .

57 . Raz S , Klutke CG , Golomb J . Four-corner bladder

and urethral suspension for moderate cystocele . J

Urol 1989 ; 142 (3) : 712 – 715.

58 . Bruskewitz RC et al. Bladder neck suspension

material investigated in a rabbit model . J Urol 1989 ;

142 (5) : 1361 – 1363 .

59 . Zimmern PE , Leach G , Sirls L . Four-corner blad-

der neck suspension. In: Atlas of the urological

clinics of North America , Leach, GE editor , W.B.

Saunders : Philadelphia , 1994 : 29 – 36 .

60 . Ridley J . The Goebel–Stockel sling operation.

In : TeLinde’s operative gynecology , Thompson J ,

Mattingly RF editors , . Lippincott : Philadelphia ,

1985 .

61 . Goebel R . Zur operativen besteitigung der anger-

borenen incontinenz vesicae . Zeitscher Gynakol

1910 ; 2 : 187 – 191 .

62 . Frangenheim P . Zu operativen behandlung der

inkontinenz der mannlichen harnohre . Ver Dtsch

Ges 1914 ; 43 : 149 – 154 .

63 . Stoeckel W . Uber die verwendung der museuli

pyramidalis bei der operitaven behandlung der

incontinentia urinae . Zentralbl Gynakol 1917 ;

41 : 11 – 19 .

64 . Thompson R . A case of epispadias associated with

complete incontinence treated by rectus transplan-

tation . Br J Dis Child 1923 ; 20 : 146 – 151 .

65 . Martius H . Sphnicter-und Harnrohrnplastik aus

dem Musculus Bulbocavernosus . Chirurg 1929 ;

1 : 769 .

66 . Price P . Plastic operations for incontinence of urine

and feces . Arch Surg 1933 ; 26 : 1043 – 1048 .

67 . Aldridge A . Transplantation of fascia for relief of

urinary stress incontinence . Am J Obstet Gynecol

1942 ; 44 : 398 – 411 .

68 . McLaren HC . Late results from sling operations . J

Obstet Gynaecol Br Commonw 1968 ; 75 (1) : 10 – 13 .

69 . McGuire EJ , Lytton B . Pubovaginal sling procedure

for stress incontinence . J Urol 1978 ; 119 (1) : 82 – 84 .

130 M.P. Rutman and J.G. Blaivas

70 . Blaivas JG , Jacobs BZ . Pubovaginal fascial sling

for the treatment of complicated stress urinary

incontinence . J Urol 1991 ; 145 (6) : 1214 – 1218 .

71 . Morgan TO , Jr , Westney OL , McGuire EJ . Pubovaginal

sling: 4-Year outcome analysis and quality of life

assessment . J Urol 2000 ; 163 (6) : 1845 – 1848 .

72. Chaikin DC , Rosenthal J , Blaivas JG . Pubovaginal

fascial sling for all types of stress urinary incon-

tinence: Long-term analysis . J Urol 1998 ;

160 (4) : 1312 – 1316 .

73 . Mason RC , Roach M . Modified pubovaginal sling

for treatment of intrinsic sphincteric deficiency . J

Urol 1996 ; 156 (6) : 1991 – 1994 .

74 . McGuire EJ et al. Experience with pubovaginal

slings for urinary incontinence at the University of

Michigan . J Urol 1987 ; 138 (3) : 525 – 526 .

75 . Cross CA , Cespedes RD , McGuire EJ . Our experience

with pubovaginal slings in patients with stress urinary

incontinence . J Urol 1998 ; 159 (4) : 1195 – 1198 .

76 . Romero Perez P et al. [Partial parietal cystectomy

and cystoplasty using a lyophilized human dura mater

patch as an alternative in palliative surgery for bladder

cancer] . Arch Esp Urol 1990 ; 43 (8) : 867 – 875 .

77 . Ramos C et al. [Vesicovaginal fistulas: Correction

using lyophilized dura mater] . Actas Urol Esp

1991 ; 15 (2) : 143 – 147 .

78 . Sampaio JS et al. Surgical correction of severe

Peyronie’s disease without plaque excision . Eur

Urol 1992 ; 22 (2) : 130 – 133 .

79 . Villavicencio Mavrich H et al. Experience with

lyophilized human dura mater for urethral stric-

tures . J Urol 1998 ; 160 (4) : 1310 – 1311 .

80 . Enzelsberger H , Helmer H , Schatten C . Comparison

of Burch and lyodura sling procedures for repair of

unsuccessful incontinence surgery . Obstet Gynecol

1996 ; 88 (2) : 251 – 256 .

81 . Rottenberg RD et al. Urodynamic and clinical

assessment of the Lyodura sling operation for

urinary stress incontinence . Br J Obstet Gynaecol

1985 .; 92 (8) : 829 – 834 .

82 . Handa VL et al. Banked human fascia lata for the

suburethral sling procedure: A preliminary report .

Obstet Gynecol 1996 ; 88 (6) : 1045 – 1049 .

83 . Buck BE , Malinin TI . Human bone and tissue allo-

grafts. Preparation and safety. Clin Orthop Relat

Res 1994 ; 303 : 8 – 17 .

84 . Buck BE , Malinin TI , Brown MD . Bone trans-

plantation and human immunodeficiency virus.

An estimate of risk of acquired immunodeficiency

syndrome (AIDS) . Clin Orthop Relat Res 1989 ;

240 : 129 – 136 .

85 . Amundsen CL et al. Outcome in 104 pubovaginal

slings using freeze-dried allograft fascia lata from a

single tissue bank . Urology 2000 ; 56 (6 Suppl 1) : 2 – 8 .

86 . Malinin TI et al. Incidence of clostridial contamina-

tion in donors’ musculoskeletal tissue . J Bone Joint

Surg Br 2003 ; 85 (7) : 1051 – 1054 .

87 . Kainer MA et al. Clostridium infections associated

with musculoskeletal-tissue allografts . N Engl J

Med 2004 ; 350 (25) : 2564 – 2571 .

88 . Hathaway JK , Choe, JM . Intact genetic material is

present in commercially processed cadaver allo-

grafts used for pubovaginal slings . J Urol 2002 ;

168 (3) : 1040 – 1043 .

89 . Choe JM , Bell T . Genetic material is present in

cadaveric dermis and cadaveric fascia lata . J Urol

2001 ; 166 (1) : 122 – 124 .

90 . Simonds RJ et al. Transmission of human immuno-

deficiency virus type 1 from a seronegative organ

and tissue donor . N Engl J Med 1992 ; 326 (11) :

726 – 732 .

91 . Liscic RM et al. Creutzfeldt–Jakob disease in a

patient with a lyophilized dura mater graft . Acta

Med Croatica 1999 ; 53 (2) : 93 – 96 .

92 . Miyashita K et al. Creutzfeldt–Jakob disease in

a patient with a cadaveric dural graft . Neurology

1991 ; 41 (6) : 940 – 941 .

93 . Fushimi M et al. PLEDs in Creutzfeldt–Jakob

disease following a cadaveric dural graft . Clin

Neurophysiol 2002 ; 113 (7) : 1030 – 1035 .

94 . Chaikin DC , Blaivas JG . Weakened cadaveric fas-

cial sling: An unexpected cause of failure . J Urol

1998 ; 160 (6 Pt 1) : 2151 .

95 . Pa S Sutaria. Tensile strength of cadaveric fascia lata

allograft is not affected by current methods of tissue

preparation. 1998; J Urol 161:(4) Abstract 1194.

96 . Lemer ML . Chaikin DC , Blaivas JG . Tissue strength

analysis of autologous and cadaveric allografts for

the pubovaginal sling . Neurourol Urodyn 1999 ;

18 (5) : 497 – 503 .

97 . Wright EJ et al. Pubovaginal sling using cadav-

eric allograft fascia for the treatment of intrinsic

sphincter deficiency . J Urol 1998 ; 160 (3 Pt 1) :

759 – 762 .

98 . Brown SL , Govier FE . Cadaveric versus autolo-

gous fascia lata for the pubovaginal sling: Surgical

outcome and patient satisfaction . J Urol 2000 ;

164 (5) : 1633 – 1637 .

99 . Kobashi KC , Mee SL , Leach GE . A new tech-

nique for cystocele repair and transvaginal sling:

The cadaveric prolapse repair and sling (CAPS) .

Urology 2000 ; 56 (6 Suppl 1) : 9 – 14 .

100 . Fitzgerald MP , Mollenhauer J , Brubaker L . Failure

of allograft suburethral slings . BJU Int 1999 ;

84 (7) : 785 – 788 .

101 . Carbone JM et al. Pubovaginal sling using cadav-

eric fascia and bone anchors: Disappointing early

results . J Urol 2001 ; 165 (5) : 1605 – 1611 .

10. Surgery for SUI: Historical Review 131

102 . Frederick RW , Leach GE . Cadaveric prolapse

repair with sling: Intermediate outcomes with

6 months to 5 years of follow-up . J Urol 2005 ;

173 (4) : 1229 – 1233 .

103 . Jarvis GJ , Fowlie A . Clinical and urodynamic

assessment of the porcine dermis bladder sling in

the treatment of genuine stress incontinence . Br J

Obstet Gynaecol 1985 ; 92 (11) : 1189 – 1191 .

104 . Hilton P . A clinical and urodynamic study compar-

ing the Stamey bladder neck suspension and subu-

rethral sling procedures in the treatment of genuine

stress incontinence . Br J Obstet Gynaecol 1989 ;

96 (2) : 213 – 220 .

105 . Iosif CS . Porcine corium sling in the treatment of

urinary stress incontinence . Arch Gynecol 1987 ;

240 (3) : 131 – 136 .

106 . Barrington JW et al. The use of porcine dermal

implant in a minimally invasive pubovaginal sling

procedure for genuine stress incontinence . BJU Int

2002 ; 90 (3) : 224 – 227 .

107 . Rutner AB , Levine SR , Schmaelzle JF . Processed

porcine small intestine submucosa as a graft mate-

rial for pubovaginal slings: Durability and results .

Urology 2003 ; 62 (5) : 805 – 809 .

108 . Pelosi MA II , Pelosi MA III , Pelekanos M . The

YAMA UroPatch sling for treatment of female stress

urinary incontinence: A pilot study . J Laparoendosc

Adv Surg Tech A 2002 ; 12 (1) : 27 – 33 .

109 . Bracht , [Simplified operation for incontinence.] .

Arch Gynakol , 1951 ; 180 : 163 – 164 .

110 . Hohenfellner R , Petrie E . Sling procedure in sur-

gery. In : Surgery of female incontinence , Stanton ,

STE editor , . Springer :: Berlin , 1986 : 105 – 113 .

111 . Zoedler D . Zur operativen Behandlung der weibli-

chen Stress inkontinenz . Z Urol 1961 ; 54 : 355 .

112 . Williams TJ , Telinde RW . The sling operation for

urinary incontinence using mersilene ribbon . Obstet

Gynecol 1962 ; 19 : 241 – 245 .

113 . Moir JC . The gauze-hammock operation. (A modi-

fied Aldridge sling procedure) . J Obstet Gynaecol

Br Commonw 1968 ; 75 (1) : 1 – 9 .

114 . Nichols DH . The Mersilene mesh gauze-ham-

mock for severe urinary stress incontinence . Obstet

Gynecol 1973 ; 41 (1) : 88 – 93 .

115 . Morgan JE . A sling operation, using Marlex polypro-

pylene mesh, for treatment of recurrent stress inconti-

nence . Am J Obstet Gynecol 1970 ; 106 (3) : 369 – 377 .

116 . Morgan JE , Farrow G.A , Stewart FE . The Marlex

sling operation for the treatment of recurrent stress

urinary incontinence: A 16-year review . Am J

Obstet Gynecol 1985 ; 151 (2) : 224 – 226 .

117 . Stanton SL , Brindley GS , Holmes DM . Silastic

sling for urethral sphincter incompetence in women .

Br J Obstet Gynaecol 1985 ; 92 (7) : 747 – 750 .

118 . Horbach NS et al. A suburethral sling procedure

with polytetrafluoroethylene for the treatment of

genuine stress incontinence in patients with low

urethral closure pressure . Obstet Gynecol 1988 ;

71 (4) : 648 – 652 .

119 . Weinberger MW , Ostergard DR . Long-term clinical

and urodynamic evaluation of the polytetrafluor-

oethylene suburethral sling for treatment of genu-

ine stress incontinence . Obstet Gynecol 1995 ;

86 (1) : 92 – 96 .

120 . Choe JM , Staskin DR . Gore-Tex patch sling: 7

years later . Urology 1999 ; 54 (4) : 641 – 646 .

121 . Norris JP , Breslin DS , Staskin DR . Use of synthetic

material in sling surgery: A minimally invasive

approach . J Endourol 1996 ; 10 (3) : 227 – 230 .

122 . Staskin DR , Choe JM , Breslin DS . The Gore-tex

sling procedure for female sphincteric inconti-

nence: Indications, technique, and results . World J

Urol 1997 ; 15 (5) : 295 – 299 .

123 . Kobashi KC et al. Erosion of woven polyester pub-

ovaginal sling . J Urol 1999 ; 162 (6) : 2070 – 2072 .

124 . Ulmsten U , Johnson P , Petros P . Intravaginal sling-

plasty . Zentralbl Gynakol 1994 ; 116 (7) : 398 – 404 .

125 . Ulmsten U , Petros P . Intravaginal slingplasty (IVS):

An ambulatory surgical procedure for treatment of

female urinary incontinence . Scand J Urol Nephrol

1995 ; 29 (1) : 75 – 82 .

126 . Petros PP . The intravaginal slingplasty operation,

a minimally invasive technique for cure of urinary

incontinence in the female . Aust N Z J Obstet

Gynaecol 1996 ; 36 (4) : 453 – 461 .

127 . Petros PE . New ambulatory surgical methods using

an anatomical classification of urinary dysfunc-

tion improve stress, urge and abnormal emptying .

Int Urogynecol J Pelvic Floor Dysfunct 1997 ;

8 (5) : 270 – 277 .

128 . Rodriguez LV , Raz S . Polypropylene sling for the

treatment of stress urinary incontinence . Urology

2001 ; 58 (5) : 783 – 785 .

129 . Deval B et al. A French multicenter clinical trial of

SPARC for stress urinary incontinence . Eur Urol

2003 ; 44 (2) : 254 – 258 ; discussion 258–259 .

130 . Dargent D et al. Insertion of a sub-urethral sling

through the obturating membrane for treatment of

female urinary incontinence . Gynecol Obstet Fertil

2002 ; 30 (7–8) : 576 – 582 .

131 . Leach GE . Bone fixation technique for transvaginal

needle suspension . Urology 1988 ; 31 (5) : 388 – 390 .

132 . Scott FB , Bradley WE , Timm GW . Treatment of

urinary incontinence by an implantable prosthetic

urinary sphincter . J Urol 1974 ; 112 (1) : 75 – 80 .

133 . Scott FB , Bradley WE , Timm GW . Management of

erectile impotence. Use of implantable inflatable

prosthesis. Urology 1973 ; 2 (1) : 80 – 82 .

132 M.P. Rutman and J.G. Blaivas

134 . Costa P et al. The artificial urinary sphincter AMS

800: Our experience in women with or without uter-

ine prolapse . Acta Urol Belg 1995 ; 63 (2) : 45 – 46 .

135 . Costa P et al. The use of an artificial urinary sphinc-

ter in women with type III incontinence and a nega-

tive Marshall test . J Urol 2001 ; 165 (4) : 1172 – 1176 .

136 . Leo ME , Barrett DM . Success of the narrow-backed

cuff design of the AMS800 artificial urinary sphinc-

ter: Analysis of 144 patients . J Urol 1993 ; 150 (5 Pt 1) :

1412 – 1414 .

137 . Light JK , Reynolds JC . Impact of the new cuff

design on reliability of the AS800 artificial urinary

sphincter . J Urol 1992 ; 147 (3) : 609 – 611 .

138 . Wang Y, HR . Artificial sphincter: Transvaginal

approach In : Female urology , Raz S editor , W.B.

Saunders : Philadelphia , 1996.

133

Open Retropubic Suspensions

Marshall–Marchetti–Krantz Procedure

Historical Perspective

The abdominal approach for repair in incontinence

is premised on recreating the elevation of the bladder

neck. In 1949, Marshall et al. reported on their expe-

riences with 50 patients [1] . They had observed that

patients with urinary retention following rectal resec-

tion were not helped by transurethral resection of the

vesical neck; however, if the perineum were elevated,

patients then could void. Based on these findings,

they proposed a technique to elevate the bladder neck

and the anterior bladder wall out of the pelvis. In their

series, 82% of patients had excellent results.

The initial description of the Marshall–Marchetti–

Krantz (MMK) procedure by Marshall et al. [1] in

1949 called for three pairs of figure-eight periu-

rethral sutures placed through the lateral urethral

wall on either side of midline. The stitches then are

sutured to the appropriate location into the perios-

teum of the symphysis pubis. Number 1 chromic

catgut was the suture recommended by Marshall

and his colleagues. Additionally, three stitches

were placed in the musculature of the lower and

lateral portions of the bladder. These then were

placed into the posterior portion of the rectus mus-

cle. The goal of the second set of sutures was to

pull the bladder anteriorly into the space of Retsius.

A penrose drain was placed prior to closure.

Later, Marchetti [2] provided an update of his

results and a modification of the original proce-

dure. He found that elevation and fixation of the

bladder neck to the posterior surface of the perios-

teum to be critical for success. The procedure was

modified to avoid placing stitches through the wall

of the urethra. This reduced the incidence of hema-

turia and risk of urethral injury. He recommended

a “stout bite of the vaginal wall” in a periurethral

location. In addition, he stopped placing a drain in

seven of his patients.

Operative Technique

Over the years, modifications include foregoing the

sutures placed in the anterior bladder wall, the total

number of sutures placed, and the type of suture.

The basic procedure starts with placing the patient

in a low lithotomy position or frog-legged supine

on the operating table. The abdomen and vagina

should be prepped and a catheter placed to depend-

ent drainage. A lower midline or Pfannenstiel inci-

sion can be made. The rectus muscle then is split in

the midline and the space of Retsius cleared over-

lying the urethra and the bladder neck. In patients

with previous repair, Webster and Guralnick advo-

cate a formal urethrolysis in order to fully mobilize

the bladder neck [3] .

The surgeon’s nondominant hand should be placed

in the vagina to assist elevation of the paravaginal

tissues adjacent to the bladder neck and urethra.

Absorbable (0-chromic) suture or permanent suture

(0-Prolene, Ethicon, Somerville, NJ) should be

placed first at the bladder neck in a periurethral loca-

tion through the anterior vaginal wall (Fig. 11.1 ).

The stitch should be placed approximately 2–3 mm

Chapter 11

Surgery for Stress Urinary Incontinence:

Open Approaches

Meidee Goh and Ananias C. Diokno

134 M. Goh and A.C. Diokno

away from the urethra in the midline. One or two

additional sutures can be placed more distally on

either side of midline. Each of these sutures would

then be placed into the fibrocartilage of the symphy-

sis pubis (Fig. 11.2 ). Following tying these sutures,

the bladder and urethra then be can inspected

cystoscopically to ensure that there is no injury to

the urethra or ureters [4] . Care should be taken to

recognize and treat any bladder injury during this

dissection. Instillation of the bladder with indigo

carmine or methylene blue could facilitate identi-

fication of an injury. If significant venous bleeding

occurs, a figure-eight suture to control the bleeding

may be necessary.

Outcomes A meta-analysis by Mainprinze and col-

leagues showed a wide range of success from 29 to

100% [5] . In their review of 56 articles, they found

that some authors worried that failure occurred

secondary to use of an absorbable suture and they

tried other suture material such as linen, silk,

Mersilene (Ethicon, Somerville, NJ), and Tevdek

(Teleflex Medical, Research Triangle Park, NC)

suture. One surgeon tried placing talc in the wound

in an attempt to facilitate scar formation. The over-

all success rate was 86.1%; however, 11.4% of the

patients did not have long-term data to complete

analysis. Furthermore, the success rate decreases

over time. At 15 years, the overall success rate had

decreased to 75% [6] .

Clemens et al. [7] noted a more substantial loss

in efficacy over time. Using Kaplan–Meier analy-

sis, they estimated the 10- and 15-year cure rates to

be 59 and 41%, respectively. The most rapid loss

of continence occurred within the first 5 postop-

erative years. Their initial cure rate was lower at

57%. Czalpicki and colleagues reported on similar

decreases in the cure rate over time. They found a

reduction of success from 81% at 6 months to a low

of 28% at 10 years. Mean duration of continence

was approximately 6½ years [8] .

Fig. 11.1. The first suture is placed in the periurethral

tissue at the bladder neck and secured to the periosteum

of the symphysis pubis. Elevation of the anterior vagi-

nal wall with the hand may be helpful to determine the

appropriate depth for suture placement

Fig. 11.2 . Sagittal section showing support of the blad-

der neck and urethra following the tying of the sutures to

the fibrocartilage of the symphysis pubis. Overelevation

of the urethra should be avoided to prevent kinking of

the urethra

11. Surgery for Stress Urinary Incontinence: Open Approaches 135

In their review of 680 patients, Park and Miller

[9] found that the MMK provided a cure in 86% of

their 680 patients regardless of suture type (absorb-

able vs. nonabsorbable). Others have reported suc-

cess rates from 83 to 100% [10, 11] .

Quadri and colleagues studied 30 women rand-

omized to MMK or Burch and found 100% con-

tinence in the MMK group and 66% continence

in the Burch group. They believed that the use of

videourethroscopy during the MMK procedure

allowed better control of the tensioning of the

sutures, thus leading to their high success rate.

Nonetheless, they noted a delay of recovery of

spontaneous voiding in some patients. Their aver-

age time to spontaneous voiding was 20.5 days

(range of 13.4 days) [11] .

Successful outcomes also may depend on patient

selection. Bladder instability, prolapse, and recur-

rence of incontinence following a previous surgery

could contribute to a poor outcome. Milani et al.

reported that surgery was successful in 83% of

those with stable bladders but only 38% in those

with unstable bladders [12] . Arnold et al. reported

similar findings in 1973 [13] .

Complications

With the MMK procedure, the complications of

concern include osteitis pubis, postoperative uri-

nary retention, and de novo bladder urgency/over-

activity. Studies report overall complication rates

ranging from 11.4 to 21% [5, 10] .

The most worrisome complication is osteitis

pubis, which presents as discomfort over the pubis.

Coughing and ambulation may worsen the dis-

comfort. Radiographic studies are not always con-

clusive for osteitis pubis. The reported incidence

of osteitis pubis ranged from 3.2 to 10%, with

symptoms occurring within 1–8 weeks following

surgery [10, 14, 15 ]. The recommended treat-

ment includes rest, nonsteroidal anti-inflammatory

agents, and systemic steroid treatment.

Postoperative urinary retention can be divided

into short-term and long-term urinary retention.

In Parnell’s series [10] , 27% of patients had

short-term urinary retention with an average dura-

tion of retention of 12.2 days. Only 2 of the 158

patients (1.4%) had long-term urinary retention.

Carr and Webster reported that approximately

12% of patients undergoing MMK develop chronic

urinary retention [16] . The majority of patients

notice the symptoms immediately postoperatively.

Resolution of the retention was achieved in 86% of

patients who underwent a retropubic urethrolysis

and 73% of patients who underwent a transvaginal

urethrolysis.

Other complications noted in the review by

Mainprize and Drutz [5] include direct injuries

to the urinary tract: bladder tears (0.7%), urethral

obstruction (0.5%), and sutures in either the blad-

der or urethra (0.1%). Prolonged retention occurred

in 3.6%, retroperitoneal hematoma in 0.3%, and

fistulae in 0.3%. They reported an overall surgical

complication rate of 21%.

Burch Colposuspension

Historical Perspective

In 1961, John C. Burch reported on a modification

of the MMK procedure [17] . He had encountered

difficulty performing the MMK when the sutures

in the periosteum would not hold. He had first tried

securing the sutures to the arcus tendineus fascia

pelvis with the goal of also treating an anterior and

posterior cystocele. Over time he found that this

was a poor site to anchor sutures, and he then set-

tled on using Cooper’s ligament. He recommended

the placement of three sutures of No. 2 chromic

catgut to be placed in the paravaginal tissues at the

bladder neck and then secured to the appropriate

location in the ligament. He reported 100% conti-

nence in his first 53 patients.

He then reported on a larger series of 143 patients

with 93% continence [18] . Critics complained that

this high continence rate might have been second-

ary to the fact that most patients had the Burch as

their first incontinence operation. His preference

for chromic catgut remained. He believed the cat-

gut was less likely to be problematic if the bladder

was entered and that it would not form a fistula

tract if placed through and through in the vagina.

Thus, the Burch procedures performed today are

based on his initial work.

Operative Technique

The patient can be placed in low lithotomy posi-

tion with Allen Yellofin

® stirrups (Allen Medical

Systems, Inc., Acton, MA) or in a frog-legged

136 M. Goh and A.C. Diokno

position on the operating table. Administration of

prophylactic antibiotic and use of sequential com-

pression devices to prevent deep venous thrombosis

are advised. The abdomen, vagina, and perineum

should be prepped. A foley catheter should be

placed in a sterile fashion to allow identification of

the bladder neck and drain the bladder.

The retropubic space then is reached through a

low midline or Pfannesteil incision. The anterior

bladder wall and urethra should be freed of over-

lying fat in order to facilitate identification of the

bladder neck junction. Care should be taken during

this dissection, as this area is extremely vascular.

Fingers placed in the vagina allow the elevation

of the lateral vaginal fornix. Two pairs of sutures of

a No. 1 or 0 nonabsorbable monofilament sutures

should be placed on the endopelvic fascia and

vaginal wall lateral to the bladder neck and proxi-

mal urethra (Fig. 11.3 ). The distal sutures should

be placed first at the level proximal urethra, fol-

lowed by one or two pairs of sutures placed more

proximally at the bladder neck. If bleeding occurs

during placement of these sutures, additional fig-

ure-eight sutures may be necessary. Under most

circumstances, hemostasis is accomplished once

the sutures are tied to Cooper’s ligament.

The sutures then are attached to Cooper’s liga-

ment in the position directly above the suture

(Fig. 11.4 ). With all sutures secured to Cooper’s

ligament, the sutures are tied to elevate the parau-

rethral tissue. There should be no compression of

the urethra against the pubic bone. A suture bridge

between the ligament and the vaginal wall may be

present. Once the sutures are tied, cystoscopy with

administration of indigo carmine can be performed

to rule out ureteral and vesical neck injury.

Prior to closure, a penrose drain or closed suction

drain may be placed lateral to the sutures, although

this is not required [19] . The authors have not used

any drains in the last 15 years and have not had an

adverse event. If a drain is used, the drain then can be

removed on the first to third day following surgery.

A voiding trial can be performed on the first post-

operative day, although the average time to voiding

reported by McLennan and colleagues was 6.7 days

[20] . In our experience, 85% of patients undergoing

the Burch procedure have a successful voiding trial

during the first 1 or 2 days postprocedure.

Outcomes

Initial success rates for the Burch procedure reported

in studies range from 75–90% [21– 23] . Long-term

outcomes reported by Nithara and colleagues are

less positive [24] . Continence in 60 patients was

evaluated over a mean period of 6.9 years. Sixty-

nine percent of the patients remained continent at

long-term follow-up. Galloway [25] also reported

deterioration of continence over time. While 84%

of patients in his study were dry immediately fol-

lowing surgery, only 44% were dry at mean follow-

up of 4.5 years. Furthermore, Galloway showed

individuals who had previous incontinence surgery

had a lower success rate (63%).

In contrast, Feyereisl and colleagues [23] noted

that success was not diminished by previous surgi-

cal procedures for incontinence. They found that

Fig. 11.3 . Burch sutures should be placed lateral to the

bladder in the area of the vaginal fornix. Locating the

vaginal fornix can be facilitated by elevation of the ante-

rior vaginal wall Fig. 11.4. Burch sutures elevate and support the urethra

11. Surgery for Stress Urinary Incontinence: Open Approaches 137

continence was maintained in 81.6% of the women

5–10 years after a Burch procedure. In a Cochrane

Library database review of 33 trials by Lapitan and

colleagues [26] , the overall cure rate of those stud-

ies ranged from 68.9 to 88%. They found a slight

decrease in the success rate to 70% at 5 years.

Alcalay et al. demonstrated that the decline in the

cure rate stabilized at 69% at 10–12 years [22] .

Sand and colleagues [27] suggested patients with

a low preoperative urethral closure pressure (UCP)

were more likely to fail. They found the failure rate

to be 54% in those with a UCP less than 20 cm of

H

2 0, while those with a UCP greater than 20 cm of

H

2 0 had a lower failure rate of 18%. Earlier work

by McGuire [28] and Hilton and Stanton [29] had

suggested that patients who have failed multiple

anti-incontinence procedures in the past are likely

to have lower urethra closure pressures. Koonings

et al. [30] also found a lower cure rate in those with

low urethral pressure versus those with normal ure-

thral pressures (50% vs. 77%).

The number of sutures may affect outcome. In

a study by Ladwig et al. [31] , the Burch procedure

was modified to allow use of only one pair of sutures

in 86% of 374 patients. Subjective cure rates ranged

from 39.7 to 50%, depending on the severity of

the incontinence. Results of this study suggest that

placement of additional sutures may affect long-

term outcomes. However, approximately 30% of the

patients in Ladwig’s study had at least one previous

failed anti-incontinence procedure.

Complications

Postoperative complications of the Burch procedure

include voiding dysfunction, de novo urge, and pelvic

organ prolapse, in particular enteroceles. The dura-

tion of catheterization can range from 1 to 12 days.

Kjølhede and Ryden reported that 8.8% of Burch

procedure patients had an in-dwelling catheter

longer than 2 weeks [32] . In the study with Nitihara

et al. 90% of their patients were able to void 5 days

following surgery [24], while mean time to resump-

tion of voiding following a Burch procedure was 6.5

days in a study by Quadri et al. [11].

In one long-term study, a 16% incidence of de

novo urge resulted in patient dissatisfaction with

surgery despite the correction of the anatomy [24] .

Other studies estimate the incidence of de novo

urgency at 6–27% [33, 34] . Gleason et al. [35]

reported the development of urgency in 50% of

patients; however, their procedure had been modi-

fied to include a cystotomy to aid determination of

suture tension. Anticholinergics were helpful but

were given judiciously in order to avoid develop-

ment of urinary retention.

In his series of 143 cases, Burch reported the

development of a postoperative enterocele in 7.6% of

cases [18] . Galloway reported enterocele formation

in 2 of 50 (4%) patients and uterine prolapse in 2 of

50 (4%) patients [25] . Others report an incidence of

enterocele formation at between 2 and 27% [4] .

Laparoscopic Retropubic

Suspensions

Laparoscopic retropubic urethropexies were intro-

duced by Vancaillie and Schuessler [36] as a mini-

mally invasive option for management of stress

urinary incontinence. Many variations of the tech-

nique have been tried including use of staples and

mesh, staples and suture, gasless laparoscopy, and

different numbers of sutures.

Most of the laparoscopic studies have reported

success in the range of 69–100%, with decreases

in length of stay, intra-operative blood loss, less de

novo urgency, and postoperative voiding dysfunc-

tion [37] . However, in most of the studies the mean

operative time was increased in comparison to the

open technique.

Liu et al. [38] published a study of 132 patients

that demonstrated a 97% cure rate and a 10%

complication rate (follow-up ranged from 3 to 27

months). The complications experienced included

four bladder injuries and one uretheral obstruction.

In the beginning of his series, Liu had performed

the laparoscopic Burch procedure with one suture

per side, but he eventually switched to two sutures

per side [39] . He had concerns as to whether one

set of sutures was sufficient in the long term.

Moehrer et al. [40] performed a meta-analysis

of four randomized clinical trials in the Cochrane

Incontinence Review Group’s database and dem-

onstrated no difference in outcomes between open

and laparoscopic Burch procedure. Subjective per-

ception of cure was equivalent between the laparo-

scopic and open Burch groups. When the success

rate was evaluated on the basis of urodynamic

138 M. Goh and A.C. Diokno

testing, the cure rate was lower in the laparoscopic

Burch group.

Although operating time was longer, the laparo-

scopic Burch procedure patients experienced less

postoperative pain, shorter length of stay in the

hospital, and time to return to normal function

was shortened [40] . However, the complication

rate with the laparoscopic procedure was found be

higher and was related to surgeon experience. The

major intraoperative and short-term complications

included bladder and bowel injury in 0–25% [37] .

The most common injury was bladder perforation

and the incidence decreased with increasing expe-

rience. Two cases of foreign body erosions have

been reported following the use of tacks and mesh

to assist the laparoscopic procedure [41] .

While initial results for the laparoscopic proce-

dure have been good, few studies have reported on

long-term follow-up. At the 3 years following initial

surgery, the percentage of cured patients ranged from

40 to 60% [42] . McDougall and colleagues showed

even further deterioration in success at 4 years to

30% [43] . In contrast, a study by Ross did not dem-

onstrate deterioration in efficacy at 5 years [44] .

Pubovaginal Sling

Historical Perspective

Von Giordano introduced the first urethral sling by

wrapping a gracilis muscle graft around the ure-

thra in 1907 [45] . The first true pubovaginal sling

was performed in 1910, when Goebell rotated the

pyramidalis muscle beneath the urethra and joined

them in the midline [46] . Aldridge further modi-

fied the technique by suturing two strips of fascia

beneath the urethra [47] .

In 1978, McGuire and Lytton popularized the

modern autologous fascial sling with the use of

rectus fascia [48] . Since then, there have been many

adaptations to the sling, including changing the type

of sling material (Table 11.1), as well as the use of

bone anchors to secure the sling in position.

Operative Technique

Prior to the procedure, patients can be taught

intermittent self-catherization. However, if they

are physically unable to catherize themselves, a

suprapubic tube can be placed at the time of sur-

gery in order to facilitate checking their postvoid

residuals following surgery. Perioperative antibiot-

ics and prophylaxis for deep venous thrombosis

should be utilized. The patient should be placed in

the lithotomy position and a foley catheter placed

to drain the bladder.

A combined abdominal and vaginal approach

can be used. A low transverse midline incision can

be made and dissection carried down to the rectus

fascia. The rectus fascia then is cut transversely

and freed inferiorly from the attachments to the

muscle below in a cephalad and caudad manner.

A strip of rectus fascia measuring 1.5 cm in width

by 6–8 cm in length can be harvested (Fig. 11.5 )

[49] . Additional lengths of fascia have been uti-

lized. Blaivas [50] advocates the use of a full-length

rectus fascia sling (15 cm), while others have used

much shorter “patch” slings [51, 52] . The ends of

the sling then are prepared for transfer with placement

Table 11. 1. Pubovaginal sling material options.

Material Source

Autologous Rectus fascia, fascia lata, vaginal wall

Allogenic Cadaveric fascia lata, cadaveric dermis

Xenografts Porcine dermis, porcine intestinal

submucosa

Synthetics Polyester, Gore-tex, silicone,

polypropylene, polytetrafluoroethylene

Fig. 11.5 . The rectus fascial strip measuring 6–8 cm can

be harvested from the lower leaf of the rectus fascia

11. Surgery for Stress Urinary Incontinence: Open Approaches 139

of a 0-Vicryl suture (Ethicon, Somerville, NJ) in a

helical fashion.

A midline incision should be made in the ante-

rior vaginal wall at the level of the bladder neck.

Hydrodissection of the anterior vaginal wall can be

done to facilitate the dissection. The dissection of

the anterior vaginal wall is completed laterally on

both sides up to the level of the endopelvic fascia.

Using a sharp and blunt dissection, a Crawford

clamp is passed from the abdominal incision below

the rectus fascia to the tunnel in the anterior vagi-

nal wall (Fig. 11.6 ). Cystoscopy with a 70° lens

then should be performed to check for bladder

perforation once both clamps have been passed.

Typically, the injury occurs at the 1 o’clock and

11 o’clock position within the bladder. If an injury

has occurred, the clamp should be removed and

repassed. The foley catheter should be left in place

for a longer period if perforation should occur.

A larger injury may require formal closure.

If both clamps are in position, the sling sutures

then can be grasped and pulled upward to the

abdominal incision from the vaginal incision. The

sling can be secured in position at the bladder neck

using 2–0 Vicryl (Ethicon, Somerville, NJ) suture.

Care should be taken to ensure that both ends of

the sling pass through the endopelvic fascia [53] .

The sling sutures then should be passed under the

lower leaf of the rectus fascia. The rectus fascia then

should be closed before tying the sutures in the mid-

line over the fascia. The sutures should be tied with

enough to tension to stabilize the urethra but still

allow easy passage of two fingers under the suture.

Wright and colleagues [54] recommend check-

ing sling tension by placing a cystoscope in the

urethra. The sling should be tied such that 30° rota-

tional descent of the scope is still possible. Govier

et al. [55] recommend easy placement of one finger

under the sling suture. The urethra should be able

to move approximately 1 cm with traction on the

foley. Ghoniem [56] advocates adjusting the sling

using the Q-tip method.

The abdominal and vaginal incisions are then

closed. A vaginal pack can be left in place and the

catheter allowed to dependently drain. A voiding

trial can be performed the following day as long as

the patient is ambulatory.

Alternatively, the procedure can be performed

through a vaginal approach alone using the cadaveric

transvaginal sling (CaTS) technique popularized by

Kobashi and Leach [45] . This alternative technique

allows placement of the sling with only a vaginal

incision. An inverted U-shaped incision is made in

the anterior vaginal wall from the distal urethra to

the bladder neck. The pubic bone is then exposed

lateral to the urethra and the inferior surface of the

bone cleared of tissue. Bone anchors are then placed

transvaginally into the under surface of the pubic

bone (Fig. 11.7 ). The 0-Prolene sutures (Ethicon,

Somerville, NJ) then are passed through the ends of

Fig. 11.6 . The Crawford clamp is passed from the abdom-

inal incision through the endopelvic fascia to the vaginal

incision below

Fig. 11.7 . In-Fast™ Ultra Sling System anchoring sys-

tem for placement of cadaveric transvaginal sling. The

bone anchors are placed into the pubic bone. Image cour-

tesy of American Medical System, Minnetonka, MN

140 M. Goh and A.C. Diokno

a prepared cadaveric strip of fascia (2 × 7 cm). The

sling should be tied with a right angle between the

urethra and the sling. The urethral incision then is

closed and a vaginal pack placed.

Outcomes

Autologous Slings

In McGuire and Lytton’s paper, 80% of the 52

patients were cured and 20 of 29 (67%) patients

had their detrussor instability resolved [57] . This

was updated further by Morgan et al., who reviewed

their 4-year experience with 247 women [58] .

Overall continence rate was 88% at a mean follow-

up of 51 months. Patients with type 2 (abdominal

leak point pressure greater than 90 cm H

2 0 and

urethral mobility greater than 2 cm) stress inconti-

nence had a higher success rate (91%) than patients

with type 3 (abdominal leak point pressure less

than 90 cm H

2 0) stress urinary incontinence (84%).

In the 88 patients with at least 5 years of follow-up,

85% were still continent. Eighty-one of the 109

(74%) patients with preoperative urge incontinence

had resolution of their urge symptoms.

Chaikin et al. reported excellent long-term results

as well [50] . One year following surgery, 94% of

their patients were cured of their stress urinary

incontinence, and at 10 years, 95% of their patients

remained continent. Most of the failures were sec-

ondary to persistent urge symptoms. De novo urge

incontinence occurred in 3%. The patients who had

persistent stress incontinence despite surgical treat-

ment were found to have a fixed pipe-stem urethra.

Others have seen similar results with 94 to 97%

of patients cured of their stress urinary incon-

tinence and urgency resolved in two thirds of

patients with OAB [59, 60] . De novo urgency rates

were reported at 2–12%.

Allograft/Synthetic Material

Cure rates for stress urinary incontinence in stud-

ies using cadaveric allograft are comparable to

autograft. In a study by Wright et al. [61] , 92

patients were followed for 11.5 months. Fifty-

nine patients received allograft fascia lata and

33% received autograft. The success rate was

93% for the autograft group and 93% for the

allograft group. Mean duration of suprapubic

tube placement was equivalent: 12 days for the

autograft and 11 days for the allograft. Flynn and

Yap [62] presented additional data to support the

equivalence of cadaveric fascia lata to autograft

fascia at 2-year follow-up. Seventy-one percent

of the allograft group was cured, while 77% of

the autograft group was cured. The majority of

failures presented at 2 to 3 years following initial

surgery. Brown and Govier [63] reported similar

outcomes for 104 patients who underwent pub-

ovaginal slings with cadaveric fascia lata versus

autologous fascia lata. Eighty-five percent of the

cadaveric fascia group was cured of stress incon-

tinence, while 90% of the autologous fascia group

was cured.

Other groups have cautioned against the use

of allograft material due to issues of durability.

Fitzgerald and colleagues [64] reported on 7 of

35 patients who autolyzed their sling within 6

months of surgery. Carbone et al. [65] raised

similar concerns about the longevity of allograft

material. In their study of 154 patients who under-

went pubovaginal sling with cadaveric fascia lata

and bone anchors, 40% of the patients developed

recurrent stress urinary incontinence. Most of

these failures occurred within the first 10 months

postprocedure.

Cure rates for synthetic slings range from 77 to

90%, with mean follow-up duration of 4–8 years

[66] . Erosions into the vagina and into the urethra

remain concerns with using synthetic materials [67] .

Complications

The pubovaginal sling has not been popular despite

the high success rate. This may be due to the higher

risk of complications in comparison to other alter-

natives for management of stress urinary inconti-

nence. Most of the issues arise from tensioning the

sling too tightly, which is more likely to occur with

a new practitioner of the technique. Possible prob-

lems that could arise include retention, de novo

urge incontinence, and erosion, particularly with

the use of synthetic slings [50] .

Postoperative urinary retention is the most com-

mon complication following placement of pub-

ovaginal slings. The retention is likely to resolve

within the first month postoperatively; however,

if retention has not resolved during this period, it

is unlikely to do so. The risk for retention ranges

from 0 to 17% [49] .

11. Surgery for Stress Urinary Incontinence: Open Approaches 141

Morgan and colleagues [58] reported that 94%

of their patients experienced transient urinary

retention. Mean duration of catherization was 8.4

days. Within 1 month of their operation, 92% of

the patients had returned to normal voiding. Five

patients had voiding difficulty secondary to ure-

thral hypersuspension, which resolved following

urethrolysis. No sling erosions were reported.

Zaragosa [60] reported that 60% of his patients

developed transient urinary retention. All patients

who developed urinary retention subsequently

were able to void within 10 days. Chaikin et al.

[50] reported permanent urinary retention in four

patients in a series of 251. Two of the four had

concomitant prolapse repairs.

Rates of de novo urge have ranged from 5 to

11% [50, 60, 68] . A trial of anticholinergics, either

single or combination, can be attempted. If urgency

is persistent, outlet obstruction secondary to the

sling should be ruled out. However, if the urgency

has been present for a long duration, the symptoms

are unlikely to resolve even with treatment of the

obstruction. In a refractory situation, a trial of sac-

ral neuromodulation can be attempted.

There have been many synthetic materials on

the market: polypropylene, nylon, silicone, poly-

glactin, and polytetrafluoroethylene. The American

Urological Association guidelines in 1997 reported

0.007% vaginal or urethral erosions with autolo-

gous fascial slings and 0.027% erosion rate with

synthetic slings [67] . The erosion rates (vagina and

urethra) are highest for silicone, polytetrafluroeth-

ylene, and polyester; these rates range from 11 to

55% [69– 71] . The bovine collagen-impregnated

woven polyester mesh sling ProtoGen™ (Boston

Scientific, Natick, MA) subsequently was taken

off the market in 1999 due to its high erosion

rate. The erosions typically occurred within the

first year of placement, but they can occur up to

7 years following initial surgery. Average time to

erosion was 7.3 months [72, 73] . Many erosions

presented as recurrent urinary tract infections,

obstructive voiding symptoms, vaginal pain or

pressure, suprapubic pain, and recurrent stress

urinary incontinence. Factors that may increase the

risk of urethral erosion include poor vascularity

secondary to estrogen deficiency or previous radia-

tion treatment, excessive tension at time of surgery,

traumatic catherization, and forceful urethral dila-

tion [74] . A transvaginal approach can be utilized

to remove the eroded sling. If the sling eroded into

the urethra, synthetic material should be removed

as completely as possible, followed by debridment

of the urethral edges and closure in multiple layers.

A Martius labial fat pad graft can be placed to bol-

ster the repair. Both Kobashi et al. and Amundsen

et al. recommend delayed sling placement to man-

age recurrent SUI [75, 76] .

Artificial Urinary Sphincters

Historical Perspective

The first artificial urinary sphincter (AS-721) was

placed in 1973 by Scott and colleagues [77] . The

device (Fig. 11.8 , see also Chap. 29) had four

components: a fluid reservoir, an inflatable cuff, an

inflation pump, and a deflation pump. In order to

Fig. 11.8 . First artificial urinary sphincter (AS-721) had

four components: reservoir, reinflation pump, cuff, and

deflation pump (clockwise from the top)

142 M. Goh and A.C. Diokno

void, patients would squeeze the deflation pump on

the left side. The fluid then would run back into the

reservoir. When they were done voiding, the right-

sided inflation pump then was squeezed to return

fluid back to the cuff from the reservoir. There

was a valve in the system that would regulate the

pressure in the cuff. Failures of the device tended

to occur at this valve [78] . The subsequent modifi-

cations of the device revolved around replacing the

valve with a pressure balloon and changing the cuff

material to an all-silicone elastomer [79] .

The AMS-800 (Fig. 11.9 ) was introduced in 1982,

with three components: a cuff, a pressure-regulating

balloon, and a pump. The pump consists of a valve,

a refill-delay resistor, and a deactivation button.

The refill-delay resistor enables the cuff to refill

automatically in approximately 2 min, allowing the

patient adequate time to finish voiding. After 1987,

the narrow backing cuff was introduced to allow

more even distribution of pressure across the ure-

thra, increasing the durability of the device.

While popular in men with postprostatectomy

stress urinary incontinence, the use of artificial

urinary sphincters (AUS) in women has not been

as popular. This may be due in part to the techni-

cal challenge related to the scarring created by

previous attempts at anti-incontinence procedures

and the availability of sling options with less risk.

However, the AUS still should be considered for

a woman with stress incontinence who has failed

sling surgery.

Operative Technique

The patient should receive preoperative broad-

spectrum antibiotics, such as ampicillin/vanco-

mycin and gentamicin. The patient should be posi-

tioned in low lithotomy or frog-legged position to

allow access to the vagina and urethra. The abdo-

men, perineum, and vagina should be prepped and

draped in a sterile fashion.

In women, the cuff of sphincter is placed at

the bladder neck. Two approaches are possible:

abdominal and transvaginal [80, 81] . In either

approach, the artificial sphincter is left deactivated

at the end of the case. The artificial sphincter is

activated 6 weeks following surgery.

In the retropubic approach, a Pfannensteil inci-

sion is made and a plane is developed in the space

of Retsius to expose the bladder neck. The dissec-

tion is often difficult in the midline if the patient

has undergone previous incontinence surgery. In

this situation, the dissection can begin in the lateral

perivesical space where there is less scar tissue

and continued medially until the adhesions in the

midline are taken down sharply. A modified right-

angle clamp is placed in the urethrovaginal septum

to separate the bladder neck and urethra from the

vagina (Fig. 11.10 ). A hand in the vagina during

this dissection can be helpful. If there is difficulty

in identifying the vesicourethrovaginal junction,

a midline cystotomy can be made [82] . A 2-cm

area should be cleared at the bladder neck to allow

placement of the cuff. Once the cuff is placed, the

cuff tubing then is advanced through the rectus

muscle and anterior rectus fascia to a location

close to the internal inguinal ring. The pump then

is placed in a subcutaneous pocket in the labia. The

reservoir then is placed in the prevesical space,

underneath the rectus fascia (Fig. 11.11 ). All con-

nections then are made.

Alternatively, Hadley [83] and Appell [81] sug-

gest that approaching cuff placement around the

bladder neck transvaginally may be technically

easier. An inverted U-shaped incision should be

made in the anterior vaginal wall. Dissections then

should be continued laterally to the endopelvic

Fig. 11.9. AMS-800 artificial urinary sphincter with

cuff, pressure-regulating balloon reservoir, and pump.

The pump contains a refill-delay resistor, which allows

automatic refilling of the cuff

11. Surgery for Stress Urinary Incontinence: Open Approaches 143

fascia on both sides of the urethra. The endopelvic

fascia is penetrated laterally and the retropubic

space entered. The anterior wall of the urethra then

is mobilized sharply off of the posterior aspect of

the pubic bone. Following completion of this dis-

section, the bladder neck is sized and the appropri-

ate cuff placed. A limited Pfannensteil incision

then is made to place the reservoir under the rectus

fascia. The tubing from the cuff then is passed

from the vaginal incision to the abdominal incision

using a tonsil clamp. The subcutaneous tunnel to

the labia from the abdominal incision then is made

to place the pump. All the tubing is connected. The

incisions are all closed and a vaginal pack with

estrogen cream can be placed.

Outcomes

Appell [81] reported that in his 34 patients undergo-

ing the transvaginal technique 91% of his patients

were dry when the device was originally placed. The

remaining three patients were dry after revisions for

mechanical issues. Others report an 81–92% conti-

nence rate [84, 85] . Petero and Diokno [86] reported

84% satisfactory continence rate with their long-

term review of 55 women who had received artificial

sphincters. Thirty-five (64%) of the women were

completely dry. Interestingly, nine of the women

were dry without activation of the device. With a

mean follow-up of 8.1 years, 56% of the women

eventually required revisions. The revisions were

mechanical in approximately half the cases. The

remaining revisions were secondary to nonmechani-

cal failure (cuff erosion, loose/tight cuff, infection,

pain, reservoir migration, insufficient pressure in

reservoir) and iatrogenic issues (prolonged cather-

ization leading to erosions).

Webster and colleagues [87] also published their

long-term data on 25 women with artificial sphinc-

ters. Ninety-two percent had marked improved of

their incontinence with use of no pads. Four (17%)

of the patients have had an average of two revisions

in 7–8 years following initial placement of AUS.

They had noticed that none of the revisions had

occurred after 1983, when a modification had been

made to the design of the cuff.

In terms of pregnancy with AUS, Fishman and

Scott [88] reported that delivery can occur safely

even if the cuff is not deactivated. They published

a series of seven women who underwent five

vaginal deliveries and four cesarean sections. All

the devices were functioning postpartum. Toh and

Diokno recommend deactivation of the artificial

urinary sphincter in order to minimize the risk for

cuff erosion following labor [89] .

Summary

Open retropubic suspensions (MMK and Burch)

have excellent outcomes both short and long term.

The MMK does have a higher incidence of voiding

dysfunction in comparison to the Burch procedure.

Both techniques require experience in tensioning

Fig. 11.11. The reservoir for the AMS 800 is placed under

rectus fascia. The pump is placed in the labium majora

Fig. 11.10 . Placement of a modified right-angle clamp

to facilitate dissection of the posterior wall of the urethra

from the anterior vaginal wall. Placement of a nondomi-

nant hand in the vagina also could assist dissection in

this plane

144 M. Goh and A.C. Diokno

the sutures to avoid producing an overcorrection of

the urethral position and subsequent voiding dys-

function. Both techniques may be less successful

in the situation of low UCPs (<20 cm H

2 0). In this

situation, pubovaginal slings may be more versa-

tile. Pubovaginal slings can be used to manage both

hypermobility and intrinsic sphincter deficiency.

For the patient with the fixed pipe-stem urethra,

AUS may be most helpful. Of all four open surgi-

cal procedures for stress incontinence, artificial

sphincters require the most experience to place in

women. Most of the women presenting for AUS

placement have failed several anti-incontinence

procedures, making periurethral dissection for cuff

placement challenging.

Both the introduction of tension-free vaginal tape

(TVT) in 1996 by Ulmsten and the transobturator

tape (TO) in 2003 by De Lorme have dramatically

changed the treatment of stress incontinence. Both

procedures are minimally invasive and adjustable.

The ability to loosen the sling within the first post-

operative week and to quickly resolve retention has

reduced dramatically the morbidity of incontinence

surgery. As more data become available regarding

the long-term efficacy of TVT and TO, the role of

the open procedures in the management of stress

urinary incontinence will continue to evolve.

References

1 . Marshall V , Marchetti , A , Krantz K . The correction

of stress incontinence by simple vesicourethral sus-

pension . Surg Gynec Obstet 1949 ; 88 : 509 – 518 .

2 . Marchetti A . The female bladder and urethra before

and after correction for stress incontinence . Am J

Obstet Gynec 1949 ; 58 : 1145 – 1154 .

3 . Webster G , Guralnick M . Retropubic suspension

surgery for female incontinence. In : Walsh PC , Retik

AB , Vaughn ED , et al., eds. Campbell’s urology , 8th

edition . Philadelphia : Saunders 2002 : 1140 – 1150 .

4 . Alcalay M , Stanton J . Retropubic suspensions. In :

Stanton S , Zimmern P , eds. Female pelvic recon-

structive surgery . London : Springer , 2003 : 83 – 107 .

5 . Mainprize TC , Drutz HP . The Marshall–Marchetti–

Krantz procedure: A critical review . Obstet Gynecol

Surg 1988 ; 43 : 724 – 729 .

6 . McDuffie RW , Litin RB , Blundon KE . Urethrovesical

suspension (Marshall–Marchetti–Krantz): Experience

with 204 cases . Am J Surg 1981 ; 141 : 297 – 298 .

7 . Clemens JQ , Stern JA , Bushman WA , et al. Long-

term results of the stamey bladder neck suspension:

Direct comparison with the Marshall–Marchetti–

Krantz procedure . J Urol 1998 ; 160 : 372 – 376 .

8 . Czaplicki M , Dobron´ski P , Torz C , et al. Long-term

subjective results of Marshall–Marchetti–Krantz

procedure . Eur Urol 1998 ; 34 : 118 – 123 .

9 . Park GS , Miller EJ . Surgical treatment of stress

urinary incontinence: A comparison of the Kelly

plication, Marshall–Marchetti–Krantz, and Pereyra

procedure . Obstet Gynecol 1998 ; 71 : 575 – 579 .

10 . Parnell JP , Marshall Vh , Vaughan , ED . Primary

management of urinary stress incontinence by the

Marshall–Marchetti–Krantz vesicourethropexy . J

Urol 1982 ; 127 : 679 – 682 .

11 . Quadri G , Magatti , F , Belloni C , Barisani D , Natale

N . Marshall–Marchetti–Krantz urethropexy and

Burch colposuspension for stress urinary inconti-

nence in women with low pressure and hypermo-

bility of the urethra: Early results of a prospective

randomized clinical trial. Am J Obstet Gynecol

1999 ; 181 : 12 – 18 .

12 . Milani R , Scalambrino S , Quadri G , Algeri M ,

Marchesin R . Marshall–Marchetti–Krantz proce-

dure and Burch colposuspension in the surgical

treatment of female urinary incontinence . Br J

Obstet Gynecol 1985 ; 92 : 1050 – 1053 .

13 . Arnold EP , Webster JR , Loose H , Brown AD , et al.

Urodynamics of female incontinence: Factors influ-

encing the results of surgery . Am J Obstet Gynecol

1973 ; 117 : 805 – 813 .

14 . Zorzos I , Paterson PJ . Quality of life after a Marshall–

Marchetti–Krantz procedure for stress urinary

incontinence . J Urol 1996 ; 155 : 259 – 262 .

15 . Lee RA , Symmonds RE , Goldstein RA . Surgical

complications and results of modified Marshall–

Marchetti–Krantz procedure for urinary inconti-

nence . Obstet Gynecol 1979 ; 53 : 447 – 450 .

16 . Carr LK , Webster GD . Voiding dysfunction follow-

ing incontinence surgery: Diagnosis and treatment

with retropubic or vaginal urethrolysis . J Urol 1197 ;

157 : 821 – 823 .

17 . Burch JC . Urethrovaginal fixation to Cooper’s

ligament for correction of stress incontinence,

cystocele and prolapse . Am J Obstet Gynecol 1961 ;

81 : 281 – 290 .

18. Burch JC. Cooper’s ligament urethrovesical suspen-

sion for stress incontinence. Am J Obstet Gynecol

1968; 764–774.

19 . Tanagho EM . Colpocystourethropexy: The way we

do it . J Urol 1976 ; 116 : 751 – 753 .

20 . McLennan MT , Bent AE. Fascia lata suburethral

sling vs. Burch retropubic urethropexy: A compari-

son of morbidity . J Reprod Med 1998 ; 43 : 488 – 494 .

21. Columbo M, Scalambrino S, Maggioni A, et al.

Burch colposuspension versus modified Marshall–

11. Surgery for Stress Urinary Incontinence: Open Approaches 145

Marchetti–Krantz urethropexy for primary genuine

stress urinary incontinence: A prospective, rand-

omized trial. Am J Obstet Gynecol 171:1573–1579.

22 . Alcalay M , Monga A , Stanton SL . Burch colpo-

suspension: A 10–20 year follow up . Br J Obstet

Gynaecol 1995 ; 102 : 740 – 745 .

23 . Feyereisl J , Dreher E , Haenggi W , et al. Long-term

results after Burch colposuspension . Am J Obstet

Gynecol 1994 ; 171 : 647 – 652 .

24 . Nitahara KS , Aboseif S , Tanagho EA . Long-term

results of coplocystourethropexy for persistent or

recurrent stress incontinence . J Urol 1999 ; 162 :

138 – 141 .

25. Galloway NTM, Davies N, Stephenson TP. The

complications of colposuspension. Br J Urol 1987;

60–122–124.

26 . Lapitan MC , Cody DJ , Grant AM . Open retropubic

suspension for urinary incontinence in women.

Cochrane Database Syst Rev 2003 ; 1 : CD002912 .

27 . Sand PK , Bowen LW , Panganiban R , et al. The

low pressure urethra as a factor in failed retropubic

urethropexy . Obstet Gynecol 1987 ; 69 : 399 – 402 .

28 . McGuire EJ . Urodynamic findings in patients after

failure of stress incontinence operations . Prog Clin

Biol Res 1981 ; 78 : 351 – 360 .

29 . Hilton P , Stanton SL . Urethral pressure measure-

ment by microtransducer: The results in symp-

tom-free women and in those with genuine stress

incontinence . Br J Obstet Gynaecol 1983 ; 90 :

919 – 933 .

30 . Koonings PP , Bergman A , Ballard CA . Low ure-

thral pressure and stress urinary incontinence in

women: Risk factor for failed retropubic surgical

procedures . Urology 1990 ; 36 : 245 – 248 .

31 . Ladwig D , Milkjkovic-Petrovic L , Hewson AD .

Simplified colposuspension: A 15-year follow-up .

Aust N Z J Obstet Gynaecol 2004 ; 44 : 39 – 45 .

32 . Kjølde P , Ryden G . Prognostic factors and long-

term results of the Burch colposuspension: A ret-

rospective study . Acta Obstet Gynecol Scand 1994 ;

73 : 642 – 647 .

33 . Langer R , Ron-El R , Newman M , et al. Detrusor

instability following colposuspension for urinary

stress incontinence . Br J Obstet Gynecol 1988 ;

95 : 607 – 610 .

34 . Lose G , Jorgensen L , Mortensen SO , et al. Voiding

difficulties after colposuspension . Obstet Gynecol

1987 ; 69 : 33 – 38 .

35 . Gleason DM , Reilly RJ , Pierce JA . Vesical neck

suspension under vision with cystotomy enhances

treatment of female incontinence . J Urol 1976 ;

115 : 555 – 557

36. Vancaillie TG, Schuessler W. Laparoscopic bladder

neck suspension. J Laparoendosc Surg 1:169–173.

37 . Paraiso MF , Walters MD . Laparoscopic surgery for

stress urinary incontinence and pelvic organ pro-

lapse . Clin Obstet Gynecol 2005 ; 48 : 724 – 736 .

38 . Liu CY . Laparoscopic treatment of genuine urinary

stress incontinence . Clin Obstet Gynecol 1994 ;

8 : 789 – 798 .

39 . Lui CY . Laparoscopic retropubic colposuspension

(Burch procedure): A review of 58 cases . J Reprod

Med 1993 ; 38 : 526 – 530 .

40 . Moehrer B , Carey M , Wilson D . Laparoscopic

colposuspension: A systematic review . Br J Obstet

Gynaecol 2003 ; 110 : 230 – 235 .

41 . Kenton K , Fitzgerald MP , Brubaker L . Multiple

foreign body erosions after laparoscopic colposus-

pension with mesh . Am J Obstet Gynecol 2002 ;

157 : 252 – 253 .

42 . Winfield HN . Laparoscopic bladder neck suspen-

sions. In : Stanton Sl , Zimmern PE , eds. Female pel-

vic reconstructive surgery . London : Springer , 2003 :

101 – 107 .

43 . McDougall EM , Heidorn CA , Portis AJ , et al.

Laparoscopic bladder neck suspension fails the test

of time . J Urol 1999 ; 162 : 2078 – 2081 .

44 . Ross J . Laparoscopy or open Burch colposuspen-

sion . Curr Opin Obstet Gynecol 1998 ; 10 : 405 – 409 .

45. Kobashi KC, Leach GE. Fascial slings. In: Stanton

Sl, Zimmern PE, eds. Female pelvic reconstructive

surgery. London: Springer, 2003:93–101.

46 . Wilson TS , Lemack GE , Zimmern PE . Management

of intrinsic sphincteric deficiency in women . J Urol

2003 ; 169 : 1662 – 1669 .

47 . Aldridge AH . Transplantation of fascia for relief of

urinary stress incontinence . Am J Obstet Gynecol

1942 ; 44 : 398 – 411 .

48 . McGuire EJ , Lytton B . Pubovaginal sling procedure

for stress incontinence . J Urol 1978 ; 119 : 82 – 84 .

49 . McGuire EJ , Clemens JQ. Pubovaginal slings. In :

Walsh PC , Retik AB , Vaughn ED , et-al. , eds.

Campbell’s urology , 8th edn . Philadelphia : Saunders

2002 : 1140 – 1150 .

50 . Chaikin DC , Rosenthal J , Blaivas JG . Pubovaginal fas-

cial sling for all types of stress urinary incontinence:

Long-term analysis . J Urol 1998 ; 167 : 1312 – 1316 .

51 . Chopra A , Raz S , Stothers L. Technique of rectan-

gular fascial slings. In : Raz S , editor. Female urol-

ogy . New York : Springer , 1995 : 392 – 394 .

52 . Karram MM , Bhatia NN . Patch procedure: Modified

transvaginal fascia lata sling for recurrent or severe

stress urinary incontinence . Obstet Gynecol 1990 ;

75 : 461 – 463 .

53 . McGuire EJ , Clemens JQ. Pubovaginal slings. In :

Walsh PC , Retie AB , Vaughn ED , et al., eds.

Campbell’s urology , 8th edn . Philadelphia : Saunders

2002 : 1140 – 1150 .

146 M. Goh and A.C. Diokno

54 . Wright EJ , Iselin CE , Carr LK , et al. Pubovaginal

sling using cadaveric allograft fascia for the treat-

ment of intrinsic sphincter deficiency . J Urol 1998 ;

160 : 759 – 762 .

55 . Govier Fe , Gibbons RP , Correa RJ , et al. Pubovaginal

slings using fascia lata for the treatment of intrinsic

sphincter deficiency . J Urol 1997 ; 157 : 117 – 121 .

56 . Ghoniem GM . Modified rectus fascia suburethral

sling . Tech Urol 1996 ; 2 : 16 – 21 .

57 . McGuire EJ , Lytton B . Pubovaginal sling procedure

for stress incontinence . J Urol 1978 ; 119 : 82 – 84 .

58 . Morgan TO , Westney OL , McGuire EJ . Pubovaginal

sling: 4-year outcome analysis and quality of life

assessment . J Urol 2000 ; 163 : 1845 – 1848 .

59. Fulford SC, Flynn R, Barrington J, et al. An assess-

ment of the surgical outcome of urodynamic effects

of the pubovaginal sling for stress incontinence and

the associated urge symptoms. 1999; 1:135–137.

60 . Zaragosa MR . Expanded indications for the pub-

ovaginal sling: treatment of type 2 or 3 stress uri-

nary incontinence . J Urol 1996 ; 156 : 1620 – 1622 .

61. Wright JE, Iseling CE, Carr LK, et al. Vaginal

sling using cadaveric allograft fascia for the treat-

ment of intrinsic sphincter deficiency. J Urol 1998;

759–762.

62 . Flynn BJ , Yap WT . Pubovaginal sling using allo-

graft fascia late versus autograft fascia for all types

of stress urinary incontinence: 2-year minimum

follow-up . J Urol 2002 ; 167 : 608 – 612 .

63 . Brown S , Govier F . Cadaveric versus autologous fas-

cia lata for the pubovaginal sling: Surgical outcome

and patient satisfaction . J Urol 2000 ; 164 : 1633 – 1637 .

64 . Fitzgerald MP , Mollenhauer J , Brubaker . Failure

of allograft suburethral slings . BJU Int 1999 ; 84 :

785 – 788 .

65 . Carbone JM , Kavaler E , Hu JC , Raz , S . Pubovaginal sling

using cadaveric fascia and bone anchors: Disappointing

early results . J Urol 2001 ; 165 : 1605 – 1611 .

66 . Choe JM , Ogan K , Battino BS . Antimicrobial mesh

versus vaginal wall sling: A comparative outcomes

analysis . J Urol 2000 ; 163 : 1829 – 1834 .

67 . Leach GE , Dmochowski RR , Appell RA , et al.

Female stress urinary incontinence clinical guide-

lines panel summary report on surgical manage-

ment of female stress urinary incontinence . J Urol

1997 ; 158 : 875 – 880 .

68 . Carr LK , Walsh PJ , Abraham VE , et al. Favorable out-

come of pubovaginal slings for geriatric women with

stress incontinence . J Urol 1997 ; 157 : 125 – 128 .

69 . Chin YK , Stanton SL . A follow-up of silastic sling

for genuine stress urinary incontinence . Br J Obstet

Gynaecol 1195 ; 102 : 143 – 147 .

70 . Leach GE , Kobashi KC , Mee SL , et al. Erosion of

women’s polyester synthetic sling (“ProtoGen”) pub-

ovaginal sling . J Urol 1999 ; 161 : 106 , abstract 400

71 . Bent AE , Ostergard DR , Zwick-Zaffuto M . Tissue reac-

tion to expanded polytetrafluoroethylene suburethral

sling for urinary incontinence: Clinical and histological

study . Am J Obstet Gynecol 1993 ; 169 : 1198 – 2004 .

72 . Ahmed MM , Hai MA , Ibrahim SA , et al. Outcomes

following polypropylene mesh pubovaginal slings

for stress urinary incontinence . J Urol Suppl 1999 ;

162 : 2070 , abstract 397 .

73 . Kobashi KC , Dmochowski R , Mee SL , et al.

Erosion of woven polyester pubovaginal sling . J

Urol 1999 ; 162 : 2070 – 2072 .

74 . Amundsen CL , Flynn BJ , Webster GD . Urethral

erosions after synthetic and nonsynthetic pubovagi-

nal slings: Difference in management and conti-

nence outcome . J Urol 2003 ; 170 : 134 – 137 .

75 . Amundsen CL , Flynn BJ , Webster GD . Urethral

erosions after synthetic and nonsynthetic pubovagi-

nal slings: Difference in management and conti-

nence outcome . J Urol 2003 ; 170 : 134 – 137

76 . Kobashi KC , Dmochowski R , Mee SL , et al.

Erosion of woven polyester pubovaginal sling . J

Urol 1999 ; 162 : 2070 – 2072 .

77 . Scott FB , Bradley WE , Timm GW . Treatment of

urinary incontinence by an implantable prosthetic

sphincter . J Urol 1974 ; 112 : 75 – 80 , discussion 1130 .

78 . Seigel SW . History of the prosthetic treatment of

urinary incontinence . Urol Clin North Am 1989 ;

16 : 99 – 104 .

79 . Scott BF . The artificial urinary sphincter: Experience

in adults . Urol Clin North Am 1989 ; 16 : 105 – 117 .

80 . Abbassian A . A new operation for the insertion

of the artificial urinary sphincter . J Urol 1988 ;

140 : 512 – 513 .

81 . Appell RA . Techniques and results in the implan-

tation of the artificial urinary sphincter in women

with type III stress urinary incontinence by vaginal

approach . Neurourol Urodyn 1988 ; 7 : 613 – 619 .

82. Salisz JA, Diokno AC. The management of injuries

to the urethra, bladder or vagina encountered during

difficult placement of the artificial urinary sphincter

in the female patient. J Urol 1992:1528–1530.

83 . Hadley HR . Insertion of artificial urinary sphincter

in women. In : Vasavada SP , Appell RA , Sand PK ,

et al., eds. Female urology, urogynecology, and

voiding dysfunction . New York : Marcel Decker ,

2005 : 319 – 328 .

84 . Thomas H , Venn SN , Mundy AR . Outcome of the

artificial sphincter in female patients . J Urol 2002 ;

167 : 1720 – 1722 .

11. Surgery for Stress Urinary Incontinence: Open Approaches 147

85 . Light JK , Scott FB . Management of urinary incon-

tinence in women with the artificial urinary sphinc-

ter . J Urol 1985 ; 134 : 476 – 478 .

86 . Petero VG , Diokno A . Comparison of the long-term

outcomes between incontinent men and women

treated with artificial urinary sphincter . J Urol 2006 ;

175 : 604 – 609 .

87 . Webster GD , Perez LM , Khoury JM , Timmons SL .

Management of type III stress urinary incontinence

using artificial urinary sphincter . Urology 1992 ;

36 : 499 – 503 .

88 . Fishman IJ , Scott FB . Pregnancy in patients with

the artificial urinary sphincter . J Urol 1993 ; 150

(2 pt 1) : 340 – 341 .

89 . Khailee T , Diokno AC . Management of intrinsic

sphincter deficiency in adolescent females with

normal bladder emptying function . J Urol 2002 ;

168 : 1150 – 1153 .

149

Introduction

The idea of increasing urethral resistance by an

injectable agent was first reported in 1938. Twenty

women had either sodium morrhuate or cod-liver

oil injected into the anterior vaginal wall to pro-

voke an inflammatory response, resulting in scar

formation and contracture of tissue around the

urethra. Seventeen patients reported being cured

or improved, but pulmonary infarction and cardi-

opulmonary arrest were reported [1] . In 1955, the

first injections into the urethra were reported by

Quackels. Two patients were treated successfully

without complications [2] . In 1963, Sachse used

Dondren, a sclerosing agent, to treat 7 women and

24 men. Four women and 12 men were reported as

cured but several patients experienced pulmonary

embolism [3] . These first bulking agents were far

from ideal. Such an ideal agent would be nonim-

munogenic, hypoallergenic, biocompatible, and

nonmigratory, and would heal with minimal fibro-

sis and retain its bulking effect over a long period

of time [4] .

Mechanism

Injectable agents work by forming a “seal” through

restoring mucosal coaptation (see Fig. 12.1 ). They

have several advantages over surgical procedures

in treating stress urinary incontinence (SUI).

Compared to surgical procedures that create a

functional obstruction, injectable agents restore

continence by increasing urethral resistance at

rest. With bulking agents, the urethra maintains its

ability to funnel and open, keeping urethral resist-

ance low during micturition. This spares a resultant

increase in detrusor pressure (P

det ),which could

lead to overactive bladder symptoms and/or upper

tract damage. In comparison, surgical procedures

may result in increased resistance at rest and during

micturition by not allowing the urethra the same

physiological movement. Most bulking agents

are placed at the level of the bladder neck within

the smooth muscle in the area of the continence

mechanism (see Fig. 12.2 ). Since the placement is

within the urethra, “intraurethral” is more accurate

than the commonly used terms “periurethral” or

“submucosal.”

Criteria for Selection

Ideal patients for intraurethral bulking have SUI

due to intrinsic sphincter deficiency (ISD) and a

normal contractile bladder. Clues such as leaking

a large amount of urine with cough or sneeze,

significant leakage on exertion, leakage while

supine, bed-wetting, or leakage with the sensation

of urinary urgency may suggest ISD. On physi-

cal examination, the patient should have a well-

supported, fixed urethra. This can be determined

by placing a cotton swab through the urethra with

the tip just past the urethrovesical junction. If the

angle is greater than 30° from the horizontal or

change in angle is greater than 30° when the patient

Chapter 12

Surgery for Stress Urinary Incontinence:

Minimally Invasive Procedures

Eric A. Hurtado and Rodney A. Appell

150 E.A. Hurtado and R.A. Appell

bears down or coughs, the patient is said to have a

hypermobile rather than fixed urethra [5, 6] .

The use of intraurethral bulking agents in women

with urethral hypermobility, type II incontinence,

is an area of controversy. A comparison between

pubovaginal slings and intraurethral collagen injec-

tions was performed by Kreder et al. In their study,

they compared success rates in patients with ISD

alone or mixed with urethral hypermobility. In the

mixed group, those receiving a pubovaginal sling

faired better with a cure rate of 81% versus 25%

in the collagen group [7] . However, the collagen

group received only a single injection, whereas it

has been demonstrated that many patients require

between two and three injection sessions to affect

their continence [8] . In another study, despite more

injections and amount of material injected in the

group with urethral hypermobility, both those

with and without hypermobility had equal success

[9] . In a later study by Herschorn and Radomski,

no statistically significant difference was found

between those with and without urethral hypermo-

bility. Over time, 72% remained dry at 1 year, 57%

at 2 years, and 45% at 3 years with no significant

difference between the type of incontinence and

time to failure [10] . Others have documented simi-

lar findings in patients with urethral hypermobility

or type II incontinence [11– 14] .

Fig. 12.1. ( a ) Bladder neck prior to injection. ( b ) Bladder neck after injection

Fig. 12.2. Illustration of coaptation at continence

mechanism

12. Surgery for Stress Urinary Incontinence: Minimally Invasive Procedures 151

Urodynamics should be performed to rule out

other causes of urinary incontinence such as detru-

sor overactivity. Urethral function can be assessed

by measuring the abdominal leak point pressure

(ALPP), which is the amount of abdominal pres-

sure ( P abd ) necessary to overcome the bladder’s

continence mechanism. The definition of ISD by

ALPP has varied from a low ALPP (65 cm H

2 O) to

an ALPP less than 100 cm H

2 O. An absolute value

for ALPP suggesting ISD has become unimportant

due to limitations in urodynamic testing as well as

different values used by different clinicians. With

videourodynamics, radiographic evidence of an

open bladder neck and proximal urethra without

detrusor contraction during the storage phase of the

bladder is believed to imply ISD.

As more is understood about the continence

mechanism, it appears that most women with

SUI have some component of ISD, since there

are numerous women with urethral hypermobility

who do not leak with significant intra-abdominal

pressures. Women who do have a fixed, nonmobile

urethra, however, are more likely to have a greater

degree of ISD [15] . Exclusion criteria for intraure-

thral bulking would include urinary incontinence

due to abnormal detrusor contractions, active uri-

nary tract infection, or allergy to the material used

as a bulking agent.

Key Concept

• Ideal patients for intraurethral bulking have SUI

due to ISD and a normal contractile bladder

• Most women with SUI have some component of

ISD

Injection Techniques

When performing intraurethral bulking, precise

placement of the bulking material into the wall of

the proximal urethra near the bladder neck in the

area of the continence mechanism is of the utmost

importance. The plane of delivery, tissue quality at

the injection site, and cause of incontinence are all

important factors in successful therapy. If material

is delivered too distally, the treatment is likely to

fail and may cause irritative voiding symptoms.

Prior to injection, patients are placed in lithotomy

position and prepped in standard sterile fashion.

A local anesthetic in the form of 20% benzocaine

ointment or cream may be applied to the vestibule

covering the urethra and a topical 2% lidocaine

jelly may be applied to urethra. Two to four millili-

ters of 1% lidocaine are then injected periurethrally

at the 3 and 9 o’clock positions.

Key Concept

• Precise placement of the bulking material into

the wall of the proximal urethra near the bladder

neck in the area of the continence mechanism is

of the utmost importance.

Transurethral Injection

There are several approaches that may be taken

when performing injections of bulking agents. It

may be performed by placing a needle through a

cystourethroscope and injecting suburothelially, also

known as a “transurethral injection” [16] . A 0-, 12-,

or 30-degree lens is best for providing a good view

of the urethra as well as the injection needle. Once

the cystourethroscope is placed into the urethra

and passed into the bladder, the bladder usually is

drained as the patient’s bladder may become dis-

tended toward the end of the procedure. The endo-

scope then is backed to the midurethra at which time

the needle is deployed at the 4 o’clock position. The

needle then is inserted submucosally into the ure-

thral muscle beyond the midurethra and advanced to

the proximal urethra near the bladder neck. Once the

desired positioning is achieved, the bulking agent is

slowly delivered to allow it to spread underneath the

urethral mucosa. Once the mucosa on that side has

expanded to the midline, the needle is slowly with-

drawn while injecting. Attention is then turned to the

8 o’clock position where the technique is repeated.

After completion of both sides, a fair amount of

coaptation should be noted.

In order to create an easier, more reliable

transurethral delivery, a new device has been cre-

ated called the “implacer” (Q-Med AB, Uppsala,

Sweden). This device consists of four preloaded

syringes with bulking material covered by an

outer sleeve that is placed into the urethra. Once

the syringes are advanced, the needles enter the

submucosa at the midurethra in four distinct areas.

The location of the midurethra is measured by a

152 E.A. Hurtado and R.A. Appell

urethral catheter. The only recommended anesthe-

sia consists of intraurethral lidocaine and a periu-

rethral block. The touted benefits of this device

include the elimination of cystourethroscopy for

placement of the bulking agent and a reproducible

method of bulking agent placement. In the United

States, this device currently is under investigation.

Yet to be determined is whether injection at the

midurethra will be as efficacious as injection at the

bladder neck or the equivalent to the varied midure-

thral slings currently in use.

Key Concept

• Once the mucosa at the 4 o’clock position

has expanded to the midline, the technique is

repeated again at the 8 o’clock position.

• A 0-, 12-, or 30-degree lens is best for providing

a good view of the urethra as well as the injection

needle.

Periurethral Injection

Injections also may be performed periurethrally

via a needle placed percutaneously lateral to the

urethral meatus and parallel to the urethra (see

Fig. 12.3 ). While the needle is placed, the urethra

is visualized through a cystourethroscope [17, 18] .

Localization of the needle tip may be facilitated

by preinjecting the urethra with methylene blue

during the periurethral approach [19] . With the

periurethral approach, there often is less bleeding,

which can improve visualization. There also is less

extrusion of the material injected, although this

depends on the type of material injected as well.

The desired amount of coaptation is the same as

when performed via a transurethral technique.

After the periurethral block, a 20-gauge spinal

needle is placed at the 4 o’clock position into

the periurethral tissue within the lamina propria.

Urethroscopy is then performed as the needle is

further inserted with minimal resistance up to

the level of the bladder neck. The needle is then

rocked in a horizontal plane to assess the location

of the needle tip, ensuring placement at the proper

depth. The material is then injected slowly while

observing for coaptation similar to the transure-

thral technique, and the process is repeated at the

8 o’clock position. If material is noted in the lumen

of the urethra, the needle is removed and relocated

to a more anterior position where the injection is

repeated again. Once sufficient coaptation is noted,

the procedure is ended. A needle with a “bent

tip” has been manufactured (Boston Scientific

Inc, Natick, MA) to facilitate placement into the

proper plane. With advancement of the needle, the

tip is brought more medially. These needles were

designed to ease the injection of Durasphere™,

since a larger bore size (18-gauge) also aids in the

passage of the particles.

The differences between the transurethral and

periurethral techniques were reviewed by Faerber

et al. In their study, they found similar outcomes

with no significant differences in adverse events

using collagen. Of significance, the amount of

material injected was less using a transurethral

approach [20] . A prospective, randomized com-

parison was later performed in women again with

no noted differences in efficacy, but a higher rate

of urinary retention and also an increased volume

of injected material was seen in the periurethral

group [21] . It appears that a periurethral approach

tends to use larger volumes of material and has

been noted to have a longer learning curve than the

transurethral approach.

Fig. 12.3 . Technique of periurethral approach

12. Surgery for Stress Urinary Incontinence: Minimally Invasive Procedures 153

Ultrasound Guidance

Although transurethral and periurethral injections

are the most commonly performed, injections also

may be performed in females with use of an ultra-

sound probe [22] . Theoretically, this technique

circumvents the passage of instruments through the

urethra, which may alter the placement of the bulk-

ing agent affecting coaptation. First, a transrectal

ultrasound probe with a biopsy port is placed into

the vagina. Once the bladder neck has been identi-

fied, a needle of the same type for transurethral

injection is placed through the port. Longitudinal

views by ultrasound are used to determine coapta-

tion of the bladder neck. Studies have demonstrated

that three-dimensional ultrasound views may predict

long-term outcomes and may provide an objective

measure for amount of material to be placed [23] . In

later studies with three-dimensional ultrasound, col-

lagen injections were shown to maintain their vol-

ume and ultrasound appearance with an associated

improved continence and quality of life. It also was

found that the most desirable appearance on ultra-

sound was either a circumferential or horseshoe

configuration [24] . Regardless of the technique,

coaptation of the urethra is the goal.

Postoperative Care

Immediate postoperative complications are rare.

After completion of the procedure, the patient

should demonstrate the ability to void. If the

patient is in acute urinary retention, most often

they will be able to urinate shortly after the periu-

rethral block loses effect. Meanwhile, the patient is

usually catheterized with a small 10- to 14-French

catheter to relieve the patient’s full bladder after

cystourethroscopy. An indwelling foley catheter

should be avoided since there is a theoretical risk

of the bulking agent molding around the cath-

eter and losing its effect, although there is no

evidence to support that short-term catheterization

decreases the efficacy of intraurethral bulking. If

long-term catheterization is necessary, a suprapu-

bic catheter until return of voiding would be best

to avoid disrupting the placement of the bulking

agent. After injection, treatment with antibiotics

is recommended for 2–3 days to avoid urinary

tract infections. Many patients will require more

than one session to achieve maximal continence.

Different waiting periods are required for each

individual bulking agent. Bulking agents such as

collagen can be repeated after 1 week (in the origi-

nal multicenter study a 4-week waiting period was

used). Ethylene vinyl alcohol copolymer requires

a 3-month wait, allowing for ingrowth of the

spongiform material. With polytetrafluoroethylene,

a 4-month wait is required, since improved coapta-

tion occurs with time. On repeat injection if erosion

is noted, injection into that side should be avoided

until re-epithelialization occurs.

Irritative voiding symptoms also may develop

after placement of bulking agents. Surprisingly,

in a study by Steele et al., 50% of patients were

reported to have developed de novo detrusor over-

activity [13] . In a study by Cross et al., 28% of

patients were found to have de novo urge inconti-

nence without ISD when undergoing urodynamics

for posttreatment incontinence [25] . Stothers et al.

reported a 12.6% rate of de novo urgency with

urge incontinence in 337 women enrolled in a

prospective of which 21% failed anticholinergic

treatment [26] . Commonly, minor urethral bleeding

may occur. If the urethral mucosa becomes dis-

rupted, perforation and extravasation of the bulking

agent may occur. An advantage of the periurethral

approach involves placement of the bulking agent

without disruption of the mucosa.

Key Concept

• If the patient is in acute urinary retention a cath-

eterize with a small 10- to 14-French catheter to

relieve the patient’s full bladder.

Injectable Agents

Other methods of treatment for SUI include ure-

thropexies, slings, and artificial urinary sphincters.

Often bulking agents are compared to these other

methods of treatment. What has been demonstrated

in some studies is that midurethral slings and

Burch urethropexies tend to have higher failure

rates in patients with a “fixed urethra” [27, 28] .

These patients are better off treated with intraure-

thral bulking agents, bladder neck slings, or arti-

ficial urinary sphincters. Compared to injectable

agents, the artificial urinary sphincter and bladder

neck slings both involve undergoing a surgical pro-

cedure that involves surgical risk as well as the risk

154 E.A. Hurtado and R.A. Appell

of anesthesia, whereas the intraurethral bulking

agent involves only local anesthesia and minimal

complications.

Comparing the different injectable agents is a

difficult task. There are few controlled, long-term

studies involving commonly used bulking agents.

Even within those rare studies, there are many

variables that make it difficult to compare one to

another. This is due to the different patients with

different severities and etiologies of stress incon-

tinence. Not all studies differentiate the results

in patients with and without urethral hypermo-

bility and/or ISD. The procedures themselves

have also varied due to different technical factors

such as injection technique and instrumentation.

Additionally, reported results have been largely

subjective rather than objective measures, creat-

ing a difficult situation in which to compare data.

Variability also exists within the reported outcomes

as different criteria have been used to define

“cured” or “improved.”

Auotologous Materials

Autologous Blood

Autologous blood is readily available and acces-

sible. In a study of 14 women, 30 ml of blood

was obtained in a heparinized syringe from the

antecubital vein. Continence was achieved after

two treatments. Unfortunately, all patients became

incontinent again after 10–17 days [18] .

Autologous Fat

Autologous fat is another readily available bioma-

terial. Although not as accessible as blood, it can

be obtained easily through liposuction. In 1989,

this technique was reported in ten women [29] .

In a different study with 1-year follow-up, 0 of

5 men and 5 of 15 women reported improvement

[30] . In a study by Santarosa and Blaivas, 83% of

12 women with ISD were subjectively improved,

although, at 1 year the results were much lower

[31] . Looking at women with urethral hypermobil-

ity, Blaivas et al. reported poor results [32] . Even

more discouraging in a randomized, double-blind,

controlled trial, fat was found to be as effective as

the saline control group at 6 months [33] .

These poor results are thought to be secondary to

fat degradation. After injection, neovascularization

never becomes adequate at the fat graft’s center

leaving only a miniscule amount of viable fat,

which may hinder its bulking effect. After 3 weeks,

60% of the fat injected is degraded [34] . Once the

fat is reabsorbed, inflammation occurs with result-

ing fibrosis, which leads to the bulking effect [31] .

Although this material is accessible and complica-

tions are rare, it has been reported to be associated

with systemic embolization and death [33, 35] .

Therefore, use of autologous fat as a bulking agent

is discouraged.

Biomaterials

Glutaraldehyde Cross-Linked Bovine

Collagen (GAX-Collagen)

Of all the injectables, glutaraldehyde cross-linked

bovine collagen (GAX-collagen) is probably the

most used with the most publications describing

its safety and efficacy. Before its use as a bulking

agent, bovine dermal collagen was primarily used

to make absorbable sutures and hemostatic agents.

When used as a bulking agent, bovine collagen is

cross-linked with glutaraldehyde to create a stabi-

lized, fibrillar collagen that confers resistance to

denaturation by collagenases. It consists of 35%

purified bovine collagen in a phosphate buffer. The

collagen itself is composed of 95% type I collagen,

which is the type found predominately in ligaments

and confers structural strength; however, between

1 and 5% is composed of type III collagen, which

is the type abundant in vaginal tissue, giving

added flexibility [36] . GAX-collagen is prepared

by selective hydrolysis of the collagen molecule

at the nonhelicoidal amino-terminal and carboxy-

terminal segments, also known as telopeptides.

This serves two functions. One is to decrease the

antigenicity, and the other is to increase resistance

to collagenases to increase the durability of the

implant [37, 38] .

When injecting this material, the surgeon inserts

the exact amount needed to achieve the desired

effect, since there is no expansion or shrinking after

injection. Acting as a matrix, it promotes ingrowth of

new collagen within the implant [39] . Since GAX-

collagen is both biocompatible and biodegradable,

12. Surgery for Stress Urinary Incontinence: Minimally Invasive Procedures 155

only minimal inflammatory changes occur [40] .

After 12 weeks, the collagen starts to degrade, but

persists up until 19 months [41] . Despite the fact that

GAX-collagen is degraded, it maintains effective-

ness in 80% of those who became continent, which

is thought to be secondary to the ingrowth of new

collagen [42] .

In one series, it was reported that 55% of women

could achieve continence after one injection ses-

sion [43] . In a multicenter clinical study involving

127 women with ISD, 88 patients completed 2-year

follow-up. At 2 years, 46% of patients were dry

and 34% were significantly improved, requiring

only a single pad or tissues. Urodynamic studies

also revealed a rise of 40 cm H

2 O in abdominal

LPP. A mean volume of 18.4 ml of GAX-collagen

with a mean of 2.1 (±1.5) treatment sessions were

given to those who achieved continence [44] . Other

independent studies have supported these results

[9, 45, 46] . These reported rates have compared

favorably with other treatment modalities for ISD

[47] . As time progresses, a noted decline in effi-

cacy has been witnessed. Forty-five percent of

elderly women were improved at 24.4 months in

a report by Winters et al. Of note in this group,

at an average of 7.9 months, 40% required more

injections. After additional material was injected,

only 42% became continent again [12] . Forty-two

patients with ISD were followed at an average of

46 months by Richardson et al. In their series, they

reported a 40% dry rate, 43% improved rate, and

a 17% rate of failure [48] . At 50 months, Corcos

and Fournier reported a cured rate of 30% and

improved rate of 40% in 40 women, although four

women in the cured group and five women in the

improved group required “maintenance” injections

[49] . In a study up to 5 years, Gorton et al. reported

that only 26% of 53 women reported continued

improvement [50] .

Few complications have been found with the use

of GAX-collagen. In the US clinical trials, 15%

developed transient urinary retention, 5% had a

urinary tract infection (UTI), and 1% of patients

experienced irritative voiding [51] . Rates of de

novo urgency and frequency have been reported

to range from 10-as high as 50% [13, 49]. There

has been no evidence of foreign body response

or migration [39] . This is due partly to the small

amount of glutaraldehyde in GAX-collagen, which

creates minimal immunoreactivity and cytotoxicity

[52] . GAX-collagen is biocompatible and allows

fibroblasts to deposit native collagen as well as

neovascularization to occur as the implant is

degraded over 12 weeks [53] . After 10–19 months

all of the implant has completely degraded [40] .

Only a mild inflammatory response has been

associated after injection [54] . In a report of two

postmortem patients having had laryngeal implants

of GAX-collagen, an inflammatory response was

nearly absent and the implanted collagen was

colonized with host cells and new vessels [41] .

However, there have been several case reports of

sterile abscesses at the injection sites of which

some required drainage [35, 55] .

One potential hazard of GAX-collagen involves

an allergic reaction to the bovine protein, although

reduced by cross-linking and skin testing.

Approximately 4% of female patients will have a

positive skin test, which precludes them from treat-

ment, although many are unlikely to suffer from an

allergic reaction [44] . Despite being extraordinarily

rare, delayed hypersensitivity has been reported.

These have occurred at the skin test site and some-

times have been associated with arthralgia [56] .

Currently, there is no evidence to support that

GAX-collagen injections are associated with any

medical disorder as disorders have been found to

occur in even lower rates in the general population

[39, 47] . Overall, due to its complete degradation

with minimal inflammatory response and lack

of migration, GAX-collagen has been the most

popular intraurethral bulking agent used to treat

incontinence.

Key Concept

• As time progresses, a noted decline in efficacy

has been witnessed.

• Approximately 4% of female patients will have

a positive skin test, which precludes them from

treatment.

Synthetic Materials

Polytetrafluoroethylene (Polytef™)

In 1973, Berg first reported the use of polytetrafluor-

oethylene (PFTE) in a glycerol paste used on three

women with ISD after surgery. These women were

156 E.A. Hurtado and R.A. Appell

treated successfully; however, two women required

repeat injection and one patient experienced asymp-

tomatic bacteriuria [57] . Many authors have been

able to demonstrate this material’s efficacy as a

bulking agent [58– 63] . Success rates have ranged

from 70 to 90% with PFTE [64] . This material

also was studied by the Department of Technology

Assessment of the American Medical Association

and found to be an easily performed, effective treat-

ment with good short-term results [65] . However,

longer follow-up has proven otherwise. In one

study, a 38% success rate between 21 and 72 months

(mean, 49 months) was noted in women [66] .

In addition to the shortcomings in long-term effi-

cacy, rates of urinary retention have ranged from 20

to 25% [67] . Transient irritative voiding symptoms

may develop in approximately 20% of patients

[62] . Urinary tract infection has been reported to

occur at a rate of 2% [61] .

Of greater concern, the long-term safety pro-

file of this agent has been brought into question.

Foreign body reaction with granuloma formation

is a known risk [68] . After injection, histiolytic

and giant cells are responsible for this reaction.

Particles have been found in blood vessels as well

as lymphatics. These particles have been thought to

elicit an allergic response in some patients, which

is believed to be responsible for culture-negative

fevers in 25% of patients. Five percent of patients

also complain of transient perineal discomfort with

spontaneous resolution, which also is thought to be

an immune-related phenomenon [67, 69] .

Once inside blood vessels or lymphatics, par-

ticles can migrate to distant locations. In animal

models, PTFE particles have been found in pelvic

lymph nodes, lungs, brain, kidneys, and spleen at

1 year [70, 71] . Particle migration to distant sites

has been reported in humans as well. First reported

by Mittleman and Marraccini in 1983, a PTFE

granuloma was found in the lung of a patient 2

years after injection [72] . Claes et al. reported on a

patient who was experiencing fevers with biopsy-

proven PTFE granulomas in the lung 3 years after

PTFE injection [73] . In another field, PTFE was

used to inject the larynx for vocal cord paralysis.

Twenty months after injection, a granuloma was

found in the anterior lobe of the thyroid [74] .

Despite granuloma formation, patients rarely

have had any clinical consequences. It is the for-

mation of granulomas and their association with

cancer that is of more concern. Sarcomas have

been induced in rats and mice with material related

to PTFE [75] . Hakky et al. reported a chondrosa-

rcoma of the larynx 6 years after treatment of the

vocal cords for paralysis, although PTFE has not

been linked to carcinogenesis with 30 years of

use as a bulking agent for the urethra and larynx

[76] . In fact, there have been only reported cases

of cancer near PTFE injections sites, but none

have demonstrated PTFE as the precipitating fac-

tor [77– 79] . This risk was reviewed by Dewan.

It was concluded that the available evidence did

not support PTFE as a carcinogenic agent, but

suggested that if a risk existed, it was low [80] . In

1995, Dewan reviewed the risk of both PTFE and

Bioplastique in a rat model. A similar incidence of

tumors was found in the PTFE, Bioplastique, and

control group [81] . Additional late adverse events

include fibrosis of the urethra and granuloma balls

in the bladder at a rate of 15% [66] . Currently, the

US Food and Drug Administration (FDA) is inves-

tigating the product to better clarify its safety and

efficacy in the treatment of urinary incontinence

with ISD and is not available on the market.

Key Concept

• Particle migration with granuloma formation to

distant sites has been reported, although patients

rarely have had any clinical consequences.

Silicone Polymers (Macroplastique™,

Bioplastique™)

Silicone polymers such as Macroplastique™ and

Bioplastique™ are made of polydimethylsiloxane

macroparticles suspended in a carrier hydrogel

consisting of polyvinylpyrrolidone (povidone). The

solid particles make up 33% of the total volume and

are greater than 100 µ m in size. Silicone polymer

was first used in 1992 with encouraging short-term

follow-up. In 84 patients cure was attained in 82%

[81] . Like other agents as time progressed, the cure

rate fell to 70% at 14 months [82] . In other studies

with Macroplastique™, 19.6% were considered

cured and 41.1% significantly improved at 19

months [83] . In another study using the Stamey

grading system, as well as the King health ques-

tionnaire at 12 months, 57.1% patients considered

themselves cured and 19% improved. From the

12. Surgery for Stress Urinary Incontinence: Minimally Invasive Procedures 157

surgeon’s subjective grading 38.1% were cured

and 28.6% improved. The authors concluded that

Macroplastique™ had acceptable outcomes for

the patient and the surgeon [84] . To date there has

been one prospective, randomized study comparing

Macroplastique™ to GAX-collagen in 62 women.

The authors concluded that there was no signifi-

cant objective difference between the two agents

at 12 months. The only difference was that the

Macroplastique™ group had less volume injected,

although pretreatment pad test loss was signifi-

cantly less in that group [85] .

Complications with use of this material included

urinary retention at a rate of 5.9–17.5%, urinary fre-

quency at a rate of 0–72.4%, dysuria from 0 to 100%,

and UTI 0–6.25% [86] . A study to determine the

migratory properties of this material was performed

on dogs. Small particles were found in the lungs,

kidney, brain, and lymph nodes within 4 months of

injection. In comparison, only one large particle was

found in the lung without any associated reaction

[87] . In a rat model, four sarcomas with Bioplastique

group were associated with silicone particles [80] .

Given the recent controversy over silicone used in

breast implants as well as the possibility of migra-

tion, it is unlikely that silicone will become a popular

agent for intraurethral injections.

Carbon-coated Zirconium Beads

(Durasphere™ and Durasphere EXP™ )

Durasphere™, a new synthetic material, was

approved by the FDA in 1999. It is composed of

pyrolytic carbon-coated zirconium oxide beads in

a 2.8% beta-glucan water-based gel. Bulking effect

lasts for at least 2 years as the beads are encap-

sulated into the periurethral tissue. Compared to

collagen, it is an inert and nonimmunogenic mate-

rial eliminating the need for skin testing. However,

Durasphere™ can be more technically difficult to

inject given its higher viscosity.

Durasphere™ was compared to GAX-collagen in

a multicenter, randomized, controlled, double-blind

study with follow-up at 1 year. The Durasphere™

group achieved improvement in one Stamey grade

or more in 80% of patients compared to 69% of

patients in the GAX-collagen group, although the

difference did not reach statistical significance. Pad

weights at 12 months were equivalent between the

two groups. The Durasphere™ group had a sig-

nificantly smaller volume injected and was more

successfully treated with a single injection [88] .

Although permanent, questions concerning longev-

ity similar to GAX-collagen were brought forth.

Panneck et al. noted a decrease in success from

77% at 6 months to 33% at 12 months in a group of

13 women. In their study, one female patient also

was noted to have asymptomatic distant particle

migration into the regional and distal lymph nodes

[89] . Due to intraneedle resistance secondary to

bead size, injection of Durasphere™ can be techni-

cally difficult. In response to this issue, Madjar

et al. used a periurethral approach at a single

injection site. With 92% of 46 patients achieving

excellent or good coaptation, 65% considered them-

selves cured or improved at a mean of 9.4 months.

Additionally, 50% of 36 patients had 24-h pad test

with 8 gm or less of urine [90] . Long-term data have-

been reported in a multicenter, comparative trial of

Durasphere™ and GAX-collagen. Durasphere™

remained effective in 33% of patients at 24 months

and 21% at 36 months. Those who received GAX-

collagen reported effectiveness in 19% of patients

at 24 months and 9% at 36 months. However, when

controlled for differences in follow-up time, the

time to failure between the two groups did not reach

statistical significance. Interestingly, one third of

each group felt that treatment was successful [91] .

In the trials for FDA approval, the most com-

mon adverse events were acute retention ( ≤ 7 days)

at 13%, dysuria at 12%, UTI at 9%, and hematuria

at 6%, and retention >7 days at 6%. Other adverse

events occurred at ≤ 4% [92] . There also have been

case reports of sterile abscess formation. In one

series, two of four abscesses required incision and

drainage [93] .

Durasphere’s™ beads are much larger than

either PFTE or silicone polymers. In spite of their

size, there have been reports of migration despite

lacking clear evidence [89, 94] . As determined by

studies involving polytetrafluorethylene, macro-

phages are able to phagocytize particles smaller

than 80 µ m. Once phagocytized, the particles then

can be carried to different parts of the body. Since

Durasphere ranges from 212 to 500 m m, phago-

cytosis and therefore migration should not occur.

Case reports involving beads found in lymphat-

ics and so forth are likely due to a high-pressure

embolization effect, which may displace beads

into vascular or lymphatic spaces. Delivery with

158 E.A. Hurtado and R.A. Appell

large particles under low pressure should elimi-

nate the risk of embolization. Durasphere-EXP™

is a modification of the original Durasphere™

that should allow lower pressure injection due the

smaller bead size (95–550 µ m, yet above 80 µ m to

avoid migration).

Key Concept

• Durasphere™ achieved improvement in one

Stamey grade or more in 80% of patients com-

pared to 69% of patients in the GAX-collagen

group, although the difference did not reach sta-

tistical significance.

Ethylene Vinyl Alcohol Copolymer

(Tegress™, Uryx™)

Approved by the FDA in 2004, Tegress™ is com-

posed of 8% ethylene vinyl alcohol (EVOH) copol-

ymer dissolved in dimethyl sulfoxide (DMSO),

which is a permanent, hypoallergenic, nonimmu-

nogenic implant. It comes prepared in 3 ml glass

vials with a 3 ml DMSO-compatible syringe. The

material is injected via a 25-gauge needle. Once

Tegress™ is exposed to fluid within the tissue, the

DMSO diffuses out, causing the precipitation of

EVOH into a soft, spongy, hydrophilic material.

The time required for the chemical reaction to occur

is within 60 s. Care must be taken to avoid contami-

nation of this agent with fluid prior to injection. At

1 month, an acute inflammatory response has been

noted to be at its greatest. This effect lasts until 3

months when the reaction has become more mild

and localized with some resultant mineralization.

There has been no evidence of EVOH affecting

tissue at remote sites from the injection site. There

also has been no evidence of migration.

When EVOH is used as a bulking agent, a dif-

ferent technique must be applied. If an excessive

amount of material is injected, erosion through

the urethral mucosa is likely to occur. In order

to decrease the risk of erosion, the manufacturer

suggests injecting at a more distal location in the

urethra approximately 1.5 cm distal to the bladder

neck. Each injection is to take place over 1 min

with an additional minute waited to allow the

chemical reaction to occur before removing the

needle [95] . When the needle is removed, a twist-

ing motion often helps to separate the precipitated

material off the needle tip and minimize the length

of tail left at the injection site. Injections should

not be performed until coaptation is noted, which

is dissimilar to many of the other bulking agents.

Urethral coaptation may suggest that too much

material may have been injected [96] .

Currently for EVOH, the only large study is from

the trial for FDA approval. A multicenter, prospec-

tive, randomized trial was conducted with 177 of 253

women completing follow-up at 12 months compar-

ing EVOH to GAX-collagen. The first 16 patients

were excluded from the data, since they were the first

patients undergoing a new technique. At 12 months,

efficacy was assessed by Stamey grade, pad weight,

and quality of life questionnaire: 18.4% of patients

were dry by Stamey grade of those who received

EVOH compared to 16.5% of those who received

collagen. The difference between the two groups

who had improvement by at least one Stamey grade

did not reach clinical significance. In respect to pad

weights, 37.8% were dry in the EVOH group com-

pared to 32.1% undergoing collagen injection. This

study resulted in FDA approval of EVOH [95, 97] .

In the trials for FDA approval, EVOH has been

shown to have similar rates and severity of adverse

events when compared to collagen. The one excep-

tion is the rate of material exposure of 16%.

During this study, it was noted that the exposure

rate was higher with periurethral injection, and

therefore is not recommended. Exposed material

did not result in any adverse consequences and

usually resolved. However, in the authors’ experi-

ence erosion rates of 37% in women and 41% in

men necessitated multiple office visits for several

patients with severe dysuria [98, 99] . Other com-

mon adverse events included UTI (29%), delayed

voiding (18%), dysuria (18%), urinary urgency

(14%), and frequency (13%). Interestingly, 9% of

patients developed urge incontinence and 8% had

worsening of incontinence [95] .

Key Concepts

• With EVOH, injections should not be performed

until coaptation is noted, which is dissimilar to

many of the other bulking agents.

Calcium Hydroxyapatite (Coaptite ® )

Approved in December 2005, calcium hydroxya-

patite is a synthetic agent that consists of car-

boxymethylcellulose in the form of an aquaeous

12. Surgery for Stress Urinary Incontinence: Minimally Invasive Procedures 159

gel. It is the same material found in bone and teeth

and has been used in dental work as well as bone

healing. Calcium hydroxyapatite is biocompatible,

does not encapsulate, and facilitates ingrowth of

native tissues. This material also can be identified on

radiographic studies as well as ultrasound. Another

advantage includes ease of injection of material.

In a study with 1-year follow-up, seven of ten

women reported substantial improvement in con-

tinence, a 90% decrease in mean pad weight, and

increase in mean Valsalva leak point pressure

from 39 to 46 cm H

2 O [100] . In the data for FDA

approval, 158 patients received Coaptite

® with a

mean follow-up of 11.2 months. No statistical dif-

ference was found in change in Stamey grade, pad

weight, or quality of life when compared to GAX-

collagen as the control [101] .

Common adverse events from the FDA data

included urinary retention (41%), hematuria (19.6%),

dysuria (15.2%), and UTI (8.3%). Changes in

voiding occurred with urinary urgency at 7.6%,

frequency at 7.0%, and urge incontinence at 5.7%.

Two serious adverse events occurred, with one ero-

sion through the vaginal wall that required surgery

and dissection into the bladder and another causing

tissue bridging of which no surgical correction was

needed. Overall, the erosion rate was 1.3% [101] .

Key Concept

• No statistical difference was found in change in

Stamey grade, pad weight, or quality of life when

compared to GAX-collagen as the control.

Future Agents

In patients with minimal urethral–vesical junc-

tion mobility, ISD, and a stable bladder with an

adequate capacity, intraurethral injections can offer

treatment responses similar to those of surgical

correction with minimal complications. However,

most of these data are short-term with a scarcity

of data over 5 years, and the majority of studies

followed at much less time. For GAX-collagen,

reinjection rates can be as high as 22% at 32

months after having achieved continence [102] .

The other injectable agents on the market have

much fewer data, and they lack long-term follow-

up. For patients who are younger, the cost of rein-

jection can become significant.

Although numerous injectable agents have entered

the market over the last several years, the search for

the ideal bulking agents continues. Listed below are

some of the current agents undergoing investigation.

Hyaluronic Acid

Made of a water-insoluble complex glycosaminogly-

can, which itself is composed of disaccharide units,

hyaluronic acid has completed a stage I study [103] .

This type of hyaluronic acid is cross-linked, highly

biocompatible, as well a nonimmunogenic, making

it well tolerated with some longevity before under-

going absorption. The molecules weigh between 8

and 23 million molecular weight. This agent comes

dissolved in normal saline to allow ease of injec-

tion. Currently, the FDA has given approval to start

a stage II multicenter study to compare hyaluronic

acid to GAX-collagen.

Hyaluronic Acid and Dextranomer

Microspheres

Hyaluronic acid and dextranomer microspheres are

complex sugar polymers which are glycosaminogly-

can and cross-linked dextran, respectively. Each

polymer has its own function. Hyaluronic acid

serves as a carrier and is degraded and reab-

sorbed within 2 weeks, while the dextranomer

microspheres function as the bulking agent. The

dextranomer microspheres may last up to 4 years

due to slow degradation [104] . Similar to collagen

with ease of injection, it provides a foundation

for fibroblasts to deposit new collagen. Currently,

clinical trials in the United States are underway.

This agent already is approved in Europe. In the

United States, it is only approved for the treatment

of vesicoureteral reflux in children in which it has

been used extensively. In a study by Stenberg

et al., only 3 of 20 patients (15%) failed this treat-

ment and in those who responded, 57% had a sus-

tained response [105] . A new device known as the

“implacer” has been studied with this agent as well.

This device allows the placement of four syringes

of material to be placed via a transurethral tech-

nique without cystourethroscopy. Van Kerrebroeck

et al. reported a significant decrease in incontinent

episodes, with 69% of patients improving on the

6-point perception scale in a study of 42 patients

over 1 year [106] .

160 E.A. Hurtado and R.A. Appell

Bioglass

Bioglass is an inert compound derived from cal-

cium oxide, calcium silicone, and sodium oxide. In

animal models, it has been demonstrated to elicit a

minimal inflammatory response and no toxicity has

been found. Similar to other agents, the compound

serves as a framework for fibroblasts to deposit col-

lagen to integrate host tissue with the implant [107] .

Currently, no human trials have been performed.

Autologous Tissue

Described by Atala et al., intraurethral bulking with

autologous chondrocytes could be performed by

harvesting chondrocytes from the patient’s auricu-

lar surface. Tissue engineering then is required to

culture and expand these cells and place them in

an alginate polymer for insertion into the urethral

submucosa [108] . In one study of 32 patients, 16

were dry and 10 improved at 12 months [109] . This

technique is to be assessed in a multicenter trial.

Harvesting myoblasts from the biceps muscle is

another tissue-engineering concept being considered

[110] . Using autologous tissue alleviates problems

with biocompatibility. Since these tissues can con-

tinue to grow and thrive in their environment, they

should maintain longevity as well. An additional

advantage of muscle cells is that they differentiate

into smooth or striated muscle, which can actively

help to improve the mucosal seal. This agent has

much promise in the human model [111, 112] .

Disadvantages to tissue engineering include cost

as well as safety. Enormous expense can be gener-

ated from tissue engineering as well as the possibil-

ity of stored cells for potentially further treatment.

Safety also is a concern, since there is no way to

predict how many cells are required upon implan-

tation as well as the potential of mixing specimens

in laboratory facilities prior to injection. Further

research is needed to investigate this technique

before clinical trials can be considered.

Microballoons

The first microballoons were placed via a periure-

thral approach and had encouraging results [113] .

However, trials in the United States were never

conducted due to problems in the way the micro-

balloons were delivered. New balloons have been

developed that allow for balloon adjustment. These

are placed via a periurethral approach as before and

currently are being investigated worldwide. The

new devices are placed at the level of the bladder

neck and are outside the urethra rather than intrau-

rethrally. The balloon then can be filled through a

port that is accessible through the labium similar

to the pump from an artificial urinary sphincter.

In contrast to intraurethral agents, local anesthetic

is not sufficient, requiring an operative room with

regional or general anesthesia.

Conclusion

Currently, injectable agents are best used for those

who are good candidates for successful treatment,

those who wish to avoid a surgical procedure, or

those who have problematic medical comorbidi-

ties that preclude them from undergoing surgical

correction. Research continues the search for an

effective, inert, nonmigratory, nonimmunogenic

material that allows incorporation into native tis-

sue, maintains its shape, and injects with ease.

Currently, intraurethral bulking remains an art, as

there is no exact measurement or amount of mate-

rial used for each patient to achieve continence.

References

1 . Murless BC . The injection treatment of stress

incontinence . J Obstet Gynecol Br Emp 1938 ;

45 : 521 – 524 .

2 . Quackels R . Deux incontinence apr; ages adenon-

ectomie: Queries par injection de paraffine dans la

perin; aaee . Acta Urol Belg 1955 ; 23 : 259 – 262 .

3 . Sachse H . Treatment of urinary incontinence with

sclerosing solutions: Indications, results, complica-

tions . Urol Int 1963 ; 15 : 225 – 244 .

4 . Dmochowski RR, Appell RA . Injectable agents

in the treatment of stress urinary incontinence

in women: Where are we now? Urology 2000 ;

56 (Suppl 6A) : 32 – 40 .

5 . Crystle CD , Charme LS , Copeland WE . Q-tip test

in stress urinary incontinence . Obstet Gynecol

1971 ; 39 : 313 – 315 .

6 . Appell RA , Ostergard D . Practical urodynamics .

Illustr Med Female Urol Ser 1992 ; 2 : 4 – 29 .

7 . Kreder KJ , Austin JC . Treatment of stress urinary

incontinence in women with urethral hypermobil-

ity and intrinsic sphincter deficiency . J Urol 1996 ;

156 : 1995 – 198 .

12. Surgery for Stress Urinary Incontinence: Minimally Invasive Procedures 161

8 . Smith DN , Appell RA , Winters JC , et al. Collagen

injection therapy for female intrinsic sphincter defi-

ciency . J Urol 1997 ; 152 : 1275 – 1278 .

9 . Herschorn S , Radomski SB , Steele DJ . Early expe-

rience with intraurethral collagen injection for uri-

nary incontinence . J Urol 1992 ; 148 : 1797 – 1800 .

10 . Herschorn S , Radomski SB . Collagen injections

for genuine stress urinary incontinence: Patient

selection and durability . Int Urogynecol J 1997 ;

8 : 18 – 24 .

11 . Faerber GJ . Endoscopic collagen injection therapy

for elderly women with type I stress urinary incon-

tinence . J Urol 1995 ; 153 : 527A .

12 . Winters J , Chiverton A , Scarpero H , et al. Collagen

injection therapy in elderly women: Long-term

results and patient satisfaction . Urology 2000 ;

55 : 815 – 818 .

13 . Steele AC , Kohli N , Karram MM . Periurethral

collagen injection for stress incontinence with and

without urethral hypermobility . Obstet Gynecol

2000 ; 95 : 322 – 331 .

14 . Bent , AE , Foote , J , Siegel S , et al. Collagen

implant for treating stress urinary incontinence in

women with urethral hypermobility . J Urol 2001 ;

166 (4) : 1354 – 1357 .

15 . Winters JC . Urodynamics in the era of tension-free

slings . Curr Urol Rep 2004 ; 5 (5) : 343 – 347 .

16 . O’Connell HE , McGuire EJ . Transurethral collagen

therapy in women . J Urol 1995 ; 154 : 1463 – 1465 .

17 . Appell RA . Injectables for urethral incompetence .

World J Urol 1990 ; 8 : 208 – 211 .

18 . Appell RA . The periurethral injection of autologous

blood . Presented at the American Urogynecologic

Society annual meeting , Toronto , 1994 .

19 . Neal ED Jr , Lahaye ME , Lowe DC . Improved

needle placement technique in periurethral collagen

injection . Urology 1995 ; 45 : 865 – 866 .

20 . Faerber GJ , Belville WD , Ohl DA , et al. Comparison

of transurethral versus periurethral collagen injec-

tion in women with intrinsic sphincter deficiency .

Tech Urol 1998 ; 4 (3) : 124 – 127 .

21 . Schulz JA , Nager CW , Stanton SL , et al. Bulking

agents for stress urinary incontinence: Short-term

results and complications in a randomized com-

parison of periurethral and transurethral injection .

Int Urogynecol J Pelvic Floor Dysfunct 2004 ;

15 : 261 – 265 .

22 . Appell RA . Collagen injections. In : Raz S , ed.

Female urology . 2nd ed . Philadelphia : WB Saunders ,

1996 : 399 – 405 .

23 . Defreitas GA , Wilson TS , Zimmern PE , et al.

Three-dimensional ultrasonography: An objective

outcome to assess collagen distribution in women

with stress urinary incontinence . Urology 2003 ;

62 : 232 – 236 .

24 . Poon CI , Zimmern PE , Defreitas GA , et al. Three-

dimensional ultrasonography to assess long-term

durability of periurethral collagen in women with

stress urinary incontinence due to intrinsic sphinc-

teric deficiency . Urology 2005 ; 65 : 60 – 64 .

25 . Cross CA , English SF , Cespedes RD , et al. A follow-

up on transurethral collagen injection therapy for

urinary incontinence . J Urol 1998 ; 159 : 106 – 108 .

26 . Stothers L , Goldenberg SL , Leone EF . Complications

of periurethral collagen injection for stress urinary

incontinence . J Urol 1998 ; 159 (3) : 806 – 807 .

27 . Bergman A , Koonings PP , Ballard CA . Negative

Q-tip test as a risk factor for failed incontinence sur-

gery in women . J Reprod Med 1990 ; 34 (3) : 193 – 197 .

28 . Segal JL , Vasallo BJ , Kleeman SD , et al. The effi-

cacy of tension-free vaginal tape in the treatment of

five subtypes of stress urinary incontinence . Int J

Pelvic Floor Dysfunct 2006 ; 17 (2) : 120 – 124 .

29 . Gonzalez de Garibay AS , Castro-Morrondo JM ,

Castro-Jimeno JM . Endoscopic injection of autolo-

gous adipose tissue in the treatment of female

incontinence . Arch Esp Urol 1989 ; 42 : 143 – 146 .

30 . Gonzalez de Garibay AS , Castillo-Jimeno JM ,

Villanueva-Perez PI . Treatment of urinary stress

incontinence using paraurethral injection of autolo-

gous fat . Arch Esp Urol 1991 ; 44 : 595 – 600 .

31 . Santarosa RP , Blaivas JG . Periurethral injection

of autologous fat for the treatment of sphincteric

incontinence . J Urol 1994 ; 151 : 607 – 611 .

32 . Blaivas JG , Herwitz D , Santarosa RP , et al.

Periurethral fat injection for sphincteric inconti-

nence in women . J Urol 1994 ; 151 : 419A .

33 . Lee PE , Kung RC , Drutz HP . Periurethral autolo-

gous fat injection as treatment for female stress

urinary incontinence: A randomized double-blind

controlled trial . J Urol 2000 ; 165 : 153 – 158 .

34 . Bartynski J , Marion MS , Wang TD . Histopathologic

evaluation of adipose autografts in a rabbit ear

model . Otolaryngology 1990 ; 102 : 314 .

35 . Sweat SD , Lightner DJ . Complications of sterile

abscess formation and pulmonary embolism fol-

lowing periurethral bulking agents . J Urol 1999 ;

161 : 93 – 96 .

36 . Moalli PA , Shand SH , Zyczynski HM , et al.

Remodeling of vaginal connective tissue in patients

with pelvic organ prolpase . Obstet Gynecol 2005 ;

106 (5 Pt 1) : 953 – 963 .

37 . DeLustro F , Dasch J , Keefe J , et al. Immune

response to allogeneic and xenogeneic implants

of collagen and collagen derivatives . Clin Orthop

1990 ; 260 : 263 – 279 .

38 . McPherson JM , Sawamura S , Armstrong R . An

examination of the biologic response to injectable

glutaraldehyde cross-linked collagen implants .

J Biomed Matter Res 1986 ; 20 : 93 – 97 .

162 E.A. Hurtado and R.A. Appell

39 . DeLustro F , Keefe J , Fong AT , et al. The biochem-

istry, biology, and immunology of injectable colla-

gens: Contigen Bard collagen implant in treatment

of urinary incontinence . Pediatr Surg Int 1991 ;

6 : 245 – 251 .

40 . Canning DA , Peters CA , Gearhart JR , et al. Local

tissue reaction to glutaraldehyde cross-linked

bovine collagen in the rabbit bladder . J Urol 1988 ;

139 : 258 – 259 .

41 . Remacle M , Marbaix E . Collagen implants in

the human larynx . Arch Otorhinolaryngol 1988 ;

245 : 203 – 209 .

42 . Appell RA . Collagen injection therapy for urinary

incontinence . Urol Clin North Am 1994 ; 21 : 177 – 182 .

43 . Appell RA . New developments: Injectables for

urethral incompetence in women . Int Urogynecol J

1990 ; 1 : 117 – 119 .

44 . Appell RA , McGuire EJ , DeRidder PA , et-al.

Summary of effectiveness and safety in the prospec-

tive, open, multicenter investigation of Contigen

implant for incontinence due to intrinsic sphincteric

deficiency in females . J Urol 1994 ; 151 : 418A .

45 . Striker P , Haylen B . Injectable collagen for type 3

female stress incontinence: The first 50 Australian

patients . Med J Aust 1993 ; 158 : 89 – 91 .

46 . Swami SK , Eckford SD , Abrams P . Collagen injec-

tions for female stress incontinence: Conclusions

of a multistage analysis and results . J Urol 1994 ;

151 : 479A .

47 . Appell RA . Use of collagen injections for treat-

ment of incontinence and reflux . Adv Urol 1992 ;

5 : 145 – 165 .

48 . Richardson TD , Kennelly MJ , Faerber GJ .

Endoscopic injection of glutaraldehyde cross-linked

collagen for the treatment of intrinsic sphincteric

deficiency in women . Urology 1995 ; 46 : 378 – 381 .

49 . Corcos J , Fournier C . Periurethral collagen injec-

tion for the treatment of female stress urinary

incontinence: 4-year follow-up results . Urology

1999 ; 54 : 815 – 818 .

50 . Gorton E , Stanton S , Monga A , et al. Periurethral

collagen injection: A long-term follow-up study .

BJU Int 1999 ; 84 : 966 – 971 .

51. Bard CR, Inc. PMAA submission to United States

Food and Drug Administration for IDE G850010,

1990.

52 . Ford CN , Martin CW , Warren TF . Injectable colla-

gen in laryngeal rehabilitation . Laryngoscope 1984 ;

95 : 513 – 518 .

53 . Stegman S , Chu S , Bensch K , et al. A light and

electron microscopic evaluation of Zyderm and

Zyplast implants in aging human facial skin: A pilot

study . Arch Dermatol 1987 ; 123 : 1644 – 1649 .

54 . DeLustro F , Condell RA , Nguyen MA , et al. A

comparative study of the biologic and immunologic

response to medical devices derived from dermal

collagen . J Biomed Mater Res 1986 ; 20 : 109 – 120 .

55 . McLennan MT , Bent AE . Suburethral abscess:

A complication of periurethral collagen injection

therapy . Obstet Gynecol 1998 ; 92 : 650 – 652 .

56 . Stothers L , Goldenberg SL . Delayed hypersensitiv-

ity and systemic arthralgia following transurethral

collagen injection for stress urinary incontinence . J

Urol 1998 ; 159 : 1507 – 1509 .

57 . Berg S . Polytef augmentation urethroplasty:

Correction of surgically incurable urinary incon-

tinence by injection technique . Arch Surg 1973 ;

107 : 379 – 381 .

58 . Politano VA , Small MP , Harper JM , et al. Periurethral

Teflon injection for urinary incontinence . J Urol

1974 ; 111 : 180 – 183 .

59 . Heer H . Die Behandlung der Harnin-kontinenz mit

der Teflon-paste . Urol Int 1977 ; 32 : 295 – 302 .

60 . Lampante L , Kaesler FP , Sparwasser H . Endourethrale

submukose Tefloninjektion zur Erzielung von

Harninkontinenz . Akt Urol 1979 ; 10 : 265 – 272 .

61 . Lim KB , Ball AJ , Feneley RCL . Periurethral Teflon

injection: A simple treatment for urinary inconti-

nence . Br J Urol 1983 ; 55 : 208 – 210 .

62 . Schulman CC , Simon J , Wespes E , et al. Endoscopic

injection of Teflon for female urinary incontinence .

Eur Urol 1983 ; 9 : 246 – 247 .

63 . Deane AM , English P , Hehir M , et al. Teflon

injection in stress incontinence . Br J Urol 1985 ;

57 : 78 – 80 .

64 . Appell RA . Commentary: Periurethral poly-

tetrafluoroethylene (Polytef) injection. In : Whitehead

ED , ed. Current operative urology . Philadelphia : JB

Lippincott , 1990 : 63 – 66 .

65 . Cole HM . Diagnostic and therapeutic technology

assessment (DATTA) . JAMA 1993 ; 269 : 2975 – 2980 .

66 . Buckley JF , Lingham K , Meddings RN , et al.

Injectable Teflon paste for female stress inconti-

nence: Long-term follow-up and results . J Urol

1993 ; 149 : 418A .

67 . Politano VA . Periurethral polytetrafluoroethylene

injection for urinary incontinence . J Urol 1982 ;

127 : 439 – 442 .

68 . Stone JW , Arnold GE . Human larynx injected with

Teflon paste: Histologic study of innervation and tis-

sue reaction . Arch Otolaryngol 1967 ; 86 : 550 – 562 .

69 . Politano VA . Periurethral Teflon injection for uri-

nary incontinence . Urol Clin North Am 1978 ;

5 : 415 – 422 .

70 . Malizia AA Jr , Reiman JM , Myers RP , et al.

Migration and granulomatous reaction after periu-

rethral injection of Polytef (Teflon) . JAMA 1984 ;

251 : 3277 – 3281 .

71 . Vandenbossche M , Delhobe O , Dumortier P , et al.

Endoscopic treatment of reflux: Experimental study

12. Surgery for Stress Urinary Incontinence: Minimally Invasive Procedures 163

and review of Teflon and collagen . Eur Urol 1994 ;

23 : 386 .

72 . Mittleman RE , Marraccini JV . Pulmonary Teflon

granulomas following periurethral Teflon injection

for urinary incontinence . Arch Pathol Lab Med

1983 ; 107 : 611 – 612 .

73 . Claes H , Stroobants D , van Meerbeek J , et al.

Pulmonary migration following periurethral poly-

tetrafluoroethylene injection for urinary inconti-

nence . J Urol 1989 ; 142 : 821 – 822 .

74 . Sanfilippo F , Shelburne J , Ingram P . Analysis of a

Polytef granuloma mimicking a cold thyroid nod-

ule 17 months after laryngeal injection . Ultrastruct

Pathol 1980 ; 1 : 471 – 475 .

75 . Oppenheimer BS , Oppenheimer ET , Stout AP , et al.

The latent period in carcinogenesis by plastics in

rats and its relation to the presarcomatous stage .

Cancer 1958 ; 11 : 204 – 213 .

76 . Hakky M , Kolbusz R , Reyes CV . Chondrosarcoma

of the larynx . Ear Nose Throat J 1989 ; 68 : 60 – 62 .

77 . Lewy RB . Experience with vocal cord injection .

Ann Otol Rhinol Laryngol 1976 ; 85 : 440 – 450 .

78 . Montgomery WW . Laryngeal paralysis – Teflon

injection . Ann Otol 1979 ; 88 : 647 – 657 .

79 . Dewan PA . Is injected polytetrafluoroethylene

(Polytef) carcinogenic? Br J Urol 1992 ; 69 : 29 – 33 .

80 . Dewan PA , Owen AJ , Byard RW . Long-term histo-

logical response to subcutaneously injected Polytef

and Bioplastique in a rat model . Br J Urol 1995 ;

76 (2) : 161 – 164 .

81 . Buckley JF , Scott R , Meddings , et al. Injectable

silicone microparticles: A new treatment for female

stress incontinence . J Urol 1992 ; 147 : 280A .

82 . Buckley JF , Lingham K , Lloyd SN , et al. Injectable

silicone macroparticles for female urinary inconti-

nence . J Urol 1993 ; 149 : 402A .

83 . Radley SC , Chapple CR , MItsogiannis IC , et al.

Transurethral implantation of Macroplastique for

the treatment of female stress urinary incontinence

secondary to intrinsic sphincteric deficiency . Eur

Urol 2001 ; 39 : 383 – 389 .

84 . Tamanini JT , D’Ancona CA , Tadini V , et al.

Macroplastique implantation system for female

stress urinary incontinence . J Urol 2003 ; 169 : 2229 –

2233 .

85 . Anders K , Khullar V , Cardozo L , et al. Gax-

collagen or Macroplastique . Does it make a differ-

ence? Neururol Urodyn 1999 ; 18 : 297 – 298 .

86 . Ter Meulen PH , Berghmans LC , van Kerrebroeck

PE . Systematic review: Efficacy of silicone micro-

implants (Macroplastique) therapy for stress uri-

nary incontinence in adult women . Eur Urol 2003 ;

44 : 573 – 582 .

87 . Henly DR , Barrett DM , Weiland TL , et al. Particulate

silicone for use in periurethral injections: Local tis-

sue effects and search for migration . J Urol 1995 ;

153 : 2039 – 2043 .

88 . Lightner D , Calvosa C , Andersen R , et al. A new

injectable bulking agent for treatment of stress

urinary incontinence: Results of a multicenter,

randomized, controlled, double-blind study of

Durasphere . Urology 2001 ; 58 : 12 – 15 .

89 . Pannek J , Brands FH , Senge T . Particle migra-

tion after transurethral injection of carbon coated

beads for stress urinary incontinence . J Urol 2001 ;

166 : 1350 – 1353 .

90 . Madjar S , Covington-Nichols C , Secrest CL . New

periurethral bulking agent for stress urinary inconti-

nence: Modified technique and early results . J Urol

2003 ; 170 : 2327 – 2329 .

91 . Chrouser KL , Fick F , Goel A , et al. Carbon coated

zirconium beads in beta-glucan gel and bovine

glutaraldehyde cross-linked collagen injections for

intrinsic sphincteric deficiency: Continence and

satisfaction after extended follow-up . J Urol 2004 ;

171 : 1152 – 1155 .

92. United States Food and Drug Administration:

Durasphere™ Injectable Bulking Agent. Summary

of Safety and Effectiveness Data, 1999. www.fda.

gov/cdrh/pdf/p980053.html.

93 . Madjar S , Sharma AK , Waltzer WC , et al.

Periurethral mass formations following bulking

agent injection for the treatment of urinary inconti-

nence . J Urol 2006 ; 175 : 1408 – 1410 .

94 . Ritts RE . Particle migration after transurethral

injection of carbon coated beads . J Urol 2002 ;

167 : 1804 – 1805 .

95. United States Food and Drug Administration.

URYX ® Urethral bulking agent – P030030 Part

II: Summary of safety and effectiveness data, 2004.

http://www.fda.gov/cdrh/PDF3/p030030b.

96 . Dmochowski RR , Appell RA . Advancements in

minimally invasive treatments for female stress

urinary incontinence: Radiofrequency and bulking

agents . Curr Urol Rep 2003 ; 4 : 350 – 355 .

97 . Dmochowski RR . Tegress ™ Urethral implant phase

III clinical experience and product uniqueness . Rev

Urol, 2005 ; 7 (Suppl 1) : S22 – 26 .

98. Hurtado EA, McCrery RJ, Appell RA. The safety and

efficacy of ethylene vinyl alcohol copolymer as an intra-

urethral bulking agent in women with intrinsic urethral

deficiency. Int Urogynecol J 2007; 18:869–873.

99 . Hurtado EA , McCrery RJ , Appell RA . Complications

of ethylene vinyl alcohol copolymer as an intra-

urethral bulking agent in men with stress urinary

incontinence . Urology 2008 ; 71 : 662 – 65 .

100 . Mayer R , Lightfoot M , Jung I . Preliminary evalu-

ation of calcium hydroxylapatite as a transure-

thral bulking agent for stress urinary incontinence .

Urology 2001 ; 57 : 434 – 438 .

164 E.A. Hurtado and R.A. Appell

101. United States Food and Drug Administration.

Coaptite

® implanted device. www.fda.gov/cdrh/

mda/docs/p040047.html, 2005.

102 . Winters JC , Appell RA . Periurethral injection of

collagen in the treatment of intrinsic sphincteric

deficiency in the female patient . Urol Clin North

Am 1995 ; 22 : 673 – 678 .

103. Biomatrix Corporation. Formal report of feasibil-

ity study of Hylagel Uro. Corporate white paper.

Ridgefield, NJ, June 2000.

104 . Stenberg A , Larsson G , Johnson P , et al. DiHA

Dextran copolymer, a new biocompatible material for

endoscopic treatment of stress incontinent women .

Acta Obstet Gynecol Scand 1999 ; 78 : 436 – 442 .

105 . Stenberg A , Larsson G , Johnson P . Urethral injec-

tion for stress urinary incontinence: Long-term

results with dextranomer/hyaluronic acid copol-

ymer . Int Urogynecol J Pelvic Dysfunct 2003 ;

14 : 335 – 338 .

106 . Van Kerrebroeck P , ter Meulen F , Larsson G , et al.

Efficacy and safety of a novel system (NASHA/

Dx copolymer using the Implacer device) for treat-

ment of stress urinary incontinence . Urology 2004 ;

64 : 276 – 281 .

107 . Walker RS , Wilson K , Clark AE . Injectable bioglass

as a potential substitute for injectable polytetraflu-

orethylene . J Urol 1992 ; 148 : 645 – 647 .

108 . Atala A , Cima LG , Kim W , et al. Injectable alginate

seeded with chondrocytes as a potential treatment

for vesicoureteral reflux . J Urol 1993 ; 150 : 745 –

747 .

109 . Bent AE , Tutrone RT , McLennan , et al. Treatment

of intrinsic sphincter deficiency using autologous

ear chondrocytes as a bulking agent . Neurourol

Urodyn 2001 ; 20 : 157 – 165 .

110 . Yokoyama T , Chancellor MB , Watanabe T , et al.

Primary myoblast injection into urethra and blad-

der as a potential treatment of stress urinary

incontinence and impaired detrusor contractility:

Long-term survival without significant cytotoxicity .

J Urol 2000 ; 161 : 307 .

111 . Cannon TW , Lee JY , Somogyi G , et al. Improved

sphincter contractility after allogenic muscle-

derived progenitor cell injection into the denervated

rat urethra . Urology 2003 ; 62 : 958 – 963 .

112 . Peyromaure M , Sebe P , Praud C , et al. Fate of

implanted syngeneic muscle precursor cells in stri-

ated urethral sphincter of female rats: Perspectives

for the treatment of urinary incontinence . Urology

2004 ; 64 : 1037 – 1041 .

113 . Pycha A , Klinger CH , Haitel A , et al. 3 years expe-

rience with implantable microballoons for the treat-

ment of intrinsic sphincter deficiency . J Urol 2000 ;

161 : 307 .

165

Introduction

There is a spectrum of urodynamic stress incon-

tinence ranging from women with pure intrinsic

sphincter deficiency to women with only hypermo-

bility to women with a mixture of both. Bladder

neck slings previously were used in those women

where an obstructive procedure was required.

However, the introduction of midurethral slings and

the concept of “tension-free” placement of these

tapes changed this idea significantly. This type of

tape appears to be useful in treating women with

both intrinsic sphincter deficiency and bladder

neck hypermobility.

Various etiologic factors contribute to reducing

the ability of the submucosal and muscular layers

of the urethra to compress the lumen and there-

fore function as a sphincter. These factors include

trauma, denervation, or devascularization phenom-

ena such as neurological compromise (caused by

certain conditions such as sacral agenesis, spinal

cord injury, or myelodysplasia), childbirth injury,

connective tissue disorders, menopause, or exposure

to radiation.

The other management options when consider-

ing treating women with this condition include

retropubic surgery, bulking agents and artificial

urinary sphincters. Slings have better long-term

success rates compared to bulking agents [1]

and less morbidity when compared to artificial

sphincters, which can suffer malfunction or lead to

infection and erosion [2] . It also is considered the

best procedure in women with coexisting medical

problems such as obesity, which increases the risk

of operative complications and failure [3] .

Pubovaginal slings have been described as a

treatment for stress incontinence since the begin-

ning of the twentieth century. The technique of

their application and the materials used has varied.

The first descriptions of the suburethral sling

procedure occurred in the early 1900s and involved

the use of pyramidalis or gracilis muscles or rectus

sheath as a suburethral sling with or without plica-

tion of the bladder neck. The use of rectus sheath

fascia was first described in 1942 by Aldridge, and

this was further modified in 1968, when Chasse

Moir introduced the gauze hammock procedure.

Until recently slings were considered a second-

or third-line procedure in the treatment of stress

incontinence; however, since the 1990s it now is

considered that a sling procedure is indicated if

there is intrinsic sphincter deficiency with or without

hypermobility, irrespective of whether the woman

has undergone previous incontinence surgery.

Sling materials broadly include autologous mate-

rials, which include rectus fascia, dermis, and tendons;

allografts from human cadavers including rectus

fascia, dermis, and dura mater; xenografts such as

porcine or bovine dermis, bovine pericardium, dura,

or intestinal submucosa; and synthetic materials

such as Mersilene and Prolene. The length of the

sling can vary from “full length” (>20 cm) to “patch

slings” (3–5 cm).

Aldridge originally described the procedure as

an active mechanism in that the sling moves with

the abdominal wall (to which it is attached via the

Chapter 13

Surgery for Stress Urinary Incontinence:

Midurethral Slings

Demetri C. Panayi and Vik Khullar

166 D.C. Panayi and V. Khullar

abdominal aponeurosis) during episodes of increased

intra-abdominal pressure; during coughing and sneez-

ing, the sling is drawn anteriorly, therefore increasing

intraurethral closure pressure [4] . In this way the sling

procedure aims to restore sufficient outlet resistance

to the urethra during stress events to prevent leakage

without producing obstruction during voiding while

also providing some bladder neck support.

Zacharin [5] suggested that the endopelvic fascia

and pubourethral ligaments allow effective trans-

mission of increases in intra-abdominal pressure

by providing support to the urethra. The sling

therefore may be providing support and passive

resistance to the urethra in the same manner rather

than causing elevation and compression.

In summary, traditional pubovaginal slings

attempt to correct hypermobility of the bladder

neck and enhance transmission of intra-abdominal

pressure provoked by straining.

Slings that are inserted at the midurethral point

mainly use synthetic materials. Introduced in 1994,

these have grown in acceptance and the tension-

free vaginal tape (TVT) is now the most com-

mon procedure carried out for incontinence in

the world. Originally, Mersilene, a multifilament

mesh, and other low-porosity mesh materials were

employed until being replaced with polypropylene

monofilament mesh tapes because of concerns

regarding a high erosion rate with multifilaments

[6] . Polypropylene monofilament mesh currently is

considered the material of choice (

Fig. 13.1 ).

The principle behind the midurethral approach

is that incontinence results from weakening of the

existing support structures of the urethra, anterior

vaginal wall to the midurethra, and the vagina is

connected to the arcus tendinus fasciae pelvis pro-

viding support to the midurethra [7] .

The midurethral approach is favored because it

involves minimal vaginal dissection or alteration

of vaginal architecture, and therefore minimal

effect on the mobility of the proximal urethra.

Many authors believe the proximal urethra to be an

important determinant of normal voiding, which

can be affected as a complication of continence

surgery. Tape insertion is also a relatively easy pro-

cedure to technically master and is not associated

with the operative morbidity of the Burch colpo-

suspension, nor does it necessitate an abdominal

incision as pubovaginal slings do.

The mainstay of midurethral surgery is the

TVT, which employs the technique of transvagi-

nal introduction of the synthetic tape that passes

retropubically and is exposed through the anterior

abdominal wall [8] (

Fig. 13.2 ). However, a tran-

sobturator approach recently has been introduced

and despite the lack of long-term data has reported

similar cure and complication rates with a reduced

risk of bladder trauma [9– 12]

Mastery of any sling procedure requires intimate

understanding of the local anatomy to minimize

intraoperative complications and maximize surgi-

cal effect.

Fig. 13.1. The polypropylene mesh used in the Boston Scientific ObTryx System (reproduced with kind permission

of Boston Scientific Corporation)

13. Surgery for Stress Urinary Incontinence: Midurethral Slings 167

Patient Selection and Assessment

As with any surgery, prior to a sling procedure,

women need a thorough assessment including details

of genital and urinary symptoms including inconti-

nence type and severity and symptoms of vaginal

prolapse, full obstetric history, any neurological con-

ditions, and previous surgical procedures or expo-

sure to radiation. Examination should involve pelvic

floor compartment examination for demonstration

of incontinence and assessment of any other pelvic

pathology. Investigations should include urinalysis,

uroflowmetry, and postvoid residual because all pro-

cedures for treatment of incontinence can be com-

plicated by voiding difficulties especially those with

preexistent high postvoid residuals or those with

prolonged intermittent uroflow patterns. In the cases

of these patients, appropriate counseling of this

risk and training in intermittent self-catheterization

preoperatively is essential.

Further investigations prior to the sling procedure

also should include assessment of urethral mobility

(video)urodynamics, imaging of the bladder neck,

and assessment of urethral resistance via maximal

urethral closure pressure or leak point pressure. Leak

point pressures of below 60 cm H

2 O or maximal

urethral closure pressures of below 20 cm H

2 O are

diagnostic of intrinsic sphincter deficiency. The other

benefit of urodynamics is the assessment of detrusor

muscle activity, voiding function, and bladder compli-

ance. Patients with history and urodynamic evidence

of mixed incontinence present a clinical challenge

and use of anticholinergics prior to embarking on

midurethral tape procedure may be appropriate.

Patients who have had previous continence

surgery or have operative bladder symptoms also

should have urodynamic studies and may need

cystoscopic assessment of the lower urinary tract

prior to insertion of the midurethral tape.

The Tension-Free Vaginal Tape

The Gynecare TVT ( Fig. 13.3 ) system employs

a polypropylene mesh tape with a pore size of

75–150 m m. The large pores encourage incorpora-

tion into the patient’s own tissues; the mesh itself

is elastic, and hence moves with the patient’s own

movements and yet forms a backstop to actions

such as coughing, laughing, and sneezing. The

knitted monofilament provides resistance to infec-

tion. In keeping with the principles of midurethral

systems, the TVT attempts to reinforce dysfunc-

tional pubourethral ligaments, enhance connective

tissue in the paraurethral area, and create a solid

floor beneath the urethra.

This procedure was described by Ulmsten in

1995 [8] as an alternative to the more time-con-

suming and technically difficult Burch colposus-

pension. It has shown comparable cure rates as

well as shorter operating time and reduced mor-

bidity associated with it [13– 17] . The procedure

also can be performed under sedation with local

anesthesia or spinal anesthesia, thereby reducing

the anesthetic risks to the patient.

Fig. 13.2 . The correct position of the tension-free vagi-

nal tape (reproduced with kind permission of Gynecare/

Ethicon)

Fig. 13.3. The Gynecare TVT system comprising TVT

needles with removable handle, polypropylene tape, and

guide (reproduced with kind permission of Gynecare/

Ethicon)

168 D.C. Panayi and V. Khullar

Procedure

The TVT was developed as a standardized tech-

nique to allow a safe method with the best clinical

outcome. The technique described below is prone

to variation between individual operators. However,

the principles underpinning safe insertion and mini-

mal exposure to complications remain the same.

The procedure is performed with the patient in

lithotomy position with no more than 70° of hip

flexion. Vaginal examination is performed and

via abdominal palpation, the anticipated pathway

of the tape is demonstrated. A solution of 100 ml

normal saline mixed with 20 ml of 0.25% bupivic-

aine is used to infiltrate retropubically, with 40 ml

of solution infiltrated suprapubically behind the

pubic bone 3 cm from the midline. Then 20 ml of

the solution is introduced vaginally paraurethrally

under the pubic bone on each side. The aim is for

the infiltrate to follow the retropubic course of the

tape on either side of the midline. The landmarks

are the posterior surface of the pubic bone down

to the urogenital diaphragm. Further 5 ml of 0.5%

xylocaine anesthetic with 1 in 50,000 of adrena-

line is introduced into the vaginal mucosa at the

midurethral point and paraurethrally up to the uro-

genital diaphragm. A 2-cm vaginal incision is made

beneath the urethra. Through this incision, paraure-

thral dissection is undertaken bilaterally to the level

of the urogenital diaphragm. The TVT needle then

is introduced with slow, controlled pressure aimed

at the inferior tip of the ipsilateral scapula follow-

ing the pathway previously hydrodissected with

local anesthetic. A wire guide inserted into the ure-

thral foley catheter is used to deviate the bladder to

the contralateral side of needle insertion to prevent

injury. It is important to remain close to the pubic

bone before angling upward and emerging through

the skin incision in the abdomen. These are made

2–3 cm either side of the midline. Once the needle

emerges through the skin of the anterior abdominal

wall, a cystoscopy is performed to identify any

bladder trauma. This needle has a removable han-

dle and so it can be used to repeat the procedure

on the other side. Some operators perform a cough

test, which involves filling the bladder and instruct-

ing the patient to cough vigorously so that the tape

can be adjusted accordingly. If the patient is under

general anesthesia, this is not possible so the tape is

adjusted by tightening against an instrument placed

between the tape and the midurethral portion. The

tape is contained within a plastic sheath, which

serves to ease the passage of the tape through the

tissues and prevent its contamination. Once final

tensioning adjustments have been made, the sheath

is removed and the tape is cut flush to the abdomi-

nal skin, which is lifted under tension to allow

the tape to lie free of the incision and no further

tightening occurs. The vaginal skin is closed with

absorbable suture and the abdominal incisions can

be closed with suture or with glue.

Complications

The advantage of the TVT is that it is minimally

invasive, can be carried out under local or spinal

anesthesia, and in some units is carried out as a day

case procedure. As a result it has a relatively low

complication rate when compared to Burch colpo-

suspension, the gold standard treatment for stress

incontinence [14, 17] .

However, some of the risks associated with

continence procedures do apply to TVT. The more

common complications include voiding difficulties

(7–20%), urgency (1–20%), urinary tract infec-

tion, (4–15%), bladder injury (2–5%), hematoma

(1–3%), wound infection (1%), bleeding (1–3%),

and vaginal (0.7%)/urethral (2.7%) erosion.

Outlet obstruction also can manifest as urinary

retention, high postoperative residuals, urgency

or worsening of previous urgency. Difficulty in

voiding may be associated with increased tension

in the tape itself. It is important to remember that

the tape is intended to be placed “tension-free”

and overzealous tightening of the vaginal tape can

lead to voiding difficulties or retention. Obstructive

symptoms usually resolve with time. Uncommonly,

patients need a repeat procedure to transect, loosen,

or remove the tape, or require clean intermittent

catheterization. Long-term retention is a rare com-

plication of TVT (0.6–3.8%).

As insertion of the needles into the vagina and

through the anterior abdominal wall is performed

blindly, one might perceive that there is consider-

able risk of breaching the abdominal cavity and/or

causing serious vascular damage. However, these

occurrences are rare, with bowel perforation

reported at a very low rate (0.03–0.05%), as is

severe vascular injury (0.04–0.08%).

13. Surgery for Stress Urinary Incontinence: Midurethral Slings 169

Evidence-Based Clinical Outcome

The majority of recent studies reflect a favorable cure

rate compared with Burch colposuspension and other

continence procedures [1, 11, 14– 21] . Ward et al. [17] ,

in a cohort of 344 patients with 175 undergoing TVT

and 169 undergoing Burch, found a cure/improve-

ment rate of 66% in the TVT group after 6-month

follow-up compared with 57% in the Burch group.

The cure criteria were negative cystometry and nega-

tive pad test. At 2 years the same group demonstrated

63% cure rate versus 51% for the Burch group.

Paraiso et al. [16] compared TVT to laparo-

scopic Burch colposuspension in 72 patients, with

cure criteria of urodynamic studies at 1 year and no

symptomatic leakage. Thirty-six underwent TVT

and 36 underwent laparoscopic Burch colposus-

pension. They found a cure rate of 97% in the TVT

group compared to 81% in patients who underwent

the laparascopic Burch.

Rechberger et al. [21] studied 100 patients, 50 of

whom underwent TVT and 50 had multifilament

intravaginal slingplasty, a modification of TVT. The

cure rates at 4–18 months were defined as being free

of symptoms of stress incontinence and having nega-

tive supine and standing cough stress test. They also

defined improvement as having symptomatic stress

incontinence but improved from the preoperative

state. They found an 88 and 80% cure rate in the TVT

and intravaginal slingplasty groups, respectively.

Dietz et al. [19] looked at 106 patients, 69 of whom

underwent TVT, while 37 had suprapubic pubic arch

sling procedure (SPARC ), another modification of

TVT. The cure rate at 6 weeks to 18 months was

defined as a negative cough stress test and subjective

cure of symptoms reported by the patient. There was

a 94% cure rate associated with TVT, with a 74%

cure rate with patients who had SPARC.

Other authors report similar rates of success: Wang

et al. (2003) with an objective cure rate of 82%; Ustun

et al. (2003) and Liang et al. (2002) determined an

83% cure rate. There also is considerable long-term

evidence to support the use of TVT [18, 22– 25] .

Transobturator Approach

The theory of the transobturator route is an exten-

sion of the principles of the mechanism of action

of the TVT. The transobturator approach involves

placement of midurethral tape through the obtu-

rator membrane ( Fig. 13.4 ). Although there is a

lack of long-term data regarding this approach,

the current data suggest a comparable continence

and complication rate with TVT, with some stud-

ies suggesting a reduction in incidence of bladder

trauma compared to TVT or colposuspension

[9– 12, 26] .

Procedure

The technique for introduction of the tape is divided

into two categories. The “outside-to-in” or “inside-

to-out” methods. The description “inside to out”

refers to the introduction of the tape from the vaginal

incision, with it emerging “outward” or lateral to the

thigh folds. The “outside-to-in” method involves the

tape entering through an incision lateral to the labia

majora and emerging in the vaginal incision.

The inside-to-out tape is the tension-free vaginal

tape-obturator (TVT-O) manufactured by Gynecare.

The first difference between this tape and the TVT

procedure is the positioning of the patient. For all

transobturator methods the patient is in lithotomy

with 120° hyperflexion. The first step is to mark

the exit points of the tape in the lateral thigh folds.

Using a marker pen, the exit points of the tape are

designated. These are 2 cm lateral to where a line

parallel and 2 cm superior to a horizontal line inter-

sects the thigh folds.

Fig. 13.4. Schematic showing the transobturator route

(reproduced with kind permission of Boston Scientific

Corporation)

170 D.C. Panayi and V. Khullar

The TVT-O equipment itself consists of the

polypropylene mesh with large open-knit pores,

which is blue for easy identification, a winged

guide along which the helical passers are intro-

duced, and tip tubing that is held allowing the heli-

cal passers to be withdrawn.

Once the exit points have been marked and the

equipment is assembled and checked, local anes-

thetic is infiltrated into the vagina and a vaginal inci-

sion is made in a similar fashion to the TVT. The

dissection, however, is laterally and toward the ischi-

opubic ramus. A “give” will be felt as the obturator

membrane is breached. The metal winged guide

then is inserted following the pathway of dissec-

tion and passes through the obturator membrane.

The helical passers then are introduced along

the gutter of the metal guide. Once through the

obturator membrane the helical passers are rotated

under controlled pressure and turned so their tips

emerge at the designated exit points marked at the

start of the procedure. The plastic tip tubings are

externalized through the skin and then grasped

with clamps, allowing the helical passer to be with-

drawn by performing the introduction maneuver in

reverse. The procedure is repeated on the contral-

ateral side of the patient. The plastic sheath around

the tape is removed simultaneously, allowing the

tape to be centered correctly and the tension of the

tape is adjusted as for a TVT. The vagina then is

closed with absorbable suture and the skin over the

tape can be glued or sutured.

The “outside-to-in method” is performed with the

patient in the same position as inside to out. There

are many more systems available for this method,

including Monarc (American Medical Systems),

Eris (Mentor), and Obtryx™ Transobturator Mid-

Urethral Sling System (Boston Scientific) ( Fig 13.5 ).

This employs the Advantage™ Mesh, a polypro-

pylene mesh with a detangled suburethral segment

with a large pore size >100 m m.

For this method the incision is made on the lateral

aspect of the labia majora at the level of the clitoris,

posterior to the insertion of the adductor longus

muscle tendon and 1–2 cm lateral to the ischopubic

ramus. The vaginal incision then is made after infil-

tration with local anesthetic. The helical introducer

then is introduced through the skin directed in a

perpendicular fashion to the skin. Once the distinct

sensation of breaching the obturator membrane is

felt, the helical introducer is rotated medially to

emerge in the vagina onto the tip of the index finger

of the operator, which serves to protect the urethra

and allow controlled passage of the helical intro-

ducer. Once the tip of the introducer has emerged in

the vaginal incision, the operator should verify that a

vaginal mucosal “button-hole” has not been created

and check the urethra for any trauma. Once this has

been confirmed, the tape is attached onto the tip of

the introducer using various methods. Once the tape

is secured, the helical introducers are rotated back

in a reverse fashion and out through the original

skin incision. This procedure then is repeated on the

contralateral side. The tension of the tape is adjusted

using a pair of scissors or clamp between it and the

urethra. Because of the much-reduced incidence

of bladder injury associated with the obturator

approach, cytoscopy is not universally practiced;

however, it is good practice to perform cytoscopy

following the insertion of the tape. The vagina and

skin incisions are closed in a similar fashion to the

inside-to-out technique.

Complications

There are similar risks associated with the tran-

sobturator approach as there are with the TVT.

The risk of bladder injury is reported to be lower

than in the retropubic approach, with inside-to-out

method using the TVT-O associated with the

lowest incidence.

Fig. 13.5. Helical passers and polypropylene tape of

the Obtryx transobturator system (reproduced with kind

permission of Boston Scientific Corporation)

13. Surgery for Stress Urinary Incontinence: Midurethral Slings 171

Vaginal tape erosion or exposure in the vagina

or bladder remain risks with all synthetic slings.

There are two separate processes occurring,

although the mechanism is not entirely clear. First

is a failure of primary vaginal healing resulting in

the tape becoming exposed in the vagina often as

a result of infection. Second, there is tape migra-

tion, which may be associated with mechanical

friction or failure of integration of the tape into

the host’s tissues. It has been suggested that tapes

with larger pore sizes integrate more effectively,

and hence are associated with reduced incidence

of erosion. Should tape erosion occur, then it may

be necessary to remove the tape, especially if a

multifilament tape such as ObTape or IVS tape

was used.

There appears to be a lower incidence of post-

operative voiding dysfunction associated with the

transobturator tapes compared to the retropubic

tapes. The risk of de novo urgency is reported

between 2 and 7%; however, De Tayrac et al.

(2004 ) and Mansoor et al. (2003 ) found no differ-

ence in voiding difficulties or retention between

TVT and transobturator tapes with between 1 and

15% rate of voiding obstruction has been reported

in the literature.

Other complications associated specifically with

transobturator tapes include hematoma or neu-

ropathic trauma leading to postoperative leg or

groin pain, which has been observed in 2–15% of

cases depending on the study quoted. In all cases,

the pain was temporary and usually responded to

standard oral analgesia.

Evidence-Based Clinical Outcome

More research is required into the clinical effec-

tiveness of the transobturator tape. The body of

evidence is inferior to that which supports the case

for the TVT, particularly in terms of long-term

data. However, results are encouraging, with clini-

cal effectiveness in the limited numbers of studies

comparable to the TVT procedure.

De Tayrac et al. [2004 ] looked at 61 patients:

31 had TVT and 30 had transobturator suburethral

tape (TOT). The definition of cure was negative

stress test and symptomatic dryness. The cure rates

were 84% for TVT and 90% for TOT after 1-year

follow-up. Similarly, Delorme et al. [27] found a

91% cure rate after 17 months follow-up. Costa et

al. [28] stated an outcome of 80.5% cure rate, with

a mean of 7 months follow-up with a cough stress

test and questionnaire-based assessment. More

recently, a meta-analysis considering studies com-

paring TVT to the transobturator approach using

the “inside-to-out” and “outside-to-in” methods

[9] showed that the transobturator approach was

associated with similar cure rates and reduced

rates of bladder injury and voiding difficulties;

however, mesh erosion, vaginal injuries, and leg

or groin pain were more common with TVT-O.

Mean follow-up in these studies, however, was 7

months and this remains the weakness in the evi-

dence for using the transobturator approach. One

recent study by Giberti and co-authors [29] studied

108 women with a mean follow-up of 2 years and

reported subjective cure rates and objective of 92

and 80%, respectively.

The potential advantages of the obturator

approach make it appear to be an attractive alterna-

tive to the TVT. The procedure is shorter and an

easier technique to master and it does not involve

proximity to the pelvic vasculature or intra-abdom-

inal organs, and therefore does not encumber the

risk of their injury. The risks of lower urinary tract

injury appear to be less than TVT, and thus do not

necessitate cystoscopy, although it remains good

practice to perform this procedure after insertion

of any tape.

Despite these points for optimism, there needs to

be a larger body of evidence to support its clinical

effectiveness with long-term follow-up.

Suprapubic Pubic Arch Sling

(SPARC) Procedure

This system is a similarly minimally invasive sling

procedure using a loosely knitted self-fixating

4–0 propylene mesh, which is positioned at the

midurethra via passing suspension needles “from

above” through incisions on the anterior abdominal

skin and emerging in the vaginal incision. This is

effectively the TVT method using the “outside-to-

in” principle. Its mechanism of action mirrors the

principles behind all midurethral tapes: forming an

anatomical hammock and following the role of the

pubourethral ligament and paravaginal structure in

supporting the urethra.

172 D.C. Panayi and V. Khullar

As well as the mesh itself, the SPARC equip-

ment (American Medical Systems) is composed of

disposable suspension needles, dilator-connectors

to which the tape is attached that permit untwist-

ing of the mesh after attachment, a plastic sheath

surrounding the mesh, and an absorbable colored

tensioning suture knotted at intervals within the

mesh sling preventing pretensioning of the mesh

when the sheath is withdrawn as well as allowing

intra- and postoperative sling adjustment.

Procedure

The SPARC procedure can be performed under gen-

eral, regional, or local anesthesia. The patient is in

the lithotomy position and with the bladder emptied.

The entry points for the suspension needles are

located 1.5 cm either side of the midline over the

symphysis pubis and it is here that stab incisions

are made. A 2–3-cm vaginal incision is made over

the area of the midurethra, which can be preceded

by infiltration to aid dissection of the plane between

the vaginal epithelium and the periurethral fascia.

Using scissors this plane is developed to the border

of the pubic ramus at the level of the midurethra,

creating adequate room for the surgeon’s finger to

be inserted, thereby allowing controlled passage

of the suspension needles through the periurethral

fascia and into the vaginal incision.

The suspension needle is passed through the

abdominal incisions and downward onto the sym-

physis pubis before being passed along the superior

surface of the bone and downward through the

rectus fascia and muscle. It then is rotated along

the posterior surface of the bone through the space

of Retzius before being guided inferiorly until

reaching the endopelvic fascia. Staying in close

proximity to the pubic bone minimizes the risk of

bowel, blood vessel, bladder, or urethral injury. The

finger in the vaginal incision then palpates the needle

tip and directs it to the point of perforation of the

endopelvic fascia, which is as lateral as possible

against the inferior border of the pubic ramus. Once

the endopelvic fascia has been breached, the sus-

pension needle tip can be controlled along the dis-

sected plane with the vaginal finger checking that

no “button-holing” has occurred. The procedure

is repeated on the contralateral side followed by

cystoscopy with a filled bladder including careful

inspection of the urethra. The sling is attached to the

needle tips with its markings positioned centrally.

With this system the connectors snap and click

into place before the needles are directed backward

into the retropubic space by the surgeon and then

upward to be withdrawn through the abdominal

skin incisions. The tape can be adjusted in a similar

fashion to other slings by inserting a pair of scis-

sors, clamp, or dilator between it and the midurethra

and applying traction to its ends. Once satisfactory

tension is achieved, the plastic sheaths can be with-

drawn and the mesh is cut flush to the skin before

the skin is lifted to cover the mesh ends. Closure of

the abdominal skin incisions as with the TVT can

be with absorbable suture, glue, or steri-strips, and

the vagina is closed with absorbable sutures.

Complications

Postoperative de novo urgency and voiding dif-

ficulties including urinary retention remain a com-

plication with this system as with all continence

procedures. As with other sling procedures, care

must be taken to avoid excessive tension applied to

the sling intraoperatively; also this system contains

a tensioning suture that provides a restraint to sling

stretching which may occur during loosening of the

sling during the procedure.

Bladder and urethral injury are a recognized

complication of this procedure but with an inci-

dence no greater than with TVT. Good technique

and cytoscopy during the procedure if injury is

suspected are essential. The incidence of bowel or

blood vessel injury remains relatively rare.

Tape exposure in the vagina may result from failure

of primary wound healing especially as a result of

infection, a recognized risk of synthetic sling materi-

als. Tape erosion into the bladder or urethra usually

occurs as a result of perforation during the procedure.

Evidence-Based Clinical Outcome

Dietz and co-authors [19] compared SPARC to

TVT in 106 women: 69 underwent the TVT proce-

dure and 37 underwent the SPARC procedure. The

follow-up of these patients ranged from 6 weeks

to 18 months, with cure being defined as negative

cough stress test. A cure rate of 94% was reported

with TVT and 78% with SPARC.

13. Surgery for Stress Urinary Incontinence: Midurethral Slings 173

Primus [30] with a group of 103 women fol-

lowed up after 1 year reported a cure rate of 84%,

where cure was defined as a negative cough stress

test and a pad weight test less than 1 g.

Lord et al. [31] had a cohort of 290 women: 147

underwent TVT and 154 had SPARC. He reported

similar objective cure rates of stress incontinence

symptoms at 6-week follow-up with 97.4% in the

TVT group and 97.4% in the SPARC group, but a

statistically significantly higher subjective cure rate

in the TVT group (87.1% vs. 76.5% for SPARC).

He also reported no statistically significant dif-

ference between the rates of bladder perforation,

hemorrhage, or de novo urgency, although a higher

incidence of acute retention was noted with the

SPARC system, requiring statistically significantly

more adjustments of the tape in theatre.

Gandhi and coauthors [32] in 2006 also reported

higher subjective and objective cure rates in TVT

compared to SPARC in 122 women in a retrospec-

tive study. However, Tseng and co-authors [33] , in

a randomized study in 2005, reported no statisti-

cally significant difference in cure rates, although

more bladder injuries occurred with SPARC, which

was not statistically significant. They concluded

that both procedures were equally effective.

As with the transobturator systems, SPARC’s

effectiveness, particularly in the long term, does

not yet have the evidence base to support it and

further study is needed.

Tension-Free Vaginal Tape-Secur

(Tvt-S)

This is a smaller device produced by Gynecare (see

Fig. 13.6 ). Its purported advantages over the current

sling procedures is that it has all the benefits of a

minimally invasive procedure but avoids the nerve

structures that may result in postoperative pain, as

well as avoiding the discomfort associated with the

sites where the tape exits in the abdominal or thigh

skin. It also is inserted via a simpler method and can

employ the retropubic or transobturator pathways.

In the retropubic pathway due to its size it avoids

proximity to the bowel or major vessels by not

reaching the region close to the peritoneal cavity.

It requires a small skin incision of only 1 cm and

minimal paraurethral dissection ( Fig. 13.7 ).

Following the transobturator route this sling

reaches but does not penetrate and emerge from the

obturator membrane, and thus it is proposed that

the postoperative leg or groin pain associated with

TVT-O will be eliminated ( Fig. 13.8 ).

At this stage there is little in the way of evidence to

support the effectiveness of this device, and hence its

application can only remain in the field of research.

Fig. 13.6 . The TVT-Secur system (reproduced with kind

permission of Gynecare/Ethicon)

Fig. 13.7 . The position of the TVT-Secur system when

adopting the retropubic route (reproduced with kind per-

mission of Gynecare/Ethicon)

174 D.C. Panayi and V. Khullar

Summary

All midurethral slings apply the same basic mecha-

nism of action by providing suburethral support,

and thereby mimicking the function of the pub-

ourethral ligaments and paravaginal tissues. Their

mechanism of action stems from the importance of

midurethral stabilization, which prevents the sepa-

ration of the posterior urethral wall from the ante-

rior urethral wall during rotational motion around

the inferior portion of the pubic ramus, which

appears to be integral to continence. Elevation of

the bladder neck, which is the role of pubourethral

slings and retropubic urethropexies, may no longer

be necessary to achieve continence.

Currently, the TVT is the most common continence

procedure carried out worldwide. Of all the synthetic

sling procedures it has the largest body of randomized

controlled studies supporting its use. It has similar

success rates when compared with the gold standard

procedure—the Burch colposuspension—with lower

operative morbidity associated with it.

The transobturator method is supported by produc-

tion of many systems of which the majority employ

the outside-to-in method. Only the Gynecare TVT-O

system uses the inside-to-out approach. The tran-

sobturator method is considered to have a reduced

incidence of bladder or urethral injury, particularly

the inside-to-out method, with comparable success

rates to TVT in the small amount of evidence avail-

able regarding its effectiveness. There is limited

information regarding the long-term outcome of this

method and further study is required.

The SPARC system was proposed to have a

reduced incidence of visceral injury, although this

has yet to be supported by the literature. What little

evidence is available regarding this method reports

comparable success rates to TVT; however, data

regarding long-term follow-up are awaited.

Female incontinence remains a hotbed for the

development of new devices that reduce complica-

tion rates and are technically easier to perform with

comparable results to traditional procedures. The

TVT-Secur is another system involving a consider-

ably small mesh that can be employed via the tran-

sobturator pathway where the obturator membrane

is not penetrated, or via the retropubic route where

its size prevents it from risking bowel or blood ves-

sel injury. Its application remains in the sphere of

clinical research until further evidence is gathered to

support more widespread use.

References

1 . Cody J , Wyness L , Wallace S , et al. Systematic

review of the clinical effectiveness and cost-effec-

tiveness of tension-free vaginal tape for treatment of

urinary stress incontinence . Health Technol Assess

2003 ; 7 (21) : iii1 – iii189.

2 . Diokno AC . Erosions of the artificial urinary sphinc-

ter: Risk factors, outcomes and management . Nat

Clin Pract Urol 2006 ; 3 (11) : 580 – 581 .

3 . Mukherjee K , Constantine G . Urinary stress inconti-

nence in obese women: Tension-free vaginal tape is

the answer . BJU Int 2001 ; 88 (9) : 881 – 883 .

4 . Hilton P . A clinical and urodynamic study compar-

ing the Stamey bladder neck suspension and subu-

rethral sling procedures in the treatment of genuine

stress incontinence . Br J Obstet Gynaecol 1989 ;

96 (2) : 213 – 220 .

5 . Zacharin RF . The suspensory mechanism of the

female urethra . J Anat 1963 ; 97 : 423 – 427 .

6. Andonian S, St-Denis B, Lemieux MC, Corcos J.

Prospective clinical trial comparing Obtape(R) and

DUPS to TVT: One-year safety and efficacy results.

Eur Urol 2007.

7 . DeLancey JO . Structural aspects of the extrinsic

continence mechanism . Obstet Gynecol 1988 ; 72

(3 Pt 1) : 296 – 301 .

Fig. 13.8. The position of the TVT-Secur system when

adopting the transobturator route without passing through

the obturator membrane (reproduced with kind permis-

sion of Gynecare/Ethicon)

13. Surgery for Stress Urinary Incontinence: Midurethral Slings 175

8 . Ulmsten U , Petros P . Intravaginal slingplasty (IVS):

An ambulatory surgical procedure for treatment of

female urinary incontinence . Scand J Urol Nephrol

1995 ; 29 (1) : 75 – 82 .

9 . Latthe PM , Foon R , Toozs-Hobson P . Transobturator

and retropubic tape procedures in stress urinary

incontinence: A systematic review and meta- analysis

of effectiveness and complications . BJOG 2007 ;

114 (5) : 522 – 531 .

10 . Liapis A , Bakas P , Giner M , Creatsas G . Tension-free

vaginal tape versus tension-free vaginal tape obturator

in women with stress urinary incontinence . Gynecol

Obstet Invest 2006 ; 62 (3) : 160 – 164 .

11 . Neuman M . TVT and TVT-Obturator: Comparison

of two operative procedures . Eur J Obstet Gynecol

Reprod Biol 2007 ; 131 (1) : 89 – 92 .

12 . Zullo MA , Plotti F , Calcagno M , et al. One-year

follow-up of tension-free vaginal tape (TVT) and

transobturator suburethral tape from inside to out-

side (TVT-O) for surgical treatment of female stress

urinary incontinence: A prospective randomised

trial . Eur Urol 2007 ; 51 (5) : 1376 – 1384 .

13 . Dean N , Herbison P , Ellis G , Wilson D . Laparoscopic

colposuspension and tension-free vaginal tape: a sys-

tematic review . BJOG 2006 ; 113 (12) : 1345 – 1353 .

14 . El-Barky E , El-Shazly A , El-Wahab OA , Kehinde

EO , Al-Hunayan A , Al-Awadi KA . Tension-free

vaginal tape versus Burch colposuspension for treat-

ment of female stress urinary incontinence . Int Urol

Nephrol 2005 ; 37 (2) : 277 – 281 .

15 . Kuuva N , Nilsson CG. Tension-free vaginal tape pro-

cedure: An effective minimally invasive operation

for the treatment of recurrent stress urinary inconti-

nence ? Gynecol Obstet Invest 2003 ; 56 (2) : 93 – 98 .

16 . Paraiso MF , Walters MD , Karram MM , Barber

MD . Laparoscopic Burch colposuspension versus

tension-free vaginal tape: A randomized trial . Obstet

Gynecol 2004 ; 104 (6) : 1249 – 1258 .

17 . Ward KL , Hilton P . A prospective multicenter

randomized trial of tension-free vaginal tape and

colposuspension for primary urodynamic stress

incontinence: Two-year follow-up . Am J Obstet

Gynecol 2004 ; 190 (2) : 324 – 331 .

18. Chene G, Amblard J, Tardieu AS, et al. Long-term

results of tension-free vaginal tape (TVT) for the

treatment of female urinary stress incontinence. Eur

J Obstet Gynecol Reprod Biol 2006.

19 . Dietz HP , Foote AJ , Mak HL , Wilson PD . TVT and

SPARC suburethral slings: A case-control series .

Int Urogynecol J Pelvic Floor Dysfunct 2004 ; 15 (2) :

129 – 131 .

20. Meschia M, Bertozzi R, Pifarotti P, et al. Peri-

operative morbidity and early results of a ran-

domised trial comparing TVT and TVT-O. Int

Urogynecol J Pelvic Floor Dysfunct 2007.

21 . Rechberger T , Rzezniczuk K , Skorupski P , et al.

A randomized comparison between monofilament

and multifilament tapes for stress incontinence sur-

gery . Int Urogynecol J Pelvic Floor Dysfunct 2003 ;

14 (6) : 432 – 436 .

22 . Holmgren C , Nilsson S , Lanner L , Hellberg D . Long-

term results with tension-free vaginal tape on mixed

and stress urinary incontinence . Obstet Gynecol

2005 ; 106 (1) : 38 – 43 .

23 . Hualde AA , Jimenez CJ , Sarmiento GC et al. [TVT:

Our experience five years and six months later] .

Actas Urol Esp 2006 ; 30 (2) : 181 – 185 .

24 . Nilsson CG , Kuuva N , Falconer C , Rezapour M ,

Ulmsten U . Long-term results of the tension-free

vaginal tape (TVT) procedure for surgical treatment

of female stress urinary incontinence . Int Urogynecol

J Pelvic Floor Dysfunct 2001 ; 12 Suppl 2 : S5 – S8 .

25 . Nilsson CG , Falconer C , Rezapour M . Seven-year

follow-up of the tension-free vaginal tape proce-

dure for treatment of urinary incontinence . Obstet

Gynecol 2004 ; 104 (6) : 1259 – 1262 .

26 . Botros SM , Miller JJ , Goldberg RP , et al. Detrusor

overactivity and urge urinary incontinence following

trans obturator versus midurethral slings . Neurourol

Urodyn 2007 ; 26 (1) : 42 – 45 .

27 . Delorme E , Droupy S , de TR , Delmas V . [Transo-

bturator tape (Uratape). A new minimally invasive

method in the treatment of urinary incontinence in

women] . Prog Urol 2003 ; 13 (4) : 656 – 659 .

28 . Costa P , Grise P , Droupy S , et al. Surgical treatment of

female stress urinary incontinence with a trans-obturator-

tape (T.O.T.) Uratape: Short term results of a prospective

multicentric study . Eur Urol 2004 ; 46 (1) : 102 – 106 .

29 . Giberti C , Gallo F , Cortese P , Schenone M . Transo-

bturator tape for treatment of female stress urinary

incontinence: Objective and subjective results after

a mean follow-up of two years . Urology 2007 ;

69 (4) : 703 – 707 .

30 . Primus G . One year follow-up on the SPARC sling

system for the treatment of female urodynamic stress

incontinence . Int J Urol 2006 ; 13 (11) : 1410 – 1414 .

31 . Lord HE , Taylor JD , Finn JC , et al. A randomized

controlled equivalence trial of short-term complica-

tions and efficacy of tension-free vaginal tape and

suprapubic urethral support sling for treating stress

incontinence . BJU Int 2006 ; 98 (2) : 367 – 376 .

32 . Gandhi S , Abramov Y , Kwon C , et al. TVT versus

SPARC: Comparison of outcomes for two midure-

thral tape procedures . Int Urogynecol J Pelvic Floor

Dysfunct 2006 ; 17 (2) : 125 – 130 .

33 . Tseng LH , Wang AC , Lin YH , Li SJ , Ko YJ .

Randomized comparison of the suprapubic arc sling

procedure vs. tension-free vaginal taping for stress

incontinent women . Int Urogynecol J Pelvic Floor

Dysfunct 2005 ; 16 (3) : 230 – 235 .

177

Part IV

Management of Urge Incontinence

179

Introduction

Urge urinary incontinence is defined as the invol-

untary loss of urine accompanied by or preceeded

by an urge to urinate [1] . In the normal continent

patient, as the bladder fills with urine it will

distend, sending afferent signals to the bladder

neck and urethra via the sympathetic outflow

tracts, leading to contraction of the urethral

sphincter and inhibition of the detrusor muscle.

Urge incontinence can develop if this delicate

neurophysiological pathway is disrupted, lead-

ing to uncontrolled detrusor contractions [2] .

Treatments for this condition consist of behav-

ioral therapies, medical therapies, and surgical

interventions. Over many years behavioral thera-

pies have developed from simple practices such as

fluid management and voiding diaries to sophis-

ticated biofeedback techniques with electrical

stimulation. Many practitioners consider behav-

ioral therapy as a first-line treatment option for

urge incontinence. The Agency for Health Care

Policy and Research in 1996 published guidelines

for the treatment of urinary incontinence and cited

behavioral therapy as a first-line treatment option

[3] . Behavioral therapies consist of dietary modi-

fication, bladder training, pelvic floor muscle

exercises (PFME), biofeedback, functional elec-

trical stimulation (FES), and functional magnetic

stimulation (FMS).

Dietary Modification

Anecdotal evidence suggests that reducing bladder

irritants such as acidic foods, artificial sweeteners,

caffeine, alcohol, or certain fruits may improve

urinary incontinence [4] . Research, however, has

not demonstrated clear evidence that this is true.

Studies examining the role of alcohol with lower

urinary tract dysfunction show both no effect and

a protective effect [5] . A cross-sectional study of

4,000 men examining the role of food and alcohol

in the development of overactive bladder syndrome

(OAB) found that alcohol consumption was protec-

tive in developing overactive bladder syndrome and

that only potatoes appeared to have an association

with worsening symptoms [6] . A different cross-

sectional study of 6,424 women with stress and

urge incontinence/OAB found that there was no

association between alcohol consumption and the

presence of OAB/urge incontinence [7] . This same

study, however, found that smoking, obesity, and

consumption of carbonated beverages was associ-

ated with OAB/urge incontinence [7] .

Caffeine is a xanthine derivative found naturally

in coffee beans, tea leaves, and cocoa beans. It is

thought to have an excitatory effect on the detru-

sor muscle and has been shown to cause detru-

sor contractions on urodynamic testing [8] . Two

small studies utilizing psychiatric patients demon-

strated that withdrawal of caffeine was associated

Chapter 14

Behavioral Treatments for Urge

Incontinence

Howard B. Goldstein and Kristene E. Whitmore

180 H. B. Goldstein and K.E. Whitmore

with a decrease in frequency of incontinent epi-

sodes [9, 10] . A study of 41 women with urinary

incontinence (stress, urge, and mixed) showed

no statistical association between caffeine intake

and incontinence [11] . It is difficult to draw any

definitive conclusions from the research regarding

caffeine intake and its possible association with

urge incontinence. Good evidence to suggest that

it is associated with urge incontinence and that

eliminating it from the diet will improve or cure the

condition does not currently exist.

Most patients with urinary incontinence believe

that by restricting their fluid intake, they can reduce

their incontinence episodes. This often leads to

other medical conditions such as dehydration and/

or constipation. In a retrospective study of 126

women, Wyman et al. found that there was a weak

association between fluid consumption and degree

of urinary incontinence [12] . In another study of 128

patients with urinary incontinence (stress, urge, and

mixed), Griffiths et al. found that fluid intake was

strongly associated with the amount of fluid voided

per void and only slightly associated with number

of incontinence episodes. They also found that

among patients with urge incontinence there was

a small association between reducing the amount

of evening fluid intake and reducing number of

nocturnal enuresis episodes [13] . The evidence does

not suggest that reducing fluid intake during the day

will improve urge urinary incontinence. There may

be a slight improvement in nocturia and nocturnal

enuresis in reducing evening fluid intake.

Bladder Training

In a case report in 1966, Jeffcoate et al. first described

bladder training as a treatment for urinary inconti-

nence [14] . This therapy relies on the theory that

urinary urgency develops first in a patient and this

leads to urinary frequency. As this cycle progresses,

the patient develops a decreased bladder capacity,

which then will lead to detrusor overactivity. The

detrusor overactivity then will progress to urge

incontinence [15] . If one can break the urinary

frequency, then the urgency might stop, which will

lead to improvement of the detrusor overactivity

and urge incontinence. To accomplish this goal the

brain must be trained to ignore the signals from the

detrusor muscle. In our practice we first start with

a 3-day voiding diary. The voiding diary will help

determine the voiding interval. At the beginning,

the patient should be told to void at an interval

shorter than their actual interval determined by

the voiding diary. If, for example, a patient has a

voiding interval of 1 h, then the patient should be

instructed to void every 45 min for 1 week and

then increase the interval by 15 min each week.

At the time that the voiding diary is examined any

patterns of incontinent episodes associated with

fluid intake or medication times should be exam-

ined. If, for example, the patient is ingesting large

quantities of fluid before bedtime and then finds

that she wakes five to seven times at night to void

with some incontinent episodes, then she should

be instructed to reduce the fluid intake at night to

reduce the nocturia and nocturnal enuresis. The

voiding interval should be increased weekly until a

normal interval is accomplished. If during the inter-

val the patient has the urge to void, then she should

be taught strategies to help ignore the sensation.

At this point the patient can use other behavioral

therapies to help suppress the desire. Such thera-

pies as deep breathing, quick pelvic floor muscle

contractions in succession (quick flicks), meditation,

and distraction techniques such as balancing one’s

checkbook can help suppress the urge ( Fig. 14.1 ).

In a study of 123 women with either intrinsic

sphincter deficiency ( n = 88) or urge incontinence

( n = 35) who received bladder training, there was

a 57% reduction in incontinence episodes. In this

study the patients underwent urodynamic testing

both pre- and posttreatment. Interestingly, after the

bladder training therapy the urodynamic testing

results remained the same and the bladder capacity

on voiding diary did not change after successful

bladder training therapy [16] . These findings make

one wonder what exactly changes after successful

bladder training. Does successful bladder training

only affect the brain and its response to detrusor

signaling or is there something happening at the

level of the detrusor muscle to cause this change?

In a study utilizing biofeedback-assisted PFME

and urge strategies such as deep breathing for urge

incontinence, patients underwent pre- and post-

treatment urodynamic testing to assess the treat-

ment’s effect on bladder sensation and capacity.

Patients reported an 80% reduction in incontinence

14. Behavioral Treatments for Urge Incontinence 181

episodes, yet there were no significant changes in

bladder capacity [17] .

Cure rates with bladder training have varied

from 26 to 90% [18, 19] ( Table 14.1 ). A Cochrane

Database meta-). A Cochrane Database meta-analy-

sis conducted in 2003 of all trials evaluating bladder

training found that bladder training may be helpful

for the treatment of urinary incontinence [20] . There

are no standardized bladder-training programs so it

is problematic to compare one trial to another. In

each study authors often used different programs

and added other modalities such as biofeedback or

PFME.

Bladder training is a valuable tool for the treat-

ment of urge urinary incontinence. We suggest that

it should be used in a multimodal program with

other behavioral treatments in order to achieve the

greatest success.

Pelvic Floor Muscle Exercises

PFME were first described by Arnold Kegel, an

obstetrician and gynecologist, in 1948. He noticed

that through exercise he could improve the strength

of the pelvic floor muscles, which leads to improved

postpartum urinary incontinence. Since his pub-

lished paper, PFME have become synonymous with

Kegel exercises. Kegel applied basic muscle physi-

ology and rehabilitation to the pelvic floor. He noted

that inactive, injured muscle will lose approximately

80% of its weight, while active, injured muscle will

only lose approximately 20% of its weight [25] . In

the postpartum period, by exercising the injured

pelvic floor muscles, the degree of muscle wasting

could be reduced.

In Kegel’s original paper he described the

method for identifying the correct muscles for

Fig. 14.1 . Pelvic and sexual health institute bladder training program

STEP ACTIVITY COMMENT

1 3 Day Voiding Diary Obtain number of voids

along with volume of fluid

intake and medications.

2

Review voiding diary and

calculate average voiding

interval.

Educate patient on fluid

intake and appropriate times

to take medications.

3

Set voiding interval 15

minutes less than average

voiding interval.

Encourage patient using

positive reinforcement.

Teach other behavioral

techniques such as pelvic

floor muscle exercises, deep

breathing, etc to overcome

urgency between voiding

interval.

4

Return to office in 1-2

weeks, review progress, and

increase voiding interval by

15 minutes.

Each week increase voiding

interval by 15 minutes until

a normal interval in

achieved.

182 H. B. Goldstein and K.E. Whitmore

rehabilitation by placing a finger 1 cm from the

introitus immediately inside the pubic rami along

the lateral side wall. He described having the

patient contract that muscle while simultaneously

palpating the abdominal wall to ensure she did not

contract the rectus abdominis muscles. He empha-

sized that the purpose is for the patient to contract

the pubococcygeus muscle only [25] .

The pubococcygeus muscle is composed of both

type 1 (slow twitch) and type II (fast twitch) muscle

fibers [26] . Type I fibers are fatigue resistant and

depend on oxidative respiration. These fibers can pro-

duce muscle contractions over long periods of time,

yet they are not extremely forceful. Type II fibers are

resistance prone and can function under anaerobic

respiration. These fibers can produce forceful con-

tractions but only for short periods of time. In order

to reach maximum benefit from PFME, one must

exercise and develop both types of muscle fibers.

To train the slow twitch fibers, one must have the

muscle sustain a contraction with a small force over

a long period of time. To train the fast twitch fibers

one must contract the muscle with a large force many

times, holding for very short periods of time [27] .

PFME programs use this knowledge to develop both

types of fibers of the levator ani muscles.

Originally it was thought that PFME therapy

would benefit only patients with stress inconti-

nence. At the moment the intra-abdominal pressure

increases as with a cough or sneeze, the patient

can quickly and forcibly contract the levator ani

muscles which will push the urethra against the

pubic symphysis, and thus occlude the urethra and

prevent any leakage. This type of PFME has been

named the “knack” or “stress strategy.” The mecha-

nism of action with urge incontinence suggests that

when a detrusor contraction occurs the individual

contracts her pelvic floor muscles, which leads the

central nervous system to send a signal to the pontine

micturition center causing inhibition of the detrusor

muscle and relaxation of the bladder [28, 29] .

The majority of research trials evaluating the

efficacy of PFME focus on patients with stress

incontinence. The largest well-designed rand-

omized trial of PFME therapy for urge inconti-

nence was conducted by Burgio et al. [22] . In this

trial she sampled 197 nondemented patients with

urge incontinence who were randomized to PFME

with biofeedback, medical therapy (oxybutynin

chloride), or placebo. After 8 weeks of therapy

the patients were offered combination therapy for

another 8 weeks. Combination therapy consisted

of medical therapy with PFME and biofeedback.

Burgio found an 80.7% reduction in incontinent

episodes in the PFME group, a 68.5% reduction of

incontinent episodes in the medical therapy group,

and a 39.4% reduction in incontinent episodes in

the placebo group (all statistically significant) [22] .

In a subsequent publication from the original trial

focusing on combination therapy, eight patients

(12.7%) in the PFME group decided to cross over

and continue with combination therapy. These eight

Table 14.1. Randomized control trials for bladder training for urge incontinence.

Author Study n Outcome P value

Wiseman et al. [21] BT vs. BT with terodiline 34 56% subjective improvement vs. 44%

subjective improvement

NS a

Szonyi et al. [22] BT vs. BT with oxybutynin 47 44% reduction in leaks per week vs. 82%

reduction in leaks per week

NS a

Burgio et al. [23] BT vs. oxybutynin vs. placebo 169 81% reduction in incontinent episodes vs.

69% reduction in incontinent episodes vs.

39% reduction in incontinent episodes

<0.001

Jarvis et al. [24] BT vs. imipramine 50 84% subjective improvement vs. 56%

subjective improvement

<0.05

a NS Not statistically significant

14. Behavioral Treatments for Urge Incontinence 183

patients had a 57.5% reduction of incontinent epi-

sodes utilizing PFME therapy. When they crossed

over their reduction rate improved to 88.5%, which

was statistically significant. Of the patients in the

medical therapy arm, 27 (41.5%) decided to cross

over and continue with combination therapy. These

27 patients had a 72.7% reduction of incontinence

episodes with medical therapy and when combined

with PFME it increased to 84.3%, which was sta-

tistically significant. This paper demonstrates the

effectiveness of PFME for the treatment of urge

incontinence and when combined with medical

therapy, the reduction in incontinence episodes

improves even more [30] . A criticism of this

study is that over half of the sample had mixed

incontinence. The medical therapy arm was biased

for failure as the medication would only address

the urge component of the mixed incontinence,

whereas the PFME/biofeedback therapy arm was

biased for success as this therapy could address

both components of the mixed incontinence [31] .

In three other randomized controlled trial trials

utilizing PFME with mixed incontinence, success

rates were reported to range from 54 to 74%. In

these studies patients were randomized to PFME

or PFME with bladder training, with a control

group consisting of no treatment [32– 34] . The

problem with trials that evaluate the efficacy of

PFME is that there are no standardized programs

that all authors follow. Each trial has a program

unique to that institution and author. Comparing

one trial to another is difficult. The authors of the

Cochrane Meta-analysis on pelvic floor muscle

training describe the problem with research into

this modality. They conclude that PFME is a

viable first-line therapy for urinary incontinence

[35] . The proper number of PFME in a program

has not been well established. Various programs

range from 45 to 200 exercises. In our practice

we have found that prescribing our patients three

sets of 15 exercises three times a week has been

successful. In a set of 15 contractions we have

the patient perform five quick flick contractions

(held for 1–2 s) and ten long contractions (held for

6–10 s). This enables us to work both the fast and

slow twitch fibers. We have the patient relax the

pelvic floor muscles after each contraction for as

long as the contraction was held. We instruct our

patients that maximum benefit may not be seen

until 4–6 months of therapy.

Biofeedback Therapy

In Kegel’s original study he found that 30% of

women evaluated could not correctly contract her

pelvic floor muscles. For these women he used

perineometry, utilizing inflatable vaginal probes

that could detect the pressure in the vagina, to teach

the patient how to correctly contract the pelvic

floor muscles [36] . Cardozo et al. described the

use of biofeedback for the treatment of detrusor

instability. She measured detrusor pressures and

recorded them on a chart which then could be con-

verted to an auditory signal the patient could hear.

The auditory signal would increase as the pressure

rose and decrease as the pressure dropped. The

patient also could see the detrusor pressure on the

screen and see the rise and fall of pressure. Using

this method the patient could both see and hear sig-

nals as the detrusor pressure changed. She studied

30 women with this technique and after an average

of five 1 h sessions the patients reported a subjec-

tive improvement or cure rate of 87% and objective

improvement or cure rate of 60% [37] .

Biofeedback is an adjunct method used along with

PFME to ensure that the patient is contracting the

proper muscles. It is based on operant conditioning

and is not a treatment in itself. It can take the form

of simple verbal feedback during a pelvic exam,

vaginal or anal electromyography studies (EMG),

or vaginal or anal manometry of the pelvic floor

muscles during a pelvic floor muscle contraction

( Fig. 14.2 ). Using visual, tactile, or auditory signals,

biofeedback allows the patient to become aware of

an unconscious function. Often this information is

recorded on a polygraph such that the information

can be tracked and observed. Biofeedback therapy

has been used in many different specialties such as

psychiatry, cardiology, and neurology.

It is estimated that 50% of patients cannot cor-

rectly contract their pelvic floor muscles with

simple instruction and approximately 25% of those

may be worsening their incontinence with the

improper pelvic floor muscle contraction or para-

doxical contraction of the rectus abdominis muscle

[3] . A study of women evaluating the EMG activity

of the pelvic floor muscles while also monitoring

the EMG activity of the abdominal muscles found

concomitant contraction of the pelvic floor mus-

cles and abdominal muscles. This increased intra-

abdominal pressure would worsen incontinence in

184 H. B. Goldstein and K.E. Whitmore

the setting of stress or urge incontinence. When

the women were told to relax their abdominal mus-

cles while contracting their pelvic floor muscles,

the EMG activity showed that their pelvic floor

muscles would only produce 25% of its maximum

contraction force [38] .

In a single-blind, randomized, controlled trial

evaluating PFME, PFME with biofeedback and func-

tional electrical stimulation (FES) for patients with

overactive bladder and/or urge incontinence, Wang

et al. found that there was no difference in subjective

improvement and cure rates among the three arms.

He also found that the arm receiving PFME with

biofeedback had a statistically significant improve-

ment of quality of life, based on scores of the King’s

Health Questionnaire compared to PFME alone. This

study also evaluated pelvic floor muscle strength

both before and after treatment. Using this parameter,

the PFME with biofeedback group had the greatest

improvement in muscle strength among the three

groups (statistically significant) [39] .

In a study evaluating which form of biofeedback

was superior; Burgio et al. randomized 222 women

to anal manometry biofeedback, verbal biofeed-

back, and a control group consisting of a self-help

booklet. All patients had either urge or mixed

incontinence. The authors found that there was a

63.1% reduction of incontinence in the anal man-

ometry group, 69.4% reduction in the verbal feed-

back, and 58.6% reduction in the control group. No

statistical significance was found among the three

groups [40] . One of the issues this study brings to

light is that biofeedback may not be necessary for

everyone. Only an estimated 50% of patients will

need biofeedback to correctly contract their pelvic

floor muscles [3] . Biofeedback should be reserved

for patients who fail a traditional PFME program.

The majority of literature on biofeedback relates

to patients with stress incontinence. In a review of

randomized clinical trials evaluating biofeedback

and PFME for the treatment of urge incontinence,

Berghman et al. found too few studies to make a

conclusion about its efficacy [41] ( Table 14.2 ).

Functional Electrical Stimulation

All of the above therapies require the active partici-

pation of the patient. FES is a behavioral therapy

that does not require active participation. By using

electrical impulses directed to the pelvic nerves,

the pelvic floor muscles will contract and poten-

tially lead to their rehabilitation. If setting the FES

to a frequency at or below 12 Hz, the pudendal and

pelvic nerve stimulation cause an inhibitory effect

on the detrusor muscle [42] . FES can be applied

1. Insert

sensor

Note reading

Fig. 14.2. Peritron vaginal perineomotry (courtesy of

Cardio Design LTD)

Table 14.2 . Randomized control trials of biofeedback therapy for the treatment of urge incontinence .

Author Study n Outcome P value

Burgio et al. [22] BF (anal manomotry) vs.

oxybutynin vs. placebo

190 81% reduction in incontinent episodes vs. 69%

reduction in incontinent episodes vs. 39%

reduction in incontinent episodes

<0.001

Burgio et al. [40] BF (anal manomotry) vs.

PFME coached vs. PFME

uncoached (given written

instructions)

195 63% reduction in incontinent episodes vs. 69%

reduction in incontinent episodes vs. 59%

reduction in incontinent episodes

NS a

a NS Not statistically significant

14. Behavioral Treatments for Urge Incontinence 185

to the pelvic floor via an anal probe, intravaginal

probe, or needle electrodes. This therapy can be

preformed either in the office or at home. Daily use

of FES will make an office-only program impracti-

cal. The most common approach to this therapy is

an initial office visit to establish correct use of the

therapy followed by home use that can be moni-

tored with frequent office visits. This therapy can

be used either to allow the patient to identify the

pelvic floor muscles and then progress to a PFME

program or can be the sole therapy for the patient.

In order for FES to work the proper nerves must

be stimulated. As the electrical impulse travels

from the device to the target its current will dimin-

ish as an inverse square of the distance from the

electrical source to the target nerve. Therefore, in

an obese patient the distance from the vaginal or

anal canal to the nerves may require much higher

currents, which can lead to heating of the tissues

and pain at the probe site compared to functional

magnetic stimulation (FMS) [43] .

Many trials have evaluated FES for the treatment

of urinary incontinence. It is difficult to compare

one trial to another as there are no standardized

settings. In each study the current, pulse dura-

tion, frequency, and cycle ratio can be different,

which may affect the outcome of the therapy. In

a randomized, double-blind, placebo-controlled

trial of 32 patients with urge incontinence being

treated with FES, Yamanishi et al. found that the

FES group had a greater cure and improvement

rate, increased cystometric capacity, and increased

capacity at first desire to void compared to the

sham group [44] .

In Wang et al., 103 women with overactive blad-

der and or urge incontinence were randomized to

either PFME, biofeedback assisted PFME, or FES.

He found that after 12 weeks of therapy 51% of

women receiving FES, 50% of women receiving

biofeedback-assisted PFME, and 38% of women

receiving PFME alone improved or were cured by

their treatments. This was not statistically signifi-

cant [39] .

In Brubaker et al., a total of 121 women with

either incontinence from detrusor overactivity,

stress incontinence, or mixed incontinence were

randomized to either FES or sham therapy. In this

study, 49.5% of patients were diagnosed with stress

incontinence, 23.2% diagnosed with urge inconti-

nence, and 27.3% diagnosed with mixed inconti-

nence. After 8 weeks of therapy the authors found

a statistically significant difference between the

pre- and posttreatment cures of detrusor overactiv-

ity in the FES group and not the sham group. She

found a cure rate of 49% in patients with detrusor

overactivity [45] .

In the proper setting, FES is an effective tool for

urge incontinence. If a patient is not able to contract

the pelvic floor muscles properly and has failed bio-

feedback therapy, then it is warranted to introduce

FES. In our practice we use it in this setting and

then progress to a biofeedback-associated PFME

program once the patient can accurately perform

pelvic floor muscle contractions. ( Table 14.3 )

Functional Magnetic Stimulation

Magnetic therapy was first used in the eighteenth

century by an Italian physician named Galvani. He

used a battery to contract a frog’s leg. Since that

time magnetic fields have been shown to cause an

alignment of electrons that can stimulate an elec-

trical impulse. One of the differences between the

generation of magnetic fields and electrical fields is

that magnetic fields do not degrade when traveling

Author Study n Outcome P value

Smith et al. [46] FES vs. propantheline 38 72% marked improvement vs. 50% marked

improvement

NS a

Yamanishi et al. [47] FES vs. sham 60 22% increase in MCC

b

vs. −9% increase in

MCC

b

0.02

Wang et al. [39] FES vs. BF vs. PFME 103 51% vs. 50% vs. 38% (at least 50% reduction in

incontinent episodes)

NS a

a NS Not statistically significant

b MCC Maximum cystometric capacity

Table 14.3. Randomized control trials of FES for the treatment of urge incontinence .

186 H. B. Goldstein and K.E. Whitmore

through tissues. Electrical fields will degrade as

they travel through clothing, skin, fat, and bone.

Magnetic fields will not. The current required to

stimulate the pudendal nerves in an obese patient

compared to a very thin patient in magnetic therapy

is the same. In FES, the current required to stimu-

late an obese patient is much greater than a thin

patient, thus increasing the likelihood of an adverse

reaction to the high current. Functional magnetic

stimulation (FMS) often is provided through a coil

implanted in a chair that the patient sits on. This

therapy can be applied while the patient remains

clothed, without the use of any probes or electrode

needles. One of the obstacles to providing this

therapy is that it cannot be applied in the home.

The magnetic chairs currently available are not for

home use so the patient must come to the office

approximately two times a week for 6 weeks of

treatment [43] ( Fig. 14.3 ). Functional magnetic

therapy works similarly to FES. At a low current it

will cause the stimulation of the pelvic and puden-

dal nerves, which will lead to a relaxation of the

detrusor muscle [48] .

In a trial comparing the efficacy of functional

magnetic therapy with FES, 32 patients with urge

incontinence were randomized to the two therapies.

The authors found that although both therapies

were efficacious, the functional magnetic therapy

sample had an increased cystometric capacity of

106% from baseline compared to an increase of

16% from baseline in the FES group (statistically

significant) [47] .

In a trial of 24 patients with urge or mixed

incontinence who underwent twice weekly treat-

ments for 8 weeks of FMS found that 58% had an

objective improvement and 71% had a subjective

improvement. Although these findings were sig-

nificantly different from pretreatment values, the

authors did not compare this therapy to any other

treatment or placebo so it is difficult to interpret

the results [43] .

Conclusion

Behavioral treatment for urge incontinence is

a viable option. Using the above therapies in a

systematic manner can lead to a successful out-

come. In our practice we first start with a voiding

diary and bladder training ( Fig. 14.4 ). We then

Fig. 14.3 . Neocontrol functional magnetic stimulation (courtesy of Neotonus Company)

14. Behavioral Treatments for Urge Incontinence 187

have the patient evaluated by our physical thera-

pist for PFME. If the patient cannot correctly

contract and relax the proper muscles, then

the patient will undergo biofeedback-assisted

PFME. If the patient still cannot properly per-

form PFME, then we implement FES. We do

not use FMS since it cannot be performed in the

home and the goal of our programs is for the

patients to undergo a home regimen with peri-

odic office visits to monitor success. After 2–3

weeks of FES we then revert back to biofeed-

back-assisted PFME. We also teach the patient

behavioral strategies to resist the urgency such

as deep breathing techniques, not running to the

bathroom, doing 5–10 quick flick PFME, and

sitting when the urgency occurs. We have found

that our algorithm has been successful for the

treatment of urge incontinence.

References

1. Abrams P , Cardoza L , Fall M , et al. The standardiza-

tion of terminology of lower urinary tract dysfunc-

tion: Report from the standardization sub-committee

of the international continence society . Neurourol

Urodynman 2002 ; 21 : 167 – 178 .

2. De Groat WC . A neurologic basis for the overactive

bladder . Urology 1997 ; 50 (Sup 6A) : 36 – 52 .

3. Fantyl JA, Newman DK, Colling J, et al. Urinary

incontinence in adults: Acute and chronic manage-

ment. Clinical practice guideline no 2, 1996 update.

Rockville (MD): US Department of Health and

Human Services, Public Health Services, Agency

for Health Care Policy and Research; March 1996.

4. Wyman J . Management of urinary incontinence in

adult ambulatory care population . Annu Rev Nurs

Res 2000 ; 18 : 171 – 194 .

5. Roe B , Doll H . Lifestyle factors and continence

status: Comparison of self-report data from a postal

survey in England . J Wound Ostomy Continence

Nurs 1999 ; 26 (6) : 312 – 313 .

6. Dallosso H , Matthews R , McGrother C , et al. The

association of diet and lifestyle factors with the

onset of overactive bladder: A longitudinal study in

men . Public Health Nutr 2004 ; 7 (7) : 885 – 891 .

7. Dallosso HM , McGrother CW , Matthews RJ , et al.

The association of diet and other lifestyle factors

with overactive bladder and stress incontinence:

A longitudinal study in women . BJU Int 2003 ; 92 :

69 – 77 .

8. Creighton SM , Stanton SL . Caffeine: Does it affect

your bladder ? Br J Urol 1990 ; 66 : 613 – 614 .

9. James JE , Sawczuk D , Merrett S . The effect of

chronic caffeine consumption on urinary inconti-

nence in psychogeriatric inpatients . Psychol Health

1989 ; 3 : 297 – 305 .

10. Edelstein BA , Keaton-Brasted C , Burg MM . Effects

of caffeine withdrawal on nocturnal enuresis, insom-

nia, and behavior restraints . J Consult Clin Psychol

1984 ; 52 : 857 – 862 .

11. Tomlison BU , Dougherty MC , Pendergast JF , et al.

Dietary caffeine, fluid intake, and urinary inconti-

nence in older rural women . Int Urogynecol J 1999 ;

10 : 22 – 28 .

12. Wyman JF , Elswick RK , Wilson MS , et al. Relationship

of fluid intake to voluntary micturitions and urinary

Fig. 14.4. The Pelvic and sexual

health institute behavioral treat-

ment algorithm

Voiding Diary

Bladder Training

PFME Assessment

Correct Contraction Incorrect Contraction

PFME Program Biofeedback associated PFME program

Functional Electrical Stimulation

Not successful

188 H. B. Goldstein and K.E. Whitmore

incontinence in women . Neurourol Urodyn 1991 ; 10 :

463 – 473 .

13. Griffiths DJ , McCracken PN , Harrison GM , et al.

Relationship of fluid intake to voluntary micturi-

tion and urinary incontinence in geriatric patients .

Neurourol Urodyn 1993 ; 12 : 1 – 7 .

14. Jeffcoate T , Francis W . Urinary incontinence

in the female . Am J Obstet Gynecol 1966 ; 94 :

604 – 618 .

15. Burgio KL . Current perspectives on management of

urgency using bladder and behavioral training . J Am

Acad Nurse Pract 2004 ; 16 (10) : 4 – 7 .

16. Fantl JA , Wyman JF , McClish DK , et al. Efficacy of

bladder training in older women with urinary incon-

tinence . JAMA 1991 ; 265 (5) : 609 – 613 .

17. Goode PS , Burgio KL , Locher JL , et al. Urodynamic

changes associated with behavioral and drug treat-

ment of urge incontinence in older women . J Am

Geriatr Soc 2002 ; 50 : 808 – 16 .

18. Hu TW , Igou JF , Kaltreider DL , et al. A clini-

cal trial of a behavioral therapy to reduce urinary

incontinence in nursing homes . JAMA 1989 ; 261 :

2656 – 2662 .

19. Jarvis GJ , Millar DR . Controlled trial of blad-

der drill for detrusor instability . BMJ 1980 ; 281 :

1322 – 1323 .

20 . Wallace SA , Roe B , Williams K , et al. Bladder train-

ing for urinary incontinence in adults (Cochrane

Review) . In: the Cochrane Library. Aberdeen, UK:

John Wiley and Sons, Ltd ; 2004 ;2.

21. Wiseman PA , Malone-Lee J , Rai GS . Terodiline

with bladder retraining for treating detrusor instabil-

ity in elderly people . BMJ 1991 ; 302 : 994 – 996 .

22. Szonyi G , Collas DM , Ding YY , et al. Oxybutynin

with bladder retraining for detrusor instability in

elderly people: A randomized controlled trial . Age

Ageing 1995 ; 24 : 287 – 291 .

23. Burgio KL , Locher JL , Goode PS , et al. Behavioral

vs. drug treatment for urge urinary incontinence in

older women: A randomized controlled trial . JAMA

1998 ; 280 (23) : 1995 – 2000 .

24. Jarvis GJ . A controlled trial of bladder drill and drug

therapy in the management of detrusor instability . Br

J Urol 1981 ; 53 : 565 – 566 .

25. Kegel , AH . Progressive resistance exercises in the

functional restoration of the perineal muscles . Am J

Obstet Gynecol 1948 ; 56 : 238 – 248 .

26. Gosling JA , Dixon JS , Critchley HOD , et al. A com-

parative study of the human external sphincter and

the periurethral levator ani muscles . Br J Urol 1981 ;

53 : 35 – 41 .

27. American College of Sport’s Medicine. Guidelines

for exercise testing and prescription, 2nd ed.

Philadelphia: Lea and Febiger, 1993.

28. Messelink EJ . The overactive bladder and the role

of the pelvic floor muscles . Br J Urol 1999 ; 83 (S2) :

31 – 35 .

29. Shafik A , Shafik IA . Overactive bladder inhibition

in response to pelvic floor muscle exercises . World

J Urol 2003 ; 20 (6) : 374 – 377 .

30. Burgio KL , Locher JL , Goode PS . Combined behav-

ioral and drug therapy for urge incontinence in older

women . J Am Geriatr Soc 2000 ; 48 (4) : 370 – 374 .

31. Bo K , Berghmans LCM . Nonpharmacologic treat-

ments for overactive bladder-pelvic floor exercises .

Urology 2000 ; 55 (Suppl 5A) : 7 – 11 .

32. Burns P , Pranikoff K , Nochajski M , et al. Treatment

of stress incontinence with pelvic floor exercises and

biofeedback . J Am Geriatr Soc 1990 ; 38 : 341 – 344 .

33. Obrien J , Austin M , Sethi P , et al. Urinary incontinence:

Prevalence, need for treatment, and effectiveness of

intervention by nurse . BMJ 1991 ; 303 : 1308 – 1312 .

34. Lagro-Janssen ALM , Debruyne FMJ , Smits AJA ,

et al. The effects of treatment of urinary incontinence

in general practice . Fam Pract 1992 ; 9 : 284 – 289 .

35. Hay-Smith EJC , Dumoulin C . Pelvic floor muscle

training versus no treatment, or inactive control

treatments, for urinary incontinence in women .

Cochrane Database Syst Rev 2006 ; 1 : CD005654 .

36. Kegel AH . Stress incontinence of urine in women:

Physiological treatment . J Int Col Surg 1956 ; 25 :

487 – 499 .

37. Cardozo LD , Abrams PD , Stanton SL , et al.

Idiopathic bladder treated by biofeedback . BJU

1978 ; 50 (7) : 521 – 523 .

38. Neumann P , Gill V . Pelvic floor and abdominal mus-

cle interaction: EMG activity and intra-abdominal

pressure . Int Urogynecol J 2002 ; 13 : 125 – 132 .

39. Wang AC , Wang Y , Chen M . Single-blind, rand-

omized trial of pelvic floor muscle training, bio-

feedback-assisted pelvic floor muscle training, and

electrical stimulation in the management of overac-

tive bladder . Urology 2004 ; 63 : 61 – 66 .

40. Burgio KL , Goode PS , Locher JL , et al. Behavioral

training with and without biofeedback in the treat-

ment of urge incontinence in older women . JAMA

2002 ; 288 (18) : 2293 – 2299 .

41. Berghmans LC , Hendricks HJ , de Bie RA , et al.

Conservative treatment of urge urinary incontinence:

A systematic review of randomized clinical trials .

BJU Int 2000 ; 85 : 254 – 263 .

42. Amaro JL , Gameiro MO , Padovani CR . Effect of

intravaginal electrical stimulation on pelvic floor mus-

cle strength . Int Urogynecol J 2005 ; 16 : 355 – 358 .

43. Chandi DD , Groenendijk PM , Venema PL .

Functional extracorporeal magnetic stimulation as

a treatment for female urinary incontinence: “The

chair.” BJU Int 2004 ; 93 : 539 – 542 .

14. Behavioral Treatments for Urge Incontinence 189

44. Yamanishi T , Yasuda K , Sakakibara R , et al.

Randomized, double-blind study of electrical stimu-

lation for urinary incontinence due to detrusor over-

activity . Urology 2000 ; 55 : 353 – 357 .

45. Brubaker L , Benson J , Bent A , et al. Transvaginal

electrical stimulation for female urinary incontinence .

Am J Obstet Gynecol 1997 ; 173 (3) : 536 – 540 .

46. Smith JJ . Intravaginal stimulation randomized trial .

J Urol 1996 ; 155 : 127 – 130 .

47. Yamanishi T , Sakakibara R , Uchiyama T , et

al. Comparative study of the effects of mag-

netic versus electrical stimulation on inhibition

of detrusor overactivity . Urology 2000 ; 56 :

777 – 781 .

48. Goldberg RP , Sand PK . Electromagnetic pelvic

floor stimulation for urinary incontinence and

bladder disease . Int Urogynecol J 2001 ; 12 :

401 – 404 .

191

Introduction

Urgency urinary incontinence (UUI) occurs in about

one third of patients with overactive bladder (OAB),

and hence is present in about 5% of the general adult

population [1, 2] . As discussed elsewhere in this

book, its prevalence increases with age [1, 2] . The

prevalence of OAB is above average among patients

seeing a physician for any reason, ie, irrespective of

their urinary symptoms [3] , or in residents of nursing

homes. Pharmacotherapy is the mainstay of manage-

ment of UUI patients. While the following focuses

on patients with incontinence, it should be noted

that continent OAB patients may have quantitatively

similar symptoms and distress [4] . While the effects

of medical treatment have been poorly explored in

continent compared to incontinent OAB patients,

limited data suggest that most of the following also is

applicable to the continent OAB population [4, 5] .

Underlying Concepts

Medical treatment of UUI in principle could work

on various levels involved in the control of bladder

function including the sensory mechanisms, the

smooth muscle cell, and the central nervous system.

Several recent reviews have discussed potential sites

of action and the involved mechanisms in great

detail [6– 10] . Currently used approaches are limited

largely to the use of muscarinic acetylcholine recep-

tor antagonists. Their use is based on the idea that

muscarinic receptors are the physiologically most

relevant receptors in mediating bladder contraction.

Although the bladder of humans and various ani-

mal species expresses much more M

2 than M

3

muscarinic receptors, bladder contraction occurs

largely if not exclusively via the M

3 subtype [11] ,

an observation that is supported by studies with

M

3 receptor knockout mice [12] . Nevertheless, M

2

receptors also can contribute to bladder contraction,

and their role may increase under some pathological

conditions [7] . While original concepts have focused

largely on muscarinic receptors on the bladder

smooth muscle cells, it now is apparent that the

urothelium not only expresses such receptors [13]

but also may be a mediator of the therapeutic effects

of muscarinic antagonists [14] . The relative roles of

urothelium versus smooth muscle in the effects of

muscarinic antagonists currently are under investi-

gation. Moreover, an additional site of action in the

central nervous system has been proposed [15] .

Available Drugs and Their

Properties

Many muscarinic receptor antagonists are now

available for clinical use, some of them in multi-

ple pharmaceutical formulations. These include

immediate-release (IR), extended-release (XL),

and transdermal (TD) formulations of oxybutynin

[16– 19] and IR and XL formulations of tolterodine

[19, 20] . Other drugs have been in clinical use in

selected countries such as propiverine [21] . More

recently additional drugs were introduced, after

Chapter 15

Pharmacotherapy of Urgency Incontinence

Martin C. Michel

192 M.C. Michel

having been available in few countries for a long

time, and/or have been made available on a wider

scale. These include darifenacin [22, 23] , solif-

enacin [23, 24] , and trospium [23, 25] . Moreover,

additional muscarinic receptor antagonists such

as fesoterodine, which is metabolized to the same

active compound as tolterodine, are currently in

late stages of clinical development [26] .

The various muscarinic receptor antagonists

differ in their affinity profile for subtypes of

muscarinic receptors ( Table 15.1 ). In this regard

propiverine, tolterodine, and trospium have very

similar affinity for all subtypes of muscarinic

receptors; oxybutynin and solifenacin are moder-

ately selective for M

3 relative to M

2 receptors; and

darifenacin is selective for M

3 relative to M

2 and,

to a lesser extent, to M

1 receptors. All these drugs

have been shown to inhibit the contraction of iso-

lated bladder strips elicited by muscarinic receptor

antagonist in vitro and also to inhibit nonvoiding

contractions of the urinary bladder in animal mod-

els of OAB. While some drugs have been better

documented in this regard than others, there is little

reason to believe that any of them should behave

qualitatively differently in the bladder compared

to the others.

The pharmacokinetic properties of the various

muscarinic antagonists vary considerably and have

been reviewed comprehensively for most agents

[28] . A summary including the corresponding infor-

mation for the newer agents is presented in Table

15.2 . Based on their affinity for the target receptors

and their pharmacokinetic properties, the various

drugs also differ in their recommended therapeutic

Table 15.1. Muscarinic receptor subtype affinity of clinically used antagonists

a.

M 1 M 2 M 3 M 4 M 5

Darifenacin 7.3 46 0.79 46 9.6

Oxybutynin 1.0 6.7 0.67 2.0 11.0

Propiverine 230 347 175 154 364

Solifenacin 25 125 10 ? b ?

Tolterodine 3.0 3.8 3.4 5.0 3.4

Trospium 0.75 0.65 0.50 1.0 2.3

aDrug affinities are given in nmole/liter, with a smaller value representing a higher affinity, and are based on [7, 27] . Note that

some drugs (eg, oxybutynin, tolterodine) form active metabolites in vivo, but their affinities are similar to those of the respective

parent compound

b?, affinity not reported

Table 15.2. Key pharmacokinetic properties and standard doses of clinically used muscarinic receptor antagonists a

.

tmax (h) b t1/2 (h)

Oral bioavailability

(%) Elimination route Dosage

Darifenacin 7 3 15–19 Hepatic, CYP 2D6

and 3A4

1 × 7.5–15 mg

Oxybutynin IR 0.5–1 2–4 2–11 Hepatic, CYP 3A4 3–4 × 2.5–5 mg

Oxybutynin XL 5 16 – c 2–3 × 5 mg

Propiverine 2 15 40 Hepatic, CYP 3A4 3–4 × 5–10 mg

Solifenacin 4–6 45–55 88 Hepatic, CYP 3A4 1 × 5–10 mg

Tolterodine IR 1–2 3 – d Hepatic, CYP 2C9,

2D6 and 3A4

2 × 2 mg

Tolterodine XL 4 6–8 1 × 4 mg

Trospium 5–6 20 10 Renal, >50% in

active form

2 × 20 mg

a For details see [17– 22, 24, 25, 28, 29]

b

t max , time to reach maximal plasma concentration after oral administration; t 1/2 : elimination half-life

c The oral bioavailability of the XL formulation is increased by about 50% for the parent compound, whereas that of the active

metabolite is decreased by about 30%

d

Absolute bioavailability dependent on genotype for CYP 2D6 ranging from 26% in extensive metabolizers to 91% in poor

metabolizers. Note that t max

and t 1/2 are not applicable to the TD formulation of oxybutynin, which has the same elimination route;

the standard dosing is one patch (delivering 3.9 mg/day) every 3–4 days [16]

15. Pharmacotherapy of Urgency Incontinence 193

doses ( Table 15.2 ). In this context it also should be

considered that some muscarinic antagonists undergo

extensive metabolism and that in some cases such

metabolites may contribute to the observed clinical

effects of said drugs in a relevant manner [30, 31] .

Considerations for the

Interpretation of Clinical Data

The interpretation of the available data on the

clinical effects of muscarinic antagonists in OAB

is complicated by a number of factors that dif-

fer markedly among reported studies. One set of

important variables relates to the characteristics of

the patient population being investigated. For exam-

ple, patients previously being treated for this condi-

tion may respond differently from those who are

treatment-naïve. This is exemplified by studies with

oxybutynin TD where, starting from similar base-

line values of about 30 incontinence episodes per

week, two studies in unselected patients reported

median reductions by 18 episodes [32] , whereas

one in known oxybutynin responders found median

reductions by 25 episodes [33] . Another patient-

related difference among studies is the question

of continent versus incontinent patients. As the

development programs for most drugs have used

the number of incontinence episodes as the primary

endpoint, their pivotal studies were based solely on

incontinent patients. In contrast, the development

program for solifenacin has used the number of

micturitions as the primary endpoint, and accord-

ingly has included both continent and inconti-

nent patients. However, recent studies indicate that

muscarinc receptor antagonists also are effective

relative to placebo in continent patients [5] and

that continent and incontinent patients will respond

similarly to a muscarinic antagonist if their baseline

symptoms are similar [4] . Other patient-related

variables possibly differing among studies are

patient gender and age (see below) and the recruit-

ment via specialists (urologists, urogynecologists)

versus general practitioners, but little information is

available with regard to the latter.

Reported treatment efficacies, and particularly

differences between active treatment and placebo,

also in part will depend on how they have been

assessed. For example, the inclusion criteria of

most randomized controlled trials (RCT) specify

certain minimum values for the parameter, which

also is used as the primary or secondary endpoint.

This introduces a single-sided regression-to-the-

mean phenomenon, which can contribute to the

apparently large “placebo responses” typically

seen in OAB studies. Moreover, both shorter (eg, 3

days) and longer (eg, 7 days) versions of micturi-

tion diaries are used to assess episode frequencies

of OAB symptoms. Although values from both

types of diaries are reasonably correlated, the use

of 3-day diaries for measuring inclusion criteria as

well as outcome parameters aggravates the single-

sided regression-to-the-mean phenomenon. Thus,

studies using 3-day diaries generally have reported

large responses to both placebo and active treat-

ments than those using 7-day diaries [34] . Thus,

the symptom improvement in response to placebo

only partly represents a “true” placebo effect under

such conditions. While the relative magnitude

of the placebo in the total treatment response to

incontinence medications already appears large

[35] , it may even be underestimated. Thus, the

“baseline” response symptoms reported in OAB

studies typically are measured after a single-blind

placebo run-in periods. While few data have been

published on OAB, experience from studies in male

patients with lower urinary tract symptoms sugges-

tive of benign prostatic hyperplasia suggests that

considerable symptom improvement may occur

already during such run-in periods [36] . Hence, the

reported effects of active treatment in such studies

may actually overestimate the component attribut-

able to the active ingredient.

As baseline symptoms can vary considerably

among patients, it is necessary to consider the

impact of analyzing absolute versus percent changes

and of changes of means versus those of medians.

The practical implications of absolute versus per-

cent changes is easily seen when it is considered

that a reduction of incontinence episodes by five

per week means a lot for a patient with a baseline

value of five (this patient becomes dry) but prob-

ably only a little for someone with 26 episodes per

week (this patients continues to wet herself three

times a day). Accordingly, it was found that cal-

culations of percent changes yield more consistent

measures of treatment effects [37] . Since baseline

episode frequencies of OAB symptoms in the pop-

ulation do not exhibit a Gaussian distribution, the

194 M.C. Michel

calculation of mean values, which assumes such

distribution, is not sound on a theoretical basis and

median values may be more robust. This has prac-

tical implications as, eg, studies reported consist-

ently greater reductions of urgency episodes with

placebo or solifenacin treatment if the data were

analyzed based on medians rather than means [23] .

Accordingly, the FDA now routinely requests that

submissions for approval are based on an analysis

of medians rather than means.

Another issue related to the proper statistical

analysis of clinical OAB studies concerns sec-

ondary subgroup analyses. For various reasons,

trial costs being an important one, the number of

patients in a controlled study typically is prede-

fined to yield sufficient statistical power to answer

the primary question, ie, whether the study drug is

better than placebo or a comparator drug. If second-

ary analyses are performed, eg, comparing old and

young, male and female, or more and less severely

afflicted patients, group sizes become smaller, and

hence the statistical power decreases. If such sec-

ondary analyses fail to find significant differences

among subgroups, there always is the possibility

that this may reflect a false-negative result due to

insufficient statistical power. Similarly, studies are

mostly powered to detect differences in efficacy,

ie, something that can be measured in each patient.

This means that they often are underpowered to

detect differences in tolerability, particularly if the

focus is on specific side effects that occur only in a

minority of patients. Unfortunately, the vast major-

ity of studies on OAB treatment fail to state for

which type of difference they have been powered.

Another biometrical issue is the analysis of

OAB-related symptom scales. For example, the

validated “Urgency Perception Scale” gives the

three options “usually able to finish what I’m

doing before going to toilet,” “usually able to hold

until I reach toilet,” and “usually not able to hold

urine” [38, 39] . Frequently these are scored as 1, 2,

and 3, respectively, and then group means before

and after treatment are calculated. However, such

averaging implies that two patients going from the

most severe to the medium score are statistically

the same as two going from the medium to the least

severe group or as one going from most to least

severe and one not changing. Obviously, this does

not fit clinical reality, and distribution histograms

of patients in the various subgroups before and

after treatment are a more appropriate represen-

tation of such data [4] . Similar considerations

obviously apply to other OAB rating scales.

Another consideration is that both the desired and

the adverse effects of muscarinic receptor antago-

nists are dose-dependent. Hence, a drug with an

improved efficacy/tolerability ratio may appear to

have fewer side effects for a given level of efficacy

or to be more efficacious for a given level of side

effects. This relationship is highlighted by a recent

study comparing the solifenacin with tolterodine

XL [40] . In this study solifenacin appeared to have

greater efficacy than tolterodine XL, but a closer

inspection of the data showed that this occurred

at the expense of more adverse events. In other

words, apparently the dose of solifenacin in this

study relative to its half-maximally effective dose

was higher than that of tolterodine XL. In this vein

it appears conceivable that medications allowing

the use of multiple doses allow greater flexibility in

identifying the optimal dose for a given patient.

A final general consideration relates to the com-

parison of RCT with real-life practice (RLP) stud-

ies. Contrary to common belief it cannot be said

that one type of study is scientifically superior to the

other. Rather, each study type has distinct advan-

tages and disadvantages, which need to be kept in

mind in the interpretation of the respective data.

Particularly in a condition that is characterized by

considerable treatment responses to placebo, only

RCT involving a placebo arm can prove whether

a given active treatment indeed is superior to pla-

cebo. However, in the field of muscarinic receptor

antagonists the power of placebo-controlled stud-

ies should not be overestimated, as recent research

shows that a considerable fraction of patients in

such studies can guess correctly whether they are

on active treatment or placebo [41] , which effec-

tively may unintentionally at least partly unblind

such studies. On the other hand, RCT also have

several disadvantages. As explained above their

reports frequently ignore symptom improvements

during the placebo run-in period, and the use of the

same parameter as inclusion and efficacy criterion

introduces a single-sided regression-to-the-mean

phenomenon. Moreover, such studies typically

have stringent inclusion and exclusion criteria

that question the applicability of the results to the

general patient population presenting to a physi-

cian. On the other hand, RLP studies do not allow

15. Pharmacotherapy of Urgency Incontinence 195

statements on the efficacy of a drug specifically

attributable to its active ingredient. However, they

avoid biases due to inclusion and exclusion criteria,

placebo run-in phases, and artificial cutoffs for

being eligible for treatment. This also may explain

why treatment efficacies reported from RLP stud-

ies often exceed those from RCT ( Fig. 15.1 ).

Moreover, RLP studies frequently are performed

on much larger groups of patients than RCT, and

hence are statistically better powered to allow for

subgroup comparisons. In other words, RCT have

high internal validity but limited external validity,

whereas RLP studies have lower internal but pos-

sibly higher external validity. Thus, RLP studies

reflect what physician and patient realistically can

expect from a drug in daily practice, whereas RCT

establish how much of this response is indeed due

to the active ingredient of such medication .

Clinical Experience with

Muscarinic Receptor Antagonists

Numerous placebo-controlled, double-blind ran-

domized clinical trials (RCT ) have shown that

muscarinic receptor antagonists relieve symptoms

of OAB [34, 35, 44] . Comprehensive reviews have

been published previously that summarize the

clinical data with darifenacin [22] , oxybutynin IR

[45] , oxybutynin XL [17] , oxybutynin TD [16] ,

propiverine [21] , solifenacin [24] , tolterodine IR

[20] , tolterodine XL [19] , and trospium [25] .

Readers are referred to these publications for more

details on individual drugs.

Based on requirements of the regulatory authori-

ties, such studies primarily have looked at the fre-

quency of incontinence episodes or, more recently,

of micturitions. In this regard a focus on incon-

tinence episodes neglects the fact that two thirds

of all OAB patients are continent [1, 2] and that

continent OAB can impair the quality of life (QoL)

of the afflicted patients to a similar degree as

incontinent OAB [4] . Interestingly, measurements

of treatment efficacy based on urgency or nocturia

only have emerged in recent years [23] . Moreover,

there is an ongoing debate whether the impact of

urgency for the patient is best assessed by counting

episode numbers or by one of several OAB rating

scales [38, 39, 46, 47] or concepts such as “warning

time” [48] or “urgency-free interval” [49] . Recent

data based on factor-analysis demonstrate that both

related rating scales explain a considerably greater

fraction of data variance than episodes of classic

OAB symptoms [50] . Urodynamic measurements

such as volume-to-first-contraction also have been

used to measure the efficacy of muscarinic recep-

tor antagonists [35] , but have not been the primary

endpoint of registration studies.

Fig. 15.1. Comparison of treatment responses during

randomized controlled trials (RCT) and real-life practice

(RLP) studies. Data are shown at baseline and after treat-

ment (post-RX) and are based on data from the pivotal

registration RCT [34, 42] and RLP performed in Germany

[4, 43] . For each drug the response parameter defined as

the primary endpoint in the pivotal RCT was used

196 M.C. Michel

In 2003, a meta-analysis of the efficacy and tol-

erability of muscarinic receptor antagonists in the

treatment of OAB was published by the Cochrane

collaboration, which largely was based on studies

with the IR formulations of oxybutynin, propiv-

erine, tolterodine, and trospium [35] . This meta-

analysis reported only moderate efficacy compared

to placebo, eg, an improvement of leakage episodes

by 0.56 per day and of micturitions by 0.59 per day.

Newer studies using XL formulations of oxybu-

tynin or tolterodine as well as newer agents tend to

report a somewhat greater but still only moderate

advantage over placebo [34, 44] . This apparently

moderate efficacy of muscarinic receptor antago-

nists relative to placebo has sparked a debate about

the usefulness. However, even if a major part of the

effects of such medications occurs independently

of their active ingredients, the overall effect in

daily clinical practice is considerable (Fig. 15.1 ).

In general, muscarinic receptor antagonists can

be considered to be a safe class of drugs. Side

effects are dominated by those to be expected

based on their mechanism of action and relate to

the blockade of muscarinic receptors in the sali-

vary glands (dry mouth), the gastrointestinal tract

(constipation), and the eye (blurred vision, accom-

modation disorders). Although most muscarinic

receptor antagonists used in the treatment of OAB

also will block M

2 receptors, a subtype relevant for

the control of heart rate [51] , clinically relevant

heart rate elevations surprisingly have not been a

prominent feature of such drugs [52, 43] . Similarly,

it is interesting to note that muscarinic antagonists

in the treatment of OAB apparently do not promote

urinary retention [35] . However, drugs blocking M

1

receptors in the central nervous system may have

adverse effects on cognitive function [53] . While

central nervous system effects, particularly cogni-

tive side effects, have not been reported often in

the treatment of OAB, this may represent an under-

reporting, since physicians treating OAB may not

always carefully test cognitive function.

As outlined above, there is considerable hetero-

geneity among patient populations under investiga-

tion and methods of data analysis and presentation

among studies. This makes it very difficult to

perform meaningful indirect comparison among

the various muscarinic receptor antagonists. On the

other hand, numerous studies have reported on ran-

domized, double-blind studies directly comparing

muscarinic receptor antagonists. In the interpreta-

tion of such studies it should be considered that

the minimum difference in incontinence episodes

noticeable by a patient in a QoL assessment tool is

three episodes per week [54] . Most direct compara-

tive studies have profiled agents against oxybutynin

IR. Such studies were performed for oxybutynin

XL [55, 56] , oxybutynin TD [33] , darifenacin [52] ,

propiverine [57] , tolterodine IR [58, 59] , toltero-

dine XL [60] , and trospium [61, 62] . Across the

board these studies show that oxybutynin IR has

a worse efficacy/tolerability ratio than any other

approach including XL and TD formulation of

oxybutynin. Such findings have been substantiated

by smaller clinical pharmacological studies on

salivation [63] , central nervous effects [64] , sleep

[65, 66] , and ocular effects [67] , confirming that

oxybutynin IR despite its wide use probably is the

least suitable treatment option for OAB patients.

For clinical comparisons among the muscarinic

receptor antagonists with better efficacy/tolerabil-

ity ratios, most studies have profiled drugs against

either of the two tolterodine formulations, most

likely because tolterodine is the international mar-

ket leader. In comparison with tolterodine, IR stud-

ies were presented for darifenacin [68] , oxybutynin

XL [69– 71] , oxybutynin TD [32] , propiverine [72] ,

and solifenacin [73, 74] . More recently, data also

have been presented for comparisons with toltero-

dine XL for oxybutynin XL [75] or solifenacin

[40] . Although many of these studies have reported

minor differences in efficacy and/or tolerability

among drugs (not surprisingly always in favor of

the company sponsoring the study), the overall

evidence does not suggest that any of these drugs is

superior to the others for general use by a clinically

relevant margin.

Treatment Strategy

A rational basis for a differential use of the various

agents mainly is based on factors of convenience,

eg, the need for a single pill per day and, more

importantly, aspects related to safety and tolerabil-

ity. For example, trospium is the only drug that is

largely excreted by the kidneys in its active form

( Table 15.2 ); this may be beneficial in patients

with impaired liver function but disadvantageous

in those with impaired renal function. In patients

15. Pharmacotherapy of Urgency Incontinence 197

where even minor adverse effects on cognitive

function would be disadvantageous, a drug with

a well-documented lack of effect on cognitive

function such as darifenacin may deserve prefer-

ential attention [76] . Tolterodine and trospium also

appear to lack major adverse effects on cognitive

function [64– 66] .

Moreover, potential differences in the efficacy

and tolerability among patient groups have to

be considered. In this regard, experimental and

clinical evidence indicate that men and women

respond similarly to the treatment with muscarinic

antagonists [77] . Nevertheless, the vast majority of

all current prescriptions of muscarinic antagonists

are for women. This may at least partly reflect

concerns regarding the use of such drugs in men

with enlarged prostate glands, although the valid-

ity of such concerns has been questioned recently

[78] . Another factor to be considered is patient

age. Despite a reduced muscarinic receptor expres-

sion in the aged bladder [79] , treatment responses

to muscarinic receptor agonists remain largely

unchanged in the elderly [77, 80] . However, it may

be necessary to adapt the dose of some drugs in the

elderly in order to accommodate age-related altera-

tions of pharmacokinetics, eg, with trospium.

A major fraction of patients with OAB/UUI

concomitantly have stress urinary incontinence, ie,

mixed incontinence. Duloxetine is the only proven

medication to treat stress urinary incontinence

[81] . Both muscarinic receptor antagonists [46, 82]

and duloxetine [83] have shown efficacy in women

with mixed incontinence. However, at present lit-

tle information is available about how these two

approaches behave in direct comparison and/or

what the role of a possible combination treatment

might be. In the absence of such data, it appears

prudent to base the initial treatment decision in

mixed incontinence patients on the predominant

character of the symptoms.

Finally, after the best possible treatment has

been chosen and administered, the question arises

about how long a given drug needs to be adminis-

tered. While there is no evidence to suggest that the

OAB syndrome will “heal” spontaneously on drug

treatment, the clinical experience suggests that not

all patients have a degree of symptoms requiring

long-term treatment. This was exemplified by a

study in which patients, who had successfully

responded to a 3-month treatment with a mus-

carinic antagonist, were systematically withdrawn;

within a 1-month observation thereafter, only 35% of

patients requested to be put back on treatment [84] .

While more data is clearly required in this regard,

it appears that not all OAB patients will require

continuous treatment.

Conclusions and Future Directions

Muscarinic receptor antagonists have proven use-

ful in the treatment of OAB, but there clearly

is room for improved treatment modalities with

regard to efficacy and/or tolerability, particularly in

patients refractory to muscarinic antagonists [85] .

Therefore, a variety of options currently are under

investigation to expand our therapeutic approaches.

Among these the use of botulinum toxin, which

prevents acetylcholine release in the bladder prob-

ably has advanced most [86, 87] . While the prom-

ising reports and the availability of this drug make

it tempting to use it, the published evidence is not

yet sufficient to support its routine clinical use.

Moreover, botulinum toxin has not been registered

as a medication to treat OAB in any major country,

and hence can be considered only as an off-label

use. Other approaches in various stages of inves-

tigation include β 3 -adrenoceptor agonists [88] ,

agonists of VR1 vanilloid receptors such as resin-

eferatoxin [89] , potassium channel openers [90] ,

and neurokinin receptor antagonists [91] . However,

clinical data, particularly studies comparing their

efficacy and safety to those of muscarinic recep-

tor antagonists, remain to be reported before any

of these can be considered a viable alternative for

clinical use.

References

1 . Milsom I , Abrams P , Cardozo L , et al. How wide-

spread are the symptoms of an overactive bladder

and how are they managed? A population-based

prevalence study . BJU Int 2001 ; 87 (9) : 760 – 766 .

2 . Stewart WF , van Rooyen JB , Cundiff GW , et al.

Prevalence and burden of overactive bladder in the

United States . World J Urol 2003 ; 20 : 327 – 336 .

3 . Goepel M , Hoffmann J , Piro M , et al. Prevalence and

physician awareness of symptoms of urinary bladder

dysfunction . Eur Urol 2002 ; 41 (3) : 234 – 239 .

4 . Michel MC , de la Rosette JJMCH , Piro M , Schneider

T . Comparison of symptom severity and treatment

198 M.C. Michel

response in patients with incontinent and continent

overactive bladder . Eur Urol 2005 ; 48 (1) : 110 – 115 .

5 . Abrams P , Swift S . Solifenacin is effective for the

treatment of OAB dry patients: A pooled analysis .

Eur Urol 2005 ; 48 : 483 – 487 .

6 . Abrams P , Andersson K-E , Buccafusco JJ , et al.

Muscarinic receptors: Their distribution and func-

tion in body systems, and the implications for

treating overactive bladder . Br J Pharmacol 2006 ;

148 : 565 – 578 .

7 . Hegde SS . Muscarinic receptors in the bladder:

From basic research to therapeutics . Br J Pharmacol

2006 ; 147 (Suppl. 2) : S80 – S87 .

8 . Peters SLM , Schmidt M , Michel MC . Rho kinase:

A target for treating urinary bladder dysfunction ?

Trends Pharmacol Sci 2006 ; 27 (9) : 492 – 497 .

9 . Andersson K-E , Arner A . Urinary bladder contrac-

tion and relaxation: Physiology and pathophysiol-

ogy . Physiol Rev 2004 ; 84 : 935 – 986 .

10 . Andersson K-E , Wein AJ . Pharmacology of the

lower urinary tract: Basis for current and future

treatments of urinary incontinence . Pharmacol Rev

2004 ; 56 (4) : 581 – 631 .

11 . Schneider T , Fetscher C , Krege S , Michel MC .

Signal transduction underlying carbachol-induced

contraction of human urinary bladder . J Pharmacol

Exp Ther 2004 ; 309 (3) : 1148 – 1153 .

12 . Matsui M , Motomura D , Karasawa H , et al. Multiple

functional defects in peripheral autonomic organs in

mice lacking muscarinic acetylcholine receptor gene

for the M 3 subtype . Proc Natl Acad Sci USA 2000 ;

97 (17) : 9579 – 9584 .

13 . Wuest M , Kaden S , Hakenberg OW , et al. Effect of

rilmakalim on detrusor contraction in the presence

and absence of urothelium . Naunyn-Schmiedeberg’s

Arch Pharmacol 2005 ; 372 (3) : 203 – 212 .

14 . Chess-Williams R . Muscarinic receptors of the uri-

nary bladder: Detrusor, urothelial and prejunctional .

Auton Autacoid Pharmacol 2002 ; 22 : 133 – 145 .

15 . Kono M , Nakamura Y , Ishiura Y , et al. Central mus-

carinic receptor subtypes regulating voiding in rats .

J Urol 2006 ; 175 (1) : 353 – 357 .

16 . Davila GW . Transdermal oxybutynin: A new

treatment for overactive bladder . Expert Opin

Pharmacother 2003 ; 4 (12) : 2315 – 2324 .

17 . Michel MC . A benefit-risk assessment of

extended-release oxybutynin . Drug Saf 2002 ;

25 (12) : 867 – 876 .

18 . Andersson K-E , Chapple CR . Oxybutynin and

the overactive bladder . World J Urol 2001 ;

19 (5) : 319 – 323 .

19 . Rovner ES , Wein AJ . Once-daily, extended-release

formulations of antimuscarinic agents in the treat-

ment of overactive bladder: A review . Eur Urol

2002 ; 41 (1) : 6 – 14 .

20 . Clemett D , Jarvis B . Tolterodine. A review of its use

in the treatment of overactive bladder . Drugs Aging

2001 ; 18 (4) : 277 – 304 .

21 . Madersbacher H , Mürtz G . Efficacy, tolerability

and safety profile of propiverine in the treatment of

the overactive bladder (non-neurogenic and neuro-

genic) . World J Urol 2001 ; 19 : 324 – 335 .

22 . Haab F . Darifenacin for the treatment of overactive

bladder . Women’s Health 2005 ; 1 (3) : 331 – 343 .

23 . Michel MC , de la Rosette JJMCH . Role of mus-

carinic receptor antagonists in urgency and nocturia .

BJU Int 2005 ; 96 (Suppl. 1) : 37 – 42 .

24 . Payne CK . Solifenacin in overactive bladder syn-

drome . Drugs 2006 ; 66 (2) : 175 – 190 .

25 . Rovner ES . Trospium chloride in the management of

overactive bladder . Drugs 2004 ; 64 (21) : 2433 – 2446 .

26 . Cole P . Fesoterodine, an advanced antimuscarinic

for the treatment of overactive bladder: A safety

update . Drugs Future 2004 ; 29 (7) : 715 – 720 .

27 . Guay DRP . Clinical pharmacokinetics of drugs used

to treat urge incontinence . Clin Pharmacokin 2003 ;

42 (14) : 1243 – 1285 .

28 . Wuest M , Weiss A , Waelbrock M , et al. Propiverine

and metabolites: Differences in binding to mus-

carinic receptors and in functional models of detru-

sor contraction . Naunyn-Schmiedeberg’s Arch

Pharmacol 2006 ; 374 (2) : 87 – 97 .

29 . Michel MC , Hegde SS . Treatment of the overactive

bladder syndrome with muscarinic receptor antagonists

– A matter of metabolites ? Naunyn-Schmiedeberg’s

Arch Pharmacol 2006 ; 374 (2) : 79 – 85 .

30 . Dmochowski RR , Nitti V , Staskin D , et al.

Transdermal oxybutynin in the treatment of adults

with overactive bladder: Combined results of two

randomized clinical trials . World J Urol 2005 ;

23 : 263 – 270 .

31 . Davila GW , Daugherty CA , Sanders SW . A short-

term, multicenter, randomized double-blind dose

titration study of the efficacy and anticholingeric side

effects of transdermal compared to immediate release

oral oxybutynin treatment of patients with urge uri-

nary incontinence . J Urol 2001 ; 166 (1) : 140 – 145 .

32 . Michel MC , Oelke M , Zinner N . Novel muscarinic

antagonists to treat incontinence and/or overactive

bladder . Drug Discov Today Ther Strateg 2005 ;

2 (1) : 1 – 6 .

33 . Herbison P , Hay-Smith J , Ellis G , Moore K .

Effectiveness of anticholinergic drugs com-

pared with placebo in the treatment of overac-

tive bladder: Systematic review . Br Med J 2003 ;

326 (7394) : 841 – 844 .

34 . Chapple CR , Wyndaele JJ , Nordling J , et al.

Tamsulosin, the first prostate-selective α 1A -adren-

oceptor antagonist. A meta-analysis of two rand-

omized, placebo-controlled multicentre studies in

15. Pharmacotherapy of Urgency Incontinence 199

patients with benign prostatic obstruction (sympto-

matic BPH) . Eur Urol 1996 ; 29 : 155 – 167 .

35 . Landis JR , Kaplan S , Swift S , Versi E . Efficacy of

antimuscarinic therapy for overactive bladder with

varying degrees of incontinence severity . J Urol

2004 ; 171 (2) : 752 – 756 .

36 . Freeman R , Hill S , Millard R , et al. Reduced percep-

tion of urgency in treatment of overactive bladder

with extended-release tolterodine . Obstet Gynecol

2003 ; 102 (3) : 605 – 611 .

37 . Cardozo L , Coyne KS , Versi E . Validation of the

urgency perception scale . BJU Int 2005 ; 95 : 591 – 596 .

38 . Chapple CR , Martinez-Garcia R , Selvaggi L , et al.

A comparison of the efficacy and tolerability of

solifenacin succinate and extended release tolterod-

ine at treating overactive bladder syndrome: results

of the STAR trial . Eur Urol 2005 ; 48 : 464 – 470 .

39 . DuBeau CE , Khullar V , Versi E . “Unblinding” in

randomized controlled drug trials for urinary incon-

tinence: Implications for assessing outcomes when

adverse effects are evident . Neurourol Urodyn 2005 ;

24 (1) : 13 – 20 .

40 . Chapple C , Khullar V , Gabriel Z , Dooley JA . The

effects of antimuscarinic treatments in overactive

bladder: A systematic review and meta-analysis . Eur

Urol 2005 ; 48 (1) : 5 – 26 .

41 . Yarker YE , Goa KL , Fitton A . Oxybutynin. A

review of its pharmacodynamic and pharmacoki-

netic properties, and its therapeutic use in detrusor

instability . Drugs Aging 1995 ; 6 (3) : 243 – 262 .

42 . Khullar V , Hill S , Laval K-U , et al. Treatment

of urge-predominant mixed urinary incontinence

with tolterodine extended release: A randomized,

placebo-controlled trial . Urology 2004 ; 64 (2) :

269 – 275 .

43 . Zinner N , Harnett M , Sabounjian L , et al. The overac-

tive bladder-symptom composite score: A composite

symptom score of toilet voids, urgency severity and

urge urinary incontinence in patients with overactive

bladder . J Urol 2005 ; 173 (5) : 1639 – 1643 .

44 . Cardozo L , Dixon A . Increased warning time with

darifenacin: A new concept in the management of

urinary urgency . J Urol 2005 ; 173 (4) : 1214 – 1218 .

45. Khullar V, Hill S, Solanki J, Barr A. Tolterodine

increases the urgency-free time interval: A sensory

or motor effect? http://www.continet.org/publica-

tions/2004/PDF/0172.PDF. 2004. 23–11–2005.

46 . Michel MC , Oelke M , Goepel M , et al. Relationships

among symptoms, bother, and treatment satisfaction

in overactive bladder patients . Neurourol Urodyn

2007 ; 26 : 190 – 195 .

47 . Dhein S , van Koppen CJ , Brodde O-E . Muscarinic

receptors in the mammalian heart . Pharmacol Res

2001 ; 44 (3) : 161 – 182 .

48 . Chapple CR , Abrams P . Comparison of darifenacin

and oxybutynin in patients with overactive bladder:

Assessment of ambulatory urodynamics and impact

on salivary flow . Eur Urol 2005 ; 48 (1) : 102 – 109 .

49 . Michel MC , Wetterauer U , Vogel M , de la Rosette

JJMCH . Cardiovascular safety of solifenacin in rou-

tine clinical use . Urology 2006 ; 68 : 71 – 72 .

50 . Ancelin ML , Artero S , Portet F , et al. Non-

degenerative mild cognitive impairment in elderly

people and use of anticholinergic drugs: Longitudinal

cohort study . Br Med J 2006 ; 332 : 455 – 458 .

51 . Homma Y , Koyama N . Minimally clinically impor-

tant change in urinary incontinence detected by a

quality of life assessment tool in overactive blad-

der syndrome with urge incontinence . Neurourol

Urodyn 2006 ; 25 (3) : 228 – 235 .

52 . Anderson RU , Mobley D , Blank B , et al. Once daily

controlled versus immediate release oxybutynin

chloride for urge urinary incontinence . J Urol 1999 ;

161 (6) : 1809 – 1812 .

53 . Versi E , Appell R , Mobley D , et al. Dry mouth

with conventional and controlled-release oxybu-

tynin in urinary incontinence . Obstet Gynecol 2000 ;

95 (5) : 718 – 721 .

54 . Madersbacher H , Halaska M , Voigt R , et al. A

placebo-controlled, multicentre study comparing

the tolerability and efficacy of propiverine and

oxybutynin in patients with urgency and urge incon-

tinence . BJU Int 1999 ; 84 (6) : 646 – 651 .

55 . Abrams P , Freeman R , Anderström C , Mattiasson

A . Tolterodine, a new antimuscarinic agent: As

effective but better tolerated than oxybutynin in

patients with overactive bladder . Br J Urol 1998 ;

81 : 801 – 810 .

56 . Malone-Lee J , Shaffu B , Anand C , Powell C .

Tolterodine: Superior tolerability than and compa-

rable efficacy to oxybutynin in individuals 50 years

old or older with overactive bladder: A randomized

controlled trial . J Urol 2001 ; 165 (5) : 1452 – 1456 .

57 . Homma Y , Paick JS , Lee JG , Kawabe K . Clinical

efficacy and tolerability of extended-release toltero-

dine and immediate-release oxybutynin in Japanese

and Korean subjects with an overactive bladder: A

randomized, placebo-controlled trial . BJU Int 2003 ;

92 : 741 – 747 .

58 . Madersbacher H , Stöhrer M , Richter R , et al.

Trospium chloride versus oxybutynin: A rand-

omized, double-blind, multicentre trial in the treat-

ment of detrusor hyperreflexia . Br J Urol 1995 ;

75 : 452 – 456 .

59 . Halaska M , Ralph G , Wiedemann A , et al. Controlled,

double-blind, multicentre clinical trial to investigate

long-term tolerability and efficacy of trospium chlo-

ride in patients with detrusor instability . World J

Urol 2003 ; 20 : 392 – 399 .

200 M.C. Michel

60 . Chancellor MB , Appell RA , Sathyan G , Gupta SK .

A comparison of the effects on saliva output of oxy-

butynin chloride and tolterodine tartrate . Clin Ther

2001 ; 23 (5) : 753 – 760 .

61 . Todorova A , Vonderheid-Guth B , Dimpfel W . Effects

of tolterodine, trospium chloride, and oxybutynin on

the central nervous system . J Clin Pharmacol 2001 ;

41 : 636 – 644 .

62 . Diefenbach K , Donath F , Maurer A , et al.

Randomised, double-blind study of the effects of

oxybutynin, tolterodine, trospium chloride and pla-

cebo on sleep in healthy young volunteers . Clin

Drug Invest 2003 ; 23 (6) : 395 – 404 .

63 . Diefenbach K , Arold G , Wollny A , et al. Effects on

sleep of anticholinergics used for overactive bladder

treatment in healthy volunteers aged >50 years . BJU

Int 2005 ; 95 : 346 – 349 .

64 . Altan-Yaycioglu R , Yaycioglu O , Akova YA , et al.

Ocular side-effects of tolterodine and oxybutynin, a

single-blind prospective randomized trial . Br J Clin

Pharmacol 2005 ; 59 (5) : 588 – 592 .

65 . Romanzi L , DelConte A , Kralidis G . Impact of

darifenacin versus tolterodine on incontinence epi-

sodes in patients with overactive bladder . Obstet

Gynecol 2005 ; 105 : 88S .

66 . Sussman D , Garely A . Treatment of overactive blad-

der with once-daily extended-release tolterodine

or oxybutynin: The antimuscarinic clinical effec-

tiveness trial (ACET) . Curr Med Res Opin 2002 ;

18 (4) : 177 – 184 .

67 . Diokno AC , Appell RA , Sand PK , et al. Prospective,

randomized, double-blind study of the efficacy and

tolerability of the extended-release formulations of

oxybutynin and tolterodine for overactive bladder:

Results of the OPERA trial . Mayo Clin Proc 2003 ;

78 : 687 – 695 .

68 . Sand PK , Miklos J , Ritter H , Appell R . A compari-

son of extended-release oxybutynin and tolterodine

for treatment of overactive bladder in women . Int

Urogynecol J 2004 ; 15 : 243 – 248 .

69 . Jünemann K-P , Halaska M , Rittstein T , et al.

Propiverine versus tolterodine: Efficacy and toler-

ability in patients with overactive bladder . Eur Urol

2005 ; 48 : 478 – 482 .

70 . Chapple CR , Arano P , Bosch JLHR , et al. Solifenacin

appears effective and well tolerated in patients with

symptomatic idiopathic detrusor overactivity in a

placebo- and tolterodine-controlled phase 2 dose-

finding study . BJU Int 2004 ; 93 (1) : 71 – 77 .

71 . Chapple CR , Rechberger T , Al-Shukri S , et al.

Randomized, double-blind placebo- and tolterodine-

controlled trial of the once-daily antimuscarinic

agent solifenacin in patients with symptomatic over-

active bladder . BJU Int 2004 ; 93 (3) : 303 – 310 .

72 . Appell RA , Sand P , Dmochowski R , et al. Prospective

randomized controlled trial of extended-release

oxybutynin chloride and tolterodine tartrate in

the treatment of overactive bladder: Results of

the OBJECT Study . Mayo Clin Proc 2001 ; 76 :

358 – 363 .

73 . Kay G , Crook T , Rekeda L , et al. Differential effects

of the antimuscarinic agents darifenacin and oxy-

butynin ER on memory in older subjects . Eur Urol

2006 ; 50 : 317 – 326 .

74 . Michel MC , Schneider T , Krege S , Goepel M . Do

gender or age affect the efficacy and safety of tol-

terodine ? J Urol 2002 ; 168 (3) : 1027 – 1031 .

75 . Chapple CR , Roehrborn CG . A shifted paradigm for

the further understanding, evaluation, and treatment

of lower urinary tract symptoms in men: Focus on

the bladder . Eur Urol 2006 ; 49 (4) : 651 – 659 .

76 . Schneider T , Hein P , Michel-Reher M , Michel

MC . Effects of ageing on muscarinic receptor

subtypes and function in rat urinary bladder .

Naunyn Schmiedebergs Arch Pharmacol 2005 ;

372 (1) : 71 – 78 .

77 . Zinner NR , Mattiasson A , Stanton SL . Efficacy,

safety, and tolerability of extended-release once-

daily tolterodine treatment for overactive bladder

in older versus younger patients . J Am Geriatr Soc

2002 ; 50 : 799 – 807 .

78 . Michel MC , Oelke M . Duloxetine in the treatment

of stress urinary incontinence . Womens Health

2005 ; 1 (3) : 345 – 358 .

79 . Michel MC , de la Rosette JJMCH , Piro M , Goepel

M . Does concomitant stress incontinence alter the

efficacy of tolterodine in patients with overactive

bladder ? J Urol 2004 ; 172 (2) : 601 – 604 .

80 . Bump RC , Norton PA , Zinner NR , Yalcin I . Mixed

urinary incontinence symptoms: Urodynamic find-

ings, incontinence severity, and treatment response .

Obstet Gynecol 2003 ; 102 (1) : 76 – 83 .

81 . Choo M-S , Song C , Kim JH , et al. Changes in overac-

tive bladder symptoms after discontinuation of success-

ful 3-month treatment with an antimuscarinic agent: A

prospective trial . J Urol 2005 ; 174 (1) : 201 – 204 .

82 . Sahai A , Khan MS , Arya M , et al. The overactive

bladder: Review of current pharmacotherapy in

adults. Part 2: Treatment options in cases refractory

to anticholinergics . Exp Opin Pharmacother 2006 ;

7 (5) : 529 – 538 .

83 . Sahai A , Khan M , Fowler CJ , Dasgupta

P . Botulinum toxin for the treatment of lower uri-

nary tract symptoms: A review . Neurourol Urodyn

2005 ; 24 (1) : 2 – 12 .

84 . Schurch B . Botulinum toxin for the manage-

ment of bladder dysfunction . Drugs 2006 ;

66 (10) : 1301 – 1318 .

15. Pharmacotherapy of Urgency Incontinence 201

85 . Michel MC , Vrydag W . α 1 -, α 2 -, and β -Adrenocep-

tors in the urinary bladder, urethra and prostate . Br J

Pharmacol 2006 ; 147 (Suppl. 2) : S88 – S119 .

86 . Avelino A , Cruz F . TRPV1 (vanilloid receptor) in

the urinary tract: Expression, function and clini-

cal applications . Naunyn Schmiedebergs Arch

Pharmacol 2006 ; 373 : 287 – 299 .

87 . Chapple CR , Patroneva A , Raines SR . Effect of an

ATP-sensitive potassium channel opener in subjects

with overactive bladder: A randomized, double-

blind, placebo-controlled study (ZD0947IL/0004) .

Eur Urol 2006 ; 49 : 879 – 886 .

88 . Sellers DJ , Chapple CR , Hay DPW , Chess-Williams R .

Depressed contractile responses to neurokinin A in idi-

opathic but not neurogenic overactive human detrusor

muscle . Eur Urol 2006 ; 49 (3) : 510 – 518 .

89 . Maruyama S , Oki T , Otsuka A , et al. Human mus-

carinic receptor binding characteristics of antimus-

carinic agents to treat overactive bladder . J Urol

2006 ; 175 (1) : 365 – 369 .

90 . Croom KF , Keating GM . Darifenacin in the treat-

ment of overactive bladder . Drugs Aging 2004 ;

21 (13) : 885 – 892 .

91 . van Kerrebroeck P , Kreder K , Jonas U , et al.

Tolterodine once-daily: Superior efficacy and tolera-

bility in the treatment of overactive bladder . Urology

2001 ; 57 (3) : 414 – 421 .

203

Background

Urinary urgency is defined by the International

Continence Society as a sudden and compelling

desire to pass urine that is difficult to defer [1] . In

both sexes the symptoms tend to increase as one

ages, but in women they are more often associ-

ated with urge urinary incontinence (UUI). The

overactive bladder syndrome (OAB) is defined as

urgency usually accompanied by urinary frequency

and nocturia, with or without UUI, and is widely

prevalent among women, affecting nearly 17% of

the overall female population [2] . Symptoms and

signs of urgency and UUI become more evident

after menopause, increasing with advancing age

[3] . It is estimated that the number of American

women aged 65 years and older will double in the

next 25 years to more than 40 million women by

2030 [4] , which will further increase the already

high cost of OAB to society and impairment of

quality of life for the individual [5] . Up to 39% of

new admissions to long-term care facilities report

having urinary incontinence, of which nearly two

thirds had objectively documented involuntary

bladder contractions [6] .

Effective first-line treatments for the OAB

syndrome are nonsurgical, such as pharmacother-

apy, behavioral therapy, and pelvic floor electri-

cal stimulation. Behavior modification includes

fluid and dietary changes, bladder drill entailing

scheduled voiding to restore normal cortical con-

trol over micturition, and exercises to strengthen

the pelvic floor muscles for patients with mixed

incontinence. The combination of these behavio-

ral treatment modalities may improve symptoms

by 75–80% [7] .

Antimuscarinic pharmacotherapy has become

the mainstay for persistent OAB symptoms [5] .

Goode et al. [8] found that objective bladder

capacity improved significantly with antimus-

carinic therapy compared to a group receiving

behavioral therapy [8] , but nocturia was better

treated by combined behavioral therapy and phar-

macological treatment [9] . There is evidence that

the placebo effect plays a major role in the treat-

ment of UUI [10] . Overall reduction in UUI with

placebo alone is believed to reach about 40% [11] .

As effective as antimuscarinic drugs may be, they

fail to adequately resolve symptoms in a substan-

tial number of cases, and their use is frequently

limited by side effects. The elderly are especially

susceptible to serious anticholinergic CNS side

effects such as significant memory impairment

and hallucinations [12] . Although significant CNS

reactions are not common, it generally is encour-

aged to avoid prescription of antimuscarinic med-

ications that cross the blood–brain barrier in the

elderly whenever possible [13] .

For nonresponders to these interventions, and

as first-line therapy for selected cases, a vari-

ety of nonpharmacological alternatives with

documented efficacy have been developed. The

potential benefits of complementary therapies are

that they have few, if any, adverse effects com-

pared with antimuscarinic pharmacotherapy [14] .

Acupuncture generally is well tolerated and is

Chapter 16

Alternative Therapies for Urinary Urgency

Incontinence: Acupuncture and Herbology

Sarit O. Aschkenazi and Peter K. Sand

204 S.O. Aschkenazi and P.K. Sand

an increasingly popular complement to standard

therapy for a variety of medical ailments and as

primary therapy for select cases.

Other modalities include pelvic floor electrical

stimulation (PFES) using vaginal or rectal probes

and neuromodulation. This involves either the

implantation of a sacral quadripolar electrode and

neurostimulator or transcutaneous posterior tibial

nerve stimulation in the office, which have been

offered for recalcitrant OAB symptoms. Medicare

reimbursement is available in the United States

for PFES and neuromodulation, which make them

affordable treatment options for women with OAB

symptoms [5] not responding to behavioral and

antimuscarinic pharmacotherapy. The mechanism

of action for PFES, for example, is suggested to

be stimulation of skeletal muscle contractions of

the levator ani and urethral and anal sphincters

with reflexive relaxation of the detrusor [5] . PFES

is reported to completely resolve UUI in 20% of

women and improve symptoms in 37% [15] .

Mechanisms of Action

for Acupuncture

The mechanisms of action for acupuncture have

been studied extensively to explain the its pain-

relieving effects. Controlled clinical trials dem-

onstrate that acupuncture has a clinically relevant

pain-relieving effect on certain forms of chronic

nociceptive pain [16] . One human study indicated

that acupuncture activates CNS endorphin systems,

decreasing pain sensation. Further support comes

from experimental studies in animals indicating

that acupuncture partially works through the endor-

phinergic system [17] . Urodynamic studies show

that opiate antagonists may increase intravesical

pressure, decrease bladder capacity, and lower ure-

thral closure pressure [18] . Central b -endorphins

are increased by acupuncture, potentially exerting

an inhibitory effect on the pontine micturition

center, leading to increased bladder storage. It has

been shown that there may be similarities between

the physiology of muscle training and acupuncture,

suggesting that acupuncture can simulate pelvic

floor muscle training [16] .

Peripheral circulation is increased with both

acupuncture and transcutaneous electrical nerve

stimulation in humans and animal models. Various

studies have demonstrated this effect in ischemic

skin flaps [19] , the parotid gland [20] in patients with

Raynaud’s syndrome [21] and in the uterine artery in

infertile women [22] . Elevated blood pressure can

be treated with electroacupuncture through central

sympathetic inhibition and evidence of increased

levels of b -endorphin in the cerebrospinal fluid

[16] . One study showed significant improvement in

menopausal hot flashes after a series of electroacu-

puncture treatments and suggested that acupuncture

is a viable alternative treatment of vasomotor symp-

toms in postmenopausal women [23] . Acupuncture

stimulation has been known to cause periurethral

EMG excitation [24] . Somatovisceral reflexes have

been studied and reviewed by Sato [25] . He demon-

strated that in anesthetized animals stimulation of

the perineal area induced bladder function changes

and sphincter activity that could be both excitatory

and inhibitory. The responses were segmentally

organized. The authors concluded that stimulation

of the skin, muscle, and/or joints that are innervated

by afferent nerve fibers entering the sacral spinal

cord segments could modulate bladder and sphincter

muscle reflex responses.

Reviewing the Evidence

Several studies have investigated the efficacy of

acupuncture in the treatment of lower urinary tract

complaints and chronic pelvic pain [26] . Stimulation

of the posterior tibial nerve has been shown to

activate the third sacral nerve roots that innervate

the pelvic floor. Chang was the first to report a

prospective sham-controlled study of posterior

tibial acupuncture (SP-6) for the treatment of OAB

symptoms [27] in 52 women. Bladder capacity in

the treated subjects increased in 88.5% compared

to 23.1% of control subjects. In women with initial

detrusor overactivity, 65% experienced complete

resolution of their symptoms compared to 23%

of controls. In the long-term follow-up of these

subjects [28] , which averaged 66.2 months, women

needed a mean of 4.8 repeat treatments to treat

recurrent symptoms. The authors’ conclusion was

that posterior tibial nerve acupuncture at SP-6 was

beneficial, but required repeated treatment sessions

for long-term symptom relief.

Recently, a well-planned, randomized, sham-

controlled trial was published on acupuncture

16. Alternative Therapies for Urinary Urgency Incontinence: Acupuncture and Herbology 205

treatment for OAB with UUI [29] . Eighty-seven

percent of the 85 women enrolled completed all

aspects of the study. Subjects were assigned ran-

domly to either receive acupuncture at SP-6 or a

sham acupuncture treatment designed to promote

relaxation. The primary endpoint was the number of

incontinence episodes on a 3-day diary after 4 weeks

of acupuncture treatment. Secondary endpoints were

urinary frequency, urgency, maximum cystometric

capacity, voided volumes, and quality of life metrics.

Subjects were evaluated before and after treatment by

urodynamic testing, a 3-day voiding diary, a urogeni-

tal distress inventory and incontinence impact ques-

tionnaire, and validated quality-of-life inventories.

In both the sham and treatment groups there were

significant decreases in incontinence episodes (40%

in the sham group and 59% in the active treatment

group). In the treatment group there was a significant

reduction in urinary frequency (14%) and urgency

(30%) and a 13% increase in both maximum voided

volume and cystometric capacity ( P = 0.01). Both

groups showed improved urinary distress inventory

and incontinence impact questionnaire scores, with

a 54% decrease in the treatment group and a 34%

decrease in the sham group that was better in the

active treatment group ( P < 0.001). The authors

concluded that in women with OAB symptoms, 4

weekly bladder-specific acupuncture treatments at

SP-6 caused significant symptom improvement com-

pared with sham acupuncture needle placement.

Philp et al. [30] performed a small, uncontrolled

study and found that lower extremity acupunc-

ture produced significant improvement in 77% of

20 women with idiopathic detrusor overactivity.

Acupuncture was used to treat 20 children with

nocturnal enuresis and detrusor overactivity [31] .

Nocturnal enuresis completely resolved in 11

(55%) subjects and improved in 7 (35%).

Yuksek et al. [32] aimed to assess the efficacy

of acupressure for treating nocturnal enuresis com-

pared with oxybutynin. Acupressure was adminis-

tered to 12 children by their parents, who had been

taught the technique. Pressure was applied at 16

acupuncture points including SP-6. Twelve control

children received 0.4 mg/kg oxybutynin. Parents

were asked to record incidences of bed-wetting and

subjects and/or their parents completed a questionnaire

15 days and 1, 3, and 6 months after the start of

treatment. Complete and partial responses after 6

months of treatment were seen in 83.3 and 16.7%,

respectively, of subjects treated with acupressure

and in 58.3 and 33.3%, respectively, of children

who received oxybutynin. They concluded that

nocturnal enuresis could be partially treated by

oxybutynin, but acupressure could be an alternative

nondrug therapy. Acupressure has the advantages

of being noninvasive, painless, and cost-effective.

Following the success of peripheral acupuncture

near the posterior tibial nerve, a commercially

available device for treatment of the OAB became

available.

The Stoller afferent nerve stimulator (SANS)

conveys a fine electrical current through a needle

electrode inserted adjacent to the nerve. The largest

observational study of this device [33] was per-

formed on only 15 patients with OAB. Complete

resolution of symptoms was noted in 46.7%, signifi-

cant improvement was noted in 20.0%, and a third

did not have any improvement. Urodynamic testing

showed posttreatment resolution of bladder insta-

bility in 76.9%. The maximum cystometric capac-

ity and bladder volume at normal desire to void

increased from 197 to 252 ml ( P = 0.008) and from

133 to 188 ml ( P = 0.002), respectively. Subjects

who responded had mean total daily urinary fre-

quency and nocturia decrease from 16.1 to 4.4

( P = 0.002) and 8.3 to 1.4 ( P = 0.002), respectively.

There were no adverse effects or complications

attributed to the electroacupuncture treatment.

Conclusion

It is important to be acquainted with acupuncture

as a complementary treatment modality for UUI

and OAB symptoms that are inadequately treated

with conventional pharmacotherapy and behavior

modification. After reviewing the literature avail-

able on this treatment modality, it seems that there

are preliminary data to indicate that acupuncture

may be regarded as a potential treatment option

with a safe treatment profile. The preliminary

accumulated data indicate that acupuncture may

provide short term but significantly effective symp-

tom relief. Additional research in larger study

cohorts should be performed to further investigate

what appears to be a safe treatment modality. It

may prove especially useful for women who do not

tolerate the side effects elicited by antimuscarinic

pharmacotherapy.

206 S.O. Aschkenazi and P.K. Sand

Herbology

Background

Many women turn to natural medicines for the

treatment of lower urinary tract symptoms when

conventional therapies fail to achieve sufficient

relief. There is some limited literature about herbal

medications that may ameliorate irritable bladder

symptoms. Most of the data are anecdotal and do

not rely on blinded, randomized controlled trials

but rather on descriptive case reports, case control-

led studies, and uncontrolled observational studies.

The paucity of data makes it impossible to provide

information that reliably indicates the degree of

efficacy and safety of herbal remedies; the mecha-

nism of action and active ingredients in these

herbal remedies also are poorly understood.

In this chapter we describe just a few of the myr-

iad of herbal products that are being used for the

treatment of lower urinary tract symptoms as well

as many unrelated ailments and symptoms. We will

review what is known about popular, folklore herbal

therapies that are purchased by patients “over-the-

counter.” The herbal treatments described here were

chosen because some evidence exists to suggest that

they may provide some treatment benefit. It should

be emphasized, however, that insufficient scientific

data are available to recommend these herbal treat-

ments as effective therapies.

Finally, a mention will be made of an FDA

approved treatment for lower urinary tract symp-

toms that consists of bladder installations with

dimethylsulfoxide (DMSO). This chemical,

when used intravesically, has been tested in well-

constructed research studies and is approved by

the FDA for the treatment of urinary urgency,

frequency, and nocturia associated with interstitial

cystitis. None of the treatments discussed should be

used during pregnancy and lactation.

Bladderwort

Bladderwort, or Utricularia vulgaris , is a plant

belonging to the Lentibulariaceae plant family

[34– 36] (Fig. 16.1 ).Species belonging to the

bladderwort plant family are carnivorous. The

plant grows in ponds and marshes. The stems

spread out widely and have threadlike leaves up

to 3 in long. The bladderwort does not root to the

ground: It is free-floating, with most of the plant

hanging in the water near the bottom. It floats

to the top when it is ready to flower. The flower

and the stalk can stretch up to 2feet above the

water. Attached to the leaves are tiny bladders, or

pouches, about 1/8 in. wide. The bladders have an

opening surrounded by tiny hairs. They release

slimy mucus, which smells sweet and lures small

insects such as mosquito larvae and water fleas.

When the insect gets close enough to touch the

hairs, the bladder sucks it inside. Once the insect

is trapped inside the bladder, the plant secretes

chemicals that break its prey, allowing nutrients

to be absorbed into the plant. Greater bladderwort

may have over 500 bladders on it and can eat

thousands of prey every day.

No data or references from clinical studies

were found to support the usage of bladderwort

in the treatment of lower urinary tract symp-

toms. However, anecdotally, bladderwort has been

described to have diuretic, antispasmodic, and anti-

inflammatory effects and has been used to treat

disorders of the lower urinary tract, especially con-

ditions involving complaints of urgency and UUI.

It also is used for kidney stones and urinary tract

Fig. 16.1. Bladderwort, Utricularia vulgaris

16. Alternative Therapies for Urinary Urgency Incontinence: Acupuncture and Herbology 207

infections. It had been used to promote weight loss

and to stimulate gall-bladder secretions. Topically,

bladderwort is used for burns and skin and mucous

membrane inflammation. It is prepared as a tea for

treatment of urinary symptoms.

There are insufficient data about the safety and

effectiveness of bladderwort. It should not be rec-

ommended for usage during pregnancy and lacta-

tion. Insufficient reliable information is available

about the possible mechanism of action and active

ingredients.

For its diuretic effects, bladderwort is adminis-

tered as a tea. There are no data on efficacy, and

therefore it is impossible to make a recommenda-

tion regarding the most suitable dose. The tea is

prepared by steeping 2 g of dried bladderwort leaf

in 100 ml of boiling water for 10–15 min and then

straining [35] . As a tea it also can be used as a

mouthwash. As a topical agent, it is recommended

for its anti-inflammatory effects, as well as applica-

tion in cleansers, cosmetic, and medical packs.

Pumpkin Seed Oil

Pumpkin seed oil also is known by its scientific

names, Cucumis pepo and Cucurbita galeottii ;

Cucurbita mammeata is a plant belonging to the

Cucurbitaceae plant family [35, 36] . Seeds of

autumn squash ( Cucurbita maxima ) and Canadian

pumpkin (crooked neck squash, Cucurbita mos-

chata ) have properties similar to Cucurbita pepo

seed [37] . It has been used for dysuria secondary to

bladder irritation and for the treatment of pyelone-

phritis. Pumpkin seed oil has been described as

exhibiting a diuretic effect. Animal research also

suggests that it might improve bladder and urethral

function [38] and bladder irritability. Another con-

stituent, cucurbitin, has antihelminthic effects and

has been used for treating intestinal worms. The

concentration of cucurbitin varies significantly

among Cucurbita species [36] . In men, it has been

described for the treatment of benign prostatic

hyperplasia.

There is insufficient reliable information avail-

able about the safety and effectiveness of pumpkin

seed oil. It should not be recommended for usage

during pregnancy and lactation. There are insuf-

ficient data about its interaction with other herbs

and or medications.

The roasted pumpkins seeds are considered to be

a delicious snack food, but it is recommended that

one not consume greater amounts than that found

in food or supplements. The therapeutic part of the

pumpkin is the seed. Pumpkin seeds contain fatty

oil, protein, and carbohydrates (Table 16.1 ) [39] .

Pumpkin seeds also are rich in carotenoids, includ-

ing lutein, carotene, and beta-carotene [36] . The

seed oil is rich in unsaturated fatty acids, including

47% linoleic acid, 29% oleic acid, 14% palmitic

acid, and 8% stearic acid. The oil also is rich in

vitamin E, including both gamma-tocopherol and

alpha-tocopherol (3 mg/100 g) [38] . The enzyme

acyl-coenzyme A oxidase (ACOX) is present in

the pumpkin seed. This enzyme catalyzes fatty acid

oxidation, specifically the oxidation of fatty acid

CoA esters with 4–10 carbon atoms [40] .

Bladderwrack

Bladderwrack, is known also by its scientific

names, Fucus vesiculosus and Ascophyllum nodo-

sum [33, 34] . Another Fucus species is black tang,

also know as bladder Fucus , blasentang, cutweed

Fucus , kelp, kelp-ware, knotted wrack, marine oak,

meereiche, quercus marina, rockweed, rockwrack,

schweintang, seawrack, tang, and varech. These

belong to the plant Fucaceae family(Fig. 16.2 ) .

Bladderwrack is used orally for genitourinary dis-

orders. It is described as being used for thyroid

disorders, iodine deficiency, lymphadenoid goiter,

myxedema, obesity, arthritis, rheumatism, arterio-

sclerosis, digestive disorders, heartburn, constipation,

bronchitis, emphysema, anxiety, and decreased immu-

nity and to increase energy. Topically, bladderwrack

Table 16.1. Nutritional content of raw pumpkin seeds .

Pumpkin seeds, raw 0.25 cup 186.65 calories

Nutrient Amount Nutrient density

Manganese 1.04 mg 5.0

Magnesium 184.58 mg 4.5

Phosphorus 405.03 mg 3.9

Tryptophan 0.11 g 3.3

Iron 5.16 mg 2.8

Copper 0.48 mg 2.3

Vitamin K 17.73 µ g 2.1

Zinc 2.57 mg 1.7

Protein 8.47 g 1.6

208 S.O. Aschkenazi and P.K. Sand

is used for skin diseases, burns, aging skin, and insect

bites. When used orally, bladderwrack can contain

high concentrations of iodine and heavy metals [41] .

Ingesting more than 150 m g of iodine per day can

cause hyperthyroidism or exacerbate existing hyper-

thyroidism. Heavy metal poisoning also has been

reported [42] .

Bladderwrack is likely unsafe during pregnancy

and lactation when used orally and should be avoided

[43] . There is insufficient information available

about the effectiveness of bladderwrack for any of

its described uses.

Bladderwrack is a brown seaweed. It may be

confused with bladderwort. The plant contains

high concentrations of iodine, which is present in

varying amounts. It also can contain heavy metals

such as arsenic and cadmium. Bladderwrack also is

a source of fiber, vitamin B12, and minerals such

as iron [43] . Preliminary clinical research suggests

bladderwrack might extend the menstrual cycle

and have antiestrogenic effects in premenopausal

women. It also may increase progesterone levels

[44] . Research suggests that extracts of bladder-

wrack also might have antibacterial, anti-HIV, and

antioxidant activity [45, 46] .

Fucoidan, a sulfated polysaccharide derivative

of bladderwrack, seems to be active against a

variety of viruses including the herpes virus, HIV,

and cytomegalovirus [47] . Other research suggests

that fucoidan might decrease fertility by prevent-

ing the binding of sperm to ova [48] and should

be avoided in women trying to conceive. In pre-

menopausal women, bladderwrack seems to lower

17- beta-estradiol levels and to increase progester-

one levels in a dose-dependent manner [49] .

Fucoidan also seems to stimulate the activity of

transforming growth actor (TGF)-beta to increase

fibroblast proliferation, which suggests it might be

useful for wound healing [50] . Available data sug-

gest that fucoidan also has anticoagulant, fibrino-

lytic, and antiplatelet adhesion effects [51] . Other

studies suggest that it might have antiangiogenic

and antineoplastic activity [52] . Topical adminis-

tration of bladderwrack extract might reduce skin

thickness and other signs of aging [52] .

Theoretically, concomitant use of bladderwrack

with herbs that affect platelet aggregation might

increase the risk of bleeding [52] . These herbs

include angelica, clove, danshen, fenugreek, fever-

few, garlic, ginger, ginkgo, Panax ginseng, pop-

lar, red clover, turmeric, and others. Bladderwrack

seems to have anticoagulant effects. It can increase

activated prothrombin time (aPTT) test results due

to the heparinlike activity of one of its constitu-

ents (12,797) [52] . Theoretically, taking bladder-

wrack with antiplatelet or anticoagulant drugs might

increase the risk of bruising and bleeding. These

drugs include aspirin; clopidogrel; nonsteroidal anti-

inflammatory drugs, such as diclofenac, ibuprofen,

naproxen, warfarin, and heparin; and low-molecular-

weight heparins such as dalteparin and enoxaparin.

Bladderwrack contains significant amounts of

iodine, which might exacerbate hyper- or hypothy-

roidism [53] with prolonged use. Bladderwrack

might increase serum TSH levels and might inter-

fere with the results of thyroid function tests using

radioactive iodine uptake [43] . Some medica-

tions can result in additive hypothyroid activity

when used concomitantly with bladderwrack and

may cause hypothyroidism [43] . These medi-

cations, which include methenamine mandelate,

methimazole, potassium iodide, and others, should

not be used concomitantly with bladderwrack.

Bladderwrack should be avoided in people sensi-

tive to iodine [43] .

There is no recommended typical dosage. In a

case report, heavy metal poisoning was described,

Fig. 16.2. Bladderwrack or Fucus vesiculosus. It is a

brown seaweed that grows along the northern coasts of

the Atlantic and Pacific oceans and Baltic sea

16. Alternative Therapies for Urinary Urgency Incontinence: Acupuncture and Herbology 209

where arsenic poisoning occurred with ingestion of

a contaminated kelp product [54] . Another case of

arsenic-related poisoning occurred with bladder-

wrack ingestion of 400 mg tid for 3 months which

resulted in renal tubular necrosis and interstitial

fibrosis [55] .

In another report, a 39-year-old obese woman

developed palpitations and syncope after taking

a weight loss supplement containing a combina-

tion of bladderwrack, dandelion, and boldo for 3

weeks. The patient was found to have a prolonged

QT-interval on ECG and frequent episodes of sus-

tained polymorphic ventricular tachycardia [56] . It

is not clear whether bladderwrack, another ingredi-

ent, or the combination of ingredients was respon-

sible for this adverse effect.

Teas

Teas have a long history of use, dating back to

China approximately 5,000 years ago. The tea

plant is native to Southeast Asia, with India and

Sri Lanka being the major producers of black and

green tea. Turkish traders reportedly introduced

tea to Western cultures in the sixth century. By the

eighteenth century, tea was commonly consumed

in England, where it became customary to drink tea

at 5 p.m. Black tea reached the Americas with the

first European settlers in 1492.

Tea varieties reflect the growing region, dis-

trict, form, and the processing method of the

leaves resulting in black, green, or oolong tea.

Drying the leaves of Camellia sinensis produces

the black tea [33, 34] . Teas long have been used

to treat a myriad of ailments. Teas have been

used to prevent kidney stones, to induce smooth

muscle relaxation, and as diuretics. Green,

black, and oolong tea are all derived from the

same plant, Camellia sinensis , which is a peren-

nial evergreen shrub. All teas are a source of

caffeine, a methylxanthine that relaxes smooth

muscle, promotes diuresis in the kidney, stimu-

lates the central nervous system, and increases

heart rate. One cup of tea contains approxi-

mately 50 mg of caffeine, compared to coffee,

which contains up to 175 mg of caffeine per

cup. Tea also contains polyphenols (catechins,

anthocyanins, phenolic acids), tannin, trace ele-

ments, and vitamins (Fig. 16.3 ) .

Chamomile

Chamomile is a common tea that has an applelike

smell and taste [33, 34] . The name “chamomile” is

derived from the Greek kamai melon, which means

ground apple. It has become a popular home remedy

for many conditions. Chamomile most often is used

for bladder irritation, vaginitis, the common cold,

diarrhea, ulcers, and in extreme cases oral mucositis.

It exerts an effect as a smooth muscle relaxant and

provides relief for skin and stomach discomfort .

However, there is not enough scientific evidence

to recommend chamomile for any health problems.

Although many uses for this tea have been tested in

humans and other animals, safety and efficacy have

not always been proven. It is crucial to emphasize

that some of the conditions for which it is used

can lead to significant morbidity if not effectively

treated and patients should be evaluated by a quali-

fied health care provider.

It is recommended not to consume chamomile tea

for 2weeks before surgery, dental, or diagnostic pro-

cedures that entail a bleeding risk. It also is advised

to use chamomile sparingly if driving or operating

machinery. It should be avoided during pregnancy

and lactation because of the paucity of information

regarding its effect on the fetus and neonate.

Fig. 16.3. Tea shrub, Camellia sinensis. Tea is made from

the dried leaves of Camellia sinensis , an evergreen shrub.

Green tea, black tea, and oolong tea are all made from

the same plant

210 S.O. Aschkenazi and P.K. Sand

There is a cross-sensitivity with related plants

such as aster, chrysanthemum, mugwort, ragweed,

or ragwort, and people allergic to these plants

should avoid chamomile. Possible adverse effects

of this tea include allergic conjunctivitis, skin

rash, vomiting when consumed in large quanti-

ties, breathing difficulties, blood pressure changes,

easy bruising, confusion, drowsiness, and pruri-

tis. Adverse reactions have been described with

concomitant use of alcohol, barbiturates, benzo-

diazepines, anticoagulants, raloxifene, tamoxifen,

sedatives, narcotics, and herbs or supplements with

similar effects.

Chamomile dosing and route of administration

have been extremely varied. For adults (18 years

and older) use has been through consuming tea,

infusions, liquid extracts, tinctures, capsules, tab-

lets, pastes, plasters, ointments, douches, mouth

rinses, and alcoholic extracts. There are not enough

scientific data available to recommend the usage

for children and adolescents younger than 18.

Sweet Sumach

Sweet sumach also is known as aromatic sumac,

fragrant sumac, polecatbush , skunkbrush and

squawbush. Its scientific name is Rhus aromatica ,

belonging to the family of Anacardiaceae. Sweet

sumach belongs to the same family as poison ivy

and can cause similar dermal reactions [57] . This

plant has been used orally for urinary urgency, fre-

quency, urinary incontinence, and nocturnal enu-

resis. The applicable part of sweet sumach is the

root bark. This species of sumach, usually growing

about 4 ft high, was introduced into England as an

ornamental shrub in 1759. The bark is used in tan-

ning. The wood exudes a peculiar odor and is used

by the Native-Americans in Arizona, California,

and New Mexico for making baskets (Fig. 16.4 ) .

There is very little scientific information about

this product and insufficient reliable information

available about the safety and effectiveness of

sweet sumach. It should be avoided during preg-

nancy and lactation.

Not enough reliable information is available

regarding the possible mechanism of action and

active ingredients. Adverse reaction to topical

application of sweet sumach can cause contact

allergic dermatitis in susceptible individuals [1] .

Goldenrod

Goldenrod also is known as Aaron’s rod, Canadian

goldenrod, early goldenrod, european goldenrod and

woundwort. Its scientific names are Solidago vir-

gaurea (European goldenrod), Solidago canadensis

(Canadian goldenrod), and Solidago gigantea (early

goldenrod). The goldenrods belong to the family

of Asteraceae/Compositae. The pharmaceutically

active part of goldenrod is the above-ground part of

the plant. Goldenrods are very common wildflow-

ers throughout Europe and North America. Over 50

species of goldenrod are known and most of them

are very similar and difficult to tell apart. All gold-

enrods are late bloomers, flowering in late summer

into the fall. Most species have spectacular dis-

plays of bright yellow flowers, which are clustered

on long stalks. Most goldenrods have long, narrow

leaves. Some species’ leaves have smooth edges

and some are toothed. Goldenrods vary in height,

with 6 feet being the tallest ( Solidago gigantean) .

Some, such as Solidago Canadensis, have pleasant

Fig. 16.4. Sweet sumach also known as Rhus aromatica

16. Alternative Therapies for Urinary Urgency Incontinence: Acupuncture and Herbology 211

odors. Goldenrods are extremely important to other

wildlife, especially insects (Fig. 16.5 ). .

Goldenrod is classified as a diuretic but without

increased electrolyte excretion [58] . The anti-

inflammatory and aquaretic effects of goldenrod

may be due to their saponin and flavonoid con-

stituents. Goldenrod also might have bacteriostatic

activity. This plant is used orally as a diuretic. It

is thought to have anti-inflammatory and antispas-

modic effects. It also is used orally to alleviate

symptoms of gout, arthritis, eczema, and other skin

conditions. Goldenrod also is used for acute exacer-

bations of pulmonary tuberculosis, diabetes melli-

tus, hepatomegaly, hemorrhoids, internal bleeding,

allergic rhinitis, asthma, and prostatic hypertrophy.

It is recommended that it be taken with copious

amounts of fluids to increase urine flow in order to

treat and prevent lower urinary tract disorders, such

as urinary tract infections (UTIs) [59] , urinary cal-

culi, and urolithiasis. Topically, goldenrod is used

as a mouth rinse for gingival inflammation and

pharyngitis and to improve wound healing. There

is insufficient reliable information available about

the safety and effectiveness of goldenrod, and it

should be avoided in pregnancy and lactation.

Orally, goldenrod may cause an allergic reaction

in individuals sensitive to the Asteraceae/Compositae

family. Some members of this family include rag-

weed, chrysanthemums, marigolds, and daisies.

Its use is contraindicated with concomitant con-

gestive heart failure or renal impairment because

of the considerable fluid shifts that it may cause.

Theoretically, goldenrod might increase sodium

retention and worsen hypertension [59] .

There is not enough evidence to recommend dos-

ages and how much should be administered. Attention

should be given to avoid confusion with mullein

( Verbascum densiflorum ; also referred to as gold-

enrod). Early goldenrod, European goldenrod, and

Canadian goldenrod are used interchangeably.

Dimethylsulfoxide

Dimethylsulfoxide is an industrial solvent, which

also is known as dimethyl sulfoxide, dimethyl sul-

phoxide, dimethylis sulfoxidum, methyl sulphox-

ide, NSC-763, SQ-9453, and sulphinybismethane.

It is FDA approved for intravesical instillation to

treat urinary frequency, urgency, and nocturia in

interstitial cystitis patients.

Orally, DMSO has been used for the man-

agement of amyloidosis and related symptoms.

Topically, DMSO has been used to decrease pain

and speed the healing of wounds and burns. It

has been reported to treat acute musculoskeletal

injuries, headache, inflammation, arthritis, tic dou-

loureux, cataracts, glaucoma, retinal degeneration,

bunions, calluses, fungus toenails, asthma, and

cancer, and to flatten raised keloid scars.. It also

used topically to prevent tissue necrosis after

extravasation with antineoplastic agents, to treat

osteoarthritis, rheumatoid arthritis, scleroderma,

and amyloidosis.

Topically it also has been used for reducing

skin flap ischemia following surgery, for complex

regional pain syndromes, as a vehicle in combina-

tion with idoxuridine to decrease the development

of inflammatory reactions and lesions associated

with herpes zoster infection, and to decrease

the pain associated with postherpetic neuralgia.

Intravenously, DMSO also has been used to man-

age symptoms associated with secondary amy-

loidosis and to lower intracranial hypertension.

An aqueous 50% solution of DMSO is FDA

approved for intravesical use in the treatment of

interstitial cystitis [58] , and it also seems to decrease

symptoms associated with chronic inflammatory

bladder disease [60] .

DMSO may be unsafe when used topically,

especially when industrial-grade DMSO is used

for self-treatment. This is not of the same quality

of that used for medical purposes, since it may

contain impurities. DMSO readily penetrates the

Fig. 16.5 . Goldenrod

212 S.O. Aschkenazi and P.K. Sand

skin and enhances the absorption of impurities

and other substances, which may be hazardous to

health [61] . DMSO also is reported to decrease the

pain associated with postherpetic neuralgia [62] .

Trigeminal herpes zoster has been noted to be

most responsive [63] . There is insufficient reliable

information available about the DMSO’s effective-

ness for its other suggested applications. Due to

the paucity of reliable information available, it is

recommended to avoid using DMSO in pregnancy

and lactation.

The mechanism of action of DMSO is par-

tially understood. DMSO is a highly polar solvent,

which penetrates the skin easily when concentrated

(80–100%) and has a large volume of distribution

after administration [64] . It metabolizes to dimethyl

sulfone and dimethyl sulfide, the latter causing a

strong odor. DMSO’s analgesic effect is attributed to

slowing the conduction of capsaicin-sensitive nerve

fibers [65] . During bladder instillations, it might

cause the release of nitrogen oxide from afferent

neurons [66] , which acts as a peripheral neurotrans-

mitter in the function of the lower urinary tract.

DMSO also is associated with mast cell degranula-

tion, accounting for the occurrence of eosinophilia

and hypersensitivity reactions with its use.

DMSO may selectively dissolve collagen fibers,

sparing to a large extent the elastic fibers [67] . It

is thought to stabilize lysosomal membranes and

cause vasodilatation. Its anti-inflammatory, cryo-

preservative, cryoprotective, anti-ischemic, and

possible radioprotective activity [68] are attributed

to the presence of a free hydroxyl radical with

scavenging properties

DMSO exerts antimicrobial activity [68] by

altering RNA structures essential for bacterial

protein synthesis. It inhibits acetyl-cholinesterase

activity, causing lowered cardiovascular vagal

effects and increased response to nerve and muscle

stimulation of skeletal, smooth, and cardiac muscle

[68] . In vitro, DMSO increases levels of prostag-

landin-E1 (PGE1) and cyclic-AMP, which reduce

platelet aggregation, and decrease fibrinogen and

thromboxane A2 secretion, all of which protect

against ischemic injury [69] .

Intravesical instillation of DMSO may cause

adverse reactions such as hematuria due to a

chemical cystitis, bladder discomfort, or detrusor

overactivity [70] . A garliclike odor may emanate

orally and transdermally with all routes of admin-

istration, which can be very bothersome and lead to

discontinuation of treatment. Rare hypersensitivity

reactions leading to anaphylaxis can happen with

all application modes. Due to the high absorption

of DMSO, an extensive list of systemic adverse

effects has been described with topical use, includ-

ing sedation, headache, dizziness, drowsiness,

nausea, vomiting, diarrhea, constipation, anorexia,

erythema, pruritus, burning, blistering, drying and

scaling skin, dry or sore throat, cough, dry nasal

passages, dyspnea, worsening of bronchial asthma,

and an influenzalike syndrome [71– 75] .

In addition to the adverse effects listed above,

intravenous administration has the potential of

causing fluid overload, electrolyte disturbances,

especially hypernatremia, increased serum osmo-

lality and creatinine, and a diuresis. Hematologic

changes include hemolysis with hematuria and

eosinophilia. Reported, but rare, central nervous

system side effects include confusion, lethargy,

disorientation, agitation, dysarthria, hypoactive

reflexes, decreased consciousness, and encepha-

lopathy. Cardiovascular symptoms include vasodi-

lation, hypotension, chest pain, sinus tachycardia,

and weakness [76, 77] , DMSO may potentiate the

action of numerous medications in animals [67] .

Topical DMSO can increase insulin effect and

should be used with extreme caution in patients

with diabetes mellitus [65] . Elevated serum osmo-

lality can occur in patients with increased intrac-

ranial pressure. Due to reported hepatotoxicity

with DMSO intravenous administration, it is rec-

ommended to check liver and renal function tests

every 6 months [70] .

References

1. Abrams P , Cardozo L , Fall M et al. The standardiza-

tion of terminology in lower urinary tract function:

Report from the Standardization Sub-committee

of the International Continence Society. Neurouol

Urodyn 2002; 21: 167 – 178.

2 . Stewart W , Herzog R , Wein A , et al. The prevalence

and impact of overactive bladder in the US: Results

from the NOBLE program . Neurourol Urodyn

2001 ; 20 : 406 – 408 .

3 . Stewart WF , Van Rooyen JB , Cundiff GW , et al.

Prevalence and burden of overactive bladder in the

United States . World J Urol 2003 ; 20 : 327 – 336 .

4. US Census Bureau. US interim projections by age,

sex, race, and Hispanic origin. Available at: http://

16. Alternative Therapies for Urinary Urgency Incontinence: Acupuncture and Herbology 213

www.census.gov/ipc/www/usinterimproj , November

2006–12–05.

5. Fantl JA , Newman DK , Colling J , et al. Urinary incon-

tinence in adults: Acute and chronic management

1996. Rockville, MD: US Department of Health and

Human Services .

6 . Ouslander J , Leach G , Abelson S , et al. Simple

versus multichannel cystometry in the evaluation of

bladder function in an incontinent geriatric popula-

tion . J Urol 1988 ; 140 : 1482 – 1486 .

7 . Burgio KL, Locher JL, Goodle PS, et al. Behavioral

vs. drug treatment for urge urinary incontinence in

older women: A randomized controlled trial. J Am

Geriatr Soc 2000;48:370–374 .

8 . Goode PS , Burgio KL , Locher JL , et al. Urodynamic

changes associated with behavioral and frug treat-

ment of urge incontinence in olderwomen . J Am

Geriatr Soc 2002 ; 50 : 808 – 816 .

9. Martin C. Michel, Jean J.M.C.H. de la Rosette.

Role of muscarinic receptor antagonists in urgency

and nocturia. BJU Int 2005;96(Suppl. 1):37–42.

10 . Khullar V , Hill S , Laval KU , et al. Treatment of

urge-predominant mixed urinary incontinence with

tolterodine extended release: A randomized pla-

cebo-controlled trial . Urology, 2004 ; 64 : 269 – 274 .

11 . Teunissen TA , de Jonge A , van Weel C , et al.

Treating urinary incontinence in the elderly—Con-

servative therapies that work: A systematic review . J

Fam Pract 2004 ; 53 : 25 – 30 .

12 . Tsao J . Transient memory impairment and hallu-

cinations associated with tolterodine use . N Eng J

Med 2003 ; 349 : 2274 – 2275 .

13 . Beers M . Explicit criteria for determining poten-

tially inappropriate medication use by the elderly:

An update . Arch Intern Med 1997 ; 157 : 1531 – 1536 .

14 . Flaherty JH , Takahashi R . The use of comple-

mentary and alternative medical therapies among

older persons around the world . Clin Geriatr Med

2004 ; 20 : 179 – 200 .

15 . Appell RA . Electrical stimulation for the treatment

of urinary incontinence . Urology 1998 ; 51 : S24 – S26 .

16 . Bergström K , Christer P , Carlsson O , et al. Improvement

of urge- and mixed-type incontinence after acupunc-

ture treatment among elderly women – A pilot study . J

Auton Nerv Syst 2000 ; 79 (2–3) : 173 – 180 .

17 . Andersson S , Lundeberg T . Acupuncture—From

empiricism to science: Functional background to acu-

puncture effects in pain and disease . Med Hypotheses

1995 ; 45 (3) : 271 – 281 .

18 . Chai TC , Steers WD . Neurophysiology of micturi-

tion and continence in women . Int Urogynecol J

Pelvic Floor Dysfunct 1997 ; 8 (2) : 85 – 97 .

19 . Jansen G , Lundeberg T , Kjartansson J , et al.

Acupuncture and sensory neuropeptides increase

cutaneous blood flow in rats . Neurosci Lett

1989 ; 97 (3) : 305 – 309 .

20 . Blom M , Lundeberg T , Dawidson I , et al. Effects on

local blood flux of acupuncture stimulation used to

treat xerostomia in patients suffering from Sjogren’s

syndrome . J Oral Rehabil 1993 ; 20 (5) : 541 – 548 .

21 . Appiah R , Hiller S , Caspary L , et al. Treatment of pri-

mary Raynaud’s syndrome with traditional Chinese

acupuncture . J Intern Med 1997 ; 241 (2) : 119 – 124 .

22 . Stener-Victorin E , Waldenstrom U , Andersson SA ,

et al. Reduction of blood flow impedance in the

uterine arteries of infertile women with electro-

acupuncture . Hum Reprod 1996 ; 11 (6) : 1314 – 1317 .

23 . Wyon Y , Wijma K , Nedstrand E , et al. A compari-

son of acupuncture and oral estradiol treatment of

vasomotor symptoms in postmenopausal women .

Climacteric 2004 ; 7 (2) : 153 – 164 .

24 . Morrison JF , Sato A , Sato Y , et al. Long-

lasting facilitation and depression of periure-

thral skeletal muscle following acupuncture-like

stimulation in anesthetized rats . Neurosci Res

1995 ; 23 (2) : 159 – 169 .

25 . Sato A . Somatovisceral reflexes . J Manipulative

Physiol Ther 1995 ; 18 (9) : 597 – 602 .

26. Dale R . The origins and future of acupuncture. Am

J Acupunct 1982; 10: 101 – 120.

27 . Chang PL . Urodynamic studies in acupuncture for

women with frequency, urgency and dysuria . J Urol

1988 ; 140 : 563 – 566 .

28 . Chang PL , Wu CJ , Huang MH . Long-term outcome

of acupuncture in women with frequency, urgency and

dysuria . Am J Chin Med 1993 ; 21 (3–4) : 231 – 236 .

29 . Emmons SL , Otto L . Acupuncture for overac-

tive bladder: A randomized controlled trial . Obstet

Gynecol 2005 ; 1066 (1) : 138 – 143 .

30 . Philp T , Shah PJR , Worth PHL . Acupuncture in

the treatment of bladder instability . Br J Urol

1988 ; 61 : 490 – 493 .

31 . Minni B , Capozza N , Creti G , et al. Bladder insta-

bility and enuresis treated by acupuncture and elec-

tro-therapeutics: Early urodynamic observations .

Acupunct Electrother Res 1990;15 (1) :19–25.

32. Yuksek . MS . Erdem . AF . Atalay C , et al. Acupressure

versus oxybutynin in the treatment of enuresis. J Int

Med Res 2003; 31 (6) : 552 – 556.

33 . Klingler HC , Pycha A , Schmidbauer J , et al. Use

of peripheral neuromodulation of the S3 region for

treatment of detrusor overactivity: A urodynamic-

based study . Urology 2000 ; 56 (5) : 766 – 771 .

34. http://www.naturaldatabase.com.

35. http://www.naturalstandard.com.

36. Gruenwald J , Brendler T , Jaenicke C . PDR for herbal

medicines, 1st ed . Montvale, NJ: Medical Economics

Company, 1998.

214 S.O. Aschkenazi and P.K. Sand

37. Foster S , Tyler VE , Tyler’s honest herbal, 4th ed.

Binghamton, NY: Haworth Herbal Press, 1999.

38 . Zhang X , Ouyang JZ , Zhang YS , et al. Effect of the

extracts of pumpkin seeds on the urodynamics of

rabbits: An experimental study . J Tongji Med Univ

1994 ; 14 : 235 – 238 .

39 . Younis YM , Ghirmay S , al-Shihry SS . African

Cucurbita pepo L.: Properties of seed and variability

in fatty acid composition of seed oil . Phytochemistry

2000 ; 54 : 71 – 75 .

40 . De Bellis L , Gonzali S , Alpi A , et al. Purification

and characterization of a novel pumpkin short-chain

acyl-coenzyme A oxidase with structural similarity

to acyl-coenzyme A dehydrogenases . Plant Physiol

2000 ; 123 : 327 – 334 .

41 . Baker DH . Iodine toxicity and its amelioration . Exp

Biol Med (Maywood) 2004 ; 229 : 473 – 478 .

42 . Pye KG , Kelsey SM , House IM , et al. Severe

dyserythropoeisis and autoimmune thrombocyto-

penia associated with ingestion of kelp supplement .

Lancet 1992 ; 339 : 1540 .

43. Phaneuf D, Cote I, Dumas P, et al. Evaluation of the

contamination of marine algae (seaweed) from the

St. Lawrence River and likely to be consumed by

humans. Environ Res 1999; 80: S175 – S182.

44 . Skibola CF . The effect of Fucus vesiculosus , an edi-

ble brown seaweed, upon menstrual cycle length and

hormonal status in three pre-menopausal women:

A case report . BMC Complement Altern Med

2004 ; 4 : 10 .

45 . Ruperez P , Ahrazem O , Leal JA . Potential antioxi-

dant capacity of sulfated polysaccharides from the

edible marine brown seaweed Fucus vesiculosus .

J Agric Food Chem 2002 ; 50 : 840 – 845 .

46 . Beress A , Wassermann O , Tahhan S , et al. A new

procedure for the isolation of anti-HIV compounds

(polysaccharides and polyphenols) from the marine

alga Fucus vesiculosus . J Nat Prod 1993 ; 56 : 478 – 488 .

47 . Baba M , Snoeck R , Pauwels R , et al. Sulfated

polysaccharides are potent and selective inhibitors of

various enveloped viruses, including herpes simplex

virus, cytomegalovirus, vesicular stomatitis virus,

and human immunodeficiency virus . Antimicrob

Agents Chemother 1988 ; 32 : 1742 – 1745 .

48 . Patankar MS , Oehninger S , Barnett T , et al. A

revised structure for fucoidan may explain

some of its biological activities . J Biol Chem

1993 ; 268 : 21770 – 21776 .

49 . Skibola CF . The effect of Fucus vesiculosus , an edi-

ble brown seaweed, upon menstrual cycle length and

hormonal status in three pre-menopausal women:

A case report . BMC Complement Altern Med

2004 ; 4 : 10 .

50 . O’Leary R , Rerek M , Wood EJ . Fucoidan modulates

the effect of transforming growth factor (TGF)-

beta1 on fibroblast proliferation and wound repopu-

lation in in vitro models of dermal wound repair .

Biol Pharm Bull 2004 ; 27 : 266 – 270 .

51 . Durig J , Bruhn T , Zurborn KH , et al. Anticoagulant

fucoidan fractions from Fucus vesiculosus induce

platelet activation in vitro . Thromb Res 1997 ; 85 :

479 – 491 .

52 . Koyanagi S , Tanigawa N , Nakagawa H , et al.

Oversulfation of fucoidan enhances its anti-ang-

iogenic and antitumor activities . Biochem Pharmacol

2003 ; 65 : 173 – 179 .

53. Food and Nutrition Board, Institute of Medicine.

Dietary reference intakes for vitamin A, vitamin

K, arsenic, boron, chromium, copper, iodine, iron,

manganese, molybdenum, nickel, silicon, vana-

dium, and zinc. Washington, DC: National Academy

Press, 2002. Available at: http://www.nap.edu/

books/0309072794/html/.

54 . Pye KG , Kelsey SM , House IM , et al. Severe

dyserythropoeisis and autoimmune thrombocyto-

penia associated with ingestion of kelp supplement .

Lancet 1992 ; 339 : 1540 .

55 . Conz PA , La Greca G , Benedetti P , et al. Fucus

vesiculosus : A nephrotoxic alga? Nephrol Dial

Transplant 1998; 13: 526 – 527.

56 . Agarwal SC , Crook JR , Pepper CB . Herbal remedies

– How safe are they? A case report of polymor-

phic ventricular tachycardia/ventricular fibrillation

induced by herbal medication used for obesity . Int

J Cardiol 2006 ; 106 : 260 – 261 .

57. Foster S , Duke JA . The Peterson field guide to medic-

inal plants: Eastern and Central North America .

Boston, MA: Houghton Miffin, 1990.

58. Robbers JE , Tyler VE . Tyler’s herbs of choice: The

therapeutic use of phytomedicinals . New York, NY:

The Haworth Herbal Press, 1999.

59 . Wichtl MW . Herbal drugs and phytopharmaceuti-

cals. Bisset NM ,ed. Stuttgart : Medpharm GmbH

Scientific Publishers, 1994.

60 . Barker SB , Matthews PN , Philip PF , et al. Prospective

study of intravesical dimethyl sulphoxide in the

treatment of chronic inflammatory bladder disease .

Br J Urol 1987 ; 59 (2) : 142 – 144 .

61 . Prior D , Mitchell A , Nebauer M , et al. Oncology

nurses’ experience of dimethyl sulfoxide odor . Cancer

Nurs 2000 ; 23 : 134 – 140 .

62 . MacCallum FO , Juel-Jensen BE . Herpes simplex

virus skin infection in man treated with idoxuridine

in dimethyl sulphoxide. Results of double-blind

controlled trial . Br Med J 1966; 2 : 805 – 807.

63 . Wildenhoff KE , Esmann V , Ipsen J , et al. Treatment

of trigeminal and thoracic zoster with idoxuridine .

Scand J Infect Dis 1981 ; 13 : 257 – 262 .

64 . Brayton CF . Dimethyl sulfoxide (DMSO): A review .

Cornell Vet 1986 ; 76 : 61 – 90 .

16. Alternative Therapies for Urinary Urgency Incontinence: Acupuncture and Herbology 215

65 . Evans MS , Reid KH , Sharp JB . Jr. Dimethylsuloxide

(DMSO) blocks conduction in peripheral nerve C

fibers: a possible mechanism of analgesia . Neurosci

Lett 1993 ; 150 (2) : 145 – 148 .

66 . Birder LA , Kanai AJ , de Groat WC . DMSO: Effect

on bladder afferent neurons and nitric oxide release .

J Urol 1997 ; 158 : 1989 – 1995 .

67 . Jacob SW , Herschler R . Pharmacology of DMSO .

Cryobiology 1986 ; 23 : 14 – 27 .

68 . Brayton CF . Dimethyl sulfoxide (DMSO): A review .

Cornell Vet 1986 ; 76 : 61 – 90 .

69 . de la Torre JC . Role of dimethyl sulfoxide in pros-

taglandin-thromboxane and platelet systems after

cerebral ischemia . Ann N Y Acad Sci 1983 ; 411 :

293 – 308 .

70. Martindale W. Martindale the extra pharmacopoeia .

London: Pharmaceutical Press, 1999.

71 . Rosenstein ED . Topical agents in the treatment of

rheumatic disorders . Rheum Dis Clin North Am

1999 ; 25 : 899 – 918 .

72 . Merlini G . Treatment of primary amyloidosis . Semin

Hematol 1995 ; 32 : 60 – 79

73 . Trice JM , Pinals RS . Dimethyl sulfoxide: A review

of its use in the rheumatic disorders . Semin Arthritis

Rheum 1985 ; 15 : 45 – 60 .

74 . Juel Jensen BE , MacCallum FO , Mackenzie AM,

et al. Treatment of zoster with idoxuridine in

dimethyl sulphoxide. Results of two double-blind

controlled trials. Br Med J 1970; 4: 776 – 780 .

75 . Williams HJ , Furst DE , Dahl SL , et al. Double-

blind, multicenter controlled trial comparing topical

dimethyl sulfoxide and normal saline for treatment

of hand ulcers in patients with systemic sclerosis .

Arthritis Rheum 1985 ; 28 : 308 – 314 .

76 . Marshall LF , Camp PE , Bowers SA . Dimethyl sulfoxide

for the treatment of intracranial hypertension: A pre-

liminary trial . Neurosurg 1984 ; 14 (6) : 659 – 663 .

77 . Wolf P , Simon M . Dimethyl sulphoxide (DMSO)

induced serum hyperosmolality . Clin Biochem

1983 ; 16 (4) : 261 – 262 .

217

Introduction

Chronic types of lower urinary tract dysfunction,

including urgency incontinence (UI) and urgency–

frequency (UF) and nonobstructive urinary retention

(UR), still present a therapeutic challenge. Most

patients initially are treated with conservative thera-

pies including bladder retraining, pelvic floor exer-

cises, and biofeedback. In the majority of patients

this standard regimen is supported with pharmaco-

logical therapy (anticholinergics). However, approx-

imately 40% either do not achieve an acceptable

level of therapeutic benefit or remain completely

refractory to treatment. Alternative surgical pro-

cedures such as bladder transsection, transvesical

phenol injection of the pelvic plexus, augmentation

cystoplasty, and even urinary diversion have been

advocated for these chronic conditions. However,

these procedures have variable efficacy and have

been associated with significant morbidity and risk.

Therefore, research into the use of electrical current

for the treatment of lower urinary tract dysfunc-

tion has been initiated.In 1878, Saxtorph reported

intravesical electrostimulation in patients with an

acontractile bladder and complete urinary retention

[50] . He inserted a special catheter with a metal

electrode transurethrally. Years later, Ascoli and

Katona applied electrostimulation in patients with

chronic neurogenic retention and neurogenic over-

activity [1, 39] . In the field of urology electric cur-

rents were and are used particularly in the bladder,

the pelvic floor muscles, and the sacral roots [6, 7,

20] . Stimulation of the sacral nerves was developed

to electrically empty the bladder and later poststimu-

lus voiding was developed [10, 22, 36, 37] . Brindley

developed an electrode for long-term stimulation

of the spinal roots and it was implanted in the first

patient in 1972 [9] . Electrodes were implanted in

the first paraplegic patients since 1978, using direct

stimulation [11] . A study by Nashold et al. in 1971

reported on a successful implantation of a neural

prosthesis in the sacral segment of the spinal cord

[47] . The implant was used to activate voiding in a

patient with spinal cord injury. Jonas and Tanagho

tried to improve this prosthesis, since this type of

stimulation resulted not only in bladder contractions

but in urinary sphincter contractions as well [36, 37] .

Later, Tanagho and Schmidt demonstrated that the

stimulation of sacral root S3 generally modulates

detrusor and sphincter action and could be used in

clinical practice [53, 62– 64] . After two decades of

experimentation with sacral root stimulation, finally

in October 1997, sacral neuromodulation for treat-

ment of refractory UI was approved by the Food

and Drug Administration in the United States. More

then 25,000 patients have undergone sacral nerve

stimulation (SNS) since then.

The stimulation of afferent nerve fibers by elec-

trical current modulates reflex pathways involved

in the filling and evacuation phase of the mic-

turition cycle through spinal circuits mediating

somatovisceral interactions within the sacral spinal

cord. SNS is proposed to activate or “reset” the

somatic afferent inputs that play a pivotal role in

the modulation of sensory processing and micturi-

tion reflexpathways in the spinal cord [25, 43] .

Chapter 17

Sacral Nerve Stimulation for

Neuromodulation of the Lower

Urinary Tract

Dennis J. A. J. Oerlemans and Philip E. V. Van Kerrebroeck

218 D.J.A.J. Oerlemans and P.E.V.V. Kerrebroeck

Because beneficial effects can be demonstrated at

intensities of stimulation that do not activate move-

ments of striated muscle, the afferent system is the

most likely to be affected [65] . Fowler et al. dem-

onstrated that the anal sphincter reaction seen by

acute testing is the result of an afferent-mediated

response [26] .

UR and dysfunctional voiding can be resolved by

inhibition of the guarding reflexes. Detrusor overac-

tivity can be suppressed by one or more pathways, ie,

direct inhibition of bladder preganglionic neurons, as

well as inhibition of interneuronal transmission in the

afferent limb of the micturition reflex [43] .

Recent research with PET studies indicates that

at the level of the brain, the activity of centers in

the paraventricular gray involved in activation or

inhibition of the micturition reflex can be enhanced

or reduced by SNS. This results in up- or down-

grading of lower urinary tract activity [2, 4, 19] .

Blok et al. reported on the acute and chronic effects

of SNS on the brain in patients with UI. They reg-

istered differences between newly and chronically

implanted patients in brain areas involved in sen-

sory and motor learning. No differences were seen

in regional cerebral blood flow (rCBF) in areas

that are part of the micturition reflex. Changes in

rCBF were seen in specific areas: areas known to

be involved in micturition and areas involved in

awareness and awakeness. Acute SNS modulates

sensorimotor learning areas and these become less

active during chronic SNS [4] .

Selecting Patients for SNS

All patients who have symptoms of voiding dys-

function and who cannot be helped by other meas-

ures should be considered for SNS. Patient selection

begins with a careful history, physical examination,

routine urine tests, and, very importantly, the void-

ing diaries. Voiding diaries are a valuable instru-

ment during the selection of patients and must

be filled out carefully. Urodynamics are used to

identify the patients with detrusor overactivity with

or without urinary leakage or UR. Koldewijn et al.

studied predictors of success in 100 test stimulation

patients and did not find any [42] . Scheepens et al.

studied the data from 211 patients who underwent

a test stimulation [percutaneous nerve evaluation

(PNE)] to determine the clinical parameters that

can enhance the prediction of PNE success. They

found that intervertebral disk prolapse (IPD) sur-

gery, duration of complaints, neurogenic bladder

dysfunction, and UI were found to be significant

predictive factors. IPD surgery can compromise

the sacral root function and therefore can cause UI

and UR [48, 70] . In this study patients who under-

went IPD surgery had a 3.7 times higher chance

on a positive test. Patients with UI responded 2.51

times better to the PNE test. Both found duration of

complaints for more then 7 months and neurogenic

bladder dysfunction were to be negative predictors

of success. However, a PNE remains necessary to

evaluate a patient's chance of permanent implant

success objectively [52] .

Cohen et al. recently published a study on motor

versus sensory response. They concluded that a good

motor response during implantation was a predic-

tive factor (in 95% of successfully treated patients)

for success, while a sensory response was not.

Electrodes were implanted in all of these patients

under local anesthesia but with intravenous seda-

tion, and therefore the sensory perception of these

patients may be unreliable [14] .

Although not clearly reported before, it is known

that a substantial number of the patients selected

for SNS therapy have a history of psychological

dysfunction and/or sexual abuse in the past. Weil

et al. reported that special attention is needed for

this group of patients [68] . They noted that patients

with a history of psychological disorders, who had

a good response during temporary test stimula-

tion, had a far greater chance of lack of maintain-

ing effect after permanent implantation. Of these

patients, 82% showed a poor result after definitive

implantation compared to 28% of the patients with-

out a history of psychological disorders. Besides

this lack of effect, 25% of the reoperations were

done in this group, most of them with no effect.

Psychological testing or psychiatric evaluation in

case of doubt was advised before implantation of a

permanent system.

A study by Everaert et al. showed similar find-

ings [24] . In this study the two-stage procedure

was compared with the single-stage procedure.

In the two-stage implant group there were no

failures during the first stage while in the single-

stage procedure three patients had an immediate

failure. They suggested that these results might be

strongly influenced by psychological factors. Mental

17. Sacral Nerve Stimulation for Neuromodulation of the Lower Urinary Tract 219

disorders were not related to objective or subjective

success, but these cofactors surely interfere with

symptomatology and therewith coinfluencing the

results of therapy.

Technique of Sacral

Neuromodulation

SNS incorporates a temporary test stimulation pro-

cedure that allows patients and physicians to assess

SNS over a trial period [54] . This test stimulation,

also known as a PNE test, is conducted as an out-

patient procedure. Preferably it is performed under

local anesthetic and comprises two steps: acute

testing and the home evaluation phase. The original

technique was described by Schmidt [54] . A test

needle is inserted into the third sacral foramen to

stimulate the sacral root (Fig. 17.1 ). Lead migra-

tion is a known complication of this test; other

complications are technical failures or pain [57] .

Some patients who fail a PNE test are still good

candidates for SNS therapy. For these reasons a two-

stage implant technique was developed [34] . With

this technique a permanent electrode is implanted

and connected to an external stimulator (Fig. 17.2 ).

Less lead migration and a longer test period made

it possible to separate nonresponders from techni-

cal failures. Using this two-stage implant technique

eight of ten patients who failed a PNE test had a good

result with SNS therapy and were implanted with a

permanent system. A less invasive technique in com-

bination with a new designed self-anchoring lead

made it possible to test patients with this two-stage

technique [59, 60] . This “tined lead” has four sets of

self-anchoring tines and made a minimally invasive

percutaneous placement possible. The procedure

can be performed under local anesthesia, requiring

no additional incision and no additional anchoring.

Besides these advantages this way of implantation

made it possible to test the sensitive responses during

implantation and it resulted in a reduction of operat-

ing time. The tined lead-staged implant technique is

used widely in Europe and the United States [61] .

The acute phase, whether a PNE or tined lead

procedure is performed, is used to test the neu-

ral integrity, and therefore sensory and motor

responses should be obtained during this test.

The motor responses are important to identify the

right sacral root. Typical S3 stimulation results

in bellows movement of the pelvic floor, plantar

flexion of the great toe, and paresthesia in the

rectum, perineum, scrotum, or vagina. Stimulation

of the other sacral roots results in different motor

responses: S2 gives clamp movement or twisting

and pinching of the anal sphincter and plantar

flexion, with lateral rotation of the entire foot; S4

stimulation results in bellows motion of the pelvic

floor, no lower extremity activity, and a sensation

of pulling in the rectum [16] .

Fig. 17.1. Test needle inserted in the third sacral foramen

approx

1.5cm

Marked

Location - S3

Point of

Insertion

Future Pocket Site

Connection of Lead

and Percutaneous Extension

Lead

Anchor

Percutaneous Extension

Exit Site

Fig. 17.2. Permanent electrode connected to an external

stimulator

220 D.J.A.J. Oerlemans and P.E.V.V. Kerrebroeck

It can be difficult to palpate the bony landmarks,

necessary to identify the right puncture place, in

obese patients. Fluoroscopy then can be used for

S3 localization. More importantly, the use of lat-

eral imaging helps to determine the depth required

for implanting the S3 lead (Fig. 17.3 ). The use

of fluoroscopic localization of S3 allowed the

introduction of tined S3 lead and transformed the

placement of a lead from an open procedure to a

completely percutaneous one [59, 60] . The widely

adopted percutaneous use of a tined lead approach

abandoned the need for fixation of the lead by

methods such as bone anchors.

If the patient's symptoms improve at least more

than 50%, then the patient is a candidate to undergo

the stage II or permanent step in which the

permanent implantable pulse generator (IPG) is

implanted in the soft tissue of the buttock of the

patient (Fig. 17.4 ).

Relatively low amplitudes (0–3.0 V) are suffi-

cient for stimulation of the somatic nerve fibers and

to minimize the potential for nerve damage due to

overstimulation. Within the recommended stimula-

tion parameters (210 µs , 10–16 Hz) continuous

stimulation is possible without pain sensation.

Unilateral or Bilateral Stimulation

Although temporary and chronic SNS can result

in significant permanent clinical improvement,

some patients improve only partially or temporarily

[5, 69] . For these patients several methods have

been developed to improve the results [59– 61] .

The most widely accepted method to test a patient

for SNS therapy is unilateral stimulation. In some

clinics bilateral stimulation has been suggested as

a method to obtain better results [8, 32] . The bilat-

eral innervation of the bladder is the basis for this

type of intervention [21, 33] . Animal studies were

performed to find a scientific basis for the applica-

tion of bilateral stimulation. Schultz-Lampel et al.

suggest that bilateral SNS can be a more effective

technique for voiding dysfunction [56] . They con-

clude that bilateral stimulation may be more effec-

tive at lower stimulation intensities with positive

side effects such as longer stimulator battery life

and less potential nerve damage.

The only prospective randomized crossover

trial to compare unilateral approach with bilat-

eral sacral nerve stimulation was performed by

Scheepens et al. [51] . In this study, 33 patients

with chronic voiding dysfunction underwent uni-

lateral as well as bilateral test stimulation to assess

the possible advantages of bilateral stimulation.

All patients were stimulated during at least 72 h

in a unilateral and a bilateral setting with a wash-

out period of at least 48 h between these two test

periods. Standardized voiding records were used

and urine was measured using standard measur-

ing cups. They analyzed results for 12 patients

with UI and for 13 patients with nonobstructive UR.

Fig. 17.3. Lateral X-ray of a permanent lead passing

through the sacral foramen

Lead Extension

Connection of Lead

and Lead Extension

Lead

Fig. 17.4. Permanent pulse generator connected to the

electrode

17. Sacral Nerve Stimulation for Neuromodulation of the Lower Urinary Tract 221

They did not find any significant differences

comparing the results for unilateral with bilateral

stimulation. Although two patients of the retention

group started voiding during bilateral stimulation,

while during unilateral stimulation they were still

in complete retention. The reason for this result

could be that with bilateral stimulation sufficient

sacral nerve afferents are stimulated to achieve a

marked effect at the central level.

In conclusion unilateral stimulation should be

performed before bilateral sacral stimulation is con-

sidered. However, a bilateral test stimulation could

be indicated when a unilateral test fails [40, 51] .

Further research with clinical follow-up could

identify suitable patients for bilateral sacral nerve

stimulation.

Clinical Results

In 1999, a prospective randomized study was

published in which the results of SNS therapy for

UI were evaluated [55] . In total, 76 patients were

treated in a multicenter trial: 34 patients received

the implant and received chronic stimulation for 6

months, after which they completed a therapy eval-

uation test (on vs. off); 42 patients in a delay group

were treated with standard medical therapy for 6

months and were offered implantation after this

period. After 6 months the number of daily incon-

tinence episodes, the number of daily replaced

diapers, and the severity of incontinence were sig-

nificantly reduced in the stimulation group. In the

stimulation group, 16 patients (47%) were com-

pletely dry and 10 patients (29%) showed a greater

than 50% reduction in incontinence episodes. In

the delay group (controls) the average incontinence

episodes increased during 6 months of conservative

therapy from 2.63.5 heavy episodes at baseline to

3.9±3.8 heavy episodes a day at 6 months. After

18 months the efficacy appeared to be sustained.

During the therapy evaluation at 6 months the

stimulation group returned to baseline symptoms

when stimulation was stopped.

Hassouna et al. reported in 2000 on the treatment

of UF symptoms with SNS therapy [29] . In total, 51

patients—a stimulation group of 25 patients and a

control group of 26 patients—enrolled in this mul-

ticenter trial. All the patients had been tested with

a PNE test and showed satisfactory responses. The

stimulation group received implant directly after

this test and the control group received implant after

a 6-months delay period. Statistically significant

improvements were seen in the stimulation group

for diary parameters as: number of voids daily

(16.9±9.7 to 9.3±5.1), volume per void (118±74 to

226±124 ml), and degree of urgency (rank 2.2±0.6

to 1.6±0.9). In the control group no significant

changes were seen. After 6 months the stimulation

group had an evaluation test and urinary symptoms

returned to baseline when stimulation was turned

off. After reactivation of the stimulation sustained

efficacy was seen at 12 and 24 months.

A report of use of SNS in UR was published

in 2001 by Jonas et al. A total of 177 patients

with UR refractory to conservative therapy were

enrolled in this multicenter trial between 1993 and

1998 [38] . Thirty-seven patients were assigned to

treatment and 31 to the control group. At 6 months

the stimulation group showed 69% elimination of

catheterization and an additional 14% with greater

than 50% reduction in catheter volume per cathe-

terization. Temporary inactivation (3 days) of SNS

therapy resulted in significant increase in residual

volume. The effectiveness of SNS therapy was sus-

tained for 18 months after implantation.

The first medium-term follow-up results of the

above mentioned patient series were published in

2000 [57] . Results were reported for 1.5 to 3 years

of follow-up. Of 41 UI patients, 59% showed a

greater than 50% reduction in leaking episodes,

with 46% of the patients being completely dry after

3 years. After 2 years of follow-up, 56% of the UF

patients showed a greater than 50% reduction in

voids per day. In the retention group, 70% of 42

patients showed a greater than 50% reduction in

catheter volume per catheterization.

During the MDT-103 trial in 89 patients, depres-

sion and health-related quality of life (HRQOL)

were assessed [17] . Patients were divided into

a direct implant group and a delayed implant

group. At baseline they noted detectable levels of

depression in 73% of all patients. After 3 months

patients in the implanted group had a significant

improvement in depression scores. The improved

scores remained at the 6- and 12-month visits. The

scores on the SF-36 questionnaire, a questionnaire

to investigate pain, vitality, physical functioning,

social functioning, and mental health, increased

in the implant group for role-physical, pain, and

222 D.J.A.J. Oerlemans and P.E.V.V. Kerrebroeck

social functioning. This study demonstrated the

serious impact that unresolved voiding dysfunction

has on quality of life. SNS was associated with sig-

nificant improvement in depression and HRQOL.

Recently, the 5-year follow-up results of patients

included in the trial in order to obtain FDA approval

were analyzed. Of 163 patients enrolled, 152 have

received implants. Of the 163 patients, 103 (64%)

had UI, 28 (17%) UF, and 31 (19%) UR. Voiding

diaries were collected annually over 5 years. For UI

patients, the mean number of leaking episodes per

day declined from 9.6 ± 6.0 to 3.9 ± 4.0. For UF

patients, mean voids per day decreased from 19.3

± 7.0 to 14.8 ± 7.6. Mean volume voided per void

increased from 92.3 ± 52.8 to 165.2 ± 147.7 ml. In

the UR group the average number of catheteriza-

tions per day decreased from 5.3±2.8 at baseline to

1.9±2.8 at 5 years postimplant. No life-threatening

or irreversible adverse events occurred. Of 152

patients, 102 experienced 31 device-related and

240 therapy-related adverse events. Among these

therapy-related events, the most frequently reported

event was new pain or undesirable change in stimu-

lation (60 times in 41 patients). Pain at the implant

site or related to the implanted pulse generator

(IPG) was the second-most reported event (40 times

in 30 patients). However, an important finding in

this study is the high correlation between the 1- and

5-year success rates. Of the implanted patients, 84%

with UI, 71% with UF, and 78% with UR continued

to have a successful outcome at 5-year follow-up if

they were successful at 1 year [41] .

Different groups have published their long-term

results in recent years [18, 23, 67] . They all con-

clude that SNS therapy is safe and effective.

Complications

Most studies mentioned in the clinical results sec-

tion reported on complications during SNS. Siegel

et al. summarized the complications in patients who

were included in the original trials of SNS [57] .

The complications were divided into PNE-related

complications and implant-related problems. Of

the 914 test stimulation procedures done on the

581 patients, 181 adverse events occurred in 166

of these procedures (18.2% of the 914 procedures).

The vast majority of complications were related to

lead migration (108 events, 11.8% of procedures).

Technical problems and pain represented 2.6 and

2.1% of the adverse events, respectively. For the

219 patient who underwent implantation of the

permanent system, the following adverse events

were seen during follow-up: pain at neurostimula-

tor site (15.3%), new pain (9%), suspected lead

migration (8.4%), transient electric shock (5.5%),

pain at lead site (5.4%), adverse change in bowel

function (3.0%), and some less frequent events such

as technical problems, device problems, change in

menstrual cycle, and others. Surgical revisions of

the implanted neurostimulator or lead system were

performed in 33.3% of cases (73 of 219 patients) to

resolve an adverse event. Mostly this was done to

relocate the stimulator because of pain or because of

suspected lead migration. No serious adverse events,

side effects, or permanent injury were reported.

Recently our long-term follow-up results with

complication rates were published [67] . Of 149

patients analyzed, 107 had overactive bladder

symptoms and 42 had urinary retention. Mean fol-

low-up was 64.2 (SD = 38.5) months. In the whole

group 194 adverse events occurred. Six patients

had infection in their implanted system; one was

explanted for infection. Most events could be

solved by giving advice or by reprogramming the

stimulator. In all, 129 reoperations have been per-

formed and 21 patients had their system explanted.

The most frequent surgical procedures performed

were repositioning of the IPG, revision of the

electrode because of suspected lead migration,

and reoperation for parameter change in patients

implanted with the Itrell-I IPG (the first model used

for SNS). Analysis of the data shows a striking dif-

ference in the incidence of reoperations, but small

differences in subjective results in the groups of

patients implanted before or after 1996, suggesting

that a proactive approach toward adverse events is

worthwhile. In our experience with the tined lead

implantation we see a clear decrease in reoperation

rate [66] . Of 39 patients implanted with the tined

lead, van Voskuilen et al. described seven severe

adverse events on medium term, three of whom

needed a reoperation. Three patients could be

treated with one or two reprogramming sessions.

Three patients had a reoperation to reposition the

IPG after complaints of pain. These three patients

had good results afterward. One patient with an

incomplete spinal cord lesion had no benefit of the

implanted system.

17. Sacral Nerve Stimulation for Neuromodulation of the Lower Urinary Tract 223

Of 161 patients implanted with the tined lead

between July 2002 and September 2004, Hijaz

et al. described the complications seen in their

institute [31] . They had three categories for com-

plications: infections, mechanical problems, and

response-related dysfunction. In total they reported

17 explantations (10.5%). Eight explantations were

done due to infection and seven due to loss of effect.

In 26 (16.1%) patients they performed a revision

after these patients presented with a decrease in

clinical response. The reasons for revision were

mechanical (lead) problems, IPG site discomfort,

lead migration, and infectious causes. The compli-

cation rates show a decrease over the years mainly

due to technical and procedural improvements.

Gaynor-Krupnick et al. as well as Hijaz and

Vasavada presented an algorithm for evaluation and

managing of a malfunctioning neuromodulation

system [27, 30] .

Expanding Indications

With the widespread use, incidental improvements

were published for other pathological conditions.

Use of SNS for other off-label applications have

been reported for treatment of interstitial cystitis,

chronic pelvic pain, pediatric voiding dysfunction,

and neurogenic lower urinary dysfunction seen in

multiple sclerosis.

Long-term results for the use of SNS in neuro-

genic UI patients were presented by Chartier-Kastler

[13] . The results for nine patients were shown with

a mean follow-up of 43.6 months. All patients had

significant clinical improvement and five (56%)

patients were completely dry. The number of leak-

ages per day went from an initial 7.3 to 0.3 (at last

follow-up). Frequency improved after implantation

from 16.1 to 8 voids per day and the mean volume

per void increased from 115 to 249 ml.

In 2000, the first papers were published with posi-

tive results with the use of SNS in interstitial cystitis

[12, 71] . Comiter evaluated the effect of SNS ther-

apy for interstitial cystitis in a prospective study in

2003 [15] . Seventeen of 25 patients were implanted

with a permanent system. After a mean follow-up

of 14 months there were significant improvements

in daytime frequency and nocturia, which improved

from 17.1 to 8.7 and 4.5 to 1.1, respectively ( P <

0.01). Mean voided volume increased from 111 to

264 ml ( P < 0.01). Average pain score decreased

from 5.8 to 1.6 points on a scale of 0 to 10 ( P <

0.01). Interstitial Cystitis Symptom and Problem

Index scores decreased from 16.5 to 6.8 and 14.5 to

5.4, respectively ( P < 0.01).

In 2001 Siegel et al. implanted ten patients with

chronic pelvic pain [58] . These patients all had a

history of at least 6 months of pelvic pain refrac-

tory to conventional treatment without a primary

complaint of voiding dysfunction. After 9 months

of follow-up nine of ten patients had a decrease in

most severe pain scores; after a median follow-up

of 19 months six of ten patients reported significant

improvement in pain symptomatology.

After the clinical implication of SNS therapy

for voiding dysfunction, Matzel, together with

Schmidt and Tanagho, started to investigate SNS

therapy in bowel dysfunction [44, 45] . In a pro-

spective, nonrandomized, multicenter study 37

patients underwent a test stimulation with SNS

therapy for fecal incontinence [46] . Thirty-four

patients were implanted with a permanent system.

The effect on incontinence was assessed by daily

bowel habit diaries and a disease-specific quality

of life questionnaire. The frequency of incontinent

episodes per week decreased from 16.4 to 3.1 at 12

months and to 2.0 at 24 months for both urge and

passive incontinence. The mean number of incon-

tinence episodes per week, staining, and pad use

declined significantly, too. Quality of life improved

significantly in ASCRS scales,;in the SF-36 scales

only social functioning improved significantly.

Jarrett et al. did a systematic review of SNS for

fecal incontinence and constipation [35] . They

reported total continence in 41–75% of the patients

and 75–100% experienced improvement in the

incontinence symptoms. The results for patients

treated with SNS for constipation discussed in this

review seem promising, but limited data are avail-

able at this time.

The results of SNS therapy in children with neu-

rogenic bladder dysfunction are described by Guys

et al. [28] . Forty-two children with neurogenic blad-

der dysfunction, mainly due to spina bifida, were

enrolled in this prospective, randomized controlled

trial. Twenty-one patients were treated conserva-

tively while the other 21 patients were treated with

SNS therapy. After 12 months no significant better

results were seen in the group treated with SNS.

The authors stated that probably the intervention

224 D.J.A.J. Oerlemans and P.E.V.V. Kerrebroeck

group was too small or the bladder dysfunction in

these patients too severe.

During routine follow-up patients may report

improved sexual functioning after implant. Pauls

et al. recently reported a pilot study to determine

whether sacral neuromodulation has an effect

on the patient's subsequent sexual function [49] .

Eleven patients with a permanent system implanted

were questioned about their sexual function before

and after implantation. With SNS therapy sexual

frequency and Female Sexual Function Index

(FSFI) increased significantly. No correlation was

found between improvement in urinary symptoms

and FSFI scores.

Conclusions

After years of experimental therapy, initiated by

Tanagho and Schmidt, SNS now is a widely used

therapy. Although the mechanisms of action are

still not fully understood, the therapy has been

proven effective in the long term. Due to the less

invasive technique and other technical improve-

ments, it is expected that complication rates will

further decrease within the coming years. The

expanding use of SNS therapy in fields other than

urology probably will result in FDA approval for

gastrointestinal indications.Further research, pos-

sibly with the help of animal models, has to be

performed to understand in a more precise way

the mechanism of SNS therapy. Other goals in

research could be patient selection (finding ways to

identify the best candidates), the effect of SNS in

combined (urological/gynecological/gastroentero-

logical) pathology, and the effect of bilateral versus

unilateral stimulation.

References

1 . Ascoli R . 1965 . [Treatment of neurogenic bladder] .

Acta Urol Belg 33 : 76 – 83 .

2 . Blok BF . 2002 . Central pathways controlling mictu-

rition and urinary continence . Urology 59 (5 Suppl

1) : 13 – 17 .

3 . Blok BF , Groen J , Veltman D , Bosch R . 2003 . Brain

plasticity and urge incontinence: PET studies during

the first hours of sacral neuromodulation . Neurourol

Urodyn 22 : 490 – 491 .

4 . Blok BF , Groen J , Bosch JL , et al. 2007 . Different

brain effects during chronic and acute sacral neu-

romodulation in urge incontinent patients with

implanted neurostimulators . BJU Int 99 : 700 – 700 .

5 . Bosch JL , Groen J . 2000 . Sacral nerve neuromodu-

lation in the treatment of patients with refractory

motor urge incontinence: Long-term results of a

prospective longitudinal study . J Urol 163 (4) : 1219 –

1222 .

6 . Boyce WH , Lathem E , Hunt LD . 1963 . Research

related to the development of an artificial electri-

cal stimulator for the paralyzed human bladder: A

review . Trans Am Assoc Genitourin Surg 55 : 81 – 91 .

7 . Boyce WH , Lathem JE , Hunt LD . 1964 . Research

related to the development of an artificial electri-

cal stimulator for the paralyzed human bladder: A

review . J Urol 91 : 41 – 51 .

8 . Braun P , Seif C , Scheepe J , et al. 2002 . [Chronic

sacral bilateral neuromodulation . Using a mini-

mal invasive implantation technique in patients

with disorders of bladder function]. Urologe A

41 (1) : 44 – 47 .

9 . Brindley GS . 1972 . Experiments directed towards a

prosthesis which controls the bladder and the exter-

nal sphincter from a single site of stimulation . Proc

Biol Eng Soc 46th Meeting , Liverpool .

10 . Brindley GS . 1977 . An implant to empty the bladder

or close the urethra . J Neurol Neurosurg Psychiatry

40 (4) : 358 – 369 .

11 . Brindley GS . 1993 . History of the sacral ante-

rior root stimulator, 1969–1982 . Neurourol Urodyn

12 (5) : 481 – 483 .

12 . Chai TC , Zhang C , Warren JW , Keay S . 2000 .

Percutaneous sacral third nerve root neuros-

timulation improves symptoms and normalizes

urinary HB-EGF levels and antiproliferative activ-

ity in patients with interstitial cystitis . Urology

55 (5) : 643 – 646 .

13 . Chartier-Kastler EJ , Ruud Bosch JL , Perrigot M ,

et al. 2000 . Long-term results of sacral nerve stimu-

lation (S3) for the treatment of neurogenic refractory

urge incontinence related to detrusor hyperreflexia . J

Urol 164 (5) : 1476 – 1480 .

14 . Cohen BL , Tunuguntla HS , Gousse A . 2006 .

Predictors of success for first stage neuromod-

ulation: Motor versus sensory response . J Urol

175 (6) : 2178 – 2180 ; discussion 2180–2171 .

15 . Comiter CV . 2003 . Sacral neuromodulation for

the symptomatic treatment of refractory interstitial

cystitis: A prospective study . J Urol 169 (4) : 1369 –

1373 .

16 . Daneshgari F . 2006 . Applications of neuromodula-

tion of the lower urinary tract in female urology . Int

Braz J Urol 32 (3) : 262 – 272 .

17 . Das AK , Carlson AM , Hull M . 2004 . Improvement

in depression and health-related quality of life after

17. Sacral Nerve Stimulation for Neuromodulation of the Lower Urinary Tract 225

sacral nerve stimulation therapy for treatment of

voiding dysfunction . Urology 64 (1) : 62 – 68 .

18 . Dasgupta R , Wiseman OJ , Kitchen N , Fowler CJ .

2004 . Long-term results of sacral neuromodula-

tion for women with urinary retention . BJU Int

94 (3) : 335 – 337 .

19 . Dasgupta R , Critchley HD , Dolan RJ , Fowler CJ .

2005 . Changes in brain activity following sac-

ral neuromodulation for urinary retention . J Urol

174 (6) : 2268 – 2272 .

20 . Dees JE . 1965 . Contraction of the urinary bladder

produced by electric stimulation . Preliminary report.

Invest Urol 15 : 539 – 547 .

21 . Diokno AC , Davis R , Lapides J . 1973 . The effect

of pelvic nerve stimulation on detrusor contraction .

Invest Urol 11 (3) : 178 – 181 .

22 . Eidelberg E , Bors E , Woodbury CM , Brigham A .

1974 . Effect of electrical stimulation of dorsal and

ventral spinal cord roots on the cat’s urinary bladder .

Urol Int 29 (5) : 375 – 381 .

23 . Elhilali MM , Khaled SM , Kashiwabara T , et al.

2005 . Sacral neuromodulation: Long-term experi-

ence of one center . Urology 65 (6) : 1114 – 1117 .

24 . Everaert K , Kerckhaert W , Caluwaerts H , et al.

2004 . A prospective randomized trial comparing

the 1-stage with the 2-stage implantation of a pulse

generator in patients with pelvic floor dysfunc-

tion selected for sacral nerve stimulation . Eur Urol

45 (5) : 649 – 654 .

25 . Fall M , Lindstrom S . 1991 . Electrical stimulation .

A physiologic approach to the treatment of urinary

incontinence. Urol Clin North Am 18 (2) : 393 – 407 .

26 . Fowler CJ , Swinn MJ , Goodwin RJ , et al. 2000 .

Studies of the latency of pelvic floor contrac-

tion during peripheral nerve evaluation show that

the muscle response is reflexly mediated . J Urol

163 (3) : 881 – 883 .

27 . Gaynor-Krupnick DM , Dwyer NT , Rittenmeyer H ,

Kreder KJ . 2006 . Evaluation and management of

malfunctioning sacral neuromodulator . Urology

67 (2) : 246 – 249 .

28 . Guys JM , Haddad M , Planche D , et al. 2004 . Sacral

neuromodulation for neurogenic bladder dysfunc-

tion in children . J Urol 172 (4 Pt 2) : 1673 – 1676 .

29 . Hassouna MM , Siegel SW , Nyeholt AA , et al.

2000 . Sacral neuromodulation in the treatment of

urgency-frequency symptoms: A multicenter study

on efficacy and safety . J Urol 163 (6) : 1849 – 1854 .

30 . Hijaz A , Vasavada S . 2005 . Complications and trou-

bleshooting of sacral neuromodulation therapy . Urol

Clin North Am 32 (1) : 65 – 69 .

31 . Hijaz A , Vasavada SP , Daneshgari F , et al. 2006 .

Complications and troubleshooting of two-stage

sacral neuromodulation therapy: A single-institution

experience . Urology 68 (3) : 533 – 537 .

32 . Hohenfellner M , Schultz-Lampel D , Dahms S , et al.

1998 . Bilateral chronic sacral neuromodulation for

treatment of lower urinary tract dysfunction . J Urol

160 (3 Pt 1) : 821 – 824 .

33 . Ingersoll EH , Jones LL , Hegre ES . 1957 . Effect on

urinary bladder of unilateral stimulation of pelvic

nerves in the dog . Am J Physiol 189 (1) : 167 – 172 .

34 . Janknegt RA , Weil EH , Eerdmans PH . 1997 .

Improving neuromodulation technique for refractory

voiding dysfunctions: Two-stage implant . Urology

49 (3) : 358 – 362 .

35 . Jarrett ME , Mowatt G , Glazener CM , et al. 2004 .

Systematic review of sacral nerve stimulation for

faecal incontinence and constipation . Br J Surg

91 (12) : 1559 – 1569 .

36 . Jonas U , Tanagho EA . 1975 . Studies on the fea-

sibility of urinary bladder evacuation by direct

spinal cord stimulation . II. Poststimulus voiding:

A way to overcome outflow resistance. Invest Urol

13 (2) : 151 – 153 .

37 . Jonas U , Heine JP , Tanagho EA . 1975 . Studies on

the feasibility of urinary bladder evacuation by

direct spinal cord stimulation . I. Parameters of most

effective stimulation. Invest Urol 13 (2) : 142 – 150 .

38 . Jonas U , Fowler CJ , Chancellor MB , et al. 2001 . Efficacy

of sacral nerve stimulation for urinary retention: Results

18 months after implantation . J Urol 165 (1) : 15 – 19 .

39 . Katona F . 1975 . Stages of vegetative afferentation in

reorganization of bladder control during intravesical

electrotherapy . Urol Int 30 (3) : 192 – 203 .

40 . Kerrebroeck van PE , Scheepens W , de Bie R , Weil E .

2005 . European experience with bilateral sacral

neuromodulation in patients with chronic lower

urinary tract dysfunction . Urol Clin North Am

32 (1) : 51 – 57 .

41 . Kerrebroeck van PE , Voskuilen van AC , Heesakkers

JPFA , et al. 2007 . Five-year results of sacral neuro-

modulation therapy for urinary voiding dysfunction:

Outcomes of prospective, worldwide clinical study .

J Urol 178 : 2029 – 2034 .

42 . Koldewijn EL , Rosier PF , Meuleman EJ , et al. 1994 .

Predictors of success with neuromodulation in lower

urinary tract dysfunction: Results of trial stimulation

in 100 patients . J Urol 152 (6 Pt 1) : 2071 – 2075 .

43 . Leng WW , Chancellor MB . 2005 . How sacral

nerve stimulation neuromodulation works . Urol Clin

North Am 32 (1) : 11 – 18 .

44 . Matzel KE , Schmidt RA , Tanagho EA . 1990 .

Neuroanatomy of the striated muscular anal conti-

nence mechanism . Implications for the use of neu-

rostimulation. Dis Colon Rectum 33 (8) : 666 – 673 .

45 . Matzel KE , Stadelmaier U , Hohenfellner M , Gall

FP . 1995 . Electrical stimulation of sacral spinal

nerves for treatment of faecal incontinence . Lancet

346 (8983) : 1124 – 1127 .

226 D.J.A.J. Oerlemans and P.E.V.V. Kerrebroeck

46 . Matzel KE , Kamm MA , Stosser M , et al. 2004 .

Sacral spinal nerve stimulation for faecal inconti-

nence: Multicentre study . Lancet 363 (9417) : 1270 –

1276 .

47 . Nashold BS Jr , Friedman H , Boyarsky S . 1971 .

Electrical activation of micturition by spinal cord

stimulation . J Surg Res 11 (3) : 144 – 147 .

48 . O’Flynn KJ , Murphy R , Thomas DG . 1992 .

Neurogenic bladder dysfunction in lumbar interver-

tebral disc prolapse . Br J Urol 69 (1) : 38 – 40 .

49 . Pauls RN , Marinkovic SP , Silva WA , et al. 2006 .

Effects of sacral neuromodulation on female sexual

function . Int Urogynecol J Pelvic Floor Dysfunct

17 (1) : 27 – 29 .

50 . Saxtorph M . 1878 . Stricture urethrae – Fistula perinee

– Retentio urinae . Clinsk Chirurgi , Gyldendalske

Fortag Copenhagen : 265 – 280 .

51 . Scheepens WA , de Bie RA , Weil EH , van Kerrebroeck

PE . 2002a . Unilateral versus bilateral sacral neuro-

modulation in patients with chronic voiding dys-

function . J Urol 168 (5) : 2046 – 2050 .

52 . Scheepens WA , Jongen MM , Nieman FH , et al.

2002b . Predictive factors for sacral neuromodulation

in chronic lower urinary tract dysfunction . Urology

60 (4) : 598 – 602 .

53 . Schmidt RA , Bruschini H , Tanagho EA . 1979 .

Sacral root stimulation in controlled micturition.

Peripheral somatic neurotomy and stimulated void-

ing . Invest Urol 17 (2) : 130 – 134 .

54 . Schmidt RA , Senn E , Tanagho EA . 1990 . Functional

evaluation of sacral nerve root integrity. Report of a

technique . Urology 35 (5) : 388 – 392 .

55 . Schmidt RA , Jonas U , Oleson KA , et al. 1999 .

Sacral nerve stimulation for treatment of refractory

urinary urge incontinence. Sacral Nerve Stimulation

Study Group . J Urol 162 (2) : 352 – 357 .

56 . Schultz-Lampel D , Jiang C , Lindstrom S , et al.

1998 . Neurophysiologische Effekte unilateraler und

bilateraler sakraler Neuromodulation . Aktuel Urol

29 : 354 – 360 .

57 . Siegel SW , Catanzaro F , Dijkema HE , et al. 2000 .

Long-term results of a multicenter study on sacral

nerve stimulation for treatment of urinary urge

incontinence, urgency-frequency, and retention .

Urology 56 (6 Suppl 1) : 87 – 91 .

58 . Siegel S , Paszkiewicz E , Kirkpatrick C , et al. 2001 .

Sacral nerve stimulation in patients with chronic

intractable pelvic pain . J Urol 166 (5) : 1742 – 1745 .

59 . Spinelli M , Giardiello G , Arduini A , van den

Hombergh U . 2003a . New percutaneous technique

of sacral nerve stimulation has high initial success

rate: preliminary results . Eur Urol 43 (1) : 70 – 74 .

60 . Spinelli M , Giardiello G , Gerber M , Arduini A , van

den Hombergh U , Malaguti S . 2003b . New sacral

neuromodulation lead for percutaneous implantation

using local anesthesia: Description and first experi-

ence . J Urol 170 (5) : 1905 – 1907 .

61 . Spinelli M , Weil E , Ostardo E , et al. 2005 . New

tined lead electrode in sacral neuromodulation:

Experience from a multicentre European study .

World J Urol 23 (3) : 225 – 229 .

62 . Tanagho EA , Schmidt RA . 1982 . Bladder pace-

maker: Scientific basis and clinical future . Urology

20 (6) : 614 – 619 .

63 . Tanagho EA , Schmidt RA . 1988 . Electrical stimula-

tion in the clinical management of the neurogenic

bladder . J Urol 140 (6) : 1331 – 1339 .

64 . Tanagho EA , Schmidt RA , Orvis BR . 1989 . Neural

stimulation for control of voiding dysfunction: A pre-

liminary report in 22 patients with serious neuropathic

voiding disorders . J Urol 142 (2 Pt 1) : 340 – 345 .

65 . Vodusek DB , Light JK , Libby JM . 1986 . Detrusor

inhibition induced by stimulation of pudendal nerve

afferents . Neurourol Urodyn 5 (4) : 381 – 389 .

66 . Voskuilen van AC , Oerlemans DJ , Weil EH , et al.

2006a . Medium-term experience of sacral neuro-

modulation by tined lead implantation . BJU Int

99 : 107 – 110 .

67 . Voskuilen van AC , Oerlemans DJ , Weil EH , et al.

2006b . Long term results of neuromodulation by

sacral nerve stimulation for lower urinary tract

symptoms: A retrospective single center study . Eur

Urol 49 (2) : 366 – 372 .

68 . Weil EH , Ruiz-Cerda JL , Eerdmans PH , et al.

1998 . Clinical results of sacral neuromodula-

tion for chronic voiding dysfunction using uni-

lateral sacral foramen electrodes . World J Urol

16 (5) : 313 – 321 .

69 . Weil EH , Ruiz-Cerda JL , Eerdmans PH , et al.

2000 . Sacral root neuromodulation in the treatment

of refractory urinary urge incontinence: A pro-

spective randomized clinical trial . Eur Urol 37 (2) :

161 – 171 .

70 . Yamanishi T , Yasuda K , Sakakibara R , et al.

1998 . Detrusor overactivity and penile erection in

patients with lower lumbar spine lesions . Eur Urol

34 (4) : 360 – 364 .

71 . Zermann DH , Weirich T , Wunderlich H , et al. 2000 .

Sacral nerve stimulation for pain relief in interstitial

cystitis . Urol Int 65 (2) : 120 – 121 .

Overactive bladder (OAB) is a common syndrome

defined by the International Continence Society

[1] as “urgency with or without urge incontinence,

usually with frequency and nocturia, in the absence

of other pathologic or metabolic conditions to

explain these symptoms.” Most cases of OAB are

idiopathic and many respond to behavioral modi-

fication or antimuscarinic medications. However,

it is not uncommon for patients to not respond to

these interventions and to be classified as having

refractory OAB symptoms. One such refractory

case is illustrated below.

Case 1 . A 46-year-old white female presents

with complaints of urinary urge incontinence. She

leaks in moderate amounts generally on her way

to the bathroom, but also with changes in position

such as getting out of a chair or bed. She has been

tried on various combinations of anticholinergic

and tricyclic medications with mild improvement,

but the medications further worsened her constipa-

tion, which already is a significant problem for her.

She has been taught guarding maneuvers, behav-

ioral modification, and pelvic floor rehabilitation

without satisfactory improvement in her symptoms.

Past medical history is otherwise unremarkable and

past surgical history is remarkable for appendec-

tomy and hysterectomy (for large fibroids). There

is no history of back problems or neurological

disease. Physical examination is unremarkable and

urogenital examination reveals a normal meatus,

minimal cystourethrocele, and normal neurological

examination including normal perianal sensation

and rectal sphincter tone.

Voiding diary reveals a functional bladder capacity

of 300 ml, average voided volume of ~160 ml, and

two to three moderate volume leakage episodes

daily. Urodynamic studies in the standing position

at a fill rate of 60 ml/min with room temperature

sterile contrast material reveal phasic detrusor

overactivity starting at volumes of 160–180 ml

with moderate volume leakage. Bladder is nor-

mally oriented and the patient is able to void to

completion with low voiding pressures.

Although this patient responded to some degree

to anticholinergic therapy, she could not toler-

ate it due to side effects especially constipation.

Although frequency–urgency syndromes and urge

incontinence are quite common and many patients

can be adequately managed with combinations of

behavioral therapy, pelvic floor rehabilitation, and

pharmaceutical therapy, a significant minority of

patients do not respond adequately to these meas-

ures or cannot tolerate the side effects and desire

further treatment. Options generally are limited

and require major surgical procedures such as

augmentation cystoplasty, which often can result

in incomplete emptying and need for intermittent

catheterization, an alternative not acceptable for

many such patients. While sacral neuromodulation

(SNS) has been used in the treatment of refractory

OAB with reasonable success rates in appropriately

selected patients and is addressed in detail else-

where, for many patients it represents a more inva-

sive treatment option than they would like. Prior to

considering sacral neuromodulation, which is more

invasive and significantly more expensive, patients

227

Chapter 18

Peripheral Neuromodulation for the

Treatment of Overactive Bladder

Anurag K. Das

228 A.K. Das

can consider tibial nerve stimulation, a relatively

inexpensive minimally invasive procedure working

in a retrograde manner to effect sacral nerve root

function. In this chapter, I will review the history,

indications, and mechanism of action, techniques,

and outcomes of tibial nerve stimulation as a model

for peripheral neuromodulation.

History

The use of electrical stimulation for treatment of

various disorders has a long and colorful history.

Electrical stimulation was used for such disease

processes as excess libido and, of course, depres-

sion. Caldwell [2] used electrical stimulation of

the pelvic floor using implanted electrodes in an

attempt to treat stress urinary incontinence and

also attempted to treat neurogenic incontinence

with an implantable stimulator. With advances in

cardiac pacing and the improved understanding and

miniaturization of electronic instruments, interest in

neuromodulation of bladder function was revived in

the 1970s and 1980s. The Department of Urology

at the University of California, San Francisco, led

by Drs. Richard Schmidt and Emil Tanagho, was

instrumental in performing some of the early work

and laying the foundation for the use of sacral neu-

romodulation for the treatment of refractory void-

ing dysfunction. Dr. Edward McGuire [3] , in the

early 1980s, first reported using tibial stimulation

with a patch electrode, while Dr. Marshall Stoller,

in the late 1980s, pioneered the use of tibial nerve

stimulation with the percutaneous Stoller afferent

neurostimulation (SANS) method.

Mechanism of Action

The mechanism of action of peripheral nerve

stimulation (PNS) is not completely understood.

It is probable that stimulation of the tibial nerve

causes retrograde modification of S3 nerve root

function. This may be similar to sacral neuromodu-

lation, and as Chancellor and DeGroat [4, 5] have

suggested may improve somatic afferent inhibition

of sensory processing in the spinal cord. Since the

S2–4 nerve roots provide the primary autonomic

(parasympathetic through the pelvic nerve) and

somatic (pudendal nerve) innervation to the blad-

der, urethra, and pelvic floor, this processing some-

how helps in the treatment of OAB by “inhibiting”

these nerve roots. Further data to support the view

that afferent pathways play a role in SNS-related

symptom improvement come from Fowler [6, 7] ,

who suggests neuromodulation affects afferent

pathways probably through mediating changes in

spinobulbospinal pathways to the pontine mictu-

rition center. Because visceral afferents require

higher stimulation amplitudes, it is more likely that

somatic afferents play a more important role in the

mechanism involved, and thus the term “somatic

afferent inhibition.”

Indications

Peripheral neuromodulation has been used for the

treatment of refractory urge incontinence, refractory

urinary frequency–urgency syndromes, or refrac-

tory OAB syndrome, depending on one's prefer-

ence, in controlled trials. Generally, patients who

have failed or could not tolerate more conservative

therapies, such as behavioral modification, pelvic

floor rehabilitation (including pelvic floor bio-

feedback/muscular vaginal electrical stimulation),

and anticholinergic/antimuscarinic medications, are

given a trial of percutaneous peripheral neuromodu-

lation. It is important to remember that patients with

neurological disease have been excluded from most

of the trials, and thus there are few data that patients

with neurological diseases may respond well to

this modality. All patients being considered for

PNS should have a complete history and physical

examination including a genital, rectal, and neuro-

logical examination. These patients should perform

accurate voiding diaries and undergo urodynamic

studies to confirm the diagnosis and ascertain

they are suitable candidates. These patients should

have failed or could not tolerate more conservative

therapies such as behavioral modification and/or

appropriate medications.

PNS Procedure

The procedure is fairly straightforward. It is per-

formed with the patient sitting in a frog-legged

position with the soles of the feet touching. The

medial aspect of the malleolus is palpated and

18. Peripheral Neuromodulation for the Treatment of Overactive Bladder 229

a sensitive pressure point is identified approxi-

mately three finger breadths cephalad. This point

is about a fingerbreadth posterior to the edge of

the tibia. A 34-gauge, solid stainless steel nee-

dle is advanced through the skin with the aid

of an overlying plastic cylinder that is about 3

mm shorter than the needle. Once the skin is

pierced the cylinder is removed, and the needle is

advanced approximately 3–4 cm. The needle tra-

jectory is 60° from a perpendicular line along the

length of the tibia, advanced toward the patient's

head (Fig. 18.1 ). Needles may be placed bilater-

ally in a similar fashion .

A grounding pad is placed over the medial

aspect of the calcaneus. A stimulator is then con-

nected to the needle and the ipsilateral ground pad

(Fig. 18.2 ). Stimulation is titrated from 0 to 10

mA with a pulse width of 200 m s at a frequency

of 20 Hz. Proper needle placement is confirmed

with great toe flexion and/or fanning of ipsilateral

digits two through five. The therapeutic session

is 30 min long and sessions may be carried out

weekly.

Results

The results of a large multicenter study on

patients with urge incontinence and frequency–

urgency were reported by Govier et al. [8] .

Fifty-three patients who met study entry criteria

were treated for a total of 12 weeks; 47 patients

finished the trial and were evaluable. Overall,

the patients achieved a 35% reduction in daytime

and nighttime urge incontinence or leak episodes

during the 12-week treatment period ( P < 0.05).

Of the patients completing the trial, 71% were

classified by the investigators as having achieved

treatment success after 12 weeks. Success was

defined as at least a 25% reduction in daytime

and/or nighttime frequency. No serious or unan-

ticipated adverse events were reported, and no

adverse events resulted in patient discontinua-

tion from the study. There were three events that

met the definition of a primary safety endpoint

adverse event, including moderate throbbing pain

at the needle site, moderate right foot pain, and

stomach discomfort. All events resolved sponta-

neously and did not preclude further treatment.

Although the defined criteria for a successful out-

come in this trial can be debated, there certainly

appeared to be some defined improvement in

patient symptoms and in quality of life indicators

with minimal patient risk.

Another study reported by Amarenco [8] uti-

lized acute posterior tibial nerve stimulation with

surface electrodes to study changes in urodynamic

parameters in patients with detrusor overactiv-

ity including neurogenic detrusor overactivity.

Mean first involuntary detrusor contraction vol-

ume increased from 163±96 ml to 232±115 ml

during posterior tibial nerve stimulation, while

Fig. 18.1. Needle placement for tibial nerve stimulation

(SNS) (picture courtesy of Drs. P. Rosenblatt and N. Kohli)

Fig. 18.2. Tibial neurostimulation (picture courtesy of

Drs. P. Rosenblatt and N. Kohli)

230 A.K. Das

maximum cystometric capacity increased from

221±130 to 277±118 ml. Both results were statis-

tically significant at <0.0001. Other more limited

studies by Pannek [10] and Karademir [11] show

similar results.

Conclusions

Tibial nerve stimulation may be considered an

alternative for patients with urinary frequency–

urgency or urge incontinence who have not

responded to behavioral modification, biofeed-

back, and pelvic floor rehabilitation. Some may

argue that this modality may be worth trying

in patients with OAB even prior to consider-

ing anticholinergic medication, but larger-scale,

longer-term trials are needed prior to making

such a determination. However, it is clear that a

significant number of patients with OAB symp-

toms either do not respond to or cannot tolerate

the side effects of current anticholinergics, and

it is not unreasonable to try these patients on

peripheral neuromodulation such as tibial nerve

stimulation. Unfortunately, there also are many

limitations to such peripheral neuromodulation,

including insurance coverage issues in the United

States, and the requirement for the patient to

make periodic visits for needle placement and

stimulation as an implantable neuroprosthesis is

not currently available. If such an implantable

neurostimulator system becomes available and

further long-term data can show lasting improve-

ment in patient symptoms and quality of life indi-

cators, peripheral neuromodulation may develop

a much larger following as this approach offers

patients and physicians alike a less invasive and

less expensive treatment option compared to sac-

ral neuromodulation.

References

1. Abrams P, Cardozo L, Fall M, et al. The standardisa-

tion of terminology of lower urinary tract function:

report from the Standardisation Sub-committee of

the International Continence Society. Neurourol

Urodyn 2002;21:167–178.

2 . Caldwell KP . The electrical control of sphincter

incompetence . Lancet 1963 ; 2 : 174 – 175 .

3 . McGuire EJ , Zhang SC , Horwinski ER , Lytton

B . Treatment of motor and sensory detrusor

instability by electrical stimulation . J Urol

1983 ; 129 (1) : 78 – 79 .

4 . Leng WW , Chancellor MB . How sacral nerve stimu-

lation neuromodulation works . Urol Clin North Am

2005 ; 32 (1) : 11 – 18 .

5 . Yoshimura N , Seki S , Chancellor MB , et al.

Targeting afferent hyperexcitability for therapy of

the painful bladder syndrome . Urology 2002 ; 59 (5

Suppl 1) : 61 – 67 .

6 . Fowler CJ . The perspective of a neurologist on treat-

ment-related research in fecal and urinary incon-

tinence . Gastroenterology 2004 ; 126 (1 Suppl 1) :

S172 – S174 .

7 . Fowler CJ , Swinn MJ , Goodwin RJ , et al. Studies

of the latency of pelvic floor contraction dur-

ing peripheral nerve evaluation show that the

muscle response is reflexly mediated . J Urol

2000 ; 163 (3) : 881 – 883 .

8 . Govier FE , Litwiller S , Nitti V , et al. Percutaneous

afferent neuromodulation for the refractory overac-

tive bladder: Results of a multicenter study . J Urol

2001 ; 165 (4) : 1193 – 1198 .

9 . Amarenco G , Ismael SS , Even-Schneider A , et al.

Urodynamic effect of acute transcutaneous posterior

tibial nerve stimulation in overactive bladder . J Urol

2003 ; 169 (6) : 2210 – 2215 .

10 . Pannek J , Nehiba M . [Initial results of Stoller

peripheral neuromodulation in disorders of bladder

function] . Urologe A 2003 ; 42 (11) : 1470 – 1476 .

11 . Karademir K , Baykal K , Sen B , et al. A peripheric

neuromodulation technique for curing detrusor over-

activity: Stoller afferent neurostimulation . Scand J

Urol Nephrol 2005 ; 39 (3) : 230 – 233 .

231

Introduction and Indications for

the Surgical Treatment of Urge

Incontinence

Detrusor Overactivity

Detrusor overactivity (DO) is characterized by

involuntary detrusor contractions during the filling

phase and is associated with urgency or urge incon-

tinence. Urge urinary incontinence (UUI) is the

complaint of involuntary leakage accompanied by

or immediately preceded by urgency [1] . Patients

with severe DO are distressed by urinary inconti-

nence and often are desperate for treatment. The

vast majority of patients suffering from overactive

bladder and UUI can be treated successfully using a

combination of pharmacological therapy, behavio-

ral management, and lifestyle adjustments. During

the last decades the evolution in understanding the

pathophysiology of the irritative-storage symptoms,

along with the widespread adoption of urodynam-

ics, have centered treatment on drugs that modulate

the cholinergic control of detrusor contractions

during the storage phase. This has resulted in com-

petitive nonselective muscarinic antagonists having

dominated the field of overactive bladder (OAB)

treatment during the last few years.

Bladder training, pharmacotherapy, transcutaneous

electrical nerve stimulation, or S3-neuromodulation

and lately botulinum toxin type-A injections are

considered to be the major contemporary treat-

ment alternatives for OAB-related incontinence.

Consequently, the treatment of the OAB-related urge

incontinence has to follow a stepwise fashion, start-

ing with the minimal invasive and least harmful

therapy and escalating to major surgery.

Surgical treatment for intractable nonneuropathic

OAB incontinence therefore is reserved for those

who have failed an adequate trial of these measures.

However, resolution to surgery which may involve

transposition of intestinal segments into the urinary

tract (eg, augmentation enterocystoplasty) should

be the outcome of adequate counseling and com-

plete and thorough urological–urodynamic evalua-

tion, given the associated risks and complications of

these largely invasive surgical procedures.

Neurogenic Bladder Dysfunction

Neurogenic bladder dysfuntion (NBD) usually

is the result of congenital or acquired disor-

ders including myelodysplasia, multiple sclerosis,

detrusor hyperreflexia, spinal cord injury, sac-

ral agenesis, cerebral palsy, and previous pelvic

operations such as hysterectomy. In the context of

NBD the clinical picture is complicated further by

additional problems related to bladder overactivity,

including detrusor contraction and varying degrees

of bladder outflow obstruction [2] .

NBD can present clinically in a number of

ways including frequency, urgency, urinary incon-

tinence, intermittency, urinary retention, or urinary

tract infections. Before the era of clean intermit-

tent self-catheterization (CISC) [3] , many patients

with NBD had their urine diverted by means of an

ileal conduit when conservative measures failed.

Chapter 19

Surgery for Urge Urinary Incontinence:

Cystoplasty, Diversion

Petros Sountoulides and M. Pilar Laguna

232 P. Sountoulides and M.P. Laguna

Now, NBD is a major indication for augmenta-

tion cystoplasty or urinary diversion in women [4,

5] . The main indications for such surgery in this

group of patients include intractable incontinence,

deteriorating renal function, and high-pressure

bladders [6] .

Surgical Techniques for the

Management of Urge Incontinence

In recent years the mainstay of contemporary

therapy for urge incontinence has been augmenta-

tion cystoplasty, most usually using the “clam”

technique [2] . Surgical options that have been

added to the options for the management of urge

incontinence in recent years include bladder auto-

augmentation, sacral neuromodulation, and lately

bladder augmentation using tissue engineering.

It is the purpose of this chapter to focus mainly

on the role of augmentation cystoplasty, autoaug-

mentation, and urinary diversion for the contempo-

rary management of urge incontinence associated

with DO and NBD. However, the current position

of open or transurethral bladder denervation tech-

niques also will be briefly discussed (Table 19.1 ) .

Denervation Techniques

Escalating from the least invasive techniques to

major procedures for the treatment of urge inconti-

nence one has to comment on the various denerva-

tion techniques that have been described. The aim of

denervation is to interrupt the micturition reflex and

therefore reduce involuntary detrusor contractions.

Both open and endoscopic denervation tech-

niques have been used for the treatment of OAB

and neurogenic detrusor overactivity over the

years. Transvaginal or transurethral ablation of the

afferent postganglionic nerve fibers by the use of

injectable phenol or ethanol were plagued, how-

ever, by serious complications, such as vesicovagi-

nal fistulas and detrusor acontractility [7, 8] .

Subtrigonal injection of a neurolytic chemical

agent, phenol, in an aqueous solution of 5–6%, has

been described for denervation. Initial short-term

results were encouraging, reporting response rates

between 58 and 83% [9, 10] , but were not repro-

duced by subsequent studies with longer follow-up.

In fact, the procedure led to disappointing results

with sustained benefit in the long-term, progres-

sively declining from 16% (at 6 months) to 0%

(after 4 years) [11– 13] .

The technique has significant complications,

including bladder ulcers, abscesses, fistula forma-

tion, urinary retention, and significant hematuria.

The routine use of transvesical phenol injection no

longer can be supported because of its high com-

plication rate together with the fact that it produces

unreliable and short-lived results.

Ingelman–Sundberg Bladder Denervation

Procedure

The Ingelman–Sundberg procedure for the treat-

ment of urge incontinence associated with detru-

sor overactivity originally was introduced by the

surgeon with the same name in 1959 [14] . It is an

open denervation procedure, which aims at disrupt-

ing the innervation from the inferior hypogastric

plexus to the bladder. This is accomplished by

extensive dissection near the cervix via a transvaginal

Table 19.1. Results of the most frequent surgical techniques for management of urge incontinence .

Technique Results Remarks

Ingelman-Sundberg denervation 54–64% cure urge incontinence Follow-up 1 year to mean of 44 months

14% partial response

Clam enterocystoplasty Continence in NBD 72–90% Results are less satisfactory in women

Continence in DO 70–90%

Bladder autoaugmentation 80% Continence improvement in

children

No/or up to 40% increase in bladder

capacity

63% Continence improvement in adults 23–45% of children require entero-

cystoplasty

Few studies in adults

19. Surgery for Urge Urinary Incontinence 233

approach and division of the preganglionic pelvic

nerves in this region.

Patient Selection and Evaluation

Female patients with urge incontinence who had

failed conservative therapy were candidates for the

Ingelman–Sundberg procedure and initially were

subjected to subtrigonal infiltration with a local

anesthetic in order to predict the outcome of the

open denervation procedure.

The anesthetic block was given with the patient

on a cystoscopy table, and 10 ml of 0.25% bupi-

vacaine were injected using a 22-gauge spinal

needle in different areas of the region of the trig-

one via a transvaginal approach. Then the patient's

response during the action of bupivacaine (6–24 h)

was evaluated. Patients who reported significant

benefit from the injection of the local anesthetic,

interpreted as marked decrease or complete resolu-

tion of urge incontinence episodes, were offered a

transvaginal open bladder denervation [15] .

Technique and Complications

An inverted-U vaginal incision is made in the

anterior vaginal wall over the bladder trigone,

while the patient is in the dorsal lithotomy posi-

tion under regional or general anesthesia. A foley

catheter of 14–16 Ch can be placed in order to

facilitate identification of the trigone and retrac-

tion of the bladder. The vaginal epithelium and

perivesical fascia are dissected off the trigone,

while the plane of dissection is kept within the

serosal layer of the bladder. Sharp and blunt dis-

section are limited to the lateral and posterior

borders of the bladder in order to obtain access

to the terminal branches of the pelvic nerve and

divide them. After the pelvic nerve plexuses have

been dissected, the vaginal mucosa is reapproxi-

mated with a running 2–0 chromic and a povidone

iodine-soaked vaginal pack is placed.

The entire procedure does not take more than

15 min and blood loss is minimal. The urethral

catheter and vaginal pack are removed the next

morning and the patient is discharged after con-

firming that she is voiding freely. Complications

include transient retention or voiding dysfunction,

while theoretically there is a risk of inadvertent

injury to the bladder or ureter in case the dis-

section extends beyond the serosal layer of the

bladder. However, in experienced hands there

were no complications whatsoever related to this

procedure [15] .

Results

Initial results from case series were encouraging,

with the majority of patients with detrusor overac-

tivity incontinence either cured or improved [16] .

A modification of this technique with limited

vaginal dissection yielded a 64% cure rate of urge

incontinence at a mean follow-up of more than

1 year and reduced morbidity [17] (level 4 evi-

dence).

Longer-term results (mean 44 months) of the

modified Ingelman–Sundberg technique in a series

of 28 patients revealed a 54% success rate with

cessation of all urge incontinence episodes, while

another 14% showed partial response, demonstrat-

ing at least 50% decrease in urgency and urge

incontinence episodes [18] . However, the lack of

randomized controlled trials or even comparative

studies regarding the efficacy and durability of the

original or modified Ingelman–Sundberg proce-

dures limits the ability to draw more substantiated

conclusions.

Enlargement (Augmentation) Cystoplasty

Augmentation cystoplasty is a procedure during

which the bladder is enlarged (augmented) by

incorporating a selected gastrointestinal segment

as a patch into the native bladder. Augmentation

cystoplasty in the canine model was first described

in 1888 [19] . Enterocystoplasty was first performed

in humans by von Mikulicz in 1899 [20] , and later

popularized by Couvelaire [21] for the treat-

ment of the small contracted tuberculous bladder.

Bladder-augmenting, pressure-reducing sphincter

cystoplasty procedures were introduced later for

the treatment of refractory detrusor overactivity-

related incontinence [22, 23] as well as for patients

with NBD usually caused by spinal cord injury,

multiple sclerosis, and myelodysplasia [24, 25] .

The therapeutic goal for the patients with urge

incontinence is to provide adequate urinary stor-

age by creating a low-pressure reservoir with con-

venient, voluntary, and complete emptying while

preserving renal function and continence [26] . The

principle underlying any form of augmentation

234 P. Sountoulides and M.P. Laguna

cystoplasty is that by dividing a functionally overactive

bladder and interpositioning an intestinal segment

it is possible to create a bladder with an increased

functional capacity and a lower end filling pressure.

Among the factors that enhanced the adoption of

bladder augmentation techniques for the treatment

of urge incontinence, the introduction of clean

intermittent catheterization as a safe and effective

method of emptying the bladder was marginal [3] .

Additionally, the consequent wide adoption of

urodynamics proved beyond any doubt that in the

patient with NBD, a high-pressure lower urinary

tract potentially can cause upper tract dilatation,

renal dysfunction, and insufficiency [27] .

Surgical Options; Which Bowel Segment

to Use?

Theoretically every portion of the gastrointestinal

tract, as well as the ureter, has been used for blad-

der augmentation [28] . The choice of intestinal

segment is a matter of preference of the surgeon,

as it does not appear to be an important factor

for predicting success or complications, with the

exception of jejunum, which quickly fell into dis-

repute because of particular problems with water

reabsorption [29] . However, no single segment has

been proved ideal for bladder augmentation, as

each is associated with unique properties and pos-

sible complications [30] .

The cecum can be used as a detubularized patch in

conjunction with the terminal ileum as an ileoceco-

plasty, and it has advantages in cases where cysto-

plasty is part of undiversion [31] . However, the use

of cecum for augmentation cystoplasty is avoided

because of the high incidence of diarrhea and mal-

absorption associated with resection of the ileocecal

valve, and the fact that cecocystoplasties produce

50% more mucus than ileocystoplasties [26, 32] .

The sigmoid is the usual alternative to ileum

for a simple augmentation. The sigmoid has the

advantages of a thick muscular wall, large lumen

size, and abundant mesentery, ensuring adequate

neobladder capacity [33, 34] . Furthermore, sig-

moid cystoplasty appears to have significantly

less postoperative bowel dysfunction than ile-

ocystoplasty [35] . The disadvantages of sigmoid

cystoplasty are the higher risk of UTI (secondary

to colonic bacteria) and a theoretically higher

long-term risk of malignancy [26] . Therefore and

for these reasons its use is not encouraged and is

restricted in cases where the ileum has a very short

mesentery or is unavailable.The stomach occasion-

ally has been used for bladder augmentation as an

alternative to enterocystoplasty in situations where

bowel was unavailable or unsuitable. Stomach

theoretically could be an ideal material for blad-

der augmentation because it is easy to mobilize, is

well-vascularized, and produces less mucus than

bowel. Furthermore, it secretes hydrochloric acid

which has a bactericidal action (asymptomatic

bacteriuria is seen in only 20–30% of patients) [36,

37] . However, contemporary indications of gastro-

cystoplasty are limited to the occasional patient

who is predisposed to stone formation or has a his-

tory of pelvic irradiation. Complications specific to

gastrocystoplasty include mainly the “hematuria–

dysuria” syndrome due to gastric acid secretions.

This syndrome consists of bladder/urethral pain,

hematuria in the absence of infection, and skin

excoriation, which represents a serious complica-

tion seen in up to 36% of patients after gastric aug-

mentation [30] . Other complications include peptic

ulceration of the bladder, perforation of the gastric

segment due to peptic ulcer, and hypergastrinemia

with consequent metabolic alkalosis [38– 41] .

Complications associated with partial gastrectomy

include “dumping” syndrome and exacerbation of

pre-existing peptic ulcer disease or gastroesopha-

geal reflux, while there also is the risk of malig-

nancy in the gastric patch. The combination of

these problems, but particularly the hematuria–

dysuria syndrome, have reduced the use of stomach

for augmentation, except as a last resort when no

other alternatives are available [26] .

Ileum has been used to form a bladder cup [42]

or to create a simple form of cystoplasty when used

as a detubularized segment [23] . Although bowel

contractions cannot be completely abolished, detu-

bularization of the ileum is important to prevent per-

istaltic waves [43] . Moreover, detubularized ileum is

preferable to sigmoid colon because its tissue prop-

erties demonstrate better compliance and ensure the

creation of a lower pressure reservoir [44] .

Patient Selection and Evaluation

A complete evaluation of both upper and lower

urinary tracts with detailed estimation of bladder and

sphincter function is fundamental to the success of any

19. Surgery for Urge Urinary Incontinence 235

bladder augmentation procedure. Renal ultrasonog-

raphy and radionuclide scan together with serum

creatinine measurement will suffice for evaluating

renal function, while the lower urinary tract is evalu-

ated with filling and voiding videourodynamics and

cystourethroscopy. Additional studies such as elec-

tromyography may be required for the evaluation of

patients with specific neurological lesions.

In urge incontinence associated with NBD,

sphincteric function should be assessed in order

to exclude the presence of a dyssynergic sphinc-

ter, which could be managed by simultaneous

sphincterotomy. Patients with an underactive

sphincter and a normal urethra may be managed

synchronously with augmentation cystoplasty and

an artificial urinary sphincter (AUS) or periure-

thral bulking agent (Teflon, collagen, autologous

fat) or colposuspension in females [43] . The AUS

can be inserted during the same session with aug-

mentation cystoplasty in neuropathic patients [26]

with no increased risk of infection [45, 46] , while

implantation of just the cuff of the AUS initially

may prove adequate in achieving continence [47] .

In the few patients who will fail to achieve a criti-

cal balance between voiding efficacy and continence,

resorting to clean intermittent self-catheterization

(CISC) may be necessary. It has been estimated that

more than one third of patients with DO urge incon-

tinence will need to perform CISC in the long-term

after augmentation cystoplasty [48] . Therefore, the

willingness and manual dexterity to perform CISC

should be preoperatively assessed in all patients who

are candidates for the procedure [15] .

In the case of urge incontinence associated with

NBD, preoperative evaluation of the upper urinary

tracts is necessary in order to exclude the presence

of hydronephrosis and the risk of renal insufficiency

resulting from the transmission of high back pres-

sures from a reduced compliance bladder toward

the upper urinary tract. Therefore, the combination

of enterocystoplasty with other reconstructive pro-

cedures not only safeguards continence but also can

be effective in reducing the risk of reflux, associated

infection, and upper tract pressure-related injury.

Contraindications

The presence of impaired renal function is a more

controversial relative contraindication. In this case

the re-absorption of urea and electrolytes from the

bowel segment may lead to decompensation of

renal function and renal insufficiency. Although

there is evidence that augmentation in the presence

of an already impaired creatinine clearance is asso-

ciated with progressive decline in renal function,

correction of the bladder abnormality in patients

with even endstage renal failure has provided con-

tinence without adding a further negative effect in

the rate of decline in renal function [26] .

The issue of CISC already has been discussed;

unwillingness or inability to perform CISC may

render the option of augmentation cystoplasty inap-

propriate. An alternative option in these cases is the

formation of a continent diversion with a cath-

eterizable abdominal stoma using the Mitrofanoff

technique or other variations, which could be man-

aged even by patients with poor dexterity due to

neurological impairment [48, 49] .

Some indications for creating an abdominal

stoma include women with spasticity of the lower

extremities because of neurological conditions,

patients whose native urethra is obstructed or

damaged, and those with refractory sphincteric

incontinence or fistulas. Although a continent

catheterizable stoma may prove to be effective,

stomal complications are seen in almost half of the

patients [50] .

Moreover, continent diversion with the use of a

Mitrofanoff stoma is associated with a higher inci-

dence of mucus retention within the bladder, which

probably accounts for the higher incidence of stone

formation in these patients. This is the reason why

some surgeons choose to place the Mitrofanoff stoma

as low as possible on the abdominal wall, to aid the

siphon effect during bladder catheterization [29] .

Another contraindication, although not an abso-

lute one, to bowel substitution cystoplasty is the

presence of a severely irradiated bladder with the

possibility of compromised sphincter function. The

presence of intrinsic bowel disease, eg, Crohn's

disease, may affect the choice of the substitution

segment, while in cases of short gut syndrome or

previous radiotherapy the additional removal of the

bowel segment might prove disastrous [26] . Liver

function tests and arterial blood gases also should

be checked preoperatively to rule out hepatic fail-

ure, which could be aggravated by ammonia resorp-

tion through the bowel used in cystoplasty [43] .

The extremely poor results that have been dem-

onstrated in cases of severely diseased and fibrotic

236 P. Sountoulides and M.P. Laguna

bladders due to interstitial cystitis have led authors

to consider interstitial cystitis a contraindication

for any form of enterocystoplasty [50] .

The “Clam” Ileocystoplasty

Different procedures for ileocystoplasty have been

described, including the bladder augmentation

technique proposed by Leng et al. [51] , where a

detubularized U- or S- or W-shaped ileal flap is

interpositioned into an anterior wall-based cystot-

omy. However, the most frequently performed

variation of enterocystoplasty is the “clam shell”

ileocystoplasty, originally introduced by Bramble

in 1982 and later popularized by Mundy and

Stephenson [22] , will be discussed in more detail

in this chapter [23] .

The “clam” enterocystoplasty, which is a simple

augmentation ileocystoplasty, actually was devel-

oped in order to overcome certain problems that

were faced with previously used augmentation

techniques. Previous experience with simple aug-

mentation cystoplasties without bladder resection,

like the Goodwin “cup-patch” procedure [42, 52] ,

had shown that with these procedures the bladder

was actually “augmented” into a low-pressure and

a high-pressure compartment. This way, unstable

detrusor contractions would lead to the evacua-

tion of the high-pressure compartment to the low-

pressure (patch) compartment, thus leading to the

formation of a bladder diverticululum.

The rationale of the “clam” procedure is that

bladder augmentation by ileum interposition is

combined with deactivation of the detrusor by

extensively “bivalving” it. In this way when the

two parts of the reconstructed “clam bladder” con-

tract synchronously, the risk of diverticulating the

intervening U-shaped patch of ileum is minimized.

Another plausible mechanism for improvement with

the “clam” procedure involves mainly the reduction

of intravesical pressure rather than the accomplished

increase of bladder volume, since the incorporated

bowel segment remains relaxed while the bladder

contracts.

During clam ileocystoplasty the bladder is

divided almost completely by a coronal or sagit-

tal incision, which is carried down to the bladder

base within 1.5 cm of the internal urethral meatus,

just anterior to the ureteric orifice on each side.

This way the bivalved bladder resembles an open

scallop or clam, hence the term “clam shell” con-

figuration [53] .

Although there functionally is no difference

whether the bisecting incision is sagittal or coronal,

some authors have found the sagittal incision to be

technically simpler [54] . A technical point of vital

importance is that both ends of the incision are

extended right down to the bladder base to ensure

deactivation of the overactive detrusor.

An isolated, about 25-cm-long segment of ileum,

located 25–40 cm from the ileocecal valve, is ideal

for bladder augmentation as it produces the least

metabolic consequences. The ileal segment then is

incised along its antimesenteric border, detuburar-

ized, and patched to the open bladder. The ileal

patch can be sutured into the bladder defect with

a single layer of continuous vicryl [53] or a single

interrupted layer of 3–0 PGA suture. An important

technical point in this step of the procedure is to

take care not to obstruct the ureteric ostium by

including it in the anastomotic suturing.

Adequate bladder drainage after augmentation

cystoplasty is of utmost importance during the

early postoperative phase. For this reason a 19F

Jackson-Pratt fenestrated tube [55] or a 22F to 24F

catheter must be placed as a suprapubic catheter

[15] along with a large-bore urethral catheter to

ensure optimum bladder drainage. Furthermore,

the use of sling-suture-retained catheters is pre-

ferred over balloon-retained urethral catheter by

some authors, since inadvertent traction upon

a self-retained catheter may result in disastrous

disruption of the anastomotic suture line between

bowel and bladder.

Intraoperatively the anastomotic suture line

can be tested by clamping the foley catheter

while infusing saline into the suprapubic catheter.

Postoperatively, continuous normal saline irriga-

tion (2 liter/day) can be administered in order to

prevent catheter blocking by mucus or blood clots.

Continuous irrigation is usually stopped the fol-

lowing day and replaced by catheter flushing twice

daily [55] . Patients usually are discharged home a

week or more after the operation with both drain-

ing catheters in place. The suprapubic catheter

usually is removed on the 12th day and the ure-

thral catheter is removed 2 weeks postoperatively

(Fig. 19.1 ).

Modifications of the “clam” ileocystoplasty have

been described, like the star incision of the bladder as

19. Surgery for Urge Urinary Incontinence 237

Fig. 19.1. Pretransplantation clam enterocistoplasty with ileum in a young man with terminal kidney insufficiency

because of a NBD (spina bifida), with ureteral obstruction at the bladder level and low-capacity, low-compliance

bladder unsuitable for ureter reimplantation. ( a ) Cystography in the perioperative period. ( b ) Anterograde study via

nephrostomy drains showing the large dilated kidney pelvis, the tortuous and dilated ureter, and the passage of the

contrast to the isoperistaltic ileal loop (ileal chimney)

a modification of sagittal cystotomy. This variation

has been described in pediatric patients with NBD

with small, thick-walled bladders with diminished

capacities and poor compliance [56] . However, it

never proved to be superior to conventional clam

shell cystoplasty in terms of efficacy, and further-

more thoughts were raised that additional cystoto-

mies might compromise blood supply in these

patients. Another alternative is the “McGuire”

modification of the hemi-Kock procedure of a

transverse “smile” incision, which is fashioned

3 cm above the ureteral orifices, creating an anteri-

orly based detrusor flap [57] .

Follow-Up After Augmentation Cystoplasty

Lifelong follow-up of patients after augmentation

cystoplasty is crucial in achieving and maintain-

ing satisfactory results, while guarding the patient

from the long-term complications associated with

these procedures. Adequate bladder emptying is

monitored by residual urine measurement and

ultrasonography of the upper tracts biannually for

the first 2 years and then annually.

Uroflowmetry is not included in the routine fol-

low-up of patients after augmentation cystoplasty.

Alternatively, patients may undergo videourody-

namics every 6 months after augmentation to docu-

ment the presence of a good-capacity, low-pressure

bladder that empties well with low residual vol-

ume. Urodynamic studies have shown that contrac-

tility and compliance after augmentation remains

unchanged or even deteriorates in about half of

patients with neuropathic dysfunction, possibly

because intrinsic bowel dysfunction reduces bowel

compliance in these patients [58] .

Should voiding problems occur, a simple void-

ing cystourethrogram (VCUG) or even better, an

ultrasound VCUG is the investigation of choice for

the evaluation of insufficient voiding. This exami-

nation can reliably locate the site of a possible out-

let obstruction (bladder neck, urethra) and provide

information for appropriate management.

While isotope renography is indicated in cases

of possible obstruction of the upper tracts, annual

isotopic measurement of the GFR is suggested by

some authors [26] . Annual flexible cystoscopy is

commenced 5–10 years after augmentation.

238 P. Sountoulides and M.P. Laguna

Complications and Their Management

Early complications include those cardiovascular,

thromboembolic, respiratory, and gastrointestinal

complications associated with any major abdomi-

nal surgery. Augmentation cystoplasty is reported

to have 0–2.7% mortality, with higher mortality

rates and higher complication rates reported in the

earlier series where augmentation was part of uri-

nary undiversion [31, 59] (Table 19.2 ) .

Bowel-Related Complications

Complications after augmentation enterocysto-

plasty can be significant, mounting up to a rate of

20–22% in some series [57, 60] . Complications

associated with bowel are distinguished from those

that are inherent to any gastrointestinal surgery and

result from the disruption of the gastrointestinal

tract and those that arise from the resultant chronic

contact of a bowel segment with urine. Early

bowel-related complications include small bowel

leak, ileus, or bowel–bladder anastomotic leak and

fistula formation. Late gastrointestinal complica-

tions include adhesion formation, chronic bowel

obstruction, or alterations in bowel habits [55] .

Any technique of augmentation cystoplasty

requires access to the peritoneal cavity, and this

carries a considerable risk of postoperative intes-

tinal obstruction from adhesions. Although the

exact incidence of this complication is not known,

it was estimated to occur in about 10% of pediatric

patients undergoing ileocystoplasty [61] .

The onset of irregularity in bowel habits, par-

ticularly frequency and diarrhea, is one debilitating

long-term complication, with significant effect on

the patient's quality of life [62] . Up to 25–30% of

patients experience long-term problems of increased

bowel frequency and troublesome diarrhea, while a

quarter of patients with NBD have increased fecal

incontinence after enterocystoplasty [35, 63] . The

pathogenesis of postaugmentation diarrhea is not

clear. A reduction in small bowel absorption may

account partly for the increased frequency and

diarrhea, although patients with an ileocystoplasty

rarely have >30 cm of ileum resected [26] . On the

other hand, there is a clear association of detrusor

instability with irritable bowel syndrome in up to

30% of patients [64] , implying that there might be

a common intrinsic disorder of smooth muscle and

nerve supply accounting for both the bladder and

bowel problems.

Metabolic Disturbance

The incorporation of a bowel segment into the

bladder leads to the exposure of the absorptive

surface of the small intestine to urine metabolites.

This results to a certain degree in reabsorption of

water, sodium, hydrogen ions, ammonium, and

chloride and increased loss of potassium and bicar-

bonate into the urine [65, 66] .

This chronic effect may lead to the disturbance

of the acid–base balance and the development of

hyperchloremic metabolic acidosis in ileo- and

colocystoplasty. However, this complication is

almost always mild or even subclinical and only

in rare symptomatic cases requires oral bicarbo-

nate therapy [29, 67] . Chronic metabolic acidosis

causes mobilization of calcium carbonate from

Table 19.2. Complications of augmentation cystoplasty .

Early Late

Bowel related Intestinal leak Intestinal adhesions

Ileus Intestinal obstruction

Bowel-bladder leak Alteration bowel habits

Fistula Possible vitamin B12 deficiency

Bowel/urine contact related – Hyperchloremic acidosis

Growth reduction (children)

Mucus formation

Malignant transformation

Bladder perforation

Bladder stone formation

Voiding dysfunction

Intrinsic to bladder disorder UTI UTI

Bacteriuria Bacteriuria

19. Surgery for Urge Urinary Incontinence 239

bone and may lead to orthopedic problems or

growth reduction in the pediatric population [68] .

However, ileum, unlike colon, can reabsorb urinary

calcium and may be less prone to this problem.

Vitamin B12 deficiency may occur in case large

segments of terminal ileum are used, and long-term

follow-up for hematological sequela of this event is

mandatory [69] .

Mucus Formation

Mucus buildup in the augmented bladder after ente-

rocystoplasty is a problem that also arises from the

interposition of small bowel into the bladder and

has been reported by as many as 81% of patients

[55] . The average daily mucus production from both

ileum and colon when used as a cystoplasty segment

is 35–40 g, and this amount does not reduce sub-

stantially over time, despite a time-related villous

atrophy of the intestinal patch mucosa [26] .

Mucus has been implicated in stone formation

since it binds calcium from the urine and is thought

to act as nidus for calculi formation in the augmented

bladder [70] , although there is little actual evidence

of this [71] . On the contrary, mucus may have a

protective role to the bowel epithelium, from contact

with urinary carcinogens and other substances.

Preventive measures include proper patient

instruction to perform weekly or even daily bladder

wash out [15, 72] . Oral ranitidine can reduce the

amount of mucus produced [73] , while instillation

of water-soluble N -acetylcysteine into the bladder

also has been suggested for dissolving mucus [74] .

Urinary Tract Infections

The problem of recurrent urinary tract infections

(UTIs) after augmentation cystoplasty has a criti-

cal impact on the patient's perceived view of the

outcome after the procedure, owing to the added

morbidity of recurrent infection and long-term

antibiotic treatment. Patients with NBD urge incon-

tinence and high-pressure urine storage or with

significant residual urine volumes already have a

high incidence of severe symptomatic UTI before

surgical treatment with bladder augmentation [75] .

In cases of NBD requiring CISC to empty the blad-

der, nearly half of the patients already suffer from

chronic or recurrent UTIs [76] , while in most cases

the problem does not seem to respond to antibiotic

prophylaxis [77] .

Although recurrent bacteriuria can be found

in more than 75% of patients after augmenta-

tion cystoplasty [26] , the incidence of sympto-

matic UTI is lower [62, 78] . Bacteriological data

from patients who underwent the clam cystoplasty

revealed that 84% of patients on CISC had posi-

tive cultures, while bacteriuria was present even in

60% of patients who voided spontaneously [79] .

Predisposing factors to the development of UTIs

apart from the high bacterial content of bowel

include large residual volumes, the presence of

mucus, and the need for CISC. In the follow-up of

a group of 48 patients (35 with DO) who under-

went clam enterocystoplasty, 37% suffered from

recurrent UTIs requiring frequent antibiotic treat-

ment more than 1 year after surgery [55] .

Therefore, a rigorous strategy of early detec-

tion and elimination of infection is of great

importance in the follow-up of these patients.

However, after enterocystoplasty, despite the con-

tinued need for CISC, there are fewer episodes of

symptomatic UTI, especially in the patients with

NBD, probably owing to the beneficial effect of

lowering the intravesical pressure. Therefore, the

incidence of significant infective complications

after cystoplasty seems to mirror that seen in

patients with an ileal conduit or indwelling uri-

nary catheters [29] .

Malignant Transformation

The first reports of malignancies occurring in

enterocystoplasties came in the early 1970s [80,

81] . Several reports on the occurrence of tumors

after bladder augmentation procedures followed

[82– 85] . Ileocystoplasty carries a low, although

significant risk of malignancy [86] while cancers

arising within augmented bladders are aggressive

and associated with significant mortality [87] .In

particular, tumors arising after ileocystoplasty usu-

ally are located at the enterovesical anastomosis or

on the intestinal side of the bladder augmentation

[88] . Since the intact ileum rarely undergoes malig-

nant transformation, it was considered possible that

urine stasis due to the longer period of urine stor-

age within the augmented bladders together with

the large area of juxtaposition between transitional

bladder and enteric epithelium may permit forma-

tion of carcinogens and malignant transformation

of epithelial cells [87] .

240 P. Sountoulides and M.P. Laguna

The etiology of malignant transformation in

augmented bladders is probably multifactorial.

The fact that most cases occur in adults with other

potential risk factors makes it difficult to determine

the exact independent risk associated with bladder

augmentation.

On the other hand, the most common contempo-

rary indication for augmentation cystoplasty is in

children and adolescents with a NBD, the majority

of whom have no risk factors for bladder cancer

[89] . It seems reasonable to believe therefore that

bladder augmentation may be an independent risk

factor for the development of malignancy.

The majority of tumors have been adenocarci-

noma of the bowel or bladder [87] or squamous

cell carcinomas, although cases of transitional cell

carcinoma (TCC) also have been reported. Soergel

et al. found TCC to develop in 1.2% of cases after

bladder augmentation within a mean time of 19

years [89] .

One of the etiological factors for malignant

transformation was postulated to be the elevated

levels of urinary nitrosamines [90] . The basic

idea is that nitrates, which are normally excreted

in the urine, are degraded to nitrites by colonic

bacteria. Nitrites then react with urinary secondary

amines to form N -nitrosamines. These compounds

have the capability of carcinogenic activity, and

therefore may act as tumor initiators [87] . Urinary

tract infection and chronic inflammation of the

urothelium are known to be associated with an

increased risk of bladder tumor formation [82, 87] ,

while the presence of high levels of N -nitrosamines

correlates strongly with heavy bacterial growth on

urine culture in ileal cystoplasties [91] .On the other

hand, inflammatory bladder diseases not associ-

ated with bacterial infection such as tuberculosis

appeared to be associated with a significant risk of

late bladder tumor formation. There were cases of

primarily adenocarcinomas that originated near the

anastomosis after augmentation enterocystoplast-

ies, most of which were performed on small con-

tracted bladders due to genitourinary tuberculosis

[88, 92– 95] .

The etiology of these augmentation tumors prob-

ably is related to chronic inflammation, wound

healing, and malignancy. A possible explanation

why these tumors usually arise near the anasto-

motic area is that the products of inflammation and

healing may act as tumor promoters [96] . Tumor

development can be initiated with the aid of certain

growth factors such as the basic fibroblast growth

factor, which is thought to originate from the

bowel mucosa and has been shown to be elevated

in the urine of patients with enterocystoplasty

[97] . Although the exact role of elevated levels of

urinary basic fibroblast growth factor in the malig-

nant potential of clam enterocystoplasty is still

uncertain, there is clear evidence that no relation-

ship exists between bacteriuria and basic fibroblast

growth factor levels in these patients [97] .

Surveillance and Follow-Up Tactics

There is an issue as to what should be the appro-

priate surveillance for malignancy formation for

patients after bladder augmentation. Also, the time

between cystoplasty and the occurrence of tumor

is highly variable [98– 100] ; therefore, lifelong sur-

veillance is mandatory.

Initial recommendations focused on elimina-

tion of urinary infection and suggested annual

cystoscopic surveillance [53] . However, it seems

unlikely that every patient with an enterocysto-

plasty is at high risk of developing a life-threaten-

ing tumor, and malignancy in augmented bladders

is still considered to be a rare event [89, 92] .

Moreover, as the clam tumors described in the

literature have presented within a latency period

of 5–29 years (mean 18 years) [87] , some authors

suggest that lifelong cystoscopic follow-up should

start no earlier than 3 years [48] or even 10 years

after initial surgery [26, 89] . However, the fact that

the most of these tumors present incidentally and

only a few are detected by screening emphasizes

the need to develop methods of early identification

of the patients at risk of tumor formation [101] .

In this direction, the presence of genetic instabil-

ity at the enterovesical anastomosis in patients who

had undergone a clam ileocystoplasty was tested

using fluorescent in situ hybridization (FISH). The

results of this study indicated that morphologically

normal tissue obtained from the enterovesical anas-

tomosis displays evidence of chromosomal instabil-

ity that may predispose to tumor formation [101] .

However, polysomy, which is known to be an

unfavorable prognostic marker and is associated

with rapid progression of a cancer [102– 104] , was

not identified in any of the biopsies taken from

the enterovesical anastomosis. Further studies are

19. Surgery for Urge Urinary Incontinence 241

required to establish the clinical significance of the

FISH test in predicting the occurrence of tumor

after enterocystoplasty [101] . Although there are

suggestions that urine cytology should be rou-

tinely assessed in the follow-up of patients [43] ,

the presence of chronic bacterial infection and the

resultant infective changes in the bladder mucosa

render urine cytology unreliable for the diagnosis

of malignancy in augmented bladders [95] .

Perforation

Spontaneous perforation of the augmented blad-

der may occur in 5–10% of patients [105] , and is

associated with significant (>25%) mortality [106,

107] . Perforation is more common in patients with

NBD [48, 108] , in patients with recurrent UTI or

AUS implantation, and in those using CISC due to

infrequent or traumatizing bladder catheterization

[14, 105, 107– 112] . The perforation site is thought

to be located at the anastomotic suture line between

the bowel and the native bladder [26] ; however, this

is not always the case [107, 110, 111, 113] .

Bladder overdistension due to clot retention

or obstruction from mucus and the resultant high

intravesical pressures can cause transient localized

microvascular occlusion and local ischemia [111,

112, 114] . This may lead to the creation of an

ischemic scar tissue, which can easily rupture after

an abrupt increase in pressure [115] .

However, other experimental studies support

that it is the increased capacity of the enterocysto-

plasty bladder and increased wall tension, which

diminish wall thickness, that lead to perforation

[116] . Another possible reason is that repeated

bladder infections may lead to chronic inflamma-

tory changes, weakening of the bladder walls, and

perforation [108] .

Bladder perforation is a feared complication

because in cases of delayed diagnosis peritonitis may

result in severe shock, rapid deterioration, and death

[105] . Abdominal pain is usually the first symptom

and is accompanied by fever. However, the presen-

tation is variable with shoulder pain due irritation

of the diaphragm from intraperitoneal urine being

the presenting symptom [106] . Diagnostic delay

is more of a problem in neurologically impaired

patients, who due to altered sensation may develop

peritonitis and intra-abdominal abscesses without

the signs and symptoms of acute abdomen [108,

117] .In cases of intra-abdominal perforation of an

augmented bladder, signs and symptoms of acute

abdomen prevail, necessitating abdominal explora-

tion, regardless of the results of imaging studies

[113] . Ultrasound and CT usually reveal urinary

extravasation either into the local pelvic tissues or

the peritoneal cavity [118] . Routine cystography

may give false-negative results in cases of sus-

pected augmented bladder perforation and should

not be relied on for the establishment of diagnosis

of perforation [112] , although others think that a

careful cystogram under fluoroscopic control and

multiple films of the filled and drained bladder may

prove helpful [119] .Once major extravasation has

not been detected on cystography or ultrasound and

there is no evidence of acute abdomen, conservative

management with catheter drainage and antibiotics

can lead to successful resolution in more than half

the cases [29, 115] . Although in patients on CISC

whose urine are a priori infected, conservative man-

agement may prove inadequate [26] .

Stone Formation

Lower urinary tract stones are common after aug-

mentation cystoplasty and seem to occur with

increasing frequency as the follow-up lengthens.

The incidence of stones forming in enterocystoplast-

ies is reported to range from 13 to 30% in contempo-

rary series [26, 71, 78, 120] .

Stones can cause bladder irritation and patients

may present with incontinence, hematuria, or uri-

nary tract infection, although they are usually

found on routine follow-up ultrasound of patients

who have had an augmentation cystoplasty [29] .

It already has been noted that patients with an

augmented bladder that is emptied through the

urethra by “natural” voiding seldom (~2%) form a

stone [26] . On the contrary, stones occur five times

more often in patients with augmented bladders

who were on CISC via the urethra and ten times

as common in patients with Mitrofanoff abdominal

stomas, implicating stasis to be an important factor

in stone formation [121] .

Risk factors for stone formation include urine

stasis, immobilization, the presence of intravesi-

cal foreign bodies such as staples or mesh, or the

choice of the intestinal segment used for recon-

struction. It is known that gastrocystoplasties are

rarely complicated by stones [122] .

242 P. Sountoulides and M.P. Laguna

The proposed enhancing role of mucus in stone

formation in reconstructed bladders [120] is not

actually evidence-based. Although washouts of

mucus are widely recommended for the prevention

of stones, it may be that the only advantage is to

clear fragments of “sand” before a stone can be

formed [71] .

In patients with an enterocystoplasty the risk

of forming stones, especially triple phosphate

stones, is mainly attributed to the high incidence

of recurrent urinary tract infections usually from

urea- splitting bacteria [120] . Moreover, metabolic

changes induced may accentuate the risk of forming

oxalic or phosphate calcium stones. These include

moderate to severe hypocitraturia [123] , hypercal-

ciuria and mild hyperoxaluria, hyperuricosuria, and

a low urinary magnesium excretion [71] .

Regarding treatment, some form of endoscopic

or open surgical procedure is necessary since

stones in intestinal reservoirs are not amenable to

medical treatment, may act as a nidus for infection,

and have a tendency to enlarge if left in situ. Any

intervention contemplated must be tailored to the

size of the stone and the type of bladder augmen-

tation performed; however, patients with large or

multiple stones and those with no urethral access

require open surgery for removal [121] .

Voiding Dysfunction

One of the major problems of patients undergo-

ing enterocystoplasty is the high incidence of

postoperative voiding dysfunction. A priori clam

cystoplasty in particular, by dissecting the detrusor

causes some degree of outflow obstruction. In the

majority of cases, however, the urethra sphincter

mechanism fails to adjust to the creation of a low-

pressure bowel substitution cystoplasty, and patients

are unable to void sufficiently. As a result most

patients have to strain to empty their bladder, while

succeeding in effectively voiding by abdominal

straining make take up to 2–3 months for some

patients [53] .

In a cohort of patients it was estimated that in

around 20% [53] voiding will be sufficient only

after a rebalancing procedure is undertaken in

order to reduce the urethra closure pressure while

taking care not to create urethral incompetence.

Rebalancing is usually accomplished by either a

bladder neck incision for male patients, or an Ottis

sphincterotomy or a combination of the two. Some

authors used to perform a bladder neck incision

routinely in all patients who had bladder augmen-

tation [22] , sparing only young men who wish to

preserve ejaculation.

In cases where these rebalancing procedures are

not undertaken in due time or in case these pro-

cedures fail to achieve effective voiding, then the

patients will have to resort to self-catheterization.

CISC may be required for as short as a few weeks

after the operation during the “balancing” stage.

However, in general, insufficient voiding and the

need for CISC increase with time [58, 124] .

Several other factors may contribute to insuf-

ficient voiding and the need for CISC after a blad-

der augmentation procedure, including previous

operations or the presence of underactive detrusor

in spinal cord injury patients [25] . Moreover, the

significant decrease in voiding pressures recorded

in urodynamic evaluations of patients after entero-

cystoplasty, together with an increase in total blad-

der capacity, are factors further contributing to the

establishment of voiding dysfunction and obviating

the need for CISC [55, 124, 125] .

It is only logical that patients with NBD have

a higher chance of requiring CISC after bladder

augmentation, most probably because the underly-

ing neurogenic pathology generally interferes with

adequate sphincter and pelvic floor muscle relaxa-

tion. In studies of long-term outcome results after

enterocystoplasty for urge incontinence, routine

CISC was necessary for 60–75% of neuropathic

patients [26, 55] .

The need for CISC after augmentation for DO-

related urge incontinence is variable, depending to

some degree on the patient's tolerance of residual

urine. In arecent series, CISC was postoperatively

necessary for 6–39% of patients [26, 124] .

Technically, a bladder augmentation procedure

that requires CISC is considered a simple urethra-

cystoplasty and not a sphincter-cystoplasty and

some patients may actually be quite pleased with

the result [53] .

Results of Enterocystoplasty

The majority of publications regarding the results

of enterocystoplasty for the treatment of adults with

nonneurogenic urge incontinence are either small

case series or observational studies with short- or

19. Surgery for Urge Urinary Incontinence 243

longer-term follow-up (level 4 evidence). There is

a lack of randomized controlled trials comparing

either clam cystoplasty or other bladder augmenta-

tion procedure for the treatment of nonneurogenic

DO. Furthermore, it is difficult to draw general

conclusions concerning the clinical outcome in

patients withDO, mainly due to the heterogeneity

of the populations treated with most series includ-

ing varying numbers of NBD patients.

NBD Patients

Results for neuropathic bladder patients were prom-

ising, with patient's satisfaction and continence rates

escalating from 72 [55, 126] to over 90% in recent

series [26, 127] . Medium- to long-term follow-up

showed a sustained improvement in continence

exceeding 90% in neuropathic patients [55, 79] .

DO Patients

In general, the outcome in patients with DO-related

urge incontinence is highly unpredictable. Most

series show a sustained improvement in continence

exceeding 70 or even 90% in recent series [26, 54,

124, 128] .

On the other hand, there had been results on

female patients undergoing augmentation cysto-

plasty for nonneurogenic urge incontinence that

were far from optimal. Merely half the patients

(53%) were completely continent, while 39% were

not pleased and another 18% were still suffering

from incontinence postoperatively. An important

reason for these results may be the fact that more

than half of the patients suffered from associated

interstitial cystitis [129] .

However, detrusor instability after augmentation

cystoplasty for urge incontinence seems to persist

in 30% of cases postoperatively [54, 55, 125, 128] .

The long-term efficacy of the operation in main-

taining continence in patients with intractable DO

was evaluated in studies with 38 months to 8 years

follow-up (level 4), with results varying from mod-

erate to satisfactory [55, 79, 130] .

Results of Augmentation Cystoplasty in Women

There are a few studies evaluating the results

of augmentation cystoplasty solely on female

patient groups, which include patients who also

have undergone some form of bladder neck pro-

cedure [129, 131] . In one study on women with

NBD-related incontinence, a modified rectus fascial

sling procedure was combined with augmenta-

tion ileocystoplasty, achieving a 95.2% success

rate (patients dry under CIC) [131] . However,

others have challenged the hypothesis that aug-

mentation of the bladder alone is inadequate for

achieving continence in women with NBD [132] .

Ileocystoplasties were performed on 16 patients

with myelodysplasia without any additional blad-

der neck procedures, with continence achieved in

all but one [132] .

In a study on women with nonneurogenic urge

incontinence, augmentation ileocystoplasty was

combined with a modified Burch urethrovesical

suspension and yielded a 53% success rate (defined

as complete continence) and a 25% rate of occa-

sional leaks. However, 39% of patients required

regular CIC postoperatively [129] . In conclusion,

only one of two women undergoing augmentation

enterocystoplasty seems to be satisfied with the

procedure in the long-term.

Future Options

Nonpharmacological options for the future man-

agement of OAB include tissue engineering, which

is seen as an emerging therapy. This is best illus-

trated by growing bladder tissue on scaffolds for

use in augmentation cystoplasty. This greatly sim-

plifies the procedure by eliminating the need for a

bowel anastomosis [133] .

Tissue engineering currently is being explored

in order to provide an alternative to enterocysto-

plasty to avoid the use of bowel segments. These

techniques have been using cultured native urothe-

lial tissues [134] , fetal tissues, as well as colla-

gen matrices overgrown with transplanted cells.

Early results in animals using the bladder acel-

lular matrix graft with and without urothelial and

smooth muscle cell seeding were promising [135,

136] . Recent results from patients who underwent

autologous bladder transplantation with tissue

engineering were successful in terms of bladder

compliance, while none of the usual complications

associated with enterocystoplasty were encoun-

tered [137] . Other alternatives being developed

are small intestinal submucosa as a scaffold for

normal urothelial and detrusor ingrowth and pro-

gressive percutaneous dilatation for bladder tissue

244 P. Sountoulides and M.P. Laguna

expansion [138] ; again, promising early results

were reported in animal studies.

Laparoscopic augmentation cystoplasty recently

has emerged as a possible alternative to its open

counterpart. The first bladder augmentation accom-

plished entirely by laparoscopy was a gastrocysto-

plasty performed in a 17-year-old girl with a poorly

compliant bladder [139] and a small series of

laparoscopically assisted enterocystoplasties with

exteriorization of the bowel to facilitate bowel-to-

bowel reanastomosis and ileal patch construction

followed [140, 141] . The first case of ileal cysto-

plasty performed completely by laparoscopy was

described in a 31-year-old woman with NBD due

to spinal cord injury [142] . Longer-term results on

larger series are needed in order to evaluate the

pros and cons of laparoscopy in bladder augmenta-

tion procedures.

Conclusions on Augmentation Cystoplasty

In patients with intractable urge incontinence with

a severe negative impact on quality of life or in

high-pressure neurogenic bladders with a high risk

of damage to the upper urinary tract, augmentation

cystoplasty offers a considerable chance of cure.

However, it is a major abdominal intervention with

significant and potentially severe complications and

by no means is a “fit and forget” procedure. Rather,

it requires lifetime commitment, careful patient

selection, and even more careful selection of the

appropriate procedure for the individual patient.

Despite the problems encountered with certain

procedures of augmentation cystoplasty, on balance

it has been a much better form of management of urge

incontinence in patients with bladder neuropathy or

high-pressure detrusor contractions than the alterna-

tive options of rectal diversion, indwelling catheter,

or external urinary diversion [29] . Enterocystoplasty

has successfully stood the test of time in restoring

storage function by achieving a low-pressure blad-

der reservoir, despite the significant incidence of

complications and reinterventions.

Although there is no single type of bladder

augmentation appropriate for all cases, in carefully

selected, adequately counseled, and highly moti-

vated patients, the “clam” ileocystoplasty has been

proved a valuable and effective treatment option

for severe intractable urge incontinence associated

with DO and NBD.

Bladder Autoaugmentation

The theoretically appealing idea of augmenting

the bladder without the interpositioning of bowel

segments has been attempted in a number of ways.

Materials that have been used as grafts patched

onto the bladder include both synthetic (Teflon,

silicone) and natural tissues (omentum, perito-

neum, dura) [143– 146] . However, results from the

use of these materials were disappointing due to

the high incidence of adverse effects and complica-

tions encountered.

Detrusor Myectomy–Myotomy

The urothelium-lined augmentation of the bladder

(autoaugmentation) by excision of the detrusor was

described initially in experimental studies in dogs

[147] . Its clinical application initially was intro-

duced by Cartwright and Snow as an alternative

to enterocystoplasty in seven children with poorly

compliant bladders, four of whom were neurologi-

cally impaired [148] .

The surgical goal can be accomplished by either

incision (detrusor myotomy) or excision (detrusor

myectomy) of part of the detrusor muscle over the

dome of the bladder, leaving the underlying blad-

der urothelium intact [147] . No difference was

noted between detrusor myectomy versus simple

detrusor myotomy on urodynamic, radiological,

and pathological analysis in animal models [149]

and in a small series of 12 pediatric patients with

NBD [150] . In another study of 30 patients with

refractory DO, detrusor myectomy was success-

ful in as many as 80% of patients after at least 2

years of follow-up; however, more than half of the

patients required CIC [151] .

Either way, by excision of the detrusor spar-

ing the mucosa, a large epithelial bladder mucosal

“bulge” or “artificial diverticulum” is created.

This pseudodiverticulum is composed of bladder

urothelium, collagen, and some scarce detrusor

muscle bundles. The pseudodiverticulum expands

during bladder filling, thereby increasing the stor-

age capacity of the bladder, while decreasing stor-

age pressures [2] . Excision of part of the detrusor

potentially decreases the number and magnitude

of uninhibited detrusor contractions [15, 30] . On

the other hand, the emptying contraction of the

remaining detrusor is reduced, rendering CISC

19. Surgery for Urge Urinary Incontinence 245

inevitable, especially for patients with neuropathic

bladder dysfunction.

Therefore, autoaugmentation of the bladder by

detrusorectomy in theory resembles the patch graft

techniques, with the difference being that instead

of suturing on an exogenous graft material to act as

a framework for tissue regeneration, an expandable

epithelial bulge is created instead [147] .

One major advantage that makes autoaugmen-

tation attractive over enterocystoplasty is the

avoidance of use of bowel and the concomitant

complications arising from the interposition of

bowel into the bladder and interruption of the

GI tract. In autoaugmentation the patient's own

bladder is used, no suture line is created, and no

graft harvest is required, while the approach is

extraperitoneal and therefore suitable for patients

with prior abdominal surgery [48] . Operative and

recovery time as well as hospital stay are less

with autoaugmentation procedures compared to

enterocystoplasty resulting in a lower incidence of

morbidity [2, 15, 148] .

Autoaugmentation does not preclude augmenta-

tion cystoplasty either at the operative setting or

in the future should it be necessary [147, 148] .

While autoaugmentation presents certain attractive

features, there is evidence in support of a decreased

efficacy in increasing bladder capacity and reduc-

ing detrusor overactivity compared to cystoplasty

[2, 152] . Disadvantages of the procedure include

the development of fibrous tissue around the pseu-

dodiverticulum and the regrowth of the detrusor

muscle, possible reasons for the decreased durabil-

ity of the results achieved with this technique over

time [2, 48, 152] .

Fibrous tissue ingrowth also may be a possible

cause of the increased incidence of bladder rupture

following detrusor myotomy in experimental studies

[2, 116] . In addition, a higher incidence for use of

CISC following autoaugmentation has been reported

compared to augmentation cystoplasty [26] .

Autoaugmentation with the Use of

Demucosalized Gastrointestinal Segments

In initial series there also was a concern regarding

the blood perfusion of the diverticulum and the pos-

sibility of ischemic necrosis due to the removal of a

large portion of the detrusor with its blood supply

[147] . Furthermore, the development of adhesions

and fibrotic tissue between the diverticulum and

the surrounding tissues was considered to be a

cause for the poor urodynamic long-term results

seen in many patients [153– 155] .

Therefore and despite the fact that the highly

vascular lamina propria was considered adequate to

provide sufficient blood perfusion [147] , attempts

were made to improve blood supply and create a

biological backing for the diverticulum, resem-

bling the protective effects of the elastic nature

and contractile properties of the normal detrusor.

In this direction a number of variations of the

original technique, some of them incorporating

the use of various demucosalized intestinal seg-

ments on preserved urothelium, were introduced.

Gastrointestinal segments used in human and ani-

mal studies in combination with detrusor myectomy

included gastric muscle, colon, and peritoneum

while technical adaptations using rectus abdominis

muscle also have been described [153, 156– 162] .

This technique has the advantage of preventing

contact between urine and bowel segments, while

preserving native urothelium [163] .

Surgical Technique

The patient is placed in the lithotomy position

and a Foley catheter is inserted. A Pfannensteil or

lower midline incision is made and the bladder is

recovered after retraction of the rectus muscle. The

anterior wall of the bladder is identified and the

peritoneum swept away or dissected off the blad-

der dome [148] . The bladder is filled with saline

via the foley catheter and intravesical pressure is

maintained to 20 cmH

2 O during the procedure in

order to facilitate dissection. A transverse incision

is made at the intersection of the anterior wall and

dome of the bladder. The incision should gently

divide all the layers of the bladder musculature

until the gray-blue of the bladder mucosa is visual-

ized [15] . After the detrusor has been divided and

the mucosa is exposed, the remaining detrusor

fibers overlying the urothelium are gently spread

apart using a hemostat or carefully dissected using

Church scissors. Dissection between the detrusor

and the bladder urothelium continues laterally in

each direction up to the level of the vesical pedi-

cles, until the entire bladder dome and nearly half

of the detrusor have been stripped away from the

urothelium [148] . In case a mucosal tear is inadvertly

246 P. Sountoulides and M.P. Laguna

made during dissection, it can be oversewn using

4–0 or 5–0 absorbable sutures. When the dissec-

tion has finished, an omental flap can be drawn

out through a small incision in the peritoneum and

mobilized to cover the anterior bladder wall [15,

152] . Interpositioning and securing of omentum

between the serosal side of the bladder mucosa

and the perivesical fat and peritoneum potentially

facilitates distention of the created diverticulum

while protecting against perivesical fibrosis [152] .

The result is the creation of a large 8- to 12-cm

diameter disk of bladder mucosa, after the flaps of

the detrusor overlying the urothelium are dissected

free and excised. This way rehealing of the detrusor

with development of scar tissue is prevented. In the

original technique described by Cartwright and Snow

bilateral psoas hitches were performed; however, in

later series this was not deemed necessary [164] .

When the procedure is complete, a thin large blad-

der diverticulum bulging as the bladder is filled is

created. The created diverticulum continues to expand

postoperatively and bladder enlargement develops

relatively slowly over a period of several months,

which accounts for the incremental symptomatic and

urodynamic improvement noted in many patients.

Routinely drainage is not the rule; however, a

small Penrose drain can be left in the perivesical

space for safety reasons [148] . Care should be

taken to avoid inadvertent creation of a cystostomy

during dissection of the muscle from the mucosa.

In case this occurs, however, the retropubic space

should be drained [15] .

Routinely the foley catheter is removed after a

follow-up cystogram showing no extravasation is

performed on the 5–7th postoperative day [148,

152] . Some authors in more recent series remove

the bladder catheter on the first postoperative day

in neurologically intact patients, allowing them to

void spontaneously. For most patients with spinal

cord injury and children with myelodysplasia, ini-

tiation of a CISC program is warranted.

In most studies follow-up with urodynamics is

scheduled for 3 and 6 months after surgery and

yearly thereafter. Results in continence should be

obvious shortly after the autoaugmentation proce-

dure. If improvement in symptoms is not signifi-

cant during the first 4–6 weeks after surgery, repeat

urodynamic evaluation is required.

An alternative surgical approach that has been

recently explored is laparoscopic bladder autoaugmen-

tation [165– 167] ; however, comments on this

technique cannot be made in the event that data are

scarce and come from case reports with inadequate

numbers of patients and follow-up. Most recently

the first case report of detrusor myotomy using

the da Vinci surgical robot in a man with NBD

and normal bladder capacity [168] appeared. The

excellent results achieved in terms of symptoms

provide preliminary evidence of the feasibility and

efficacy of robotics for bladder autoaugmentation.

Results of Autoaugmentation

The majority of studies on bladder autoaugmentation

concentrate on children with neurological dysfunc-

tion. Initial results of autoaugmentation in seven

pediatric patients with NBD were promising in terms

of continence, with six children remaining continent

and three no longer requiring CISC [148] . The same

group in a subsequent study with a follow-up of

more than 2 years reported that 80% of patients were

continent, although a significant increase in bladder

capacity was not the rule [169] . Detrusorectomy

with the addition of a demucosalized patch of gastric

muscle to the created bladder diverticulum showed

initially favorable results in another series of four

children with neurogenic incontinence [156] .

Results from a study on pediatric patients with

NBD and low-capacity bladders who underwent

vesicomyotomy showed a mean increase in bladder

capacity of 40%, with a 33% decrease in mean leak-

point pressure [150] . However, long-term results of

the procedure in children with poorly compliant

bladders secondary to myelomeningocele were not

encouraging [154, 155] .In the study by Marte et al.

during a follow-up of 6.6 years, five of the eleven

children had to undergo ileocystoplasty because of

recurrent urinary tract infection, high-grade VUR,

and incontinence [155] . Similarly, results from

MacNeily et al. with a follow-up of 75 months

revealed that in 12 patients (71%) autoaugmenation

failed due to upper tract deterioration and ongoing

incontinence, while four patients (23.5%) required

enterocystoplasty [154] .

Although there have been encouraging results

in terms of improvement in bladder capacity for

children with myelomeningocele [170] , these have

been attributed to somatic bladder growth rather

than surgical success [154] . Results of these stud-

ies further underline the issue of proper patient

19. Surgery for Urge Urinary Incontinence 247

selection for this procedure, with patients with

poorly compliant bladders and an initial capacity of

greater than 75% of that expected for age gaining

the most benefit from the operation [170] .

Recently Perovic et al. reported improvement

in symptoms and bladder capacity [161, 162] in

children with small-capacity, low-compliance neu-

rogenic bladders. The authors performed a rectus

muscle hitch by dissecting both rectus muscles

from the fascial sheath, preserving their blood sup-

ply, and suturing them to the edges of the detrusor

as backing material for the pseudodiverticulum.

Urothelium-preserving procedures incorporat-

ing demucosalized gastric muscle and colon have

yielded satisfactory results in terms of bladder

capacity and compliance in clinical studies of chil-

dren with neurogenic bladder [156, 163, 171– 173] .

On the contrary, results of autoaugmentation cov-

ered with a peritoneal flap in animal [174] and

human studies [159] were inferior to those of con-

ventional autoaugmentation gastrocystoplasty.

These procedures, apart from being technically

demanding, are not suitable for small fibrotic blad-

ders, do not seem to be more efficacious than con-

ventional autoaugmentation, and lack long-term

results of significant numbers of patients. On the

other hand, they have the advantage of sparing the

long-term sequlae of enterocystoplasty.

There is a relative lack of studies regarding

autoaugmentation in the adult population with

and without neurological impairment. A relatively

large case series of 29 adult patients aged 14–64

years, most of whom had NBD-related inconti-

nence, revealed that during a follow-up of 7 years

after autoaugmentation, half of the patients man-

aged to void without significant residuals, while

the other half required CISC. Bladder compliance

and capacity also were improved [164] .

As previously stated, there is little evidence of

the efficacy of autoaugmentation in adults with

DO-related incontinence. In a small series of five

patients with urge incontinence, results of autoaug-

mentation were disappointing. Four patients con-

tinued to sustain involuntary detrusor contractions

resulting in incontinence at 3-month urodynamic

and clinical evaluation [175] (level 4 evidence). In

a series with 1-year follow-up, symptomatic and

urodynamic improvement was evident in 63% of

patients, with better results noted in those with

idiopathic detrusor instability (12 of 17 cured or

improved) [152] .Results from Westney et al. on

a heterogeneous group of 30 patients who under-

went autoaugmentation and were followed-up for

42 months with urodynamic studies revealed that

63% of the patients faired well in terms of increase

in bladder compliance and resolution of DO [15] .

The authors' observation that the most favorable

and consistent outcomes following autoaugmenta-

tion were noted in patients with refractory DO and

spinal cord injury were in agreement with results

from previous studies [176, 177] .

Complications of Autoaugmentation

Autoaugmentation seems to be associated with

fewer and less severe complications compared to

bladder augmentation techniques incorporating

the use of bowel. A study comparing autoaug-

mentation to enterocystoplasty revealed that 3%

of patients undergoing detrusorectomy suffered

serious complications compared to 22% in the

enterocystoplasty group [177] .

Theoretically there is a greater risk of bladder

perforation following autoaugmentation, owing to

the thinness of the mucosa in the created pseudo-

diverticulum, as has been shown in experimental

studies in rats [116] . In clinical practice, how-

ever, even in early series, there were no cases of

catheter-induced perforation, despite the fact that

all patients were put on CISC immediately after the

foley catheter was removed [148] .

Early postoperative urine extravasation was

another frequent complication in an early series

(33% incidence in the initial series by Cartwright

and Snow [148] ); however, extravasation resolved

uneventfully after 2–3 weeks of continuous bladder

catheterization. In a recent series, however, of 49

patients who underwent detrusor myectomy there

was only one case of extraperitoneal bladder leak

[15] . Recurrent UTIs following autoaugmentation

were usual in early series and were attributed to

the presence of large residuals requiring CISC

[148, 152] .

Conclusions on Bladder Autoaugmentation

There is evidence suggesting that the symptomatic

improvement obtained with autoaugmentation—

the increase in bladder capacity and the reduction

in voiding pressures—are far less pronounced than

those produced by enterocystoplasty [55, 123,

248 P. Sountoulides and M.P. Laguna

178] . However, although a definite advantage of

this technique is the lower incidence of morbidity

compared with enterocystoplasty, there is a ques-

tion as to the limited efficacy of the procedure and

the possibility that the results achieved may not be

maintained in the longer term. Probably this is one

of the reasons why this technique has never gained

wide acceptance in practice. At the end of the day,

and despite the lack of data and the low level of

evidence (level of evidence 4) autoaugmenation

can be considered to be a viable treatment option

for carefully selected patients with drug-refractory

urge incontinence, leaving the alternative of ente-

rocystoplasty for the nonresponders.

Urinary Diversion

Contemporary urinary diversion is a rare treatment

option almost exclusively reserved for patients with

NBD-related incontinence, for those patients with

intractable incontinence or severe pelvic pain who

are unsuitable for or have failed other surgical meas-

ures [179] . However, under certain circumstances,

urinary diversion may prove to be better than entero-

cystoplasty when intractable DO is associated with

severe pelvic pain [180] (Fig. 19.2 ).

Urinary diversion in patients with NBD can

be either continent or conduit (noncontinent)

diversion. Continent cutaneous urinary diversion

requires the creation of a catheterizable stoma that

is implanted either into the native bladder or into an

intestinal neobladder (Fig. 19.3 ). For the majority

of patients with neurological lesions, some form

of bladder augmentation procedure is undertaken

during the same session. The rare patient requiring

continent diversion for intractable incontinence

usually is unable to self-catheterize through the

urethra due to a nonaccessible meatus, severe

urethral stricture, or pain. Moreover, most neuro-

logically impaired patients would find it easier to

catheterize a continent abdominal stoma instead of

their native urethra. .

Construction of a continent conduit can be man-

aged by using the ileum or colon as in the Yag–Monti

procedure, the appendix as in the Mitrofanoff proce-

dure, or even occasionally the ureter. Techniques

that create a relatively small-bore outlet, such as

the ones mentioned previously, currently are being

used more commonly mainly because of the lower

incidence of adverse effects. Despite the fact that

continence rates exceeding 80% have been reported

with these techniques, these results come with a

relatively high incidence of complications.

One major complication, ranging from 12 to

30% of cases, is stomal stenosis, which is more

common when an umbilical stoma is created.

Results from early series with long-term follow-up

of the Mitrofanoff procedure in children revealed

the most frequent complications requiring surgical

revision to be stomal stenosis and persistent leak-

age [181] .

Incontinent conduit diversion became an even

more rare treatment option for patients with NBD

and urge incontinence, since the introduction of

CISC. However, these procedures still may be

viable alternative options for patients with intracta-

ble incontinence who are not able to perform CISC,

have failed previous surgery, and are not indicated

for (short bowel syndrome) or refuse continent

diversion or bladder augmentation.

Diversion options considered depend on the

individual case and include the classic Bricker ileal

conduit urinary diversion or an ileovesicostomy

“bladder chimney” procedure [182– 184] . In case a

conduit diversion is created there is a question as

to whether a cystectomy also should be performed.

Cystectomy is strongly considered in patients with

a history of chronic infections due to the high risk

of pyocystis if the bladder is left in situ [48] .

In ileovesicostomy a 15- to 20-cm segment of

terminal ileum is isolated. The proximal 6–8 cm of

this segment is opened on the antimesenteric bor-

der. The dome of the bladder is opened widely in a

transverse manner and the proximal portion of the

bowel is sutured onto the bladder. The distal por-

tion of the ileum remains tubularized and becomes

the stoma. Recently laparoscopic ileovesicostomy

for NBD has been described as an acceptable alter-

native to the open procedure [185] .

As urinary diversion is a surgical option limited

to selected patients with urge incontinence, there is

a reasonable lack of evidence relative to its efficacy

for DO incontinence (level 4 evidence). Results

from series with reasonable follow-up render incon-

tinent cutaneous ileovesicostomy a useful alterna-

tive for neurologically impaired adult patients with

urge incontinence who are unwilling or unable

to perform CISC [182, 183, 186] , with urethral

continence achieved in over 70% of patients in a

recent series [187] . Furthermore, ileovesicostomy

19. Surgery for Urge Urinary Incontinence 249

Fig. 19.2. Mainz II pouch, anal diversion. Nephrodrain left because of pyelonephritis. ( a ) After resolution of the

infective process, contrast flows down to the rectal pouch. ( b ) Filling of the Mainz II pouch. ( c ) Nuclear scan showing

good efflux of both kidneys after resolution of the pyelonephritis

250 P. Sountoulides and M.P. Laguna

Fig. 19.3. Kock continent cutaneous derivation because of urge incontinence and nephrectomy, left. ( a ) After stricture

of the Mitrofanoff (umbilical stoma), right, reflux developed. ( b ) CT scan in the same patient showing slight dilatation

of the right kidney. ( c ) CT scan showing the enormous capacity pouch occupying the small pelvis

19. Surgery for Urge Urinary Incontinence 251

can provide a safe and effective alternative for uri-

nary drainage while preserving the upper urinary

tracts in patients with detrusor hyperreflexia [188] .

Complications of incontinent conduit diversions

include upper urinary tract infections, stone forma-

tion, gastrointestinal sequlae (ileus, fistula), stomal

stenosis, and anastomotic ureteroileal stricture

[184, 188– 191] . However, there is no doubt that

any form of urinary tract reconstruction is prefer-

able over indwelling catheter placement in terms

of complications [182] , quality of life, and sexual

function especially for women with NBD-related

incontinence [192] .

References

1 . Abrams P , Cardozo L , Fall M , et al. The standardisa-

tion of terminology of lower urinary tract function:

Report from the Standardisation Sub-committee

of the International Continence Society . Neurourol

Urodyn 2002 ; 21 : 167 – 178 .

2 . Chapple CR , Bryan NP . Surgery for detrusor overac-

tivity . World J Urol 1998 ; 16 : 268 – 273 .

3 . Lapides J , Diokno AC , Silber SJ , Lowe BS . Clean

intermittent self-catheterisation in the treatment of

urinary tract disease . J Urol 1972 ; 107 : 458461 .

4 . Fontaine E , Bendaya S , Desert JF , et al. Combined

modified rectus fascial sling and augmentation ile-

ocystoplasty for neurogenic incontinence in women .

J Urol 1997 ; 157 : 109112 .

5 . Linder A , Leach G , Raz S . Augmentation cysto-

plasty in the treatment of neurogenic bladder dys-

function . J Urol 1983 ; 129 : 491493 .

6. Nabi G, Cody J, Dublin N, et al. Urinary diversion

and bladder reconstruction/replacement using intes-

tinal segments for intractable incontinence or follow-

ing cystectomy. Cochrane Database Syst Rev 2003,

Issue 1. Art. No.: CD003306. doi:10.1002/14651858.

CD003306.

7 . Harris RG , Constantinou CE , Stamey TA . Extra-

vesical subtrigonal injection of 50 percent ethanol

for detrusor instability . J Urol 1988 ; 140 : 111116 .

8 . McInerney PD , Vanner TF , Matenhelia S , Stephenson

TP . Assessment of the long term results of subtrigo-

nal phenolisation . Br J Urol 1991 ; 67 : 586587 .

9 . Blackford HN , Murray K , Stephenson TP , Mundy

AR . Results of transvesical infiltration of the pelvic

plexuses with phenol in 116 patients . Br J Urol

1984 ; 56 (6) : 647649 .

10 . Cameron-Strange A , Millard RJ . Management of

refractory detrusor instability by transvesical phenol

injection . Br J Urol 1988 ; 62 (4) : 323325 .

11 . Chapple CR , Hampson SJ , Turner-Warwick RT ,

Worth PH . Subtrigonal phenol injection. How safe

and effective is it ? Br J Urol 1991 ; 68 (5) : 483486 .

12 . Rosenbaum TP , Shaw PJ , Worth PH . Trans-trigonal

phenol failed the test of time . Br J Urol 1990 ;

66 (2) : 164169 .

13 . Wall LL , Stanton SL . Transvesical phenol injection

of pelvic nerve plexuses in females with refractory

urge incontinence . Br J Urol 1989 ; 63 (5) : 465468 .

14 . Ingelman-Sundberg A . Partial denervation of the

bladder: A new operation for the treatment of urge

incontinence and similar conditions in women . Acta

Obstet Gynecol Scand 1959 ; 38 : 487502 .

15 . Westney OL , McGuire EJ . Surgical procedures for

the treatment of urge incontinence . Techniq Urol

2001 ; 7 (2) : 126132 .

16 . Hodgkinson CP , Drukker BH . Infravesical nerve

resection for detrusor dyssynergia. The Ingelman-

Sundberg operation . Acta Obstet Gynecol Scand

1977 ; 56 (4) : 401408 .

17 . Cespedes RD , Cross CA , McGuire EJ . Modified

Ingelman-Sundberg bladder denervation procedure

for refractory urge incontinence . J Urol 1996 ;

156 (5) : 17441477 .

18 . Westney OL , Lee JT , McGuire EJ , et al. Long-term

results of Ingelman-Sundberg denervation procedure

for urge incontinence refractory to medical therapy .

J Urol 2002 ; 168 (3) : 10441047 .

19 . Tizzoni G , Foggi A . Die wiederhestellung der harn-

blase . Centralbl F Chir 1888 ; 15 : 921923 .

20 . von Mikulicz J . Zur Operation der angeborenen

Blasenpalte . Zentralb Chir 1899 ; 26 : 641 – 648 .

21 . Couvelaire R . La petite vessie des tuberculeux

genitourinaires: Essai de classification, places et

variantes des cysto-intestinoplasties . J Urol (Paris)

1950 ; 56 : 381434 .

22 . Mundy AR , Stephenson TP . “Clam” ileocystoplasty

for the treatment of refractory urge incontinence . Br

J Urol 1985 ; 57 (6) : 641646 .

23 . Bramble FJ . The treatment of adult enuresis and

urge incontinence by enterocystoplasty . Br J Urol

1982 ; 54 : 693696 .

24 . Lockhart JL , Bejany D , Politano VA . Augmentation

cystoplasty in the management of neurogenic blad-

der disease and urinary incontinence . J Urol 1986 ;

135 : 969971 .

25 . Sidi AA , Becher EF , Reddy PK , et al. Augmentation

enterocystoplasty for the management of voiding

dysfunction in spinal cord injury patients . J Urol

1990 ; 143 : 8385 .

26 . Greenwell TJ , Venn SN , Mundy AR . Augmentation

cystoplasty . BJU Int 2001 ; 88 : 511525 .

27 . McGuire EJ , McGuire R , Woodside JR , Borden TA .

Upper tract deterioration in patients with myelodysplasia

252 P. Sountoulides and M.P. Laguna

and detrusor hypertonia: A follow up study . J Urol 1983 ;

129 : 823826 .

28 . Hendren WH . Historical perspective in the use of bowel

in urology . Urol Clin N Am 1997 ; 24 : 703 – 713 .

29 . Gough JW . Enterocystoplasty . BJU Int 2001 ;

88 : 739743 .

30 . Duel BP , Gonzalez R , Barthold JS . Alternative tech-

niques for augmentation cystoplasty . J Urol 1998 ;

159 : 9981005 .

31 . Whitmore WF , Gittes RF . Reconstruction of the uri-

nary tract by cecal and ileocecal cystoplasty: Review

of a 15-year experience . J Urol 1983 ; 129 : 494498 .

32 . Murray K , Nurse DE , Mundy AR . Secreto-motor

function of intestinal segments used in lower urinary

tract reconstruction . Br J Urol 1987 ; 60 : 532535 .

33 . Hendren WH , Hendren RB . Bladder augmentation:

Experience with 129 children and young adults . J

Urol 1990 ; 144 : 445453 .

34 . Mitchell ME , Piser JA . Intestinocystoplasty and

total bladder replacement in children and young

adults . J Urol 1987 ; 138 : 579 .

35 . N'Dow J , Leung HY , Marshall C , et al. Bowel dys-

function after bladder reconstruction . J Urol 1998 ;

159 : 14701475 .

36 . Ngan JH , Lau JL , Lim ST , et al. Long-term results of

antral gastrocystoplasty . J Urol 1993 ; 149 : 731734 .

37 . Adams MC , Mitchell ME , Rink RC . Gastro-

cystoplasty: An alternative solution to the problem

of urological reconstruction in the severely compro-

mised patient . J Urol 1988 ; 140 : 11521156 .

38 . Plawker MW , Rabinowitz SS , Etwark DJ , et al.

Hypergastrinaemia, dysuria-hematuria and meta-

bolic alkalosis: complications associated with gas-

trocystoplasty . J Urol 1995 ; 154 : 546549 .

39 . Reinberg Y , Manivel JC , Froemming C , et al.

Perforation of the gastric segment of an augmented

bladder secondary to peptic ulcer disease . J Urol

1992 ; 148 : 369371 .

40 . Tiffany P , Vaughan ED Jr , Manon D , et al.

Hypergastrinaemia following antral gastrocysto-

plasty . J Urol 1986 ; 136 : 692695 .

41 . Bogaert GA , Mevorach RA , Kim J , Kogan BA . The

physiology of gastrocystoplasty: Once a stomach,

always a stomach . J Urol 1995 ; 154 : 546 – 549 .

42 . Goodwin WE , Winter CC , Baker WF . ‘Cup patch’

technique of ileocystoplasty for bladder enlargement

or partial substitution . Surg Gynecol Obstet 1959 ;

108 : 240244 .

43 . Cranidis A , Nestoridis G . Bladder augmentation . Int

Urogynecol J 2000 ; 11 : 33 – 40 .

44 . Radomski SB , Herschorn S , Stone AR . Urodynamic

comparison of ileum vs. sigmoid in augmentation

cystoplasty for neurogenic bladder dysfunction .

Neurourol Urodyn 1995 ; 14 : 231237 .

45 . Theodorou C , Plastiras D , Moutzouris G , et al.

Combined reconstructive and prosthetic surgery in

complicated lower urinary tract dysfunction . J Urol

1997 ; 157 : 472474 .

46 . Gonzalez R , Nguyen DH , Koleilat N , et al.

Compatibility of enterocystoplasty and the artificial

urinary sphincter . J Urol 1989 ; 142 : 502504 .

47 . Catto JW , Natarajan V , Tophill PR . Simultaneous

augmentation cystoplasty is associated with earlier

rather than increased artificial urinary sphincter

function . J Urol 2005 ; 173 : 12371241 .

48 . Wagg A , Majumdar A , Toozs-Hobson P , et al. Current

and future trends in the management of overactive

bladder . Int Urogynecol J 2007 ; 18 : 81 – 94 .

49 . Woodhause CRD , Macneily AE . The Mitrofanoff

principle: Expanding upon a versatile technique . Br

J Urol 1994 ; 74 : 447 – 453 .

50 . Blaivas JG , Weiss JP , Desai P , et al. Long-term

follow-up of augmentation enterocystoplasty and

continent diversion in patients with benign disease .

J Urol 2005 ; 173 : 1631 – 1634 .

51 . Leng WW , McGuire EJ . Reconstructive surgery for

urinary incontinence . Urol Clin North Am 1999 ;

26 (1) : 6180 .

52 . Goodwin WE , Turner CC . Results of ileocysto-

plasty . J Urol 1958 ; 80 : 461466 .

53 . Bramble FJ . The clam cystoplasty . Br J Urol 1990 ;

66 : 337341 .

54 . Kockelbergh RC , Tan JB , Bates CP , et al. Clam

enterocystoplasty in general urological practice . Br

J Urol 1991 ; 68 (1) : 3841 .

55 . Hasan ST , Marshall C , Robson WA , Neal DE . Clinical

outcome and quality of life following enterocystoplasty

for idiopathic detrusor instability and neurogenic blad-

der dysfunction . Br J Urol 1995 ; 76 : 551557 .

56 . Keating MA , Ludlow JK , Rich MA . Enterocystoplasty:

The star modification . J Urol 1996 ; 155 : 17231725 .

57 . Flood HD , Malhotra SJ , O'Connell HE , et al. Long-

term results and complications using augmentation

cystoplasty in reconstructive urology . Neurourol

Urodyn 1995 ; 14 (4) : 297309 .

58 . McInerney PD , DeSousa N , Thomas PJ , et al. The

role of urodynamic studies in the evaluation of

patients with augmentation cystoplasties . Br J Urol

1995 ; 76 : 475478 .

59 . Gonzales R , Sidi AA , Zhang G . Urinary undiver-

sion: Indications, technique and results in 50 cases .

J Urol 1986 ; 136 : 1316 .

60 . Mast P , Hoebeke P , Wyndaele JJ , et al. Experience

with augmentation cystoplasty: A review . Paraplegia

1995 ; 33 (10) : 560564 .

61 . Krishna A , Gough DCS , Fishwick J , Bruce J .

Ileocystoplasty in children. Assessing safety and

success . Eur Urol 1995 ; 31 : 6267 .

19. Surgery for Urge Urinary Incontinence 253

62 . Khoury JM , Timmons SL , Corbel L , Webster GD .

Complications of enterocystoplasty . Urology 1992 ;

40 : 914 .

63 . Singh G , Thomas DG . Bowel problems after entero-

cystoplasty . Br J Urol 1997 ; 79 : 328332 .

64 . Whorwell PJ , Lupton EW , Endura D , et al. Bladder

smooth muscle dysfunction in patients with irritable

bowel syndrome . Gut 1986 ; 27 : 10141017 .

65 . Nurse DE , Mundy AR . Metabolic complications

after cystoplasty . Br J Urol 1985 ; 63 : 165170 .

66 . McDougal WS . Metabolic complications of urinary

intestinal diversion . J Urol 1992 ; 147 : 11991208 .

67 . Brkovic D , Linke J , Jakse G , Bauss F . Changes in

bone structure after augmentation cystoplasty in

chronic uraemic rats . BJU Int 2005 ; 95 : 10661070 .

68 . Mundy AR , Nurse DE . Calcium balance, growth

and skeletal mineralisation in patients with cysto-

plasties . Br J Urol 1988 ; 140 : 853855 .

69 . Steiner MS , Morton RA , Marshall FF . Vitamin B12

deficiency in patients with ileocolic neobladders . J

Urol 1993 ; 149 : 255257 .

70 . Khoury A , Salomon M , Doche R et al. Stone forma-

tion following augmentation cystoplasty: The role of

intestinal mucous . J Urol 1997 ; 58 : 40 .

71 . Woodhouse CRJ , Robertson WG . Urolithiasis

in enterocystoplasties . World J Urol 2004 ;

22 : 215 – 221 .

72 . Clayman RV . Preventing reservoir calculi after aug-

mentation cystoplasty and continent urinary diver-

sion: The influence of an irrigation protocol . J Urol

2005 ; 173 : 866867 .

73 . George VK , Gee JM , Wortley MI , et al. The effect of

ranitidine on urine mucus concentration in patients

with enterocystoplasty . Br J Urol 1992 ; 70 : 3032 .

74 . Gillon G , Mundy AR . The dissolution of urinary

mucus after cystoplasty . Br J Urol 1989 ; 63 : 372374 .

75 . Krishna A , Gough DCS . Evaluation of augmenta-

tion cystoplasty in childhood with reference to

vesico-ureteric reflux and urinary infection . Br J

Urol 1994 ; 74 : 465468 .

76 . Wyndaele JJ , Maes D . Clean intermittent self-

catheterisation: A 12 year follow-up . J Urol 1990 ;

143 : 906908 .

77 . Maynard F , Diokno A . Urinary infection and com-

plications during clean intermittent catheterisa-

tion following spinal cord injury . J Urol 1984 ;

132 : 943946 .

78 . Kreder KJ , Webster GD . Management of the bladder

outlet in patients requiring enterocystoplasty . J Urol

1992 ; 147 (1) : 3841 .

79 . Fenn N , Conn IG , German KA , Stephenson TP .

Complications of clam enterocystoplasty with particular

reference to urinary tract infection . Br J Urol 1992 ;

69 (4) : 366368 .

80 . Smith P , Hardy GJ . Carcinoma occurring as a late

complication of ileocystoplasty . Br J Urol 1971 ;

43 : 576579 .

81 . Leedham PW , England HR . Adenocarcinoma

developing in an ileocystoplasty . Br J Surg 1973 ;

60 : 158160 .

82 . Golomb J , Klutke CG , Lewin KJ , et al. Bladder neo-

plasms associated with augmentation cystoplasty.

Report of 2 cases and literature review . J Urol 1989 ;

142 : 377380 .

83 . Gregoire M , Kantoff P , DeWolf WC . Synchronous

adenocarcinoma and transitional cell carcinoma

of the bladder associated with augmentation: Case

report and review of the literature . J Urol 1993 ;

149 : 115 – 118 .

84 . Gepi-Attee S , Ganabathi K , Abrams PH , MacIver

AG . Villous adenoma in augmentation colocysto-

plasty: A case report and discussion of the pathogen-

esis . J Urol 1992 ; 147 : 128130 .

85 . Shokeir AA , Shamaa M , el-Mekresh MM , et al. Late

malignancy in bowel segments exposed to urine

without fecal stream . Urology 1995 ; 46 : 657 – 661 .

86 . Ali-El-Dein B , El-Tabey N , Abdel-Latiif M , et al.

Late uro-ileal cancer after incorporation of ileum

into the urinary tract . J Urol 2002 ; 167 : 84 – 88 .

87 . Filmer RB , Spencer JR . Malignancies in bladder

augmentation and intestinal conduits . J Urol 1990 ;

143 (4) : 671678 .

88 . Stone AR , Davis N , Stephenson TP . Cancer associ-

ated with augmentation cystoplasty . Br J Urol 1987 ;

60 : 236238 .

89 . Soergel TM , Cain MP , Misseri R , et al. Transitional

cell carcinoma of the bladder following augmenta-

tion cystoplasty for the neuropathic bladder . J Urol

2004 ; 172 , 1649 – 1652 .

90 . Stewart M . Urinary diversion and bowel cancer . Ann

R Coll Surg Eng 1986 ; 68 : 98102 .

91 . Nurse DE , Mundy AR . Assessment of the malignant

potential of cystoplasty . Br J Urol 1989 ; 64 : 489 .

92 . Barrington JW , Fulford S , Griffiths D , Stephenson

TP . Tumors in bladder remnant after augmentation

enterocystoplasty . J Urol 1997 ; 157 : 482486 .

93 . Fernandez-Arjona M , Herrero L , Romero J , et al.

Synchronous signet ring cell carcinoma and squa-

mous cell carcinoma arising in an augmented ile-

ocystoplasty. Case report and review of the literature .

Eur Urol 1996 ; 29 : 125128 .

94 . Gitlin JS , Wu XR , Sun TT , et al. New concepts of

histological changes in experimental augmentation

cystoplasty: Insights into the development of neo-

plastic transformation at the enterovesical and gas-

trovesical anastomosis . J Urol 1999 ; 162 : 10961100 .

95 . Lane T , Shah J . Carcinoma following augmentation

ileocystoplasty . Urol Int 2000 ; 64 : 3132 .

254 P. Sountoulides and M.P. Laguna

96 . Ames BN , Gold LS . Too many rodent carcinogens:

Mitogenesis increases mutagenesis . Science 1990 ;

249 : 970 .

97 . Barrington JW , Fraylin L , Fish R , et al. Elevated

levels of basic fibroblast growth factor in the urine

of clam enterocystoplasty patients . J Urol 1996 ;

156 : 468 .

98 . Carr LK , Herschorn S . Early development of adeno-

carcinoma in a young woman following augmen-

tation cystoplasty for undiversion . J Urol 1997 ;

157 : 22552256 .

99 . Yoshida T , Kim CJ , Konishi T , et al. Adenocarcinoma

of the bladder 19 years after the augmentation ile-

ocystoplasty: Report of a case . Nippon Hinyokika

Gakkai Zasshi 1998 ; 89 : 54 – 57 .

100 . Koizumi S , Johnin K , Kataoka A , et al. Adeno-

carcinoma occurring 37 years after augmentation

ileocystoplasty for tuberculous bladder atrophy:

Report of a case . Hinyokika Kiyo 1997 ; 43 :

743 – 745 .

101 . Ivil KD , Doak SH , Jenkins SA , et al. Fluorescence

in-situ hybridisation on biopsies from clam ile-

ocystoplasties and on a clam cancer . Br J Cancer

2006 ; 94 : 891895 .

102 . Milsom I , Abrams P , Cardozo L , et al. How wide-

spread are the symptoms of an overactive bladder

and how are they managed? A population-based

prevalence study . BJU Int 2001 ; 87 : 760 .

103 . Krause FS , Feil G , Bichler KH , et al. Clinical

aspects for the use of DNA image cytometry in

detection of bladder cancer: A valuable tool? DNA

Cell Biol 2003 ; 22 : 721 – 725 .

104 . Deliveliotis C , Georgoulakis J , Skolarikos A , et al.

DNA ploidy as a prognostic factor in muscle inva-

sive transitional cell carcinoma of the bladder . Urol

Res 2005 ; 33 : 3943 .

105 . De Voogt HD , Rather P , Beyer-Boon ME . Urinary

cytology . New York : Springer , 1997 : 5561 .

106 . Rushton HG , Woodard JR , Parrot TS , et al. Delayed

bladder rupture after augmentation enterocysto-

plasty . J Urol 1988 ; 140 : 344346 .

107 . Couillard DR , Vapnec JM , Rentzepis MJ , et al.

Fatal perforation of an augmentation cystoplasty in

an adult . Urology 1993 ; 42 : 585588 .

108 . Elder JS , Snyder HM , Hulbert WC , et al. Perforation

of the augmented bladder in patients undergoing

clean intermittent catheterization . J Urol 1988 ;

140 : 11591162 .

109 . Anderson PA , Rickwood AM . Detrusor hyper-

reflexia as a factor in spontaneous perforation of

augmentation cystoplasty for neuropathic bladder .

Br J Urol 1991 ; 67 : 210212 .

110 . Reisman EM , Preminger GM . Bladder perforation

secondary to clean intermittent catheterization . J

Urol 1989 ; 142 : 1316—1317 .

111 . Sheiner JR , Kaplan GW . Spontaneous bladder

rupture following enterocystoplasty . J Urol 1988 ;

140 (2) : 1157 – 1158 .

112 . Crane JM , Scherz HS , Billman GF , Kaplan GW .

Ischemic necrosis: A hypothesis to explain the

pathogenesis of spontaneously ruptured entero-

cystoplasty . J Urol 1991 ; 146 : 141144 .

113 . Bauer SB , Hendren WH , Kozakewich H , et al.

Perforation of the augmented bladder . J Urol 1992 ;

148 (2) : 699703 .

114 . Rosen MA , Light JK . Spontaneous bladder rupture

following augmentation entoerocystoplasty . J Urol

1991 ; 146 : 12321234 .

115 . Essig KA , Sheldon CA , Brandt MT , et al. Elevated

intravesical pressure causes hypoperfusion in canine

colocystoplasty: A fluorometric assay . J Urol 1991 ;

146 : 551553 .

116 . Slaton JW , Kropp KA . Conservative management

of suspected bladder rupture after augmentation

enterocystoplasty . J Urol 1994 ; 152 : 713715 .

117 . Rivas DA , Chancellor MB , Huang B , et al. Comparison

of bladder rupture pressure intestinal bladder augmen-

tation (ileocystoplasty) and myomyotomy (autoaug-

mentation) Urology 1996 ; 48 : 4046 .

118 . Rogers CJ , Barber DB , Wade WH . Spontaneous

bladder perforation in paraplegia as a late com-

plication of augmentation enterocystoplasty:

Case report . Arch Phys Med Rehab 1996 ; 77 :

11981200 .

119 . Glass RB , Rushton HG . Delayed spontaneous rup-

ture of augmented bladder in children: Diagnosis

with sonography and CT . AJR Am J Roentgenol

1992 ; 158 : 833 – 835 .

120 . Braverman RM , Lebowitz RL . Perforation of the

augmented urinary bladder in nine children and

adolescents: Importance of cystography . Am J

Roentgenol 1991 ; 157 : 10591063 .

121 . Blyth B , Ewalt DH , Duckett JW , Snyder HM .

Lithogenic properties of enterocystoplasty . J Urol

1992 ; 148 : 575577 .

122 . Nurse DE , McInerney PD , Thomas PJ , Mundy

AR . Stones in enterocystoplasties . Br J Urol 1996 ;

77 : 684 – 687 .

123 . DeFoor W , Minevich E , Reeves D , et al.

Gastrocystoplasty: Long-term follow-up . J Urol

2003 ; 170 : 1647 – 1650 .

124 . Franco I , Levitt SB . Urolithiasis in the patient with

augmentation cystoplasty: Pathogenesis and man-

agement . AUA Update 1997 ; XVII : Lesson 2 , 1015 .

125 . Edlund C , Peeker R , Fall M . Clam ileocystoplasty:

Successful treatment of severe bladder overactivity .

Scand J Urol Nephrol 2001 ; 35 (3) : 190 – 195 .

126 . Sethia KK , Webb RJ , Neal DE . Urodynamic study

of ileocystoplasty in the treatment of idiopathic

detrusor instability . Br J Urol 1991 ; 67 (3) : 286290 .

19. Surgery for Urge Urinary Incontinence 255

127 . McRae P , Murray KH , Nurse DE , et al. Clam ente-

rocystoplasty in the neuropathic bladder . Br J Urol

1987 ; 60 (6) : 523525 .

128 . Beier-Holgersen R , Kirkeby LT , Nordling J . Clam

ileocystoplasty . Scand J Urol Nephrol 1994 ;

28 : 5558 .

129 . Kayigil O , Atahan O , Metin A . Experiences with

clam ileocystoplasty . Int Urol Nephrol 1998 ;

30 (1) : 4548 .

130 . Awad SA , Al-Zahrani HM , Gajewski JB , Bourque-

Kehoe AA . Long-term results and complications

of augmentation ileocystoplasty for idiopathic urge

incontinence in women . Br J Urol 1988 ; 81 (4) :

569573 .

131 . Kayigil O , Aytaç B , Çakar KS , Metin A . Clam ile-

ocystoplasty in adult nocturnal enuresis . Int Urol

Nephrol 2001 ; 32 : 647 – 649 .

132 . Fontaine E , Bendaya S , Desert JF , et al. Combined

modified rectus fascial sling and augmentation ileo-

cystoplasty for neurogenic incontinence in women .

J Urol 1997 ; 157 : 109112 .

133 . Cher ML , Allen TD . Continence in the myelodys-

plastic patient following enterocystoplasty . J Urol

1993 ; 149 : 11031106 .

134 . Wein AJ . Diagnosis and treatment of the overactive

bladder . Urology 2003 ; 62 : 2027 .

135 . Fraser M , Thomas DF , Pitt E , et al. A surgical model

of composite cystoplasty with cultured urothelial

cells; a controlled study of gross outcome and

urothelial phenotype . BJU Int 2004 ; 93 : 609616 .

136 . Yoo JJ , Meng J , Oberpenning F , et al. Bladder

augmentation using allogenic bladder submucosa

seeded with cells . Urology 1998 ; 51 : 221225 .

137 . Piechota HJ , Gleason CA , Dahms SE , et al. Bladder

acellular matrix graft: In vivo functional proper-

ties of regenerated rat bladder . Urol Res 1999 ;

27 : 206213 .

138 . Atala A , Bauer SB , Soker S , et al. Tissue engineer-

ing autologous bladders for patients needing cysto-

plasty . Lancet 2006 ; 376 : 12411246 .

139 . Satar N , Yoo JJ , Atala A . Progressive dilation

for bladder tissue expansion . J Urol 1999 ; 162 :

829831 .

140 . Docimo SG , Moore RG , Adams J , et al.

Laparoscopic bladder augmentation using stomach .

Urology 1995 ; 46 : 565 – 569 .

141 . Hedican SP , Schulam PG , Docimo SG . Laparoscopic

assisted reconstructive surgery . J Urol 1999 ;

161 : 267 – 270 .

142 . Gill IS , Rackley RR , Meraney AM , et al.

Laparoscopic enterocystoplasty . Urology 2000 ;

55 : 178181 .

143 . Meng MV , Anwar HP , Elliott SP , Stoller ML .

Pure laparoscopic enterocystoplasty . J Urol 2002 ;

167 : 1386 .

144 . Kelami A , Dustmann HO , Ludtke-Handjery A , et al.

Experimental investigations of bladder regeneration

using Teflon-felt as a bladder wall substitute . J Urol

1970 ; 104 : 693 .

145 . Goldstein MD , Dearden LC . Histology of omento-

plasty of the urinary bladder in the rabbit . Inv Urol

1966 ; 3 : 460 .

146 . Kelami A . Lyophilized human dura as a bladder

wall substitute: Experimental and clinical results .

J Urol 1971 ; 105 : 518 .

147 . Telly O . Segmental cystectomy with peritoneo-

plasty . Urol Int 1970 ; 25 : 236 .

148 . Cartwright PC , Snow BW . Bladder autoaugmen-

tation: Partial detrusor excision to augment the

bladder without the use of bowel . J Urol 1989 ;

142 : 10501053 .

149 . Cartwright PC , Snow BW . Bladder autoaugmen-

tation: Early clinical experience . J Urol 1989 ;

142 : 505508 .

150 . Johnson HW , Nigro MK , Stothers L , et al.

Laboratory variables of bladder autoaugmentation

in an animal model . Urology 1994 ; 44 : 260 .

151 . Stothers L , Johnson H , Arnold W , et al. Bladder

autoaugmentation by vesicomyotomy in the pediat-

ric neurogenic bladder . Urology 1994 ; 44 : 110 .

152 . Kumar SP , Abrams PH . Detrusor myectomy: Long-

term results with a minimum follow-up of 2 years .

BJU Int 2005 ; 96 : 341 .

153 . Swami KS , Feneley RC , Hammonds JC , Abrams

P . Detrusor myectomy for detrusor overactivity:

A minimum 1-year follow-up . Br J Urol 1998 ;

81 : 6872 .

154 . Donald HN , Mitchell ME , Mark H , et al.

Demucosalised augmentation gastrocystoplasty

with bladder autoaugmentation in pediatric patients .

J Urol 1996 ; 156 : 206209 .

155 . MacNeily AE , Afshar K , Coleman GU , Johnson

HW . Autoaugmentation by detrusor myotomy:

Its lack of effectiveness in the management of

congenital neuropathic bladder . J Urol 2003 ;

170 : 1643 .

156 . Marte A , Di Meglio D , Cotrufo AM , et al. A long-

term follow-up of autoaugmentation in myelodys-

plastic children . BJU Int 2002 ; 89 (9) : 928931 .

157 . Dewan PA, Stefanek W . Autoaugmentation gastro-

cystoplasty: Early clinical results Br J Urol 1994 ;

74 (4) : 460464 .

158 . Close CE . Autoaugmentation gastrocystoplasty .

BJU Int 2001 ; 88 (7) : 757761 .

159 . Dewan PA , Lorenz C , Stefanek W , Byard RW .

Urothelial lined colocystoplasty in a sheep model .

Eur Urol 1994 ; 26 (3) : 240246 .

160 . Oge O , Tekgul S , Ergen A , Kendi S . Urothelium-

preserving augmentation cystoplasty covered with

a peritoneal flap . BJU Int 2000 ; 85 : 802805 .

256 P. Sountoulides and M.P. Laguna

161 . Close CE, Dewan PA, Ashwood PJ, et al.

Autoaugmentation peritoneocystoplasty in a sheep

model BJU Int 2001 ; 88 (4) : 414–417 .

162 . Perovic SV , Djordjevic ML , Kekic ZK , Vukadinovic

VM . Detrusorectomy with rectus muscle hitch and

backing . J Pediatr Surg 2003 ; 38 : 1637 .

163 . Perovic SV , Djordjevic ML , Kekic ZK , Vukadinovic

VM . Bladder autoaugmentation with rectus muscle

backing . J Urol 2002 ; 168 (4 Pt 2) : 18771880 .

164 . Dewan PA . Autoaugmentation demucosalized ente-

rocystoplasty . World J Urol 1998 ; 16 : 255 .

165 . Stohrer M et al. : Bladder auto-augmentation—

An alternative for enterocystoplasty: Preliminary

results . Neurourol Urodyn 1995 ; 14 : 1123 .

166 . Ehrlich RM , Gershman A . Laparoscopic sero-

myotomy (auto-augmentation) for non-neurogenic

neurogenic bladder in a child: Initial case report .

Urology 1993 ; 42 : 175 .

167 . Poppas DP , Uzzo RG , Britanisky RG , Mininberg

DT . Laparoscopic laser assisted autoaugmentation

of the pediatric neurogenic bladder: Early experience

with urodynamic follow-up . J Urol 1996 ; 155 : 1057 .

168 . McDougall EM , Clayman RV , Figenshau RS , et al.

Laparoscopic retropubic auto-augmentation of the

bladder . J Urol 1995 ; 153 : 123–126 .

169 . Mammen T , Balaji KC . Robotic transperitoneal

detrusor myotomy: Description of a novel tech-

nique . J Endourol 2005 ; 19 (4) : 476–479 .

170 . Snow BW , Cartwright PC . Bladder autoaugmenta-

tion . Urol Clin North Am 1992 ; 23 : 323–331 .

171 . Skobejko-Wlodarsa L , Strulak K , Nachulewicz

P , Szymkiewicz C . Bladder autoaugmentation in

myelodysplastic children . Br J Urol 1998 ; 81 : 114 .

172 . Cartwright PC , Snow BW . Autoaugmentation

cystoplasty . In: Dewan P , Mitchell M , eds. Bladder

augmentation . London : Arnold , 2000 : 83 – 91 .

173 . Nguyen DH , Mitchell ME , Horowitz M , et al.

Demucosalized augmentation gastrocystoplasty

with bladder autoaugmentation in pediatric patients .

J Urol 1996 ; 156 : 206–209 .

174 . Dewan PA , Ehall H . Autoaugmentation gastro-

cystoplasty: Patient selection, outcome, and ongo-

ing research . Dialogues Pediatr Urol 1999 ; 22 : 35 .

175 . Dewan PA , Close CE , Byard RW , et al. Enteric

mucosal regrowth after bladder augmentation using

demucosalized gut segments . J Urol 1997 ; 158 : 1141 .

176 . Close CE , Dewan PA , Ashwood PJ , et al. Auto-

augmentation peritoneocystoplasty in a sheep

model . BJU Int 2001 ; 88 : 414 .

177 . Meulen PH , Heesakkers JP , Janknegt RA . A study on

the feasibility of vesicomyotomy in patients with motor

urge incontinence . Eur Urol 1997 ; 32 (2) : 166–169 .

178 . Stohrer M , Kramer G , Goepel M , et al. : Bladder

autoaugmentation in adult patients with neurogenic

voiding dysfunction . Spinal Cord 1997 ; 35 : 456 .

179 . Leng WW , Blalock HJ , Fredriksson WH , et al.

Enterocystoplasty or detrusor myectomy? Com-

parison of indications and outcomes for bladder

augmentation . J Urol 1999 ; 161 : 858 .

180 . Gurocak S , De Gier RPE , Feitz W . Bladder aug-

mentation without integration of intact bowel seg-

ments: Critical review and future perspectives .

J Urol 2007 ; 177 : 839844 .

181 . Natarajan V , Singh G . Urinary diversion for incon-

tinence in women . Int Urogynecol J Pelvic Floor

Dysfunct 2000 ; 11 : 180–187 .

182 . Appell RA . Surgery for the treatment of overactive

bladder . Urology 1998 ; 51 : 27–29 .

183 . Liard A , Séguier-Lipszyc E , Mathiot A , Mitrofanoff

P . The Mitrofanoff procedure: 20 years later . J Urol

2001 ; 165 (6 Pt 2) : 2394–2398 .

184 . Leng WW , Faerber G , Del Terzo M , McGuire EJ .

Long-term outcome of incontinent ileovesicostomy

management of severe lower urinary tract dysfunc-

tion . J Urol 1999 ; 161 (6) : 1803–1806 .

185 . Rivas DA , Karasick S , Chancellor MB . Cutaneous

ileocystostomy (a bladder chimney) for the treat-

ment of severe neurogenic vesical dysfunction .

Paraplegia 1995 ; 33 (9) : 530–535 .

186 . Atan A , Konety BR , Nangia A , Chancellor MB .

Advantages and risks of ileovesicostomy for the

management of neuropathic bladder . Urology 1999 ;

54 (4) : 636–640 .

187 . Hsu TH , Rackley RR , Abdelmalak JB , et al.

Laparoscopic ileovesicostomy . J Urol 2002 ;

168 (1) : 180181 .

188 . Gudziak MR , Tiguert R , Puri K , et al. Management

of neurogenic bladder dysfunction with incontinent

ileovesicostomy . Urology 1999 ; 54 (6) : 1008–1011 .

189 . Tan HJ , Stoffel J , Daignault S , et al. Ileovesicostomy

for adults with neurogenic bladders: Complications

and potential risk factors for adverse outcomes .

Neurourol Urodyn 2008 ; 27 : 238 – 243 .

190 . Gauthier AR Jr , Winters JC . Incontinent ileovesicos-

tomy in the management of neurogenic bladder dys-

function Neurourol Urodyn 2003 ; 22 (2) : 142–146 .

191 . Hétet JF , Rigaud J , Karam G , et al. Complications of

Bricker ileal conduit urinary diversion: Analysis of a

series of 246 patients . Prog Urol 2005 ; 15 (1) : 2329 .

192 . Watanabe T , Rivas DA , Smith R , et al. The

effect of urinary tract reconstruction on neuro-

logically impaired women previously treated

with an indwelling urethral catheter J Urol 1996 ;

156 (6) : 1926–1928 .

257

Introduction

Overactive bladder (OAB) is a syndrome character-

ized by urgency with or without urgency inconti-

nence but usually accompanied by frequency and

nocturia. The majority of patients have proven

detrusor overactivity (DO), but treatment often is

instigated without this knowledge by community

practitioners based on symptoms alone. The patho-

physiology of DO and the pharmacological options

for treating patients with this disorder has been the

focus of considerable research in recent years.

Therapeutic options are split into initial treatment

and specialized therapy. Initial treatment encom-

passes lifestyle interventions, “bladder training,” and

the use of oral anticholinergics. Pharmacotherapy

in most individuals is still the first-line treatment.

Drugs used in OAB act peripherally, with most

currently available drugs (anticholinergics) acting

on muscarinic receptors. Unfortunately, anticholin-

ergics are associated with troublesome side effects

including dry mouth, constipation, blurred vision,

drowsiness, and tachycardia and their use is limited

because of this and also because patients become

refractory to their beneficial effects. In the past

these patients were managed with augmentation

cystoplasty or urinary diversion. More recently

other options have been developed and include

sacral neuromodulation and injections of botulinum

toxin (BTX) into the bladder (Fig. 20.1 ). The use

of the latter in the lower urinary tract currently is

unlicensed and at present experimental, but it appears

to be extremely promising. This will be the focus of

this chapter, explaining its possible mechanism of

action and clinical aspects of its use in the manage-

ment of urinary tract disorders.

Botulinum Toxin

BTX is a neurotoxin produced by the gram-positive

anaerobic spore-producing organism Clostridium botu-

linum ( Fig. 20.2 ). It is one of the most poisonous natu-

rally occurring toxins known to mankind [2] . Its effects

range from food poisoning known as “botulism” to an

acute and symmetrical paralysis. The severity of its

toxic effects ranges from mild weakness to respiratory

failure, coma, and death. Seven distinct botulinum

neurotoxins (A–G) have been isolated [3] . Types A and

B presently are used in clinical medicine, but several

other types are the subject of ongoing research.

Currently two pharmaceutical companies market

botulinum toxin-A (BTX-A) in the USA and UK.

BTX-A has been marketed as BOTOX

® in the USA

(Allergan Ltd) and as DYSPORT

® in the UK (Ipsen

Ltd). Its toxicity is measured in mouse units (mU),

which is “the amount fatal to 50% of a batch of

Swiss Webster mice” [4] . One unit of BOTOX®

(Allergan, Ltd, USA) is considered equivalent to

3–4 units of DYSPORT® (Ipsen, Ltd, UK). This is

an important point to keep in mind when analyzing

different studies, so as not to inadvertently utilize

incorrect doses. Botulinum toxin type B (BTX-B) is

commercially available as MYOBLOC

® in the US

(Elan Pharmaceuticals, Inc) and NEUROBLOC

®

in Europe (Elan Pharma International Ltd).

Chapter 20

Botulinum Toxin: An Effective Treatment

for Urge Incontinence

Arun Sahai, Mohammad Shamim Khan , and Prokar Dasgupta

258 A. Sahai et al.

Mechanism of Action and Rationale

for Therapeutic Use

The neurotoxin binds to peripheral cholinergic ter-

minals and inhibits acetylcholine release at the neu-

romuscular junction. Four steps are involved in this

process: binding, translocation, cleavage, and inhibi-

tion of transmitter release, resulting in blockage of

synaptic transmission and flaccid paralysis in the tar-

get muscle ensues. Affected nerve terminals do not

degenerate and function can be recovered by axonal

sprouting and formation of new synaptic contacts [5] .

The current view is that the new axons have the abil-

ity to form functional sprouts since they contain all

the apparatus necessary for exocytosis [6] . However,

in a distinct second phase sprouts eventually degener-

ate and synaptic activity returns in the original nerve

terminals [7] . The time required to recover function

after BTX paralysis depends on toxin type and type

of nerve terminal. The process takes approximately

2–4 months at the mammalian neuromuscular junc-

tion and considerably longer in autonomic neurons,

in some cases more than a year [8] .

BTX is made within the bacterial cytosol

and released as a 150-kDa polypeptide chain.

Proteolytic cleavage results in a 100-kDa heavy

chain and a 50-kDa light chain that remains linked

by a noncovalent protein interaction and a disulfide

bond essential for neurotoxicity [9, 10] . Once the

neurotoxin is released, it diffuses to cholinergic

terminals where it binds to as yet unknown recep-

tors on the membrane surface. Once bound, the

toxin is internalized inside endocytic vesicles and

binds to the lipid bilayer of the vesicle. The heavy

chain is thought to play a key role in translocat-

ing the light chain into the cytosol, which occurs

after the cleavage of the disulfide bond between

them. The light chain contains metalloprotease

zinc-binding units that have the ability to cleave

three soluble N -ethylmaleimide-sensitive factor

attachment protein receptors (SNARE) proteins

within the nerve terminal [11] . BTXs B, D, F, and

G cleave vesicle-associated membrane protein

(VAMP)/Synaptobrevin, A and E cleave synap-

tosomal-associated protein-25 (SNAP-25), and C

cleaves both SNAP-25 and syntaxin [12] . As the

OAB Symptoms

Non - Pharmacological Therapy + / -Pharmacotherapy

Lifestyle changes Oral Anticholinergics

Bladder Training

Pelvic Floor Exercises

Alternative delivery of antichiolinergics: Transdermal/intravesical oxybutynin

Treatment Failure (Tolerance, side effects)

2nd Line Therapy

Sacral Nerve Neuromodulation, Botulinum Toxin

Treatment Failure

Surgery e.g. augmentation cystoplasty, urinary diversion

Fig. 20.1. Treatment of OAB

20. Botulinum Toxin: An Effective Treatment for Urge Incontinence 259

Fig. 20.2. Mechanism of action of BTX at the neuromuscular junction. Source [1]

SNARE proteins are essential for normal vesicu-

lar transport and fusion, botulinum neurotoxins

are able to prevent the release of acetylcholine

(ACh) at the presynaptic membrane (Fig. 20.3 ) .

Over 35 years ago, Carpenter reported the effects

of acute BTX poisoning in an in vitro rat blad-

der model [13] . His study showed a marked loss

of contraction of the bladder with an associated

decrease in ACh release from motor nerve stimula-

tion. Smith reported on the effects of BTX-A on

ACh and norepinephrine release from the bladder

and urethra of rats, respectively [14] . Rat bladders

or urethras were injected with either BTX or sham

treatment (normal saline) and the rats were sacrificed

260 A. Sahai et al.

at either 5 or 30 days. The rat bladder and urethral

strips then were isolated and an electrical field was

applied to the strips at different frequencies. During

20-Hz electrical field stimulation, ACh release from

bladder strips treated with BTX 5 days earlier was

significantly reduced when compared with controls.

Norepinephrine release from urethral strips treated

30 days prior with BTX during 20-Hz electrical

stimulation also was significantly reduced com-

pared with controls. No significant inhibitory effects

were found at lower levels of electrical stimulation

frequency. ACh release was not affected in 30-day

BTX pre-treated rat bladders at 20 Hz nor was nore-

pinephrine release affected by 5 day BTX pretreated

rat urethral strips at 20 Hz. From this the authors

concluded that the clinical effects of BTX may vary

dependent on the anatomical site of injection in the

lower urinary tract and the frequency of nerve activ-

ity. They postulated that BTX may be more effective

at higher stimulation frequencies. This may be of

potential clinical significance in cases such as DO

and detrusor sphincter dyssynergia where the abnor-

mal nerve hyperactivity affecting the bladder and

external sphincter may be inhibited while preserving

normal tonic control of bladder and external urethral

function, and thus facilitating normal voiding.

Adenosine triphosphate (ATP), a purinergic neu-

rotransmitter, is believed to be coreleased with ACh

from parasympathetic cholinergic nerve terminals

[15, 16] . It has been postulated that ATP via purin-

ergic mechanisms contributes a significant amount

to unstable contractions in IDO [17, 18] . Studies on

guinea pig [19, 20] and rat [21, 22] bladder strips

have shown that BTX is able to impair both ACh

and ATP release, suggesting that its use in treating

patients with idiopathic detrusor overactivity (IDO)

is well justified.

There has been much excitement recently about

the exact mechanism of action of BTX, particularly

in the bladder. It is believed to have an effect on the

afferent and efferent arms of the micturition reflex

and an alternative hypothesis to the long-believed

mechanism of action of efferent blockade alone has

been proposed [23] . These bladder afferent neurons

have several types of receptors, namely vanilloid,

purinergic (P2X), neurokinin, and receptors for

nerve growth factor (NGF). The neurotransmitters

acting at these receptors, namely ATP, substance

P, neurokinin A, nitric oxide, and calcitonin gene-

related peptide (CGRP), are believed to play an

important role in modulating the sensory affer-

ents in the human detrusor, especially in diseased

bladder states. The density of substance P and

CGRP immunoreactive nerves was increased by

82% in patients with IDO, suggesting that there

is an increase in these types of afferent neurons in

patients with this condition [24] . In a rat model of

chromic spinal cord injury and neurogenic detrusor

overactivity (NDO), BTX-A significantly reduced

the abnormal distension-evoked urothelial release

of ATP [25] . BTX-A also significantly reduced

the evoked release of CGRP compared to controls

from isolated rat bladders [26] . In a rat bladder pain

model, following acetic acid instillation, a signifi-

cant improvement was demonstrated in the interval

between detrusor contractions in those that had

received BTX-A with reduced CGRP release from

the bladder [27] . The toxin also has been shown

to reduce ATP and capsaicin-induced DO in a rat

model [28] . Apostolidis et al. have proposed that

the primary peripheral effect of BTX-A involves

the inhibition of ACh, ATP, and substance P release

as well as a downregulation in the expression of

capsaicin and purinergic receptors [29] . Studies of

bladder biopsies taken at 4 and 16 weeks follow-

ing intradetrusor BTX-A injections have shown

Fig. 20.3. Photomicrograph of Clostridium botulinum

stained with Gentian violet. Source: http://phil.cdc.gov/

phil/details.asp; Centers for disease control and preven-

tion – Public Health Image Library (PHIL)

20. Botulinum Toxin: An Effective Treatment for Urge Incontinence 261

a reduced expression of TRPV1 and P2X

3 in the

suburothelium of patients with NDO and IDO [30] .

Both these sensory receptors are upregulated in IDO

and NDO and their levels by 16 weeks normalize to

that of controls following administration of 200 and

300 U of BTX-A (BOTOX®, Allergan, Ltd).

Further evidence in support of the afferent mecha-

nism of action comes from a proposed antinocic-

eptive effect separate to its neuromuscular action.

Welch et al. has reported that neurotransmitter

release from rat dorsal root ganglia was inhibited

by various isoforms of BTX [31] . Another group

reported on the inhibitory effect of BTX on the

release of radioactive-labeled glutamate from rat

dorsal root ganglia [32] . In vivo studies have shown

that pretreatment with BTX significantly reduced

pain in a formalin-induced inflammatory rat model

at 5 and 12 days postinjection [33] . This was asso-

ciated with a reduction in glutamate release from

primary afferent terminal and C-fos expression

(usually expressed with neuronal stimuli) compared

with controls. It was presumed that if a peripheral

pain mediator such as glutamate release could be

reduced, peripheral sensitization would be blocked,

which would indirectly reduce central sensitization

[34] . Additional evidence comes from Jankovic and

Schwartz in their human study, treating patients with

cervical dystonia [35] . They documented that pain

improved, soon after injection with BTX, before a

reduction in muscle spasm could be detected, imply-

ing that a mechanism other than flaccid paralysis of

the muscle caused by the toxin may be involved.

As afferent mechanisms may be important in the

pathophysiology of DO, the excellent therapeutic

efficacy of BTX may be explained in part by this

proposed dual mechanism of action. In addition,

due to its antinociceptive effect seen in animal

models there is a potential for treating conditions

such as interstitial cystitis and painful bladder

syndrome whether accompanied by DO or not,

although this needs further clinical study.

Applications in Medicine

and Urinary Tract

The fact that local injection of the toxin into stri-

ated muscle can induce paralysis has spurred

researchers to investigate its effects in muscle over-

activity. Autonomic effects are also observed, as it

blocks acetylcholine release in all parasympathetic

and at postganglionic sympathetic neurons. There

is growing interest in the therapeutic application of

BTX to treat overactive smooth muscle conditions

and disorders where there is abnormal activity due

to excessive postganglionic sympathetic activity

such as hyperhidrosis.

BTX currently is licensed for use in cervical

dystonia, strabismus, blepharospasm, hemifacial

spasm, glabellar wrinkles, focal spasticity including

dynamic equines foot deformity due to pediatric

cerebral palsy, and severe primary axillary hyperhid-

rosis not adequately managed with topical agents.

It has received a lot of media attention recently for

its cosmetic potential in reducing facial wrinkles

and rejuvenating facial appearances. Only in recent

years has the urology community looked into the

potential benefit of this toxin in the urinary tract.

BTX is not currently licensed for use in the

urinary tract. Much of the preliminary work car-

ried out to date has focused on intradetrusor injec-

tions and treating DO and symptoms of OAB. It

has been used, however, with success in treating

detrusor sphincter dyssynergia following exter-

nal sphincter injections and its application has

expanded to include prostatitis, chronic prostatic/

pelvic pain, benign prostatic hyperplasia, chronic

retention, as well as other aspects of voiding dys-

function [36– 38] . The rest of this chapter will focus

on the use of BTX to treat DO and OAB.

OAB and Detrusor Overactivity

Botulinum Toxin-A

Neurogenic Detrusor Overactivity

The application of BTX-A in DO was pioneered

by Brigitte Schurch [39] . Urodynamically proven

NDO patients with spinal cord injury who emptied

their bladder with clean intermittent self-catheteri-

zation (CISC) were recruited into their preliminary

study. Patients were injected with either 200 or

300 U of BTX-A (BOTOX

® ) into the bladder at 30

different sites using a rigid cystoscope. The trigone

was spared to avoid the potential complication of

vesicoureteric reflux (VUR). At 6-week follow

up, 17 of the 19 patients were completely conti-

nent based on subjective analysis of their voiding

diaries. Two patients who remained incontinent

262 A. Sahai et al.

had moderate improvement in symptoms and had

received the lower dose of toxin at 200 U. Ten

patients managed to reduce the dose, while seven

patients discontinued anticholinergic medication

all together. Urodynamics confirmed significant

increases in mean cystometric capacity (MCC)

from a mean value of 296.3–480.5 ml and a

decrease in maximum detrusor voiding pressure

(MDVP) from 65.6 to 35.0 cm H

2 O. At 16 and 36

weeks postinjection 11 patients had been followed

up and showed ongoing improvement in bladder

function. Seven patients remained continent and

in four, mild incontinence was observed which

was attributed to bladder infection. No side effects

were observed. The effect of injections lasted for at

least 9 months, longer than the duration of efficacy

reported when the toxin had been injected into the

external urethral sphincter. This is attributed to the

different mode of action of BTX on different types

of muscle in the bladder and external sphincter.

Its efficacy in treating NDO in further small

open-labeled studies has been confirmed using 300

or 400 U (BOTOX

® ) in patients with spinal cord

injury [40– 42] or multiple sclerosis [43] . Its use in

NDO and poorly compliant bladders also had favo-

rable outcome, although an improvement in com-

pliance did not necessarily equate to continence and

vice versa [42, 44] . Significant increases in MCC

and reflex volume as well as a decrease in MDVP

also have been reported in the largest retrospective

study consisting of 200 patients with NDO, at 6 and

36 weeks following injection of 300 U (BOTOX

® )

[45] . Continence was achieved in 132 of 180

patients with 48 reporting some improvement with

incontinence. Kuo recently has conducted a com-

parative study in patients with NDO with either

cerebral vascular accident (CVA) or a suprasacral

spinal cord lesion. Both groups were injected with

200 U (BOTOX

® ) [46] . Although reflex volume

and MCC increased in those with CVA, large

postvoid residuals (PVRs) were noted with little

change in incontinence. Overall, however a suc-

cessful result (either continence or a subjective

improvement in incontinence) was noted in 50% in

those with CVA compared with 92% in the spinal

cord injury group.

More recently several studies have shown that

DYSPORT

® also has a place in managing NDO [47–

49] . Ruffion et al. reported a “good success” defined

as no leakage following treatment with either 500 or

1,000 U BTX-A (DYSPORT

® ) in 76% of patients

[50] . A dose of 1,000 U had a significantly longer

median duration of action, but one case of general-

ized muscle weakness was reported for 1 month.

Grosse et al. assessed long-term efficacy with repeat

injections of BOTOX

® and DYSORT

® [51] , where

the majority of NDO patients assessed had up to

four repeat injections without any loss of therapeu-

tic efficacy. There was no statistically significant

change in interval between injections (average 9–11

months). The authors concluded that the optimal

dose of DYSPORT

® for this indication would be

750 U. Finally, Patki et al. in their series of 37 spi-

nal cord injury patients concluded that 1,000 U was

effective in treating NDO, with improvements in

quality of life (QOL) scores and urodynamic param-

eters and additionally 50% of patients being able to

stop anticholinergic medication [52] . However, two

cases of transient muscle weakness were observed

with this dose.

Until recently there had been a lack of level I

evidence based on randomized, placebo-controlled

trials to further validate the use of BTX in this set-

ting. However, in 2005, Schurch reported the first

double-blind, randomized placebo-controlled trial

involving 59 NDO patients who were randomized

to receive in a 1:1:1 ratio, 200 or 300 U BTX-A

(BOTOX

® ) or placebo [50] . Patients were followed

up at 2, 6, 12, 18, and 24 weeks. The results are

summarized in Table 20.1 . The primary endpoint

of incontinence episodes decreased significantly

at all time points except at 12 and 18 weeks in the

200-U group. Interestingly, when compared with

placebo, improvements only reached statistical

significance in the 300-U group at 2 and 6 weeks

and in the 200-U group at 24 weeks. Patients

receiving BTX-A at either dose showed significant

improvement in quality of life as assessed by the

incontinence quality of life (I-QOL) questionnaire

administered at all follow-up timepoints. No severe

adverse events were reported. The most common

reported adverse event was urinary tract infection

in 22% of the patients. They concluded that 200 or

300 U was equally efficacious. Surprisingly, anti-

cholinergic use remained similar in the study and

no data were reported on urinary urgency or PVR.

BTX-A versus Resiniferatoxin

Resiniferatoxin (RTX) is extracted from a cactus-

like plant called Euphorbia resinifera and is an

analogue of capsaicin [51] . Both capsaicin and RTX

20. Botulinum Toxin: An Effective Treatment for Urge Incontinence 263

are vanilloids, adopting the vanillyl moiety, and

act at the transient receptor potential channel or

vanilloid subfamily member-1 (TRPV1) receptor.

Vanilloid receptors are predominantly present on

C-fiber bladder afferents and upon activation by

vanilloids initially excite but subsequently desen-

sitize the C-fibers [52] . This formed the basis of

treatment with these compounds as this abnormal

spinal micturition reflex can be blocked by their

administration, reversibly [53] . Their use at present

is experimental. Giannantoni et al. reported on

a randomized trial of RTX versus BTX-A in 25

patients with NDO secondary to spinal cord injury

[54] . Patients were randomized to receive either

O.6 m M RTX in 50 ml of normal saline or 300 U

of BTX-A (BOTOX®). Follow-up consisted of

voiding diary assessment and urodynamic studies

at 6, 12, and 18 months. RTX ( n = 13) was found

to reduce incontinence episodes and reduce the

need for catheterization compared with baseline

values at all follow-up timepoints. Continence was

achieved in five patients. There was a significant

increase in the uninhibited detrusor contraction

threshold and in MCC. The average number of

RTX instillations per patient was 8.6±1.9 with

a mean time between instillations of 51.6±8.2

days. In the BTX arm, the number of incontinence

episodes and catheterization frequency was sig-

nificantly reduced at all follow-up timepoints. At

6 and 12 months, nine patients were dry and this

reduced to 6 by 18 months. Urodynamics revealed

a significant increase in the uninhibited detrusor

contraction threshold and in MCC and a signifi-

cant decrease in maximum pressure of uninhibited

detrusor contractions (MDP) compared to baseline

values. Patients required a mean number of 2.1±0.7

treatments, with the mean time between treatments

being 6.8±1.5 months. When comparing the two

treatments there was a significant decrease in

incontinence episodes using BTX compared with

RTX at all timepoints. There was a significant

increase in the uninhibited detrusor contractions

threshold and in MCC with a significant decrease

in MDP in the BTX treatment group compared

Table 20.1. Summary of results from a double-blind, randomized placebo-

controlled trial of BTX-A in patients with NDO .

Variable/time

point (weeks) 300 u BTX-A

( n = 19) 200 u BTX-A

( n = 19) Placebo

( n = 21)

Incontinence episodes

Baseline 2.8 (1.86) 1.9 (1.78) 3.0 (3.29)

2 −1.3 (1.39) a −1.0 (1.67) b −0.2 (1.02)

6 −1.5 (2.33) a −0.9 (1.84) b −0.2 (1.45)

12 −1.2 (1.66) b −0.9 (2.14) −0.3 (1.46)

18 −1.2 (1.16) b −0.8 (2.75) −0.3 (1.59)

24 −0.9 (1.34) b −1.1 (1.92) a −0.1 (1.09)

MCC (mL)

Baseline 293.6 260.2 254.6

2 479.6 (186.1) a,b 482.5 (215.8) a,b 282.0 (27.4)

6 462.7 (169.1) a,b 448.8 (182.1) a 299.6 (45.0)

24 398.2 (92.9) b 440.9 (174.2) a,b 301.0 (41.6)

RDV (mL)

Baseline 254.8 169.1 202.4

2 198.1 (8.6) 306.9 (135.3) b 206.7 (4.3)

6 268.5 (96.0) b 234.2 (47.3) 244.6 (42.6)

24 305.4 (72.4) 327.4 (144.6) a,b 226.4 (23.5)

MDP (cm H

2 O )

Baseline 92.6 77.0 79.1

2 41.0 (−66.3) a,b 31.6 (−52.9) a,b 71.4 (−7.7)

6 45.9 (−62.2) 40.1 (−44.4) a,b 69.0 (−10.1)

24 55.2 (−35.5) a,b 48.8 (−38.7) a,b 80.6 (−1.4)

Source [50] . Mean values (mean change from baseline)

a Statistically significant within-group changes from baseline and versus placebo

b Statistically significant changes versus placebo

264 A. Sahai et al.

with RTX at 6, 12, and 18 months. Certainly in

this subgroup of patients BTX treatment appears to

be superior to RTX in terms of clinical and urody-

namic benefit.

Idiopathic Detrusor Overactivity

After successful trials of BTX-A in NDO patients,

Rapp et al. reported on the use of 300 U (BOTOX

® )

of BTX-A in patients with OAB who were pre-

dominantly nonneurogenic in origin [55] . Thirty-

five patients were initially assessed and 21 patients

(60%) showed either complete resolution or

improvement of their symptoms at 3 weeks. Overall

there was a significant improvement in qual-

ity of life as assessed by the Urogenital Distress

Inventory (UDI-6) and the Incontinence Impact

Questionnaire (IIQ-7). Twenty-four patients com-

pleted the study at 6 months of which 14 were

initial responders at 3 weeks. Of these 14 patients

quality of life also was significantly improved

at 6 months. Mean daily pad usage significantly

reduced in those with urge incontinence from 3.9

to 1.8 per day. Side effects were minimal with

mild hematuria, dysuria, and pelvic pain reported

in seven patients. A major drawback of this study

was the lack of urodynamics performed prior to

injections to confirm DO.

Smith et al. have reviewed their experience of

using BTX-A in the lower urinary tract over a 6-year

period [56] . In their series, 38 patients underwent

bladder injections for either NDO or IDO. Between

100 and 300 U of BTX-A (BOTOX

® ) was injected,

although the exact dose given for the various indica-

tions was not stated. They employed 30–40 injec-

tions in patients with NDO and ten injections for

those with IDO. The technique included injecting

the trigone. Data presented were pooled for analysis

in both NDO and IDO. Improvements were seen at

6 months in MCC, maximal voiding pressure, pad

usage, and urinary frequency. There was no signifi-

cant increase in PVR, a potential concern in patients

with OAB and IDO. An excellent response was per-

ceived (on a 3-point scale: excellent, fair response,

no improvement) by approximately 50% of the

patients with NDO and IDO. Kuo et al. reported on

suburothelial injections of 200 U in 20 patients with

nonneurogenic detrusor activity (IDO or following

transurethral resection of prostate) restoring conti-

nence in nine patients, with improvement in eight,

and failure in three at 3 months [57] . Six patients

developed transient urinary retention and ten had

a PVR of >250 ml at 2 weeks. Overall, 15 (75%)

had difficulty voiding and incomplete emptying in

the follow-up period; six required clean intermittent

self-catheterization (CISC).

Significant reductions in frequency and nocturia

and an increase in MCC at 4 and 12 weeks follow-

ing 100 U BTX-A (BOTOX

® ) have been reported

in females with IDO [58] . PVR was increased at 4

weeks but only two patients required CISC and this

was only for 1 week. At 4 weeks 18/26, 12 weeks

16/20, and at 36 weeks 1/5 were continent. Using

the King’s Health Questionnaire (KHQ) significant

subjective improvement in all urge-related param-

eters was seen at 4 and 12 weeks. Thirty-one per-

cent of women developed urinary tract infections

and there were two non-responders.

Symptomatic improvement with BTX-A is a

consistent finding from other uncontrolled stud-

ies in patients with OAB [59, 60] . Popat and

colleagues compared the response to 200 U in

IDO with 300 U in NDO and concluded that each

provided significant benefit, although the percent

reduction in urgency in the NDO group was better

compared with the IDO group at 4 and 16 weeks

postinjection [61] . The same group when analyz-

ing QOL following BTX-A treatment in NDO

and IDO patients found significant benefit when

using the UDI-6 and IIQ-7 short forms [62] . On

the whole improvement in QOL correlated with

improvements in OAB symptoms but not with uro-

dynamic changes.

In order to combat the risk of developing high

PVR in patients with IDO a recent study com-

pared bladder injections with bladder and urethral

sphincter injections in combination in 44 predomi-

nantly female patients [63] . Those with a residual

of ³ 15 ml at baseline were given the sphincteric

injection since it was felt they were more prone

to developing higher residuals following BTX.

Between 200 and 300 U were administered in total

with 50–100 U given in the external sphincter.

Improvements in frequency, pad usage, and uro-

dynamic parameters were observed and in 86%

of cases patients were willing to undergo repeat

procedures. Significant reduction in incontinence

questionnaires using the short form Urogenital

Distress Inventory (UDI-6), Symptom Severity

Index, and Symptom Impact Index also were seen

20. Botulinum Toxin: An Effective Treatment for Urge Incontinence 265

for up to 6 months. These positive results were

similar for both groups, but a significant PVR at

4 weeks was seen in those with bladder injection

alone compared to combination treatment. The

development of de novo stress incontinence in

those who received sphincteric injections was not

proven. Pad usage at 4 weeks was similar in both

groups and when assessing the incontinence ques-

tionnaires regarding this aspect, although more

patients answered in favor of stress symptoms in

the combination group, this did not reach statisti-

cal significance. No significant side effects were

reported.

The largest series to date recruited 100 patients

with symptoms of OAB and were treated with

100 U of BTX-A (BOTOX

® ) [64] . Fifty-four

patients had IDO and the remainder sensory

urgency (OAB syndrome but without DO on uro-

dynamic studies). Significant improvements in

symptomology and urodynamic parameters were

seen. Increases in MCC and first desire to void

correlated with decreases in daytime frequency

and nocturia. Efficacy was quoted as 6±2 months;

however, only 20 patients were assessed fully at 9

months. QOL as assessed by the KHQ improved

at 4 and 12 weeks in all urge related items. Ninety

percent experienced improvement in at least one

KHQ domain. Nineteen patients developed voiding

dysfunction following injections (PVR >150 ml)

but only four patients required CISC. Eight patients

were deemed to have failed treatment (no clini-

cal or urodynamic benefit). All of these had a

low detrusor compliance (<10 ml/cm H

2 O) and

had maximum bladder capacities of <100 ml due

to bladder wall fibrosis as assessed by detrusor

biopsies. Repeat injections in these cases did not

change outcome.

The first randomized placebo-controlled trial in

patients with IDO refractory to anticholinergics

was recently reported [65] involving the use of

200 U or placebo (normal saline) administered

using a flexible cystoscopic technique under local

anesthetic. Thirty-four patients were randomized:

16 to BTX-A and 18 to placebo. Baseline char-

acteristics were comparable with an almost equal

mix of males and females. The primary endpoint,

MCC, increased significantly, and improvement

in symptoms, urodynamic, and QOL parameters

using the UDI-6 and IIQ-7 was seen in patients

in the BTX-A group compared with placebo (see

Table 20.2 – 20.4 ). Four weeks after treatment, con-

tinence was restored in 2 of 16 (12.5%) of those

in the placebo group and 8 of 16 (50%) in the

BTX-A group who were incontinent at baseline.

By 12 weeks, all patients in the placebo group

were again incontinent. In the BTX-A group,

Table 20.2. Summary of results from a double-blind, randomized placebo-controlled trial of

BTX-A in patients with IDO.

Mean value BTX-A Placebo Difference between

means (95% Cl) P

Frequency

Baseline 15.44 14.33 NS

4 weeks 7.93 (–7.51) 13.30 (–1.03) −5.37 (−8.82 to −3.78) <0.0001

12 weeks 9.25 (–6.19) 13.19 (–1.14) −3.94 (−7.05 to −1.55) 0.0033

Urgency

Baseline 11.69 7.31 0.0008

4 weeks 2.48 (–9.21) 6.02 (–1.29) −3.54 (−6.56 to −1.30) 0.0047

12 weeks 3.50 (–8.19) 6.39 (–0.92) −2.89 (−6.84 to 0.50) 0.0878

Urgency incontinence

Baseline 4.98 3.91 NS

4 weeks 1.90 (–3.08) 3.17 (–0.74) −1.27 (−3.79 to −0.23) 0.0284

12 weeks 1.48 (–3.50) 3.20 (–0.71) −1.72 (−3.78 to −0.63) 0.0076

Frequency – number of micturitions per day; urgency – defined as the sudden desire to pass urine which cannot

be deferred; urgency incontinence – defined as urinary leakage associated with urgency. NS = Nonsignificant.

Voiding diary data. Source [65] Mean number of daily OAB symptoms following BTX-A treatment (mean

change from baseline). Numbers refer to an average of 3 days

266 A. Sahai et al.

Table 20.4. Summary of results from a double-blind, randomized placebo-controlled trial of

BTX-A in patients with IDO .

Mean value BTX-A Placebo

Difference between means

(95% Cl) P

IIQ-7

Baseline 18.31 14.78 NS

4 weeks 6.00 (–12.31) 10.67 (–4.11) −4.67 (−10.99 to −0.78) 0.0253

12 weeks 7.94 (–10.38) 15.39 (+0.61) −7.45 (−13.92 to −2.50) 0.0063

UDI-6

Baseline 10.75 9.50 NS

4 weeks 5.60 (–5.15) 9.00 (–0.50) −3.40 (−6.17 to −2.08) 0.0003

12 weeks 5.13 (–5.63) 10.00 (+0.50) −4.87 (−7.83 to −2.96) <0.0001

QOL data. Source [65] Quality of life after BTX-A treatment (mean change from baseline).

IIQ-7 = Incontinence impact questionnaire short form; UDI-6 = Urogenital Distress Inventory short form;

lower scores indicate better QOL. NS = Nonsignificant

Table 20.3. Summary of results from a double-blind randomized placebo-controlled trial of BTX-A in

patients with IDO.

Mean value BTX-A Placebo

Difference between means

(95% Cl) P

MCC (ml)

Baseline 181.81 198.06 NS

4 weeks t 313.25 (+131.44) 168.56 (–29.50) 144.69 (100.95 to 215.75) <0.0001

12 weeks 263.88 (+82.06) 168.17 (–29.89) 95.71 (47.47 to 172.45) 0.0011

MDP (cm H

2 O )

Baseline 85.06 78.67 NS

4 weeks 34.69 (–50.38) 75.22 (–3.44) −40.53 (−61.48 to −28.99) <0.0001

12 weeks 43.81 (–41.25) 78.67 (–0.00) −34.86 (−55.12 to −24.16) <0.0001

PVR (cm H

2 O )

Baseline 44.06 22.50 NS

4 weeks 96.13 (+52.06) 31.39 (+8.89) 64.74 (7.30 to 94.18) 0.0235

12 weeks 51.19 (+7.13) 22.50 (–0.00) 28.69 (−24.20 to 58.31) 0.4056

RDV (mL)

Baseline 124.25 122.53 NS

4 weeks 217.32 (+93.07) 100.89 (–21.64) 116.43 (62.77 to 169.23) 0.0001

12 weeks 147.33 (+23.08) 93.11 (–29.42) 54.22 (7.60 to 99.25) 0.0238

Urodynamic data. Source [65] Urodynamic parameters following BTX-A treatment (mean change from baseline).

MCC = Maximum cystometric capacity; MDP = maximum detrusor pressure during filling cystometry; PVR = postvoid

residual; RDV = reflex detrusor volume NS = Nonsignificant

50% remained continent at 12 and 24 weeks.

Following BTX-A, urinary frequency had normal-

ized in 57, 44, and 36% of patients at 4, 12, and

24 weeks, respectively. In the placebo group, only

11% showed frequency normalization at 4 and 12

weeks. Unblinding took place after 12 weeks and

data from the open labeled extension study sug-

gested the beneficial effects of BTX-A lasted at

least for 24 weeks. No major complications were

noted. Six patients, all in the BTX-A group, had

symptomatic >150 ml residual volume at follow-up

and were taught CISC.

Pediatric Use

The first published series recruited 17 children (mean

age 10.8 years) with myelomeningocoele (MMC)

and NDO resistant to anticholinergic medication

[66] . BTX-A was injected at 12 U/kg (BOTOX

® ) to

a maximum of 300 U. Significant increases in mean

reflex volume (95 vs. 201.45 ml), MCC (137.53

vs. 215.25 ml), and detrusor compliance (20.39 vs.

45.18 ml/cm H

2 O) with decreases in MDP (58.94

vs. 39.75 cm H

2 O) were observed. No side effects

were reported and the beneficial effects lasted up to

20. Botulinum Toxin: An Effective Treatment for Urge Incontinence 267

6 months. A similar study in 15 patients with MMC

and NDO confirmed clinical and urodynamic ben-

efit in patients, with a mean durability of the effect

of the toxin for 10.5 months [67] . After repeat injec-

tion of the same dose similar beneficial results were

reproduced. Twenty patients with MMC or sacral

agenesis were injected with 100–300 U of BTX-A

at 5 U/kg in another recent study [68] . Sixty-five

percent were continent after the first injection and

this was associated with significant increases in

MCC and a reduction in MDP. Treatment appeared

to last for 6–9 months and no adverse effects were

reported. Seven patients showed no response and in

six despite another injection, no improvement was

seen. Recently one study has shown the potential

benefits in children (mean age 10.8 years) with

IDO refractory to anticholinergics [69] . Assessment

was based on 15 patients with at least a 6-month

follow-up. After one injection of 100 U (BOTOX

® )

nine patients had no evidence of urgency or urgency

incontinence, three patients a partial response, and

no change in three. Eight patients maintained good

efficacy even at 12 months follow-up. Four patients

were reported to have temporary dysfunctional char-

acteristics on postinjection uroflowometry, of which

one girl required temporary CISC. One boy was

assumed to have developed VUR since he had loin

pain on voiding, although this was never substanti-

ated by micturating cystourethrogram.

It is important to point out that little is known of

the long-term effects of repeated injections in chil-

dren. However, Schulte-Baukloh et al. reported on ten

children (all of whom had three injections and four

children had five injections) who had repeat injections

of BTX-A, following on from their preliminary series

[66, 70] . Even after five injections, clear urodynamic

benefit was observed with no evidence of drug toler-

ance. The effect on MDP seemed to be better after

the third or fifth injections in contrast to after their

first. Of major concern, however, was the observation

that baseline detrusor compliance after the treatment

effect began wearing off appeared to progressively

decrease over time, from 21.7 to 10.3 ml/cm H

2 O fol-

lowing the first to after the fifth injection.

Botulinum Toxin-B

BTX-B recently has been used to treat a patient

with multiple sclerosis who had NDO resistant

to anticholinergics [71] . Before treatment, urody-

namics confirmed severe DO. A dose of 5,000 U

(MYOBLOC

® ) was given initially in ten different

sites into the bladder. Symptoms began improv-

ing within 24 h and urodynamics 2 months later

showed no evidence of DO. The effect of injec-

tion lasted approximately 4 months. Following

from this case 15 female patients with IDO were

recruited to a dose escalation study to determine

the efficacy of BTX-B (MYOBLOC

® ) [72] . The

duration of response was dose-related, with maxi-

mal benefit lasting approximately 3 months in

patients receiving 10,000 or 15,000 U. All but one

patient responded, who received the lowest dose

(2,500 U). All patients were asked to keep a void-

ing diary every 2 weeks postinjection and were

noted to have an average of 5.27 fewer episodes of

frequency per day after treatment. Since then, three

further cases have been published with patients

with NDO who were clinically suspected and

electrophysiologically proven to have resistance to

BTX-A, who were successfully treated with BTX-B

(NEUROBLOC

® ) [73, 74] .A recent double-blind,

controlled crossover trial in patients with IDO

and NDO randomized patients to either 5,000 U

of BTX-B or placebo [75] . Significant improve-

ments were observed in average voided volume,

frequency, incontinence episodes, and in quality

of life using the KHQ, but the effects appeared to

last for only 6 weeks. CISC was required in two

patients. Other side effects included constipation

( n = 2), dry mouth ( n = 2), and general malaise

was seen in one other patient. Although effective

in treating symptoms, the effects appear to be too

short-lived to merit use over BTX-A therapy. The

use of BTX-B, in our opinion, should be reserved

for those who fail treatment with or develop anti-

bodies to BTX-A.

Techniques of Intradetrusor

Administration of BTX

The original description of BTX-A injections for

the treatment of NDO was through a collagen flexi-

ble needle using a rigid cystoscope [39] . Since then

the technique has evolved, but the way in which the

toxin is administered into the bladder has not been

standardized, and indeed practice varies around the

world. In the initial experience with BTX-A and

NDO, the trigone was avoided on the assumption

that paralyzing the trigonal muscle might induce

268 A. Sahai et al.

VUR. Since then there has been mounting evidence

that BTX also may affect sensory nerves and that

afferent mechanisms have an important role in the

pathophysiology of DO [76] . Investigators in the

United States have advocated injecting the trigone

[56] based on the fact that this area of the blad-

der contains the highest density of nerve fibers,

including afferent population. These authors did

not formally assess patients for VUR but reported

no episodes of symptomatic pyelonephritis in the

treated patients. To resolve the issue as to which

method is more efficacious in the treatment of DO,

trials of trigonal versus nontrigonal injections of

BTX are eagerly awaited.

An open label study using BTX-A for both

NDO and IDO patients was begun in 2002 [61] .

Initially BTX was injected using a rigid cystoscope

under sedation. Thereafter, involved clinicians, led

by Prokar Dasgupta at the National Hospital for

Neurology and Neurosurgery, London (NHNN),

began exploring an alternative method using a

flexible cystoscope and an ultra-fine 4-mm flex-

ible needle (Olympus, Keymed, UK) to perform

injections. The objective was to ensure that the

toxin could be delivered at an optimal depth into

the submucosa or detrusor muscle, but not beyond.

Experiments were carried out that involved inject-

ing oranges under water using the ultra-fine needle,

but it was soon realized that the needle was not

steady enough to pierce the fruit’s tegument. To

overcome this difficulty a fine sheath (27 G) was

introduced through the working channel of the

cystoscope and the ultra-fine needle was passed

through this sheath. The sheath not only provided

the necessary stability to the needle resulting in

excellent operator control and precision injection,

but also provided protection to the flexible cysto-

scope in case of inadvertent puncture while feeding

the needle down the channel. This was soon trans-

lated into clinical practice, and since has become

known as the “Dasgupta technique,” a minimally

invasive daycase procedure performed under local

anesthesia [77, 78] .

Prophylactic antibiotics and 20 ml of 2% ligno-

caine intraurethral gel are administered prior to the

procedure. The injections are evenly distributed over

the dome, posterior, right, and left lateral walls of the

bladder, avoiding the trigone (Fig. 20.4 and 20.5 ).

The technique has obvious benefits in terms of cost

and ease of administration, particularly in those with

advanced neurological disease or significant comor-

bidity who are not fit for general or spinal anesthesia.

In addition, the needle length is such that injection

beyond the bladder is unlikely. Furthermore as an

ultra-fine needle is used, the chance of backflow

of the toxin after removal of the needle is reduced.

These two important considerations may challenge

the practice of using a longer and wider collagen nee-

dle with a rigid cystoscope, as traditionally employed

in mainland Europe and the United States.

The “Dasgupta technique” is quick; the proce-

dure taking on average 20 min to perform and also

is well tolerated [61] . Patients who have a good

response to treatment are willing to undergo repeat

injections when their symptoms recur, which pro-

vides the most robust evidence to the technique’s

popularity. In the very few patients who tolerated

the procedure poorly, instillation of 40 ml of 2%

lignocaine for 30 min prior to injections eased the

discomfort and made subsequent injections easily

tolerable.

This minimally invasive technique has been

adopted by some clinicians in the United States

to treat patients with refractory OAB using 100 U

of BTX-A [79] . Ten injections are utilized and

injected submucosally into the bladder base and

trigone only. In their series of ten patients similar

efficacy was reproduced compared with their older

rigid cystoscopic technique involving 30 injec-

tion sites. The added benefit appears to be that no

patient developed urinary retention or an elevated

Fig. 20.4. Dasgupta technique: mapping of BTX injections

20. Botulinum Toxin: An Effective Treatment for Urge Incontinence 269

PVR with the use of a reduced dose of BTX-A and

this modified technique.

It has been suggested that clinicians using the

technique either for the first few injections or for

teaching or demonstration purposes might add

a dye to the reconstituted BTX such as indigo

carmine [80] or methylene blue, to help identify

injected areas and facilitate placement of further

injections. Caution should be taken while doing

this as redox reagents like methylene blue can

detoxify BTX by photo-oxidation.

As there are no standardized guidelines or outcome

measures of what constitutes “success” and “failure”

with this form of therapy, evaluating which of the

currently used techniques is superior is difficult.

Further trials and perhaps head-to-head comparisons

of rigid versus flexible cystoscopic techniques with

the same outcomes being measured will establish

whether the technique of administration has a role in

efficacy of treatment. Certainly injecting the trigone

in a systematic way will not be easily achieved using

a flexible cystoscope. It is reassuring that the results

obtained using the flexible technique are comparable

to and in some cases surpass those published globally

using rigid cystoscopy.

Side Effects of BTX

Side effects of BTX are rare especially when con-

sidering its urological uses. Localized injection

into the detrusor muscle may be associated rarely

with an allergic reaction to the toxin or transient

flu-like symptoms. Depending on the technique

employed it is possible for patients to develop

hematuria which in some cases may need admis-

sion and irrigation to resolve [49] . On the whole

the injection technique is well tolerated even under

local anesthetic with discomfort scores using a ver-

bal 11-point Box Scale being 3.3±0.3 and 3.2±0.4

for patients with NDO and IDO, respectively [61] .

Doses used in the intradetrusor injection of BTX

Fig. 20.5. Suburothelial injection of BTX

270 A. Sahai et al.

are well below (one thousandth) the presumed

fatal dose in a 70-kg man [81] and as the injec-

tion is localized, minute quantities only reach the

systemic circulation. However, cases of general-

ized muscle weakness and prolonged paralysis in

upper or lower limbs have been reported following

BTX injection into the detrusor muscle [47– 49,

82] . Some authors have speculated that the cumu-

lative dose may have been too high or injection

might have taken place in a thin-walled bladder

where perivesical diffusion of the toxin took place,

although this could not be proven. Another pos-

sibility is that systemic effects may be related to

volume administered as opposed to dose.

Perhaps of greatest concern to patients is the

theoretical possibility of hypocontractility of the

detrusor resulting in voiding dysfunction with high

PVRs or frank urinary retention following BTX

injections. If this were to occur, patients would

need to perform CISC until the effects of the toxin

began to subside. This may not be of consequence

to the many NDO patients who already perform

CISC to empty their bladders but may be a major

undertaking for some patients with IDO. Patients

must have the ability to perform CISC and be coun-

seled appropriately prior to the treatment.

While using BTX-A (MYOBLOC

® ) at a dose

of 15,000 U, two patients experienced dry mouth

and generalized malaise in a recent dose escalation

study, and hence the authors have recommended

that doses above this should be avoided [72] . At

lower doses similar effects have been reported as

well as constipation [75] .

BTX treatment is to be avoided in any patient

with preexisting neuromuscular conditions such

as myasthenia gravis or Eaton-Lambert syndrome.

Aminoglycosides such as gentamycin, commonly

used by urologists, may potentiate neuromuscu-

lar weakness caused by BTX [83] , and therefore

these antibiotics also should be avoided in patients

undergoing treatment. In certain clinical situations,

repeat injections of BTX-A can cause an immune

response with the build up of tolerance to its effects

[84] , although this happens in <5% of cases. The

uses of other serotypes therefore are being inves-

tigated as an alternative therapy to type A toxin.

BTX-C is thought to give a long-lasting paralysis

similar to A [85] , whereas the VAMP-associated

toxins (B, D, F) are felt to have shorter duration

of action [86] . When comparing serotypes of the

toxin in a rat bladder model using fatigue stimu-

lation, BTX-D was shown to elicit a more rapid

response and a greater maximal inhibitory effect at

1 hour compared with type A [87] .

Many urologists have expressed concern regard-

ing the long-term effects of this form of treatment.

To date two studies have reported on the repeat-

ability and longevity of BTX treatment in both

adult and pediatric populations [47, 70] . Additional

concerns regarding histological change and long-

term fibrosis recently have been addressed [88, 89] .

Hafekamp et al. reported on a lack of structural

changes before and after BTX injections in patients

with NDO [90] . Contrary to reports with striated

muscle very little axonal sprouting was observed

following treatment. Comperat et al., when assess-

ing bladder tissue at cystectomy in those who had

previously received BTX injections within the last

year with a control group, showed no difference

in inflammation and edema [88] . Interestingly,

those who had received BTX had less fibrosis of

the bladder wall than those who had not, although

this was based on their own grading scale using a

cutoff of 20% ie, mild fibrosis if occupying <20%

of muscle fibers and/or submucosa and important

fibrosis if >20%.

Summary

In summary, BTX therapy appears to be a very attrac-

tive pharmacological agent to treat patients with DO

resistant to anticholinergics and patients with symp-

toms of OAB. Recent evidence from randomized,

controlled trials suggests that it is an effective treat-

ment in both NDO and IDO. BTX-B is probably

best reserved for those in whom treatment has failed

with BTX-A. Whether other botulinum toxins will

be come available for clinical use is not yet clear.

Certainly further studies are needed to decide what is

the optimum dose (currently being 300 U for NDO

and between 100 and 200 U for IDO), for patients

receiving BOTOX

® . For those using DYSPORT

®

for NDO there is perhaps a consensus emerging that

750 U may be the optimum dose. Dose escalation

studies currently are underway for patients with IDO

and will help clarify the optimum dose in this setting,

although the authors of this chapter believe that the

dose will depend on certain patient factors such as

severity of DO and that not one dose will “fix all,”

20. Botulinum Toxin: An Effective Treatment for Urge Incontinence 271

so to speak. The way in which the toxin is adminis-

tered into the bladder has not been standardized, and

indeed practice varies around the world. Whether the

technique of administration has a role in efficacy of

treatment also is uncertain. Further study with regard

to distribution, depth, and volume of injection are

necessary. The majority of side effects are minor

and are related to infection, hematuria, and impaired

contractility of the detrusor, resulting in high PVR.

Careful counseling is mandatory in this context and

patients’ should be both physically able and willing

to perform CISC prior to commencing treatment.

This is particularly important for those with IDO.

OAB is a chronic, debilitating condition that puts a

huge strain on health resources worldwide. BTX is

emerging as a useful therapeutic option in treating

these patients, filling the void between anticholiner-

gics and surgery. It is truly remarkable how one of

the most poisonous substances known to mankind

has been incorporated into the urologist’s armory in

treating such patients.

References

1 . Arnon SS , Schechter R , Inglesby TV , et al . Botulinum

toxin as a biological weapon: Medical and public

health management . JAMA 2001 ; 285 (8) : 1059 –

1070 .

2 . Gill DM . Bacterial toxins: A table of lethal amounts .

Microbiol Rev 1982 ; 46 (1) : 86 – 94 .

3 . Simpson LL . Molecular pharmacology of botuli-

num toxin and tetanus toxin . Annu Rev Pharmacol

Toxicol 1986 ; 26 : 427 – 453 .

4 . Harper M , Fowler CJ , Dasgupta P . Botulinum toxin

and its applications in the lower urinary tract . BJU

Int 2004 ; 93 (6) : 702 – 706 .

5 . Angaut-Petit D , Molgo J , Comella JX , et al. Terminal

sprouting in mouse neuromuscular junctions poi-

soned with botulinum type A toxin: Morphological

and electrophysiological features . Neuroscience

1990 ; 37 (3) : 799 – 808 .

6 . Meunier FA , Schiavo G , Molgo J . Botulinum neu-

rotoxins: From paralysis to recovery of functional

neuromuscular transmission . J Physiol Paris 2002 ;

96 (1–2) : 105 – 113 .

7 . de PA , Meunier FA , Molgo J , et al. Functional repair

of motor endplates after botulinum neurotoxin type

A poisoning: Biphasic switch of synaptic activity

between nerve sprouts and their parent terminals .

Proc Natl Acad Sci USA 1999 ; 96 (6) : 3200 – 3205 .

8 . Naumann M , Jost WH , Toyka KV . Botulinum

toxin in the treatment of neurological disorders of

the autonomic nervous system . Arch Neurol 1999 ;

56 (8) : 914 – 916 .

9 . de PA , Ashton AC , Foran P , et al . Botulinum A like

type B and tetanus toxins fulfils criteria for being

a zinc-dependent protease . J Neurochem 1993 ;

61 (6) : 2338 – 2341 .

10 . Schiavo G , Papini E , Genna G , Montecucco C . An

intact interchain disulfide bond is required for the

neurotoxicity of tetanus toxin . Infect Immun 1990 ;

58 (12) : 4136 – 4141 .

11 . Herreros J , Lalli G , Montecucco G , Schiavo G .

Pathophysiological properties of clostridial neu-

rotoxins. In: The comprehensive sourcebook of

bacterial protein toxins. Academic Press , London ,

2006 .

12 . Schiavo G , Matteoli M , Montecucco C . Neurotoxins

affecting neuroexocytosis . Physiol Rev 2000 ;

80 (2) : 717 – 766 .

13 . Carpenter FG . Motor responses of the urinary blad-

der and skeletal muscle in botulinum intoxicated

rats . J Physiol 1967 ; 188 (1) : 1 – 11 .

14 . Smith CP , Franks ME , McNeil BK , et al . Effect

of botulinum toxin A on the autonomic nervous

system of the rat lower urinary tract . J Urol 2003 ;

169 (5) : 1896 – 1900 .

15 . Burnstock G . Purinergic nerves . Pharmacol Rev

1972 ; 24 (3) : 509 – 581 .

16 . Mackenzie I , Burnstock G , Dolly JO . The effects

of purified botulinum neurotoxin type A on cholin-

ergic, adrenergic and non-adrenergic, atropine-

resistant autonomic neuromuscular transmission .

Neuroscience 1982 ; 7 (4) : 997 – 1006 .

17 . Bayliss M , Wu C , Newgreen D , et al . A quantita-

tive study of atropine-resistant contractile responses

in human detrusor smooth muscle, from stable,

unstable and obstructed bladders . J Urol 1999 ;

162 (5) : 1833 – 1839 .

18 . O’Reilly BA , Kosaka AH , Knight GF , et al . P2X

receptors and their role in female idiopathic detrusor

instability . J Urol 2002 ; 167 (1) : 157 – 164 .

19 . Mackenzie I , Burnstock G , Dolly JO . The effects of

purified botulinum neurotoxin type A on choliner-

gic, adrenergic and non-adrenergic, atropine-resistant

autonomic neuromuscular transmission . Neuroscience

1982 ; 7 (4) : 997 – 1006 .

20 . Smith CP , Franks ME , McNeil BK , et al . Effect

of botulinum toxin A on the autonomic nervous

system of the rat lower urinary tract . J Urol 2003 ;

169 (5) : 1896 – 1900 .

21 . Mackenzie I , Burnstock G , Dolly JO . The effects

of purified botulinum neurotoxin type A on cholin-

ergic, adrenergic and non-adrenergic, atropine-

resistant autonomic neuromuscular transmission .

Neuroscience 1982 ; 7 (4) : 997 – 1006 .

272 A. Sahai et al.

22 . Smith CP , Franks ME , McNeil BK , et al . Effect

of botulinum toxin A on the autonomic nervous

system of the rat lower urinary tract . J Urol 2003 ;

169 (5) : 1896 – 1900 .

23 . Apostolidis A , Dasgupta P , Fowler CJ . Proposed

mechanism for the efficacy of injected botulinum

toxin in the treatment of human detrusor overactiv-

ity . Eur Urol 2006 ; 49 (4) : 644 – 650 .

24 . Smet PJ , Moore KH , Jonavicius J . Distribution and

colocalization of calcitonin gene-related peptide,

tachykinins, and vasoactive intestinal peptide in nor-

mal and idiopathic unstable human urinary bladder .

Lab Invest 1997 ; 77 (1) : 37 – 49 .

25 . Khera M , Somogyi GT , Kiss S , et al . Botulinum

toxin A inhibits ATP release from bladder urothe-

lium after chronic spinal cord injury . Neurochem Int

2004 ; 45 (7) : 987 – 993 .

26 . Rapp DE , Turk KW , Bales GT , Cook SP . Botulinum

toxin type A inhibits calcitonin gene-related peptide

release from isolated rat bladder . J Urol 2006 ; 175 (3

Pt 1) : 1138 – 1142 .

27 . Chuang YC , Yoshimura N , Huang CC , et al .

Intravesical botulinum toxin A administration pro-

duces analgesia against acetic acid induced blad-

der pain responses in rats . J Urol 2004 ; 172 (4 Pt

1) : 1529 – 1532 .

28 . Atiemo H , Wynes J , Chuo J , et al. Effect of botu-

linum toxin on detrusor overactivity induced by

intravesical adenosine triphosphate and capsaicin in

a rat model . Urology 2005 ; 65 (3) : 622 – 626 .

29 . Apostolidis A , Dasgupta P , Fowler CJ . Proposed

mechanism for the efficacy of injected botulinum

toxin in the treatment of human detrusor overactiv-

ity . Eur Urol 2006 ; 49 (4) : 644 – 650 .

30 . Apostolidis A , Popat R , Yiangou Y , et al. Decreased

sensory receptors P2X3 and TRPV1 in suburothelial

nerve fibers following intradetrusor injections of

botulinum toxin for human detrusor overactivity . J

Urol 2005 ; 174 (3) : 977 – 982 .

31 . Welch MJ , Purkiss JR , Foster KA . Sensitivity

of embryonic rat dorsal root ganglia neurons to

Clostridium botulinum neurotoxins . Toxicon 2000 ;

38 (2) : 245 – 258 .

32 . Purkiss JR , Welch MJ , Doward S , et al. A method

for the measurement of [3H]-glutamate release from

cultured dorsal root ganglion neurons . Biochem Soc

Trans 1998 ; 26 (2) : S108 .

33 . Cui M , Khanijou S , Rubino J , Aoki KR . Subcutaneous

administration of botulinum toxin A reduces forma-

lin-induced pain . Pain 2004 ; 107 (1–2) : 125 – 133 .

34 . Aoki KR . Review of a proposed mechanism for the

antinociceptive action of botulinum toxin type A .

Neurotoxicology 2005 ; 26 (5) : 785 – 793 .

35 . Jankovic J , Schwartz K . Botulinum toxin injections for

cervical dystonia . Neurology 1990 ; 40 (2) : 277 – 280 .

36 . Leippold T , Reitz A , Schurch B . Botulinum toxin as

a new therapy option for voiding disorders: Current

state of the art . Eur Urol 2003 ; 44 (2) : 165 – 174 .

37 . Smith CP , Chancellor MB . Emerging role of botu-

linum toxin in the management of voiding dysfunc-

tion . J Urol 2004 ; 171 (6 Pt 1) : 2128 – 2137 .

38 . Sahai A , Khan M , Fowler CJ , Dasgupta P . Botulinum

toxin for the treatment of lower urinary tract symp-

toms: A review . Neurourol Urodyn 2005 ; 24 (1) : 2 – 12 .

39 . Schurch B , Stohrer M , Kramer G , et al. Botulinum-A

toxin for treating detrusor hyperreflexia in spinal

cord injured patients: A new alternative to anti-

cholinergic drugs? Preliminary results . J Urol 2000 ;

164 (3 Pt 1) : 692 – 697 .

40 . Kessler TM, Danuser H, Schumacher M, et al .

Botulinum A toxin injections into the detrusor: An

effective treatment in idiopathic and neurogenic

detrusor overactivity? Neurourol Urodyn 2005 ;

24 (3) : 231 – 236 .

41 . Bagi P , Biering-Sorensen F . Botulinum toxin A for

treatment of neurogenic detrusor overactivity and

incontinence in patients with spinal cord lesions .

Scand J Urol Nephrol 2004 ; 38 (6) : 495 – 498 .

42 . Hajebrahimi S , Altaweel W , Cadoret J , et al. Efficacy

of botulinum-A toxin in adults with neurogenic

overactive bladder: Initial results . Can J Urol 2005 ;

12 (1) : 2543 – 2546 .

43 . Schulte-Baukloh H , Schobert J , Stolze T , et al.

Efficacy of botulinum-A toxin bladder injections

for the treatment of neurogenic detrusor overac-

tivity in multiple sclerosis patients: An objective

and subjective analysis . Neurourol Urodyn 2006 ;

25 (2) : 110 – 115 .

44 . Klaphajone J , Kitisomprayoonkul W , Sriplakit S .

Botulinum toxin type A injections for treating neuro-

genic detrusor overactivity combined with low-com-

pliance bladder in patients with spinal cord lesions .

Arch Phys Med Rehabil 2005 ; 86 (11) : 2114 – 2118 .

45 . Reitz A , Stohrer M , Kramer G , et al. European

experience of 200 cases treated with botulinum-A

toxin injections into the detrusor muscle for urinary

incontinence due to neurogenic detrusor overactiv-

ity . Eur Urol 2004 ; 45 (4) : 510 – 515 .

46 . Kuo HC . Therapeutic effects of suburothelial injection

of botulinum A toxin for neurogenic detrusor over-

activity due to chronic cerebrovascular accident and

spinal cord lesions . Urology 2006 ; 67 (2) : 232 – 236 .

47 . Grosse J , Kramer G , Stohrer M . Success of repeat

detrusor injections of botulinum A toxin in patients

with severe neurogenic detrusor overactivity and

incontinence . Eur Urol 2005 ; 47 (5) : 653 – 659 .

48 . Patki PS , Hamid R , Arumugam K , et al. Botulinum

toxin-type A in the treatment of drug-resistant neu-

rogenic detrusor overactivity secondary to traumatic

spinal cord injury . BJU Int 2006 ; 98 (1) : 77 – 82 .

20. Botulinum Toxin: An Effective Treatment for Urge Incontinence 273

49 . Ruffion A, Capelle O, Paparel P, et al . What is the

optimum dose of type A botulinum toxin for treat-

ing neurogenic bladder overactivity? BJU Int 2006 ;

97 (5) : 1030 – 1034 .

50 . Schurch B , de SM , Denys P , et al. Botulinum toxin

type A is a safe and effective treatment for neu-

rogenic urinary incontinence: Results of a single

treatment, randomized, placebo controlled 6-month

study . J Urol 2005 ; 174 (1) : 196 – 200 .

51 . Szallasi A , Blumberg PM . Vanilloid receptors: New

insights enhance potential as a therapeutic target .

Pain 1996 ; 68 (2–3) : 195 – 208 .

52 . Chancellor MB , de Groat WC . Intravesical cap-

saicin and resiniferatoxin therapy: Spicing up the

ways to treat the overactive bladder . J Urol 1999 ;

162 (1) : 3 – 11 .

53 . Fowler CJ , Jewkes D , McDonald WI , et al.

Intravesical capsaicin for neurogenic bladder dys-

function . Lancet 1992 ; 339 (8803) : 1239 .

54 . Giannantoni A , Di Stasi SM , Stephen RL , et al.

Intravesical resiniferatoxin versus botulinum-A

toxin injections for neurogenic detrusor overactiv-

ity: A prospective randomized study . J Urol 2004 ;

172 (1) : 240 – 243 .

55 . Rapp DE , Lucioni A , Katz EE , et al. Use of

botulinum-A toxin for the treatment of refractory

overactive bladder symptoms: An initial experience .

Urology 2004 ; 63 (6) : 1071 – 1075 .

56 . Smith CP , Nishiguchi J , O'Leary M , et al. Single-

institution experience in 110 patients with botu-

linum toxin A injection into bladder or urethra .

Urology 2005 ; 65 (1) : 37 – 41 .

57 . Kuo HC . Clinical effects of suburothelial injection

of botulinum A toxin on patients with nonneuro-

genic detrusor overactivity refractory to anticholin-

ergics . Urology 2005 ; 66 (1) : 94 – 98 .

58 . Werner M , Schmid DM , Schussler B . Efficacy of bot-

ulinum-A toxin in the treatment of detrusor overactiv-

ity incontinence: A prospective nonrandomized study .

Am J Obstet Gynecol 2005 ; 192 (5) : 1735 – 1740 .

59 . Flynn MK , Webster GD , Amundsen CL . The

effect of botulinum-A toxin on patients with severe

urge urinary incontinence . J Urol 2004 ; 172 (6 Pt

1) : 2316 – 2320 .

60 . Kuo HC . Urodynamic evidence of effectiveness of

botulinum A toxin injection in treatment of detru-

sor overactivity refractory to anticholinergic agents .

Urology 2004 ; 63 (5) : 868 – 872 .

61 . Popat R , Apostolidis A , Kalsi V , et al. A comparison

between the response of patients with idiopathic

detrusor overactivity and neurogenic detrusor over-

activity to the first intradetrusor injection of botuli-

num-A toxin . J Urol 2005 ; 174 (3) : 984 – 989 .

62 . Kalsi V , Apostolidis A , Popat R , et al. Quality of

life changes in patients with neurogenic versus

idiopathic detrusor overactivity after intradetrusor

injections of botulinum neurotoxin type A and cor-

relations with lower urinary tract symptoms and uro-

dynamic changes . Eur Urol 2006 ; 49 (3) : 528 – 535 .

63 . Schulte-Baukloh H , Weiss C , Stolze T , et al.

Botulinum-A toxin detrusor and sphincter injec-

tion in treatment of overactive bladder syndrome:

Objective outcome and patient satisfaction . Eur Urol

2005 ; 48 (6) : 984 – 990 .

64 . Schmid DM , Sauermann P , Werner M , et al.

Experience with 100 cases treated with botulinum-

A toxin injections in the detrusor muscle for idi-

opathic overactive bladder syndrome refractory to

anticholinergics . J Urol 2006 ; 176 (1) : 177 – 185 .

65 . Sahai A , Khan MS , Dasgupta P . Efficacy of botuli-

num toxin-A for treating idiopathic detrusor over-

activity: Results from a single center, randomized,

double-blind, placebo controlled trial . J Urol 2007 ;

177 (6) : 2231 – 2236 .

66 . Schulte-Baukloh H , Michael T , Schobert J , et al.

Efficacy of botulinum-A toxin in children with

detrusor hyperreflexia due to myelomeningocele:

Preliminary results . Urology 2002 ; 59 (3) : 325 – 327 .

67 . Riccabona M , Koen M , Schindler M , et al.

Botulinum-A toxin injection into the detrusor:

A safe alternative in the treatment of children

with myelomeningocele with detrusor hyperreflexia .

J Urol 2004 ; 171 (2 Pt 1) : 845 – 848 .

68 . Altaweel W , Jednack R , Bilodeau C , Corcos J .

Repeated intradetrusor botulinum toxin type A in

children with neurogenic bladder due to myelom-

eningocele . J Urol 2006 ; 175 (3 Pt 1) : 1102 – 1105 .

69 . Hoebeke P , De CK , Vande WJ , et al. The effect

of botulinum-A toxin in incontinent children with

therapy resistant overactive detrusor . J Urol 2006 ;

176 (1) : 328 – 330 .

70 . Schulte-Baukloh H , Knispel HH , Stolze T , et al.

Repeated botulinum-A toxin injections in treatment

of children with neurogenic detrusor overactivity .

Urology 2005 ; 66 (4) : 865 – 870 .

71 . Dykstra DD , Pryor J , Goldish G . Use of botulinum

toxin type B for the treatment of detrusor hyperreflexia

in a patient with multiple sclerosis: A case report .

Arch Phys Med Rehabil 2003 ; 84 (9) : 1399 – 1400 .

72 . Dykstra D , Enriquez A , Valley M . Treatment of

overactive bladder with botulinum toxin type B:

A pilot study . Int Urogynecol J Pelvic Floor

Dysfunct 2003 ; 14 (6) : 424 – 426 .

73 . Pistolesi D , Selli C , Rossi B , Stampacchia G .

Botulinum toxin type B for type A resistant bladder

spasticity . J Urol 2004 ; 171 (2 Pt 1) : 802 – 803 .

74 . Reitz A , Schurch B . Botulinum toxin type B injec-

tion for management of type A resistant neuro-

genic detrusor overactivity . J Urol 2004 ; 171 (2 Pt

1) : 804 – 805 .

274 A. Sahai et al.

75 . Ghei M , Maraj BH , Miller R , et al. Effects of botu-

linum toxin B on refractory detrusor overactivity:

A randomized, double-blind, placebo controlled,

crossover trial . J Urol 2005 ; 174 (5) : 1873 – 1877 .

76 . Apostolidis A , Dasgupta P , Fowler CJ . Proposed

mechanism for the efficacy of injected botulinum

toxin in the treatment of human detrusor overactiv-

ity . Eur Urol 2006 ; 49 (4) : 644 – 650 .

77 . Harper M , Popat RB , Dasgupta R , et al. A mini-

mally invasive technique for outpatient local anaes-

thetic administration of intradetrusor botulinum

toxin in intractable detrusor overactivity . BJU Int

2003 ; 92 (3) : 325 – 326 .

78 . Sahai A , Kalsi V , Khan MS , Fowler CJ . Techniques

for the intradetrusor administration of botulinum

toxin . BJU Int 2006 ; 97 (4) : 675 – 678 .

79 . Smith CP , Chancellor MB . Simplified bladder bot-

ulinum-toxin delivery technique using flexible cys-

toscope and 10 sites of injection . J Endourol 2005 ;

19 (7) : 880 – 882 .

80 . Schulte-Baukloh H , Knispel HH . A minimally

invasive technique for outpatient local anaesthetic

administration of intradetrusor botulinum toxin in

intractable detrusor overactivity . BJU Int 2005 ;

95 (3) : 454 .

81 . Scott AB , Suzuki D . Systemic toxicity of botulinum

toxin by intramuscular injection in the monkey . Mov

Disord 1988 ; 3 (4) : 333 – 335 .

82 . Wyndaele JJ , Van Dromme SA . Muscular weak-

ness as side effect of botulinum toxin injection for

neurogenic detrusor overactivity . Spinal Cord 2002 ;

40 (11) : 599 – 600 .

83 . Santos JI , Swensen P , Glasgow LA . Potentiation

of Clostridium botulinum toxin aminoglycoside

antibiotics: Clinical and laboratory observations .

Pediatrics 1981 ; 68 (1) : 50 – 54 .

84 . Pellizzari R , Rossetto O , Schiavo G , Montecucco

C . Tetanus and botulinum neurotoxins: Mechanism

of action and therapeutic uses . Philos Trans R Soc

Lond B Biol Sci 1999 ; 354 (1381) : 259 – 268 .

85 . Eleopra R , Tugnoli V , Rossetto O , et al. Botulinum

neurotoxin serotype C: A novel effective botuli-

num toxin therapy in human . Neurosci Lett 1997 ;

224 (2) : 91 – 94 .

86 . Meunier FA , Schiavo G , Molgo J . Botulinum neu-

rotoxins: From paralysis to recovery of functional

neuromuscular transmission . J Physiol Paris 2002 ;

96 (1–2) : 105 – 113 .

87 . Smith CP , Boone TB , de Groat WC , et al. Effect of

stimulation intensity and botulinum toxin isoform

on rat bladder strip contractions . Brain Res Bull

2003 ; 61 (2) : 165 – 171 .

88 . Comperat E , Reitz A , Delcourt A , et al. Histologic

features in the urinary bladder wall affected from

neurogenic overactivity – a comparison of inflam-

mation, oedema and fibrosis with and without

injection of botulinum toxin type A . Eur Urol 2006 ;

50 : 1058 – 1064 .

89 . Haferkamp A , Schurch B , Reitz A , et al. Lack of

ultrastructural detrusor changes following endo-

scopic injection of botulinum toxin type A in

overactive neurogenic bladder . Eur Urol 2004 ;

46 (6) : 784 – 791 .

90 . Haferkamp A , Schurch B , Reitz A , et al. Lack of

ultrastructural detrusor changes following endo-

scopic injection of botulinum toxin type A in

overactive neurogenic bladder . Eur Urol 2004 ;

46 (6) : 784 – 791 .

Part V

Management of Pelvic Organ Prolapse

277

Pelvic organ prolapse is a complex, multifactorial,

and dynamic condition. First and foremost, women

presenting with disorders of the pelvic floor should

have all presenting symptoms (relating to the gas-

trointestinal and genitourinary systems) thoroughly

evaluated prior to the initiation of a treatment

plan in order to identify all dysfunctions present.

It is difficult to define the prevalence of pelvic

organ prolapse because there is no clear distinc-

tion between normal and abnormal pelvic organ

mobility [1] . Milder forms of prolapse are often

asymptomatic [2] and a large proportion of women

with symptomatic prolapse do not seek medical

help [3] . Taking this into consideration, it is evident

that pelvic organ prolapse is a common problem

affecting 10–30% of the adult female population,

predominately affecting middle-aged and elderly

women [4] .

Although surgical management of pelvic organ

prolapse often is needed and is widely available,

many women in this age group may suffer from

severe medical comorbidities and other circum-

stances that may prevent them from having surgery,

including patient choice. It is important therefore

for gynecologists to continue to be skilled in the

assessment and conservative management of pelvic

organ prolapse.

The purpose of this chapter is to provide a com-

prehensive review of the conservative management

of pelvic organ prolapse. Covered areas include

symptoms, goals, and paradigms of treatment; cur-

rent role of pessaries (including indications, inser-

tion techniques, complications, contraindications,

and factors affecting successful fitting); behavioral

methods, biofeedback, and functional electrical

stimulation (FES).

Goals and Paradigm of Treatment

Our treatment paradigm must be guided primarily

by the extent to which the condition affects the

patient's quality of life. This may be done either for-

mally with quality of life questionnaires or may be

incorporated into the overall health assessment (both

verbal and written) or by the “Bother Index,” scored

from 1 to 10. Treatment options must be matched

to the patient's specific situation, life-tyle, desires,

wishes, and medical comorbidities. For example,

some women do not want to use pessaries regularly,

but may find these devices helpful and accept-

able as a means to prevent further prolapse during

exercise. It is of paramount importance to keep in

mind our goals for each individual patient. We must

keep abreast of the latest alternative, conservative

approaches in the management of pelvic organ

prolapse in order to be able to offer our patients a

full spectrum of therapies for their conditions. Not

only are these therapies and the surgical approach

not mutually exclusive, they also may be synergis-

tic in maximizing pelvic floor strength, increasing

the durability of the surgical repair over time, and

making it less likely for her to develop a recurrent

problem. Some patients will not be surgical candidates

due to medical comorbidities. In these cases, con-

servative management may prove to be invaluable.

Chapter 21

Conservative Management of Pelvic Organ

Prolapse: Biofeedback and Pessaries

Jill Maura Rabin

278 J.M. Rabin

Some women simply will not desire surgery, and

we have a fundamental obligation as physicians to

respect our patient's decisions and offer them non-

surgical therapeutic options.

This chapter offers a spectrum of options with

which to treat our patients. A treatment plan may

dynamically change over time according to each

individual patient's situation, anatomy, and degree

of prolapse, as well as her desire and wishes for her

individual treatment paradigm in the context of her

life. By viewing the panoply of available options,

we may better serve our patients not only in the

short-term, but in formulating an effective dynamic

long-term treatment and management paradigm

and plan.

Pessaries: An Overview

Introduction

The pessary is a device or appliance of varied form

introduced into the vagina in order to support the

uterus, correct any malposition or displacement,

and may be used to prevent conception as well as

considered to be a medicated vaginal suppository

[5] . Etymologically speaking, the word pessary has

developed from the latin word “pessarium,” as well

as from the Greek word “pessos” meaning an oval

stone. This is of historic interest since many of the

original pessaries had at their core either a stone

or other rounded object and then were wrapped or

coated with various organic or inorganic material.

The purpose of this section of the chapter is to pro-

vide the practitioner with a practical guide regard-

ing pessary selection and use in the conservative

management of pelvic organ prolapse for each

individual woman.

Historical Perspective

Pessaries have enjoyed a long, rich, and colorful

history dating back to biblical times. The oldest

known reported use of the pessary was described

by Hippocrates and later Soranus and Diocles,

who used half of a pomegranate soaked in vinegar.

Many naturally occurring substances such as other

fruits and vegetables, cotton, bronze, and cork were

used to construct a pessary of either the supportive

or flap type and space-filling type. Often times

these were coated with various drugs, oil, butter,

or wax in order to enhance the therapeutic use,

enhance ease of insertion, and reduce disintegra-

tion or rotting. The bowl pessary was composed of

linen held in place with a t-binder was composed

of the Middle Ages by Trotula. In 1559, Casper

Stromayr utilized a sponge that was tightly rolled

and bound with string, then dipped in wax and

covered with butter or oil. Hendrik Van Roonhuyse

described a cork that was dipped in wax in 1663

in his operative gynecology textbook, which was

the first of its kind [6] . Over 200 pessaries had

already been created when Hugh Lenox Hodge

created the contemporary lever pessary. The vul-

canization of rubber by Goodyear in 1763 allowed

the introduction of the rubber pessary, supplant-

ing some of the early organic pessaries, adding

to the overall attraction of this already popular

mechanical device. Plastics were introduced in

the 1950s, making pessaries more comfortable;

subsequently, silicone-based products were added

to the armamentarium of flexible, soft, and inert

materials that serve as the basis of pessaries today.

In the early 1900s, pessaries enjoyed their wid-

est appeal; this declined with the introduction of

asepsis and anesthesia, which allowed for the more

widespread and safe use of surgical correction for

pelvic organ prolapse. Nevertheless, there are over

20 types of pessaries in use today, available in a

variety of sizes, and they are of ever-softer and

flexible silicone. Having said this, the ideal pessary

remains to be developed. Vaginal space not only

is three-dimensional, but is a dynamic space that

changes not only over time but with patient activity

level, as well as with patient age and comorbidities.

Therefore, it is essential that we think creatively

about the future of pessaries. The development of

such a device that is dynamic, in addition to being

supportive and space-filling, must be given serious

consideration.

Role of Pessaries and Indications

for Their Use

Pessaries are most commonly used to relieve the

symptoms associated with prolapse and are con-

sidered part of the initial treatment of primary or

recurrent prolapse. Pessaries are invaluable devices

prescribed by from 87 to 98% of gynecologists

21. Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries 279

recently surveyed [7] . The role of this supportive

device is both diagnostic as well as therapeutic and

may be considered either short-term, long-term, or

may change dynamically with a specific patient's

individual situation. Therapeutically, pessaries may

be used to relieve symptoms of primary prolapse

or recurring prolapse including symptoms of back-

ache, pelvic pressure, or various urinary symptoms

including urgency. A properly fitted pessary may

stabilize the urethrovesical junction. Urodynamic

studies indicate that there is no increase in rectal,

bladder, urethral, or detrusor pressure after pessary

placement, despite an increase in urethral closure

pressure. Thus, in most cases obstructed voiding or

stress incontinence should not result from a prop-

erly fitted pessary [8] . Therapeutically pessaries

can be enormously helpful both physically and

emotionally for women with exteriorized prolapse

including atrophic, cracked, dry, and ulcerated

vaginal skin. Not only will a minimum of 2 months

of topical estrogen cream and a subsequent place-

ment of a good fitting pessary keep this bulge in

situ, improving the patient's comfort level, but will

allow for an improvement in the local environment

including improvement in vascularity, decrease in

air drying, and friction. One study examined the

question of whether or not pessaries prevented the

progression of pelvic organ prolapse. In fact, their

data suggested there may be a therapeutic effect

associated with the use a supportive pessary [9] .

A special role for the pessary was proposed by

Nygaard for use during physical activity, sports,

and exercise when urinary incontinence is com-

mon even in young nulliparus women [10] . Patients

reporting symptom relief with pessary placement

may desire a more permanent approach to their

situation such as surgery. Pessaries are especially

useful in these cases, for example, in patients with

recurrent prolapse who require some time with the

pessary in order to recover physically, emotionally,

and financially. This also is particularly helpful in

patients who desire to wait a period of time prior

to having surgery because of their individual situ-

ation, be it professional (a teacher who may have

the entire summer for vacation may plan her pro-

lapse surgery in these months), the caregiver of a

sick husband or partner who may need to postpone

definitive corrective to a more appropriate time, or

the “snow bird.” Typically, younger patients who

benefit from symptomatic relief of their prolapse

will continue to wear a pessary until such time as

they have completed their child-bearing.

The decision of whether or not to pursue surgical

repair or to continue with long-term pessary man-

agement is an individual decision, and yet must be

looked upon as a dynamic one, with the individual

women along with her health care team. In sum-

mary, there have been no studies conducted to date

to allow a physician to know in advance which

patients are likely to accept and continue using the

pessary. It is for this reason that all patients with

symptomatic prolapse should be offered conserva-

tive management of their pelvic organ prolapse

using pessaries.

Pessary Choice

Most pessaries today are either made of inert

plastic or silicone, with the large majority com-

posed of the latter. These pessaries last longer

than the rubber types and have the advantage of

not absorbing secretions and odors. Additionally,

silicone pessaries also may be autoclaved and have

a longer shelf-life than the other available materi-

als. Borrowing one of the tenets of the principles

of pelvic surgery, the least dangerous and least

invasive procedure for the patient should be chosen

as the first choice. Similarly, in choosing a pessary,

the least invasive device should be chosen for the

patient provided it reduces the prolapse, holds the

pelvic organs in place, causes the least number

and severity of localized symptoms, requires the

least care and fewest changes possible without an

increase in the symptoms, and additionally remains

in place.

Although much has been written on the nature

of pessary choice and fitting, this is as much an

art as a science. The ultimate goal is to of fit the

patient with the largest possible pessary that does

not cause discomfort. There are two basic tenets of

pessary choice [11, 12] . The first is the introitus,

whether or not it is well-supported or relaxed.

Second is the degree of pelvic organ prolapse

including specific vaginal wall defects and overall

pelvic muscle strength.

Stage 1 to 2 symptomatic pelvic organ prolapse

generally is managed with a supportive pessary

such as a ring or a donut pessary, which is gener-

ally gentler and less invasive than some of the

other types of pessaries. Stage 3 to 4 pelvic organ

280 J.M. Rabin

prolapse usually requires a space-filling pessary

such as a Cube or a Gellhorn.

One of the major areas in which experience of

the provider comes into play in the art and science

of fitting a pessary is the realization that there are

two components in describing and in managing

women with symptomatic prolapse in regard to the

pelvic outlet (Fig. 21.1 ). It is helpful to regard the

outlet as a three-dimensional structure with two

important components, the first being the vagina.

A vagina that is nonfunneled and cylinder-shaped

will admit two or three fingers. Second, the peri-

neal body will be intact, thick, and long. Although

it has been said many times that the fitting of pes-

saries requires trial and error and that this is largely

a function of individual physician experience and

training, the greatest determinant of successful

pessary choice and fitting remains the realization

of the dual component of the three-dimensionally

supported introitus/vaginal outlet.

All pessaries sit similarly in the vagina in an

oblique position, lodged behind the pubic sym-

physis and extending to or near the levator plate

fascia (toward the sacral promontory). In other

words, pessaries basically sit in what we call the

obstetric conjugate (anteroposterior diameter of

the midplane of the bony pelvis). Pessaries that

are supportive will rely on an intact vaginal outlet

in order to stay properly positioned in the vagina

as referenced above. Women will not be able to

retain these pessaries in the face of a funneled

vagina with a relaxed vaginal outlet, especially in

cases of increased vaginal pressure occurring with

defecation, for example. Pessaries that have the

additional feature of a suction mechanism such as

the Gellhorn or Cube type are able to reduce pelvic

organ prolapse and remain in place because they

function not only as a space-filling pessary but

have the additional feature of this suction support.

Nevertheless, some of the most challenging situa-

tions of pessary fitting remain this latter example

of a relaxed vaginal outlet/deficient perineum and

a long, funneled vagina.

One small prospective study investigated the risk

associated with an unsuccessful pessary fitting trial

in women with symptomatic pelvic organ prolapse

and concluded that a short vaginal length and a

wide vaginal introitus were risk factors for unsuc-

cessful pessary fitting, and that Gellhorn pessaries

more often are needed with stage 4 prolapse [14] .

The use of a double pessary in grade 4 uterine and

vaginal prolapse was proposed by one group who

concluded that the placement of two pessaries often

will be successful in women with long-standing

Fig. 21.1. The two determinants of pessary choice (from [13] , with permission). The two factors determining pessary

choice are the degree of pelvic organ prolapse (left) and the integrity of the pelvic outlet (right). Lesser degrees of

pelvic organ prolapse usually are managed quite adequately with the less invasive, gentler ring or donut pessary. More

severe or exteriorized lesions, however, may require the Gelhorn or Cube device

21. Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries 281

grade 4 prolapse who were unable to retain a single

pessary [15] . Additionally, we have patented a pes-

sary for treating vaginal prolapse that is dynami-

cally conformable, provides support where it is

most needed, and is coated with an antibacterial

soft gel that reduces discharge, odor, and infection.

Clinical trials are currently in progress [16] .

Fitting and Insertion Techniques

After discussing the use of the pessary with the

patient, we encourage her and instruct her in self-

removal, cleaning, and reinsertion. This allows her

to have more control over her pelvic organ prolapse

and its management in private. She may take it

out at night and reinsert it in the morning in order

to minimize vaginal discharge, odor, as well as

discoloration of the pessary. She thus may utilize

the pessary when and if she decides to use it, for

instance, during specific exercises or on certain

days rather than other days when her schedule dic-

tates greater degrees of intra-abdominal pressure

increase and activity. Erosions and vaginitis may

be best minimized. These are two of most common

complications of pessary use. Finally, she will be

in control and in charge of the management of her

pelvic organ prolapse, thus making frequent visits

to the physician for cleaning and management of

the pessary unnecessary. Visits would be sched-

uled at appropriate intervals to check fit as well as

checking for erosions and lesions and additionally

for routine gynecological care (Table 21.1 ).

There is very little scientific information regard-

ing the fitting of a pessary. It is important to discuss

the use of a pessary in great detail with the patient.

In particular, instructing her how to prevent expul-

sion during urination and defecation is very helpful,

since many elderly women experience constipation.

If a pessary fits properly, it either will not be vis-

ible or will barely appear on Valsalva maneuver in

the lithotomy position with the labia separated. A

device that is too small will fall out and a device

that is too large may not fit properly in the obstetric

conjugate and will cause additional discomfort and

pressure, to say nothing of interference with micturi-

tion and defecation. It is helpful to teach the patient

to palpate the pessary and hold it in place during

Valsalva maneuver. Alternatively, squeezing the

labia together effectively closes the vaginal outlet.

In addition to instructing the patient on insertion,

it is important to go through the steps verbally prior

to initiating the fitting procedure. The patient is

asked to empty her bladder. A pelvic examination is

performed in order to assess the pelvis, the degree

and type of prolapse, the vaginal length, perineum,

and introitus. A type of pessary is chosen and a size

estimate is made. Once the pessary type is chosen it

is important to lubricate the tissues prior to reducing

any prolapse present with a water-soluble lubricant

or estrogen cream. It is important additionally to

lubricate the particular pessary to be used and to

reduce its diameter to a minimum prior to inser-

tion. The pessary will sit with its widest diameter

in an anteroposterior orientation and in the obstetric

conjugate as previously mentioned. It is important to

have the patient relax her pelvic floor prior to inser-

tion of the pessary and place it during the patient's

inhalation. A two-handed technique is performed

whereby the pessary is reduced to its smallest diam-

eter and held in the practitioner’s dominant hand.

The thumb and fingers are used to squeeze the pes-

sary. The index finger of the nondominant hand is

used to assist the patient in relaxing her introitus.

The pessary is guided into the posterior fornix

and the distal edge behind the pubic symphysis.

Some pessary types, such as a ring pessary, need

to be rotated 90°. Following this the patient must

perform a Valsalva movement and the fit must be

assessed. The pessary in situ must have a fingertip

width's room between the perimeter of the pessary

and the vaginal walls. The largest possible device

must be fit, provided it is comfortable. If the patient

T able 21.1. Step-by-step pessary-fitting technique .

Discussion of pessary use with patient

Instruct patient to empty bladder and bowels

Vaginal examination for staging of the pelvic organ prolapse

Reduction of prolapse using Trendelenberg position and steady

gentle pressure if pelvic organ prolapse is exteriorized

Approximate size estimation of pessary

Lubricate pessary: water soluble/estrogen cream/

Metronidazole vaginal /Trimosan

Reduction of diameter and or size of device as small as

possible

Place widest diameter in the anterior posterior direction

Instruct patient in pelvic floor relaxation techniques

Placement of pessary, gently using a two-handed technique

Check placement of pessary in posterior fornix and behind

pubic symphysis (obstetric conjugate placement)

Fitting of device that can be worn comfortably

282 J.M. Rabin

Table 21.2 . Testing the fit of the pessary.

Ask the patient to walk for a minimum of 15–20 min in the

exam room and not to sit, to attempt position

If discomfort, pressure, or expulsion: instruct the patient on

self-management

If expulsion of the pessary is noted: a larger or different

pessary must be tried

If the patient experiences significant discomfort or pressure:

a smaller or different pessary should be tried

The patient is asked to report any pelvic pressure or discom-

fort, a slow stream or pressured defection, or an inability

to urinate or defecate immediately

Patient is asked to return within 1 week to check pessary

placement, size, and type

Check once again after 1 month if 1 week visit was

successful

Ask the patient to make an appointment to return within 3

months if she is not self-managing, or within 6 months if

she is pursuing self-management

notes expulsion during her activities in the office,

a larger or different pessary should be tried. If she

notes pressure or discomfort in the pelvis, a smaller

or different pessary should be fitted. The patient is

instructed to report any difficulty with defecation

or urination. A test fit protocol is then conducted

(Table 21.2 ).

It is important to spend considerable time with the

patient in the examination room (either the physi-

cian, nurse, or nurse practitioner) asking the patient

to ambulate, as well as sit, to perform the Valsalva

maneuver, and to attempt to void prior to leaving

the office. Further, instructions should be given to

the patient in terms of self-management or at least

to her caregiver. Ideally, the pessary should be

removed every night, washed with soap and water,

and reinserted in the morning. Many patients prefer

to perform this exercise weekly, while others prefer

to leave it in place for 6–8 weeks at time. If the latter

scenario is the case, the patient must return at regular

intervals, depending on the individual patient from

1 to 6 months, with the average being 2–3 months.

We keep a current list of patients using pessaries

in order to ensure that each patient using a pessary

is followed regularly at intervals determined by

both the physician and patient. This will reduce

complications associated with pessary use that will

be elaborated on in a subsequent section.

While vaginal discharge is associated with long-

term pessary use, with regular follow-up the dis-

charge should not be excessive. This being stated,

if the patient notes an excessive, foul-smelling, or

bloody vaginal discharge, she should report to the

office immediately.

Successful pessary fitting is one where the

pessary is not expelled with Valsalva maneuver

or cough, and where the patient is comfortable

without pressure or pain symptoms as well as not

being aware of the pessary in situ with ambulation,

sitting, voiding, or defecation.

Care of the Pessary

Follow-up intervals for patients vary on whether

they are self-inserting and removing, or if it is

being performed by the practitioner (Table 21.3 ).

The time interval also varies with the type of pes-

sary. For example, a Gelhorn pessary or Cube may

require more frequent physician and/or patient

cleaning. Topical creams should be used and they

may be in the form of water-soluble gels, such

as KY jelly or estrogen cream, Metronidazole

vaginal gel, or Trimosan. It is helpful when the

patient presents for device check to compose a

50:50 mixture of peroxide and saline and to swab

Table 21.3. Pessary care.

Self-insertion or removal follow-up every 6 months (follow-

up varies with pessary type)

Estrogen cream, Metronidazole gel, Trimosan, (follow-up

intervals varies with pessary type)

Solution is mixed one half peroxide, one half sterile water

and vagina is swabbed out with single-use swab prior to

device removal

Lubricate fingers of glove and remove device

Device is washed and inspected

Vagina is swabbed with the peroxide, sterile water mixture;

any bleeding is noted

Vagina is carefully inspected for any erosions, ulcers, or

lesions and if found these are addressed (including biopsy

if necessary)

Mild vaginitis: vagina is irrigated and painted with Betadine;

with severe vaginitis the pessary is discontinued temporarily

and any erosions or ulcerations are addressed

If pessary is to be replaced, lubricate pessary well with

estrogen cream, Metronidazole gel, or Trimosan before it

is replaced (as in this table above)

21. Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries 283

the vagina with a large swab soaked in the mix-

ture. This helps reduce any odor from vaginal

discharge. The gloved hand is then lubricated and

one or two fingers are used to remove the pessary.

It is helpful on removal to also use the two-handed

technique in order to more adequately control the

pessary emerging from the vagina. Any bleeding is

noted. The pessary is examined for wear and tear.

Similarly the vagina is examined for any erosion,

ulceration, or necrosis and these are noted in the

chart. The patient is questioned as to the ease of her

urination and defecation, and if urinary retention is

suspected, postvoid residual via ultrasound or cath-

eterization should be performed prior to pessary

removal. The urine may be sent for culture and sen-

sitivity, especially if the patient is symptomatic. If

mild vaginitis is found, the vagina may be irrigated

and swabbed with betadine. The follow-up inter-

val in this case may need to be sooner. If severe

vaginitis, erosions, or ulcerations are identified,

the pessary is not reinserted at this visit. Once it is

cleaned, it is returned to the patient. She is asked

to return within a 1- to 2-week interval after utiliz-

ing one of the topical creams as mentioned above

to assist in the healing process. Usage of low-dose

estrogen cream (1/2–1 g two nights per week) is

recommended by many practitioners and does not

result in significant systemic absorption.

Many patients prefer to remove the device

each night, or at least once a week, to leave it out

overnight or several days, and to douche, swab the

vagina, and clean their own pessary, and reinsert it.

Once it is established that the patient is able to do

this, a follow-up of every 3–6 months is acceptable.

One study specifically studied women who self-

managed their pessaries, and the author found good

acceptance, with very little in the way of complica-

tions, and these were actually minor [17] . A new

pessary should be substituted if inspection reveals

either physical defects or cracking, or other signs

of wear and tear. Discoloration does not require

replacement. However, severe discoloration may

indicate breakdown of the silicone and substitution

may be prudent.

Types of Pessaries

See Table 21.4

The Ring Pessary With and Without

Support

There are two types of ring pessaries available:

the open ring or the ring with a supportive mem-

brane (Fig. 21.2 ). These pessaries are among the

simplest to use requiring less frequent visits, allow

for easy self-insertion, removal, and permit coitus.

The ring with supportive membrane is utilized

in patients with procidentia who otherwise may

experience organ prolapse through an open ring.

The ring pessaries themselves are considered the

least invasive and are associated with the lowest

incidence of heavy vaginal discharge. They actu-

ally are very similar in appearance to the contra-

ceptive diaphragm and are available in sizes 0–13.

The most common sizes utilized are sizes 3–5.

These are most effective for women with mild to

moderate pelvic organ prolapse. This particular

pessary does require an intact vaginal outlet. The

ring with support is especially useful for women

with an accompanying cystocele. The pessary is

folded in half and inserted in a controlled manner,

and also folded for removal. This particular type of

pesary is turned 90 degrees following insertion due

to its uni- directional bend which assists in limiting

expulsion, and similarly turned prior to removal.

The patient can assist with removal of the pessary

by bearing down as the pessary is removed, and

this will also assist in folding the ring which will

decrease its diameter and facilitate removal.The

Shaatz is a supportive pessary also used for mild to

moderate uterine and vaginal prolapse in patients

requiring a slightly greater degree of support than

those utilizing the ring pessary. It fits between the

levator muscles and ultimately into the obstetric

conjugate. Insertion and removal is similar to the

ring pessary with the exception that it may be folded

in half at any point along the circumference.

The incontinence dish and the incontinence dish

with support are used in cases of mild pelvic organ

prolapse including mild cystocele. Sizing is simi-

lar to the ring and Shaatz pessaries and are most

commonly used in sizes 3–5. The knob is intended

to be positioned at the urethrovesical junction, as

these pessaries are indicated in cases of mild stress

incontinence and most notably may be used during

exercise. Insertion and removal is similar to the

ring pessary described above.

Table 21.4. Incontinence dish and incontinence dish with support .

Pessary Type Size Mechanism of action Indications

Require

intact

vaginal

outlet Pros Cons Follow-up Comments

Schaatz Support 3–5 Fits obliquely between

pubic symphysis and

sacral promontory

(obstetric conjugate)

Mild pelvic organ pro-

lapse with or without

cystocele

Yes Easy insertion,

removal and

self-care, coitus

possible, may be

used for exercise-

specific stress

incontinence/

leakage. Vaginitis,

none to mild

Less effective for

severe pelvic

organ prolapse

Initially after

3 months,

then q3–6

months

More effective with node

(if present) anterior

near urethrovesical

junction. May cause

vaginal and rectal dis-

comfort with rotation

of node

Mild genuine stress

urinary incontinence

Donut Space

filling

2½–3 in. Fills vaginal vault

occluding facing

prolapse

Moderate to severe

uterine or vaginal

vault prolapse

Yes For moderate to

severe uterine or

vaginal vault

prolapse

Coitus not pos-

sible, vaginitis

frequent, fre-

quent removal

necessary

Monthly for

3 months

then q3

months

Deflation prior to inser-

tion, reinflation after

insertion, deflation

prior to removal

facilitates insertion and

removal

Inflato-

ball

Space

filling

Medium

and

large

Fills vaginal vault repo-

sitions pelvic organ

prolapse cephalad

and occludes upper

vagina

Moderate to severe

uterine and vaginal

prolapse

No Self-insertion and

removal.

None to mild

vaginitis

May be Difficult

to retain

Must not be used with

patient latex allergy

Gehrung Support 3–5 Supports cystocele by

directing pressure via

double arch against

anterior vaginal wall

with legs of pessary

directed posteriorally,

supporting rectocele

by double arch sitting

against rectocele and

posterior vaginal wall

with its legs directed

anteriorally

Cystocele or rectocele No Isolated cystocele

or rectocele, ease

of self-insertion

or removal, coitus

possible

Mild to moderate

vaginitis

Monthly for

the first 3

months,

then every

2–3 months

Designed specifically for

cystocele or rectocele

Gelhorn Space

filling

1–5 (3–5

most

com-

mon)

The dish portion has a

shallow cup oriented

cephalad against the

cervix or vaginal

vault reducing pro-

lapse in a cephalad

manner, the stem sits

in the vagina directed

toward the introitus

or posterior four-

chette, suction

Moderate to severe pel-

vic organ prolapse

No Excellent choice for

moderate to severe

pelvic organ pro-

lapse

Insertion and

removal may

be difficult,

severe vaginal

discharge or

vaginitis may

develop, coitus

not possible,

more frequent

patient visits

for cleaning

and manage-

ment____ may

be required

Initially 1–2

weeks and

then 1–3

months

Assure patient compli-

ance, removal may be

difficult (use of single-

tooth tenaculum or ring

forceps in nondomi-

nant hand may assist

with traction on stem,

dominant index finger

breaks suction between

vagina and dish prior to

removal portion)

Cube Space

filling

0–7 (2–4

most

com-

mon)

Severe pelvic organ

prolapse

No For severe pelvic

organ prolapse

Heavy vaginitis

and discharge,

vaginal ulcera-

tions, frequent

removals, coi-

tus not possible

Every 1–2

weeks, sub-

sequently

every 4

weeks

Cutting holes between

surfaces will decrease

the hypoxic environ-

ment and allow vaginal

discharge to escape.

Newer models have

incorporated this fea-

ture. May cause severe

vaginal ulcerations in

diabetes and patients

should be monitored

carefully.

286 J.M. Rabin

The donut pessary is considered the pessary of

choice if a person is unable to successfully retain

the ring pessary and those mentioned previously.

It is very popular for moderate to severe pelvic

organ prolapse and is considered a space-filling

pessary by supporting the prolapse by filling the

vaginal vault. It does require an intact vaginal

outlet. Follow-up is monthly for the first several

months and every 1–3 months thereafter. Once the

proper size has been chosen, the pessary is folded

in half and lubricated. In order to decrease the

diameter further, some have suggested removing

the air within the pessary utilizing a 20 cc syringe

and 18–21 gauge needle (Fig. 21.3 ). The plunger

of the syringe is removed, the needle is inserted

into the inflated pessary, and the pessary is com-

pressed allowing the air to go through the barrel of

the syringe. The pessary is then squeezed in half

to its minimum diameter and is inserted with the

widest part of the donut entering the vagina using

a two-handed technique as referenced above and

guiding the leading edge into the posterior fornix

(Fig. 21.4 ). Following this maneuver, the index

finger of the nondominant hand is placed into the

vagina and into the donut's hole, pulling the distal

edge into the introitus a bit so that a portion of the

Fig. 21.2 . Currently available vaginal pessaries (Cooper Surgical, with permission). ( a ) Smith (silicone, folding),

( b ) Hodge without support (silicone, folding), ( c ) Hodge with support (silicone, folding), ( d ) Gehrung with support

(silicone, folding), ( e ) Risser (silicone, folding), ( f ) ring with support (silicone, folding), ( g ) ring without support

(silicone, folding), ( h ) Cube (silicone, flexible), ( i ) Tandem-Cube (silicone, flexible), ( j ) rigid Gelhorn (acrylic, mul-

tiple drain), ( k ) 95% rigid Gelhorn (silicone, multiple drain), ( l ) flexible Gelhorn (silicone, multiple drain), ( m ) ring

incontinence (silicone), ( n ) Shaatz (silicone, folding), ( o ) incontinence dish (silicone, folding), ( p ) inflatoball (latex),

and ( q ) donut (silicone)

Fig. 21.3 . Donut pessary (from [67] , with permission).

After approximating the most appropriate size, the air is

removed via a 21-gauge needle and 20-cc syringe. With

the plunger out, the pessary is compressed and after

maximizing deflation, the needle is removed

21. Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries 287

pessary is visible. The needle and the syringe once

again can be inserted into the pessary without the

plunger and reinflated, allowing the donut pessary

to receive room atmospheric pressure. The pessary

then is guided cephalad with the distal end posi-

tioned behind the pubic symphysis as far as pos-

sible. Removal is facilitated by drawing the pessary

down with the examiner's index finger in order that

a portion of the pessary is visible at the introitus.

A 20-cc syringe with 18–21 gauge needle with the

plunger in can be used to withdraw 40–60 cc of air.

The pessary then is removed gently.

The inflatoball is similar to the donut in that it

is a space-occupying pessary used most often to

manage moderate to severe uterine and/or vaginal

vault prolapse. It is made of latex and should be

used with caution unless absence of latex allergy

can be confirmed. The inflatoball is similar in its

shape and mechanism of action as compared with

the donut. It was designed for self-care and can be

inflated with air once it is placed in the patient's

vagina. It is necessary to remove, cleanse the pes-

sary and vagina, and reinsert the pessary two to

three times per week since it is composed of latex

and may absorb odors. The pessary is inserted in

an oblique angle by the patient with the labia sepa-

rated, placed high in the vagina, and then inflated

by the patient with the specifically designed top,

which is then removed after inflation. It remains

inflated because of the small bead located inside a

Y connector. Once inflated the bead is placed above

the branch point of the Y connector and therefore

remains inflated. For deflation, the patient moves

the bead into one of the shorter arms of the Y thus

deflating the pessary, It is then easily removed by

the patient.

Fig. 21.4. Insertion of donut pessary. (from [67] , with permission). ( a) The deflated donut occupies less space. ( b )

When lubricated, the donut is very easily inserted through the separated labia. ( c) Once the widest part of the donut

enters the vagina through the introitus, it tends to slip away from the physician's grasp. ( d ) It is held near the introitus

with an index finger in the donut's hole so that the needle and syringe without plunger can again be inserted through

the silicone wall and the pessary reinflated by equilibrating with room atmosphere. The needle is removed and the

pessary slides apically

288 J.M. Rabin

The Gehrung pessary is a shapable pessary spe-

cifically designed for a cystocele, but also may be

used for a rectocele. For cystocele it is situated with

the convex surface against the anterior vaginal wall.

Its legs are directed posteriorally toward the pos-

terior fornix on the patient's left and right. This

pessary requires an intact vaginal outlet. Visits are

monthly and then every 1–2 months thereafter. The

Gehrung pessary is folded in half for insertion. It

is slipped into the vagina with its convex surface

upward and rotated 90° in order that its distal arch

is situated transversely behind the pubic symphysis

and the proximal arch will sit transversely high in

the vagina in the uppermost limit of the cystocele

or slightly higher. To replace rectocele, the above

maneuver is repeated with the convexity directed

downward and the double arches supporting the

rectocele. Removal is facilitated by insertion of the

dominant index finger into the vagina and gently

turning the pessary as it is drawn down toward

the introitus. Patients may assist with a Valsalva

maneuver. The Gehrung pessary will automatically

decrease its diameter as it is turned.

The Gelhorn pessary is available in either rigid

acrylic or rigid or flexible silicone but often is

used in its flexible silicone form. It is an extremely

effective pessary for patients with moderate to

severe prolapse and complete procidentia and does

not require an intact vaginal outlet. It is one of the

strongest available pessaries not only because of its

size and shape but also because of its partial suction

effect. Insertion and removal may be difficult, and

thus care is typically performed by the practitioner.

In order to minimize the vaginal discharge, which

may be moderate to severe, patients may elect to

douche two to three times per week with either

water and vinegar solution or Povidone–Iodine as

referenced above. Patients experience the greatest

success with Gelhorn pessary if there is a some-

what intact perineal body present. In order to insert

the Gelhorn pessary, the device is inserted with

lubricant liberally applied. There are two methods

of insertion (Fig. 21.5 ). Small Gelhorn pessaries

from the size of 1½–2¼ in. can be inserted directly

with the dish portion parallel to the anterior poste-

rior diameter of the introitus directing the leading

edge of the dish into the posterior fornix with the

following edge directed under the pubic symphysis

and the knob rotated perpendicular to the introitus.

The knob can be adjusted in order that the flat

portion or dish reaches the highest point against

the cervix or the upper vagina. Alternatively and

most notably, with the Gelhorn of larger size (from

2¼ to 3½ in.) a two-handed technique is adopted.

The dish is folded in half between the thumb and

forefinger to its minimum diameter. Every attempt

is made to control the pessary during insertion. It

is prudent to allow the patient a short period of

time to become used to the sensation of the pessary

placement prior to adjustment with the stem.

In order to remove the Gelhorn pessary the

thumb and forefinger of the nondominant hand

may be used while the patient is bearing down in

order to grasp the stem. Alternatively, a single-

tooth tenaculum or ring forceps can be applied to

the stem and gentle traction applied in a down-

ward fashion (Fig. 21.6 ). The index finger of the

dominant hand can be used to break the suction

by interposing the finger between the dish and the

vagina. Once the suction is broken, the examiner's

hands work synchronously to gently guide the pes-

sary out of the vagina. If erosions or ulcerations are

noted, topical low-dose estrogen should be applied

at regular intervals and the pessary should be

replaced only when complete healing is noted. This

may take from 1 to 4 weeks or longer depending

on the patient's situation. In diabetics, development

of these erosions may occur with greater regularity

and healing may be delayed.

The Cube pessary is very useful in cases of

moderate to severe prolapse and generally is used

when the above pessaries have not produced a

satisfactory result. It is a soft, self-positioning

pessary with six suction cups, one present on

each side of the cube. It is usually associated with

a high-risk of vaginal ulcerations and necrosis

most notably in patients who are diabetic and/or

atrophic. In these patients it must be used with

great caution and as a last resort; use may be

facilitated by creating small holes cut between

the cups in order to let air get into this otherwise

hypoxic environment. The pessary is inserted

by compressing it into its smallest diameter and

moved into the uppermost portion of the vagina

against the cervix and/or vaginal vault by steady

pressure. In order to remove the pessary, the labia

are separated; the string is grasped, suction is

broken, and all available sides are gently grasped,

pulled down, and out of the vagina maintaining

gentle traction on the string.

21. Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries 289

Fig. 21.5. Insertion of a Gelhorn pessary (from [67] , with permission). ( a) Metronidazole gel is copiously applied

with Gelhorn and Cube pessaries to counteract anaerobic growth in the hypoxic environment above the Gellhorn

dish or cube cup. Small Gelhorns like the one pictured (2¼ in.) can be inserted directly with the dish parallel to the

anteroposterior diameter of the introitus, inserting the side of the dish first. ( b) Alternatively, and particularly with

larger Gelhorns, the dish can be pinched or folded to compress its size and inserted obliquely through the vulva held

open with the contralateral hand. ( c) Once the dish is in the vagina, it will spontaneously and easily turn into the

proper axis. It should sit obliquely with the dish positioned under the vaginal apex and the horn pointing toward the

perineum. ( d ) After giving the patient a chance to relax, the pessary is pushed up into the vaginal apex. ( e) A properly

positioned Gelhorn pessary has its presenting horn pointing down toward the perineum and just barely visible with

the vulva held apart and the patient performing a Valsalva maneuver

290 J.M. Rabin

In addition to all of the above, a Tandem-Cube

is used for patients with moderate to severe pelvic

organ prolapse, in particular, uterine procidentia,

when a single Cube provides inadequate support.

All of the above caveats should be noted.

Lever pessaries such as Smith, Risser, and Hodge

are all variations of a design by Hodge developed

to correct a retroverted uterus by displacing the cer-

vix posteriorally. Currently, their main indication is

for the management of stress urinary incontinence

as they support the urethrovesical junction. Since

these types generally are not used in cases of pelvic

organ prolapse, they will not be covered further in

this chapter

Complications with and

Contraindications to Pessary Use

A noncompliant patient is an absolute contraindica-

tion to continue pessary use. Patients satisfied with

their pessaries continue to use them for several

years. As these women (not infrequently elderly

woman) continue the aging process, their situation

is a dynamic one and they change medically and/or

psychosocially. Many may develop diabetes, making

more frequent visits to the office necessary in order

to check for erosion and ulceration. A patient no

longer may be able to easily come to the office, often

relying on family and friends, and therefore may not

be able to keep her appointments for pessary follow-

up. Similarly along these lines, a patient's mental

status may change. She no longer may be able to

perform self-care or douche as frequently or follow-

up at the office every several months. This increases

the propensity toward an increase in vaginal dis-

charge. The neglected pessary may become trapped

in the vagina under a dense vaginal scar or cicatrix

[18] . This would necessitate surgical removal of the

pessary. The Gelhorn pessary is most often associ-

ated with serious complications when neglected

which include severe ulcerations, necrosis, and

migration of the pessary into the bowel, bladder, or

abdominal cavity. It can become densely adherent to

other pelvic structures and eventuate into a situation

that is extremely difficult to treat. These case reports

have been associated with other pessaries as well.

Applying estrogen cream to an impacted pessary

may generally assist in its removal. Migration into

bowel and bladder as mentioned above is rare, as is

fistula formation, but these have been noted in the

literature [19– 24] (Fig. 21.7 ).

The most common complication of pessary use is

irritation of the vaginal mucosa with accompanying

Fig. 21.6 . Removal of a Gelhorn pessary (from [13] , with permission). ( a) Removal is facilitated by finding the

distal horn with the fingers and grasping it with a single-toothed tenaculum. ( b ) Gentle traction on the tenaculum

posteriorly will allow an intravaginal index finger of the other hand to slip above the dish and break the suction.

Once the suction is broken, the two hands working together will gently guide the Gelhorn pessary down through the

vagina and out with the dish in the anteroposterior diameter. After removing a Gelhorn or a Cube pessary, a careful

observation of the vaginal walls, using a speculum, should be done to look for lacerations, erosions, or ulcerations.

Significant foreign body-related lesions warrant a temporary moratorium from pessary use until topical estrogen-

mediated healing occurs. Vaginal discharge can occur with any pessary and is sometimes quite copious and purulent

with the Cube and Gelhorn types. After pessary removal and inspection, the vagina can be painted with procto-swabs

soaked in povidone–iodine

21. Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries 291

discharge, odor, ulceration and bleeding, and necro-

sis. These are minimized with careful attention to

pessary care as previously mentioned. In the face

of erosions and ulcerations, pessary use should be

temporarily discontinued. Low-dose vaginal cream

two to three times per week can be used to assist in

the healing process and may be continued as part

of pessary care including lubrication subsequent

to healing of the ulcerated areas. Recurrent ero-

sions may be avoided by changing either the style

or size of pessary. If the current erosions continue

to develop, pessary use should be discontinued for

longer periods or even permanently. All suspicious

lesions should be biopsied to rule-out neoplastic

process. Cervical and vaginal carcinomas associ-

ated with pessary use have been reported, but are

rare [26] .

Despite the above, there are almost no contrain-

dications to pessary use other than the noncom-

pliant patient. With careful attention to patient

selection and meticulous follow-up care, the vagi-

nal supportive pessary serves both the practitioner

and patient well and serves an extremely valuable

clinical function.

Successful Long-Term Pessary Use

and Patient Satisfaction

The ring pessary seems to be used most often due

to its ease of use both for patients and physicians.

Complications are rare and minor complications

are generally easily dealt with [27, 28] . One study

cited a high success rate of 82% among pessary

users with a satisfaction rate of approximately 70%

in patients using a ring pessary. This study did not

distinguish patients with a successful pessary fit-

ting and those who no longer use the pessary [29] .

Hopefully future studies will answer such ques-

tions such as: which specific pessary is most suitable

for specific pelvic organ prolapse types and whether

or not pelvic floor physical therapy will enhance

the patient's ability to retain an intravaginal pessary.

These are but some of the questions that remain to

Fig. 21.7. “Fistulas associated with pessary use” (from [25] , with permission)

292 J.M. Rabin

be answered. One study from Holland concluded

that most patients using the pessary for vaginal

prolapse opted for continuation of this therapy [30] .

Interestingly and similarly a recent study found that

pessaries also can have a therapeutic effect. In 21% of

patients, an improvement of the prolapse was found

and in no women was a worsening of their prolapse

found [31] . Interestingly, although pessary use is

quite common and has remained so over the past

several decades, there has not been a full evaluation of

their efficacy in comparison to other modes of treat-

ment such as pelvic floor muscle exercise (PFME) or

surgery. Pessaries have stood the test of time and it

is important to incorporate them into gynecologists'

practices. This is a safe and useful alternative for

conditions that are seen by gynecologists every day.

Most notably and stated by Novak, as he concluded

a discussion of pessaries by quoting Bantock who

wrote, “I am not aware that there is on record a single

case in which a woman has lost her life for the use, or

even the abuse, of the vaginal pessary.” Unfortunately,

the outcomes associated with pelvic surgery are not

always as clear-cut or safe [32, 33] .

Behavioral Treatments in the

Management of Pelvic Organ

Prolapse

Prevention is the first step when employing behav-

ioral therapies for pelvic organ prolapse. There

currently is no vigorous evidence from randomized

controlled trials regarding the use of conserva-

tive interventions for the management of pelvic

organ prolapse. Nevertheless, lifestyle interven-

tions including weight loss, smoking cessation, and

reducing activities that exacerbate the prolapse,

such as lifting and coughing, as well as improv-

ing bowel habits, may ameliorate the symptoms of

pelvic organ prolapse. A program of pelvic floor

muscle education and exercise instituted prior to

the development of prolapse may prove effective in

the long-run for our generations of young women.

Appropriate abdominal and pelvic floor muscle

control during all activities of daily living, includ-

ing elimination of bladder and bowel, are essential

components of treatment. Parents can teach their

young children that urinary and defecatory func-

tions are controlled by pelvic floor muscles, and

that control of these muscles brings regular and

complete emptying of the bowel and bladder.

Young women engaging in competitive sporting

activities, most notably high impact sports such

as soccer, basketball, and gymnastics should be

taught pelvic floor muscle education and exercise

including bracing of the core trunk musculature

and pelvic floor prior to impact.

Once the diagnosis of pelvic organ prolapse has

been made, behavioral therapies may be initiated.

The essential components of behavioral therapies

are patient education regarding bowel and bladder

training, pelvic floor muscle rehabilitation includ-

ing PFME, vaginal weight-training, biofeedback

therapy (alone or in combination with PFME), and

pelvic floor electrical stimulation.

Behavioral therapies in the management of

pelvic organ prolapse serve two major roles. First

and foremost, the behavioral therapies serve as an

initial treatment point for the patient and her physi-

cian and one that may be revisited and reformatted

through the patient's life regarding her particular

subsequent lifestyle choices. Second, one of the

cornerstones of the behavioral therapies is patient

education over the course of her lifetime. Thus the

conversation may be continued between the patient

and her physician when additional behavioral and

other therapies are developed. Behavioral therapies

have large potential benefits and are associated

with very little, if any, risk. They are also ideal

therapies for the elderly patient, where the risk of

medication side effects, as well as surgical compli-

cations, can be substantial. The behavioral thera-

pies may prove to be most effective in motivated

patients with pelvic organ prolapse with or without

urinary or fecal incontinence.

Pelvic Floor Muscle Exercise

PFME is considered the cornerstone of all pelvic

floor muscle rehabilitation programs in the con-

servative management of pelvic organ prolapse.

In one extensive review of the literature regarding

the utilization of pelvic muscle exercises, it was

suggested by the authors that, “regular exercises

of the pelvic floor should be as much a part of

the preventative health-care routine of women

as annual Pap smears, and monthly breast self-

examination” [34] . The principle of restoring the

function of the segregated group of muscles with

21. Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries 293

specific program, method, or aid of reeducation

was taken from the orthopedic, neuromuscular,

plastic surgery, and physical medicine and reha-

bilitation literature noted in the gynecological

arena, a method of rehabilitation by Arnold Kegel

in his original article published in 1948. His work

in World War II on muscle function and recovery

concluded that, “in the preservation or restoration

of muscular function, nothing is more fundamental

than the frequent repetition of correctly guided

exercises” instituted by the patient's own efforts

[35] . Although his original exercise regimen was

developed for recovery in the postpartum period,

he widened the potential net of usefulness for

patients when they would come for a period of

what he called “active exercise” in order to pre-

vent pelvic organ prolapse, as well as to provide

an improvement in surgical outcome after pelvic

floor reconstructive surgery. Coordination of the

pelvic floor muscle contractions is the first step in

the pelvic floor muscle education training program

process. A multidisciplinary approach often is very

helpful including the physician, nurse practitioner,

and ultimately a physical therapist, especially if the

patient is going to continue on her particular pro-

gram for the long term. Since patients do have to be

shown how to do a pelvic floor muscle contraction,

a mirror may be helpful in order to actually observe

the contraction. This allows the patient to see her

pelvic floor elevation. Placing a tampon in the

vagina, or the examiner’s middle and index finger,

or alternatively placing a lubricated cotton swab in

the urethra may be able to help the patient actually

see her pelvic floor elevation, while observing the

perineum using a mirror. Physical examination

may allow the physician to evaluate the patient's

baseline ability to contract her pelvic floor. With

the initial pelvic floor contraction and proper pel-

vic floor elevation, the patient will observe a slight

disappearance of the end of the tampon, near the

insertion of the tampon string. The examiner will

feel and the patient will observe a pulling upward

on his or her fingers and an elevation of the pelvic

floor. Valsalva maneuver performed subsequent to

this, will allow the patient to visualize the different

between a pelvic floor contraction and a Valsalva

maneuver. She will be able to see how the Valsalva

maneuver and subsequently coughing produced

descent of the perineum and urethra. Anatomic

models may be utilized, as well as pictorial repre-

sentations of the muscles of the pelvic floor. Only

one fifth to one third of women who believe they

perform Kegel exercises (pelvic floor contractions)

correctly actually exhibit the correct technique.

Most women have to be shown how to do these

exercises correctly in the stepwise fashion [36] .

After this initial stage of observation and palpation

of the initial pelvic floor contraction by the physi-

cian and patient, the second phase of the pelvic

floor muscle education program is initiated. This

second stage is a strengthening phase, during which

time the patient attempts pelvic floor contractions

repeatedly and rapidly, counting how many times

she can do this without losing her coordination,

quickly and for 1 s each. This “flick contraction”

exercise can be performed by contracting and

relaxing the levator ani as tightly as possible for

1 s. This exercise helps to augment the fast-twitch

fibers (anaerobic-glycolytic), which are the type II

muscle fibers (largest diameter). They are the fibers

responsible for fast, forceful contractions activated

as a short-term response to increased abdominal

pressure. The third and next stage is determina-

tion and strengthening of the ability of the patient

to contract her pelvic floor after a brief rest and

hold this contraction for at least 6 s, subsequently

resting the pelvic floor for 10–12 s. This exercise

will enable the patient to sustain her pelvic floor

tone over longer periods of time and mainly are

governed by the slow-twitch fibers that are aerobic-

oxidative, (smaller diameter), and will enable to

patient to develop her baseline pelvic floor strength

over the long haul. Additionally, recruitment takes

place of the fast-twitch fibers by fast contractions

in order to develop strength as well as slow-twitch

fibers by slow contractions, as mentioned above, in

order to increase long-term endurance [37] . After a

strengthening program has been devised the fourth

and final step of the pelvic floor muscle education

program is the phase where the patient is sent home

to practice the program and gradually increase her

ability to contract her pelvic floor with exercises

referenced above. This particular phase of the pro-

gram will be most successful if a trained physical

therapist, nurse, or nurse practitioner follows the

patient on a regular basis and tracks her progress

with frequent office visits as determined by the

patient, the physician, and the physical therapist

as appropriate. It is most important that women be

taught to contract their pelvic floor muscles before

294 J.M. Rabin

any rise of intra-abdominal pressure such as lifting,

coughing, sports, or any other anticipated increase

in intra-abdominal pressure. This is also termed

“pelvic bracing” and is believed to help augment

the success of pelvic floor muscle education pro-

grams for pelvic organ prolapse. Cammu et al.

reported that the majority of patients who respond

successfully to pelvic floor muscle education pro-

grams (physiotherapy programs) remain satisfied

after 10 years or more [38] . There are various pro-

tocols with PFME currently available. The number

of contractions range from 100 per day to Kegel's

original dissertation recommending 300 contrac-

tions per day [35] . Burgio et al. recommended 45

exercises daily divided into three sessions of 15

exercises each and then increasing the length of

the sustained contraction. The use of vaginal cones

may serve as adjunctive therapy to any pelvic floor

muscle education program in order to augment

and enhance the patient's overall long-term muscle

strength. These were developed by Plevnik in order

to improve pelvic floor muscle strength. These

range in weight approximately 5–100 g, and are of

equal shape and volume as well as appearance. The

patient is asked to introduce the vaginal cone and

to attempt to retain it intravaginally by contracting

her muscles while ambulating for a period of 15–30

min, once to twice a day. This provides feedback to

the patient to maintain pelvic floor contractions and

increase hypertrophy and augment her slow-twitch

fibers responsible for this baseline pelvic floor con-

traction. The patient begins with the lowest weight

she can easily retain and is instructed to progress

to the next heaviest weight after approximately 1

month of twice daily use without this initial weight

falling out vaginally for 30 consecutive days. The

patient is then instructed to progress to the next

heaviest weight until she is able to maintain the

heaviest weight intravaginally twice daily, for

30 min, for a period of 30 days. She may continue

utilizing the weights once to twice per day for up

to 30 min. Peattie et al. studied 39 premenopausal

women and found that after 1 month of use, 70% of

patients were either improved or cured.

Recently, a new intravaginal device designed to

allow PFME to treat advanced degrees of vaginal

prolapse by acting as a space-occupying sphere

above the levators muscles has become available

(Fig. 21.8 ). The Colpexin sphere (Adamed, New

Jersey, USA) is placed into the vaginal canal, above

the levator plate, thus reducing any significant

prolapse, and allowing Kegel exercises to help

provide support to the prolapsed tissues. Over time,

the levator muscles hypertrophy and the size of

the levator hiatus decreases, leading to improved

pelvic floor support. Additional benefits include

reduction of urinary incontinence episodes with the

device in place [39] .

The Role of Biofeedback

Biofeedback is a training technique as well as a

process and is defined in the behavioral medicine

literature as “a process in which a person learns to

reliably influence physiological responses of two

kinds: either responses which are not under volun-

tary control or responses which are ordinarily eas-

ily regulated but for which regulation has broken

down due to trauma or disease” [40] . It also is a

training technique “soundly based on the principles

of human behavior and learning, and supported

by considerable evidence derived from years of

experimental investigation” [41] . Biofeedback is

used in conjunction with many of the techniques

and therapies previously mentioned in this chapter

as part of a pelvic floor muscle training program.

Biofeedback is provided to the patients with a

visual display such as light, a computerized graphic

display, or by means of an auditory signal (Fig. 21.9 ).

Vaginal or rectal probes are easy to use and comfort-

able for patients during insertion and removal, and

Fig. 21.8. Colpexin sphere in place, elevating the pro-

lapsed genital tissues above the levator muscles while the

patient performs pelvic floor exercises

21. Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries 295

also may afford the patient control over her pelvic

floor muscle biofeedback program. During the

initial phase of vaginal EMG it may be useful for

an additional surface electrodes to be placed on

accessory muscles (usually abdominal wall sensors)

in order to teach the patient to accurately isolate a

pelvic floor muscle contraction. Biofeedback ther-

apy needs to elicit low pelvic floor muscle resting

tension prior to and following an exercise session.

Patients are instructed to selectively contract and

relax their pelvic floor musculature without increas-

ing their intra-abdominal pressure.

Home training programs then may be sub-

sequently developed on an individual basis for

patients presenting with pelvic organ prolapse

either with or without stress or urge incontinence.

EMG electrodes embedded in vaginal or rectal

probes are easily utilized by patients in a home set-

ting. This affords the patient privacy as well as ease

and comfort of use.

Biofeedback when utilized as a component of

a pelvic floor exercise program ensures that exer-

cises of the pelvic floor are being performed prop-

erly. Patients may do very well with biofeedback

as part of an integrated PFME program; this may

prove to be synergistic, in regard to the patient's

ultimate outcome and satisfaction with her treat-

ment. Randomized controlled trials are needed to

determine whether the increase in pelvic floor mus-

cle strength associated with biofeedback training

programs actually result in a clinically significant

reduction in pelvic organ prolapse in the short- as

well as the long-term period. Having said this,

biofeedback is easily incorporated into any PFME

program and generally is well accepted by patients,

in particular because this gives the patient a sense

of control over her body and bodily functions.

Knowledge about anatomy and physiology may aid

the patient by gaining knowledge and thereby gain-

ing power over her own condition and may have a

positive effect on her ultimate outcome.

Functional Electrical Stimulation

Functional electrical stimulation (FES) was first

utilized in 1963 by Caldwell for correction of

urinary and fecal incontinence. Since that time

electrical stimulation has proved to be a valuable

adjunct to biofeedback and additionally as a stand-

alone method in the armamentarium of conserva-

tive alternative approaches for the management

of pelvic organ prolapse and additionally to treat

stress and urge incontinence [42] . As with the con-

servative approaches previously mentioned, elec-

trical stimulation allows the patient to learn how

to strengthen as well as more properly utilize her

pelvic floor muscles either alone or in combina-

tion with biofeedback therapy. FES in conjunction

with biofeedback therapy can enable the patient

Fig. 21.9. Biofeedback instruments

for home use (used with permis-

sion of Marks LE, OTR and

Freedman M, PT, BCIA-PMDB)

296 J.M. Rabin

to sense her pelvic floor muscles as they contract

and ultimately to be able to contract them and per-

form these exercises with or without biofeedback,

without the assistance of a pelvic floor contraction

created by electrical stimulation per se. Therefore

electrical stimulation of the pelvic floor can help

elicit a reflex contraction of the pelvic musculature,

especially during activities such as lifting, laugh-

ing, and coughing. A low-mid frequency current

(50 Hz) is utilized in order to stimulate a contrac-

tion of the levator ani muscles. It is quite bearable

to the patient. Lower frequencies (10–25 Hz) are

useful to reduce bladder overactivity.

FES is particularly useful for patients who do

not have adequate awareness of their pelvic floor

musculature and who may be unable to isolate a

pelvic floor contraction. Electrical stimulation in

these cases may help the patient properly identify

the location of the pelvic floor muscles while

providing proprioception as well as assisting the

patient in performing the contraction.

Pelvic floor exercises alone have been demon-

strated to improve pelvic floor muscle strength,

thus reducing prolapse and additionally assisting

in the reduction of incontinence [42] . Adding to

basic PFME programs, biofeedback with or with-

out electrical stimulation has been proven to be

not only comfortable for the patient, but without

significant side effects and quite synergistic in

regard to reeducation of the pelvic floor muscles

(Figs. 21.10 and 21.11 ).

The principle of electrical stimulation per se is

based on restoring normal, physiological reflex

mechanisms in abnormal muscles and nerves [43] .

Electrophysiological data suggest that a partial

denervation occurs along with weakening of the

pelvic floor musculature during childbirth. There

additionally is a loss of levator ani muscle tone.

FES promotes tissue growth and potentially nerve

regeneration. Therefore reinnervation of the pel-

vic floor may occur through the judicious use of

electrical stimulation with persistent biofeedback

therapy or electrical stimulation alone.

Fig. 21.10 . Electrical stimulation units (used with per-

mission of Marks LE, OTR and Freedman M, PT, BCIA-

PMDB)

Fig. 21.11. Vaginal and rectal

sensors for biofeedback and

electrical stimulation (used with

permission of Marks LE, OTR

and Freedman M, PT, BCIA-

PMDB)

SRS

Multiple Electrode Probe

MEP

SRS

Elan

Thought Technology Ltd.

Vaginal

Sensors

Rectal

Sensors

The Prometheus Group

Perry/Pathway

EMG/Stimulation Sensor

21. Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries 297

Vaginal muscle strength increased significantly

over that of control subjects who utilized the SHAM

device for investigating transvaginal pelvic floor

electrical stimulation for genuine stress inconti-

nence [44] . Electrical stimulation has been shown

to be effective in patients who initially are unable

to perform a pelvic floor muscle contraction or to

identify the correct muscles to contract. Thus pelvic

floor muscle education is provided through initial

stimulatory and then subsequently voluntary pelvic

floor muscle contractions [45] .

Contraindications to electrical stimulation are

fairly few: patients who utilize on-demand high

pacemakers, patients who are pregnant, patients

with postvoid urine residuals >100 ml, and patients

with urethral obstruction, bleeding (sessions must

not be held during menstruation), and urinary pel-

vic or vaginal infections.

Electrical stimulation is a valuable and effective

therapeutic tool, in particular in patients who are

unable to identify and contract the correct pelvic

floor muscles initially. Biofeedback-triggered elec-

trical stimulation may actually be more effective

than either treatment alone, and additionally has

the attraction of reducing the lag time to evident

treatment response [46] . Finally, as with other con-

servative methods for the reduction of pelvic organ

prolapse, patient motivation and commitment of

the therapist and patient are crucial elements for

successful therapeutic outcome. On average these

therapies require approximately 2 months of an

intensive program in order begin to see therapeutic

results. Additionally, in most cases, these programs

must be continued for the duration of the patient's

lifetime if improvement or cure is to be maintained.

Finally, improvement in a patient's overall pelvic

health is enormous. The results, in many cases, are

rewarding for both patient and therapist.

Conclusions

The decision to elect conservative treatment modal-

ities for pelvic organ prolapse involves a time com-

mitment on the part of both the physician and the

patient. All treatment options must be considered

carefully in the context of the individual patient's

life and health. There must be a willingness to

accept the possibility of the delayed results that may

be associated with conservative treatments. These

therapies should be considered for any patient who

is deemed to be high-risk due to medical comor-

bidities, patients who do not desire surgery or who

do desire repeat surgery, patients who are not yet

completed with their childbearing, patients who

are exceptionally motivated, and patients who are

agreeable to periodically reevaluating their unique

situations as they change dynamically over time.

Finally, in patients who elect to use pessaries, phy-

sicians must be extremely cognizant of the impor-

tance of regular routine pessary care and vigilant

in their follow-up, which must be meticulous due

to the potential for complication. Although rare,

complications due to the “forgotten pessary” must

be avoided at all costs.

Future areas of research must focus on comparing

and evaluating various conservative therapies in the

management of pelvic organ prolapse. We must sys-

tematically examine which patients would benefit

most from these therapies including pessaries, as

well as what specific type of conservative therapies

should be used and under what circumstances.

Acknowledgments. Marilyn Freedman, Physical Ther-

apist, for her editorial assistance, support, and friendship.

Elise Stettner, Physical Therapist, for her support and

her technical expertise. Susan Gimmi, for her manu-

script preparation skills. Sigrid Anderson, for typing

of the manuscript. Dennis Skahill and Adam Cooper,

NSLIJHS, for their assistance with figures and pho-

tos. Debbie Rand, Chief of Library Services, LIJMC.

Shfra Atik, Senior Librarian, LIJMC. Rita Feigenberg,

Librarian, LIJMC. Norma Frankel, Librarian, LIJMC.

Carlos Arguelles, Librarian, LIJMC. And to my family,

especially Aaron and Bobbie, for their love and encour-

agement.

References

1 . Swift S , Theofrastous JP . Aetiology and classifica-

tion of pelvic organ prolapse . In: Cardozo L , Staskin

D , eds. Female urology and urogynecology . London :

Isis Medical Media ; 2001 : 576 – 585 .

2 . Samuelsson EC , Arne Victor FT , Tibblin G ,

Svardsudd KF . Signs of genital prolapse in a Swedish

population of women 20 to 59 years of age and pos-

sible related factors . Am J Obstet Gynecol 1999 ;

180 : 299 – 305 .

3 . Karram M , Portur R . Pathophysiology, diagnosis

and management of rectoceles . In: Cardozo L .

298 J.M. Rabin

Staskin D , eds. Female urology and urogynaecol-

ogy . London : Isis Medical Media ; 2001: 616 – 625 .

4 . Olsen AL , Smith VJ , Bergstrom JO , et al.

Epidemiology of surgically managed pelvic organ

prolapse and urinary incontinence . Obstet Gynecol

1997 ; 89 : 501 – 506 .

5 . Stedman , TL . Stedman's medical dictionary .

Baltimore, MD : Williams and Wilkins , 1976 : 1062 .

6 . Miller , DS . Contemporary use of the pessary . In:

Gynecology and obstetrics , Vol. 1 . Sciarra JJ , ed.

Philadelphia : Lippincott ; 1995 : 1 – 12 .

7 . Cundiff GW , Weidner AC , Visco AG , et al. A sur-

vey of pessary use by members of the American

Urogynecologic Society . Obstet Gynecol 2000 ;

95 : 931 – 935 .

8 . Niemiec TR . Adequate follow-up “essential” after

placement of pessary . Obstet Gynecol News 1989 ;

24 : 1 .

9 . Handa VL , Jones M . Do pessaries prevent the pro-

gression of pelvic organ prolapse? Int Urogynecol J

2002 ; 13 (6) : 349 – 352 .

10 . Nygaard IE , Zinsmeister AR . Treatment of exercise

incontinence with a vaginal pessary: A preliminary

study . Int Urogynecol J 1993 ; 4 : 133 – 137 .

11 . Trowbridge ER , Fenner DE . Conservative manage-

ment of pelvic organ prolapse . Clin Obstet Gynecol

2005 ; 48 (3) : 668 – 681 .

12 . Young SB . Nonsurgical management of pro-

lapse . In: Atlas of clinical gynecology , Vol. 5 .

Thomas Benson J , ed. Philadelphia : McGraw-Hill ;

1999 : 8.1 – 8.13 .

13 . Stenchever MA , Benson JT . Atlas of clinical gynecol-

ogy, vol. V, Urogynecology and reconstructive pelvic

surgery . 2000 ; Philadelphia : Current Medicine .

14 . Clemons JL . Aguilar VC , Tillinghast TA . et al. Risk

factors associated with an unsuccessful pessary fit-

ting trial in women with pelvic organ prolapse . Am

J Obstet Gynecol 2004 ; 90 (2) : 345 – 350 .

15 . Myers DL , LaSala CA , Murphy JA . Double pessary

use in grade 4 uterine and vaginal prolapse . Obstet

Gynecol 1998 ; 91 : 1019 – 1020 .

16. Rabin JM, et al. Gelift: patent #5,894,842. April 20,

1999.

17 . Kunczicky V , Uhl-Steidl M , Pontpasch H . Safety

and acceptance of self-application of the pubic

and uretheral ring pessaries . Gynakol Geburtshilf

Rundschr 1998 ; 38 : 242 – 246 .

18 . Poma PA . Management of incarcerated vaginal pes-

saries . J Am Geriatr Soc 1981 ; 29 : 325 – 327 .

19 . Goldstein I , Wise GJ , Tancer ML . A vesicovaginal

fistula and intravesical foreign body. A rare case of

the neglected pessary . Am J Obstet Gynecol 1990 ;

163 (2) : 589 – 591 .

20 . Grody MH , Nyirjesy P , Chatwani A . Intravesical

foreign body and vesicovaginal fistula: A rare com-

plication of a neglected pessary . Int Urogynecol J

Pelvic Floor Dysfunct 1999 ; 10 (6) : 407 – 408 .

21 . Sivasuriya M . Cervical entrapment of a polyethyl-

ene vaginal ring pessary a clinical curiosity . Aust M

Z J Obstet Gynecol 1987 ; 27 : 168 – 169 .

22 . Ott R . Richte H , Behr J , Scheele J . Small bowel

prolapse and incarceration caused by a vaginal ring

pessary . Br J Surg 1993 ; 80 : 1157 .

23 . Roberge RJ , Keller C , Garfinkel M . Vaginal pessary

induced mechanical bowel obstruction . J Emerg

Med 2001 ; 20 : 367 – 370 .

24 . Meinhardt W , Schuitemaker MW , Smeets NJ ,

Venema PL . Bilateral hydronephrosis with urosepsis

due to neglected pessary. Case report . Scand J Urol

Nephrol 1993 ; 27 : 419 – 420 .

25 . Nichols DH , Randall CL . Vaginal surgery , 4th ed.

1996 ; Lippincott : Williams & Wilkins .

26 . Schraub S , Sun , XS , Maingon P , et al. Cervical and

vaginal cancer associated with pessary use . Cancer

1982 ; 69 : 2505 – 2509 .

27 . Pott-Grinstein E , Newcomer JR . Gynecologists' pat-

terns of prescribing pessaries . J Reprod Med 2001 ;

46 (3) : 205 – 208 .

28 . Sulak PJ , Kuehl TJ , Shull BL . Vaginal pessaries and

their use in pelvic relaxation . J Reprod Med 1993 ;

38 (12) : 919 – 923 .

29 . Bai SW , Yoon SB , Kwon JY , et al. A survey of the

characteristics and satisfaction degree of the patients

using a pessary . Int Urogynecol J 2005 ; 16 : 182 – 186 .

30 . Clemons JL , Aguilar VC , Sokol ER , et al. Patient

characteristics that are associated with continued

pessary use versus surgery after 1 year . Am J Obstet

Gynecol 2004 ; 191 : 159 – 164 .

31 . Morgan-Jahanshir L , Shott S , Fenner DE . Factors

affecting patients' ability to retain a pessary . AM

Urogyn Society , 19th Annual Scientific Meeting .

Washington, DC ; November 1998 .

32 . Novak E . The vaginal pessary: Its indications and

limitations . JAMA 1923 ; 80 : 1294 – 1298 .

33 . Bantock GG . In defense of the pessary . J Obstet

Gynecol Br Emp 1905 ; 7 : 17 – 29 .

34 . Wall LL , Davidson TG . The role of muscular re-

education by physical therapy in the treatment of

genuine stress urinary incontinence . Obstet Gynecol

Surg 1992 , 47 : 322 – 331 .

35 . Kegel A . A progressive resistance exercise in the

functional restoration of the perineal muscles . Am J

Obstet Gynecol 1948 ; 56 : 238 – 246 .

36 . Bo K , Larsen S , Oseid S , et al. Knowledge about

and ability to correct pelvic floor muscle exercises

in women with urinary incontinence . Neurol Urodyn

1998 ; 7 : 261 – 262 .

37 . Samples JT , Dougerthy MC , Abrams RM , Batich

CD . The dynamic characteristics of the circumvagi-

nal muscles . JOGNN 1988 ; 17 (3) : 194 – 201 .

21. Conservative Management of Pelvic Organ Prolapse: Biofeedback and Pessaries 299

38 . Cammu H , Van Nylen M , Amy J . A ten-year

follow-up after Kegel pelvic floor muscle exercises

for genuine stress incontinence . BJU Int 2000 ;

85 : 655 – 658 .

39. Lukban JC, Aguirre OA, Davila GW, Sand. Safety and

effectiveness of Colpexin Sphere in the treatment of

pelvic organ prolapse. Int Urogynecol J Pelvic Floor

Dysfunct. 2006 Sep;17(5):449–54. Epub 2005 Nov 19.

40 . Feuerstein M , Labbe EE , Kuczmierczyk AR . Health

psychology: A psychobiological perspective . 1986 ;

New York : Plenum Press .

41 . Burgio KL . Urinary incontinence; non-surgical

therapies: Biofeedback therapy . In: Benson JT , ed.

Female pelvic floor disorders . New York : WW

Norton Company ; 1992 : 210 – 218 .

42 . Caldwell KPS . The electrical control of sphincter

incontinence . Lancet 1963 ; 2 : 174 – 175 .

43 . Fall M , Erlandson BE , Carlsson CA , Lindstrom

S . The effect of intravaginal electrical stimulation

on the feline urethra and urinary bladder: neuronal

mechanisms . Scand J Urol Nephrol Suppl 1977 ;

44 : 19 – 30 .

44 . Sand PK , Richardson DA , Staskin VR , et al. Pelvic

floor electrical stimulation in the treatment of genuine

stress incontinence: A multicenter, placebo-controlled

trial . Gen Obstet Gynecol 1995 ; 173 (1) : 72 – 79 .

45 . Bo K . Effect of electrical stimulation on stress and

urge urinary incontinence. Clinical outcome and

practical recommendations based on randomized

controlled trials . Acta Obstet Gynecol Scand 1998 ;

77 (Suppl 168) : 3 – 11 .

46 . Yamanishi T , Yasuda K . Electrical stimulation for

stress incontinence . Int Urogynecol J 1998 ; 9 :

281 – 290 .

301

What drugs will not cure, the knife will; what the knife

will not cure, the cautery will; what the cautery will not

cure must be considered incurable.

Hippocrates

In reviewing the history regarding surgery for

pelvic organ prolapse, it becomes apparent that

although the evolution of medicine is amazing,

there is a constant yet dynamic ebb and flow of

conflicting theory and evidence. The literature

regarding the history of gynecologic surgery

is a testament to the fast pace of advancement

yet a controversy to what is currently practiced.

Richard H. Meade says of the task of writing the

history of surgery – “the task is undertaken with

due humility” [1] . His words resound clearly

when discussing the history and evolution of cur-

rent gynecologic surgery and in particular pelvic

floor surgery.

It appears that our first understanding and

knowledge of pelvic organ prolapse comes from

the ancient Egyptians [1] . In the Kahun papyrus

of Egypt, dating to 2000 BC, and in the Ebers

papyrus, some 500 years later, there are medical

records referring to pelvic organ prolapse [2] . Little

else is known of how ancient civilizations treated

this female condition. It has been suggested that

astringent solutions such as vinegar and pessaries

molded from beeswax or round fruit such as pome-

granates were used in ancient Egypt for reducing

prolapse, with the earliest description of a pessary

being provided by Hippocrates. A device made of

bronze, believed to be a pessary, was found in the

ruins of Pompeii [3] .

Hippocrates was also the first to provide advice

for the treatment of pelvic organ prolapse that was

considered irreducible by traditional methods.

This has become known as hippocratic succus-

sion ( Fig. 22.1 ). As depicted in this illustration,

the patient was bound by her feet and hung

upside-down along a ladderlike frame. Held in

this position for several minutes, the frame was

moved up and down behind the patient, causing

her to shake. The upside-down position, grav-

ity, and shaking were thought to help reduce the

prolapse [2] .

In 1910, Henry Wellcome, a British collector of

medical artifacts and instruments, found an incised

stone tablet in the Temple at Rom-Ourbos near the

city of Cairo. The temple, built by Ptolemy VII

(181–146 BC), depicts a number of surgical instru-

ments that are thought to be obstetric and gyneco-

logic [3] . This would suggest that there may have

been more than conservative treatment available

for pelvic organ prolapse over 2000 years ago.

Soranus of Ephesus, a physician of the Greco-

Roman Era, considered to be the authority of gyne-

cology in antiquity, is purported to have been the

first to propose and perform excision of the gan-

grenous prolapsed uterus (98–138 AD) [2] . Many

authors have suggested that although no reports

exist for the actual performance of a hysterectomy

before the sixteenth century, this procedure is men-

tioned in several ancient records, such as those of

Aretaeus of Cappodocia, between the second and

third centuries AD and again by Paulus Aegina, in

the seventh century AD [3] .

Chapter 22

Surgery for Pelvic Organ Prolapse:

An Historical Review

Baharak Amir and Alfred E. Bent

302 B. Amir and A.E. Bent

The first official record of a uterus being excised

was written by anatomist and surgeon Berengaria

da Carpi of Bologna. He witnessed his father

excise a prolapsed and gangrenous uterus vaginally

from a woman in the early 1500s [1] . It is believed

that this patient did in fact live for many more years

but was unable to enjoy intimate relations with her

husband [3] . Berengaria da Carpi also performed

the surgery himself once and subsequently assisted

a colleague with another. He describes his tech-

nique for vaginal hysterectomy as consisting of

ligating the prolapsed uterus with thick twine. This

twine was tightened progressively to the point of

severing the organ. [3] . Celebrated French surgeon,

Ambroise Paré (1509–1590), also provided similar

details of his approach for the removal of a gang-

renous prolapsed uterus [3] .

Prior to the sixteenth century, limited knowledge

of anatomy and physiology restricted appropriate

management for female pelvic organ prolapse.

Changing views of science, less hindered by reli-

gion, led to cadaveric dissections and those who

provided accounts and teaching of what lay within

the human body. Although Leonardo Da Vinci

(1452–1519) provided many beautiful illustra-

tions including those of female pelvic anatomy

(Fig. 22.2 ), few in his time were privy to his work.

It was Andreas Vesalius (1514–1564) who revolu-

Fig. 22.1. Hippocratic succussion (from

[2] , original picture from Appolonius

of Kitium, Appolonius of Kitium.

Illustrieter Kommentar zu der hippok-

ratischen Schrift h EP AP q P W N (Peri

Arthron), V.H. Schone (Ed.). Teubner,

Leipzig, 1896)

22. Surgery for Pelvic Organ Prolapse: An Historical Review 303

tionized our understanding of the human female

pelvis by providing the first accurate description

of the female genital tract through cadaveric dis-

section. His teachings and descriptions became

the foundation for anatomy and physiology of the

female pelvis (Fig. 22.3 ). Shortly thereafter, the

engravings of Johannes Scultetus (1595–1645) in

his Armementarium Chirurgicum , provide the first

illustrations in step-by-step account of pelvic sur-

gery (Fig. 22.4a, b ). In this body of work is found

the first known illustration of procidentia [2] .

During the seventeenth century, uterine prolapse

became better described and classified. Among

other gynecologic subjects in his book, the physi-

cian James Cooke (1614–1688) also describes pro-

cidentia uteri [3] . In the latter part of the century,

there appeared to be significant debate regarding

the appropriate measures to be taken with a pro-

lapsed uterus. Namely, many experts did not favor

surgical therapy and believed that all uteri could

be reduced even if temporarily with conservative

methods such as pessaries (Fig. 22.5a, b ).

It was during the eighteenth century that other

aspects of vaginal prolapse were first characterized.

Perineal and vaginal hernias were first described

by French physician Jean Mèry in 1713 [2] . The

famous Scottish obstetrician William Smellie also

provided case reports of the same in 1731. During

the middle of the eighteenth century, an interest

in relaxation of the vaginal walls, particularly

Fig. 22.2. The female organs of generation by Leonardo

da vinci (from [4] )

Fig. 22.3. The female pelvic organs as illustrated by

Vesalius (from [4] Original from De humani corporsis

fabrica , 1543)

304 B. Amir and A.E. Bent

Fig. 22.4. ( a ) 1655 edition of Aramentarium Chirurgicum by Johann Schultes (Scultetus) and selected illustrations (from

[4] ). ( b ) 1655 edition of Aramentarium Chirurgicum by Johann Schultes (Scultetus) and selected illustrations (from [4] )

22. Surgery for Pelvic Organ Prolapse: An Historical Review 305

Fig. 22.4. (continued)

306 B. Amir and A.E. Bent

Fig. 22.5. ( a , b ) The examination and reinsertion of uterine prolapse (from [4] )

cystocele and rectocele, which were termed her-

nias of the bladder and rectum, began with René-

Jacques-Croissant de Garengoet (1688–1759). He

was the first to describe using a vaginal speculum

to conduct his examination of the vagina and dif-

ferentiate areas of pelvic relaxation [5] .

Although much changed regarding our under-

standing of medicine by the valuable contributions

of those mentioned and many more to human phys-

iology and anatomy, much remained unchanged

with regard to gynecologic therapy. Prior to the

nineteenth century, treatment for female condi-

tions such as menorrhagia, pelvic organ prolapse,

and vaginal fistulae were primarily conservative

in nature. The most popular treatment for pelvic

organ prolapse remained the vaginal pessary. Many

of these pessaries were quite elaborate in design

with straps and belts to keep them in place. During

the nineteenth century and in particular after the

understanding and development of antiseptic tech-

nique, surgical therapy gained favor. The eight-

eenth century also saw the establishment of the

anatomic classification of pelvic organ prolapse

that we still use today.

The first vaginal hysterectomy specifically for

pelvic organ prolapse is believed to have been

performed by American Civil War surgeon Samuel

Choppin in 1861, in New Orleans. His patient is

said to have survived and later presented before

a medical class with her uterus held in her hand

as proof of her survival after the procedure [2] .

Other surgeons such as James Blundell in Great

Britain in 1829, and J.C. Warren in the United

States that same year had each performed vaginal

hysterectomy on a prolapsed uterus for removal of

a cancerous cervix [2] .

By the end of the nineteenth century, vaginal

hysterectomy became a primary operative proce-

dure for pelvic organ prolapse. Indeed, Parisian

physician Pierre Delbet, in 1896, described his

modification of the vaginal hysterectomy for pelvic

organ prolapse that he called “colpocystopexie,”

whereby he supported the superior aspect of the

vaginal wall to the round ligaments [2] .

The first successful abdominal hysterectomy

was performed by Walter Burnham in 1853 [6] .

Burnham was a prominent Massachusetts surgeon

and professor who had begun an exploratory

laparotomy on a female patient with a pelvic mass

when during the surgery she vomited and pushed

out an enlarged uterus. He could not reinsert the

uterus and had no choice but to remove it. His

22. Surgery for Pelvic Organ Prolapse: An Historical Review 307

patient survived this procedure and Burnham went

on to perform 15 abdominal hysterectomies, thus

introducing another means of removing the uterus.

J. Marion Sims, well known for his contributions

toward repair of vesicovaginal fistulae, was the first

to describe the vaginal repair for a cystocele. In

1866, Sims described the denudation of an ellipti-

cal segment of the anterior vaginal wall followed

by primary closure of this incision [7] . Many of the

procedures aimed to correct pelvic organ prolapse,

involved this denudation of the vaginal mucosa. In

1877, French surgeon, Leon Le Fort's procedure

involved denudation of the entire vaginal wall for

total vaginal occlusion [2] .

During the twentieth century more modifica-

tions for surgical repair of pelvic organ prolapse

occurred. Abdominal approaches evolved to cor-

rect prolapse such as D.T. Gilliam's uterine suspen-

sion in 1900 [8] , and the Manchester approach for

conserving the uterus by cervical amputation with

anterior and posterior repairs. Fothergill proposed

suturing the cardinal ligaments to the anterior

aspect of the cervix, and hence evolved the pro-

cedure known today as the Manchester–Fothergill

operation [2] .

Howard Atwood Kelly, known as the father

of modern gynecology, arrived at Johns Hopkins

University in 1888, where he became the first

professor of Gynecology with special interest in

the area of urogynecology. His many contributions

include the initiation of organized training in the

area of gynecologic and urologic surgery. It was in

1918 that urology developed as a separate specialty

following Kelly's pioneering work in cystoscopy

[9] . His other contributions include the develop-

ment of specific surgical tools such as the Kelly

clamp, which is still indispensable in vaginal and

abdominal hysterectomies, and two gynecologic

textbooks with extensive illustrations (Fig. 22.6 )

by famous Johns Hopkins' medical illustrator, Max

Brödel [10, 11] .

In 1914, Kelly and his colleague W.M. Dumm

were the first to publish their modified technique

for cystocele repair with periurethral plication

meant also to treat stress urinary incontinence [12] .

Their technique is still practiced by many surgeons

today. Many more modifications of Kelly and

Dumm's method ensued, mostly involving ways

to reinforce surgical technique to prevent the high

recurrence rate of cystocele and cure stress urinary

incontinence. In 1936, W.T. Kennedy modified

Kelly's plication technique and advocated its use

for the management of urinary incontinence at the

time of hysterectomy [2] .

As a result of the work of esteemed surgeons

such as Mayo, Heaney, Richardson, Pratt, Te

Linde, and others, vaginal hysterectomy with col-

porrhaphy became the most popular surgery for

uterovaginal prolapse in North America [13] .

With better understanding of female surgical

anatomy, the concept of central and lateral defects

to the anterior vaginal wall developed. George

R. White first described what he believed to be

the reason for the consistent failure to provide

a permanent cure for a cystocele [14] . In 1909,

he described reattachment of the vaginal sulci

to the “white line of pelvic fascia” or the arcus

tendineous fascia , and thus corrected what we

now understand as a paravaginal or lateral defect.

Although he clearly described his vaginal tech-

nique and reported excellent cure rates, it was not

until A. Cullen Richardson described four distinct

defects in the anterior vaginal wall support from his

cadaveric dissections (Fig. 22.7a, b ) and devised an

abdominal approach to correcting the anterior vagi-

nal wall defect, that the term “paravaginal defect”

was coined and this procedure gained favor [15] .

Repair of posterior vaginal defects gained momen-

tum during the past century. Prior to the twentieth

century there is a paucity of information regarding

the surgical management of such defects as rectoce-

les. R.J.C de Garengoet was the first to describe an

enterocele in 1736. He coined the term enterocele

Fig. 22.6. Max Brodel's illustration of Kelly performing

cystoscopy and catheterization of the left ureter (from

[11] )

308 B. Amir and A.E. Bent

vaginale and created a specific pessary for this con-

dition [5] . Thereafter, anatomist Edward Sandifort

in 1777, through cadaveric dissection, described

a condition he called “intestinovaginal hernia” or

perhaps what we now know as rectocele–enterocele

[3] . The reason for so little historical literature on

the management of rectoceles is likely that women

during the nineteenth and early twentieth century

were less inclined than modern women to complain

of such concerns as fecal incontinence and needing

to manually reduce posterior vaginal defects to have

bowel movements.

As with cystocele and uterine prolapse, prior to

the twentieth century, management for rectoceles

appears to have been primarily conservative. In

1867, however, Simon of Heidelberg may be con-

sidered the first to have described the technique for

repairing posterior vaginal wall defects and origi-

nated the term posterior “colporrhaphy” [16, 17] .

His technique attempted to reduce rectoceles and

uterovaginal prolapse by plication of the levator ani

muscles and the inferior aspect of the vagina [16,

18] . Hegar in 1870 went on to introduce his method

of posterior repair by creating a tight introital ring

[16] . One hundred years later, in 1970, A. Cullen

Richardson described five sites along the rectovagi-

nal fascia that could be broken and produce defects,

and as with his correction for anterior vaginal wall

defects he advocated a site-specific method for the

repair of a rectocele [15] .

With many more independent surgeons com-

municating with one another and sharing theories,

tools, and techniques many of the relatively simple

surgeries for prolapse have evolved and matured to

what are now known. In 1942, H.S. Heaney pro-

vided his experience after performing hundreds of

vaginal hysterectomies for pelvic organ prolapse,

wherein he clearly described his successful tech-

nique for the procedure [19] . In 1957, M.L. McCall

published his culdoplasty technique for repairing

an enterocele [20] .

With many more hysterectomies being per-

formed in the middle of the preceding century, a

new concern in the form of vaginal vault prolapse

developed. Now investigators were introducing

techniques for diagnosis, treatment, and preven-

tion of vault prolapse. E.H. Richardson in 1937

with the Spalding–Richardson composite operation

[21] and McCall with the posterior culdoplasty

provided efforts to prevent this complication of

hysterectomy. In 1962, Lash and Levin suggested a

radiological technique for the diagnosis of vaginal

vault prolapse [22] .

Now experts describe apical vaginal prolapse

and specialized surgeries such as sacrospinous col-

popexy, which have been introduced by Amreich,

Richter, Nichols, and Randall [23] . Sacrospinous

vaginal vault fixation was first developed by German

surgeons Amreich and Richter. This procedure is still

performed extensively in Europe and is called the

Fig. 22.7. ( a , b) A.C. Richardson's illustration of endopelvic fascia and locations of anterior vaginal wall support

defects (from [15] )

22. Surgery for Pelvic Organ Prolapse: An Historical Review 309

Amreich–Richter procedure. Nichols, who learned

the procedure from Amreich, later performed and

published information regarding this procedure with

colleague Randall, in the United States.

The abdominal counterpart for vaginal vault

prolapse, the sacrocolpopexy, was first described

by Parsons and Ulfelder, and has become another

popular method for the correction of vaginal vault

prolapse [24] . Indeed, following publication of

results from the first large series by W.H. Addison

and colleagues, it is now considered the gold stand-

ard for restoration of the vaginal vault [25] .

Today there are numerous variations for vagi-

nal vault repairs including techniques involving

suspensions to the iliococcygeus fascia [26] and

uterosacral ligaments [27] . All of these procedures

for vaginal vault prolapse are well described in the

literature, with many surgeons favoring one over

another in different circumstances and ongoing

debate regarding the best approach to take.

Also along with advanced technology has come

the use of adjuvant graft material to reinforce

repairs, whether the repair is done abdominally

or vaginally. In 1964, W.H. Ferguson was the first

to describe the use of Marlex mesh as part of the

repair for vaginal vault prolapse [28] . Traditionally,

very few biomaterials and synthetic materials were

used in vaginal surgery. In a resurgence of perform-

ing vaginal operations that are more durable, these

materials increasingly have been utilized. There is

a growing market for such materials as is gener-

ally the case with new technology, yet there is no

conclusive evidence supporting the use of either

synthetic or biological graft materials in vaginal

reconstructive surgery. Despite this, there continues

to be a steep evolution with regards to the quality

of graft material. Today, the most common bioma-

terials in use are xenograft: porcine dermis, bovine

pericardium, porcine small intestinal mucosa; allo-

graft: cadaveric fascia and dermis; and autologous:

harvested rectus fascia or fascia lata. The most

common synthetic material used today for vaginal

repairs and abdominal sacrocolpopexy continues to

be polyprolpylene as a large-pore mesh.

Since the 1970s there also has been amazing

growth in endoscopy and laparoscopy. For every

surgery there are new minimally invasive tech-

niques [29] . Many procedures such as hysterec-

tomies [30] , vault suspensions, and paravaginal

repairs [31] can be performed laparoscopically.

This has led to reduced morbidity and mortality

and reduced hospital stay and an ever-expanding

realm of new tools and techniques.

To describe the list of further developments over

the course of the last two to three decades is a

hefty task. It is sufficient to say that this aspect of

medicine—the correction of pelvic floor disorders

such as pelvic organ prolapse—remains dynamic

and is constantly evolving to improve and provide

justification for old techniques and also provide

new methods.

In order to improve the communication between

different investigators, systems for quantifying

and standardizing the severity of pelvic organ

prolapse were devised (Fig. 22.8 ). Methods that

have been used to grade pelvic organ prolapse have

included the Baden halfway system [32] and the

International Continence Society (ICS) classifica-

tion, which has adopted the Pelvic Organ Prolapse

Quantification (POP-Q) system [33, 34] .

With improved communication between inde-

pendent medical investigators and advanced tech-

nology, growth in medical knowledge during the

twentieth century can be simply described as

exponential. Specialized fields such as urology and

gynecology branched off and within them further

subspecialties such as urogynecology and pelvic

floor surgery have evolved. Each member of the

medical scientific community now has his or her

own unique area of medicine on which to concen-

trate all of their scientific efforts.

Thus the concept of evidence-based medicine

has evolved. It now is simply not enough to theo-

rize or describe exciting new tools and practices,

but now you must prove efficacy and effectiveness

under the ever-constant scrutiny of peer review.

In many respects, evidence-based medicine has

become a standard of care, but it also evokes con-

troversy, and at times confusion, particularly for

surgical techniques that have been performed for

many years but do not have sufficient evidence to

justify their practice. There are multiple ways of

correcting one aspect of a pelvic floor defect and

the modern pelvic floor surgeon must decide which

procedure, in what context, for each individual

patient is necessary.

Also, in dividing medicine into smaller com-

partments, there is some overlap of care for such

310 B. Amir and A.E. Bent

things as the female pelvic floor. This of course can

engender some degree of dispute among the differ-

ent specialties, whether good or bad, to prove one

more superior to deal with the issues at hand over

the others. Wall and Delancey in 1991 illustrate

this feud exceptionally well [35] . In modern medi-

cine, however, the ideal approach toward manage-

ment and treatment of a patient affected by a pelvic

floor disorder such as pelvic organ prolapse is as a

multidisciplinary team, including possibly a gyne-

cologist, colorectal surgeon, neurologist, urologist,

and a physiotherapist all working together toward

this common goal.

References

1 . Meade RH . An introduction to the history of general

surgery . Philidelphia , Saunders , 1968 .

2 . Emge LA , Durfee RB . Pelvic organ prolapse: Four

thousand years of treatment . Clin Obstet Gynecol

1966 ; 9 (4) : 997 – 1032 .

3 . Ricci JV . The genealogy of gynaecology . History

of the development of gynaecology throughout

the ages, 2000 B.C.–1800 A.D. Philadelphia , The

Blakiston Company , 1943 .

4 . Speert H . Iconographia gyniatrica: A pictorial his-

tory of gynaecology and obstetrics . Philadelphia ,

F.A. Davis Company , 1973 .

5 . Garengeot , René-Jacques Croissant de . Traité des

operations de chirurgie . Seconde edition , revûe, cor-

rigée & augmentée par l’auteur. Paris , chez Huart ,

1740 .

6 . Benrubi GI . History of hysterectomy . J Fla Med

Assoc 1988 ; 75 : 533542 .

7 . Drutz HP , Herschorn S , Diamant NE . Female pelvic

medicine and reconstructive pelvic floor surgery .

London , Springer , 2003 .

8 . Gilliam DT . Round ligament ventrosuspension of

the uterus . Trans Am Assoc Obstet Gynecol 1901 ;

13 : 282 .

9 . Bent AE . Howard Atwood Kelly (1858–1943) . Int

Urogynecol J 1996 ; 7 : 48 – 61 .

10 . Kelly HA . Operative gynecology, Vol. 1 , New York ,

D. Appleton , 1898 .

11 . Kelly HA , Burnham CF . Diseases of the kidneys,

ureters and bladder . New York , D. Appleton , 1914 .

12 . Kelly HA , Dumm WM . Urinary incontinence in

women without manifest injury to the bladder . Surg

Gynecol Obstet 1914 ; 18 : 444 .

13 . Rock JA , Thompson JD . Te Linde’s operative gyne-

cology , 8th edn . Philadelphia , Lippincott-Raven

Publishers , 1997 .

14 . White GR . Cystocele . A radical cure by suturing

lateral sulci of the vagina to the white line of pelvic

fascia . JAMA 1909 ; 80 (21) : 1707 – 1710 .

15 . Richardson AC , Lyon JB , William NL . A new look

at pelvic relaxation . Am J Obstet Gynecol 1976 ;

126 : 568 – 578 .

1963

Severity

(Porges)

Slight or

1st Degree

Moderate or

2nd Degree

Marked or

3rd Degree

1st Degree

2nd Degree

3rd Degree

Stage I

(−) 1 cm

( + ) 1 cm

Stage II

Stage III

Complete

eversion

Stage IV

Grade 1

Grade 2

Grade 3

AT REST STRAINING STRAINING

Grade 4

Introitus

Midplane of

vagina

Hymeneal

ring

1972

Vaginal Profile

(Baden)

1980

Grading System

(Beecham)

1996

Quantitative POP

(ICS, AUGS, SGS)

Fig. 22.8. Grading systems for degree and severity of pelvic organ prolapse

22. Surgery for Pelvic Organ Prolapse: An Historical Review 311

16 . Jeffcoat TNA . Posterior colpoperineorrhaphy . Am J

Obstet Gynecol 1959 ; 77 : 490 – 502 .

17 . Kahn MA , Stanton SL . Techniques of rectocele repair

and their effects on bowel function . Int Urogynecol J

Pelvic Floor Dysfunct 1998 ; 9 (1) : 37 – 47 .

18 . Bent AE , Ostergard DR , Cundiff GW , Swift SE .

Ostergard’s urogynecology and pelvic floor dysfunc-

tion . Philadelphia , Lippincott Williams & Wilkins ,

2003 .

19 . Heaney HS . Technique of vaginal hysterectomy .

Surg Clin North Am 1942 ; 22 : 76 .

20 . McCall ML . Posterior culdeplasty . Surgical correction

of enterocele during vaginal hysterectomy: A prelimi-

nary report. Obstet Gynecol 1957 ; 10 : 595 – 602 .

21 . Richardson EH . An efficient composite operation

for uterine prolapse and associated pathology . Am J

Obstet Gynecol 1937 ; 34 : 814 .

22 . Lash AF , Levin B . Roentgenographic diagnosis

of vaginal vault hernia . Obstet Gynecol 1962 ;

20 : 427 – 433 .

23 . Nichols DH , Randall CL . Vaginal surgery, 4th edn .

Baltimore , Williams & Wilkins , 1996 .

24 . Parsons L , Ulfelder H . An atlas of pelvic operations ,

2nd edn . Philadelphia , WB Saunders , 1968 .

25 . Addison WA , Livengood CH , Sutton GP , Parker RT .

Abdominal sacral colpopexy with Mersilene mesh

in the retroperitoneal position in the management of

post-hysterectomy vaginal prolapse and enterocele .

Am J Obstet Gynecol 1985 ; 153 : 140 – 146 .

26 . Meeks GR Washburne JF , McGehee RP , Wiser WL .

Repair of vaginal vault prolapse by suspension of

the vagina to iliococcygeus (pre-spinous) fascia . Am

J Obstet Gynecol 1994 ; 171 : 1444 – 1452 .

27. Shull BL, Bachofen C, Coates KW, Kuehl TJ. A

transvaginal approach to repair of apical and other

associated sites of pelvic organ prolapse with ute-

rosacral ligaments. Am J Obstet Gynecol 2000;

1365–1374.

28 . Ferguson WH . New functional repair of posthyster-

ectomy vaginal vault prolapse with Marlex mesh .

Am Surg 1964 ; 30 : 227 – 230

29 . Litynski GS . Endoscopic surgery: The history, the

pioneers . World J Surg 1999 ; 23 : 745 – 753 .

30 . Reich H . Laparoscopic hysterectomy . Surg Laparosc

Endosc 1992 ; 2 (1) : 85 – 88 .

31 . Ross JW . Laparoscopic approach for severe pelvic

vault prolapse . J Am Assoc Gynecol Laparosc 1996 ;

3 (4 Suppl) : S43 .

32 . Baden WF , Walker TA . Genesis of the vaginal pro-

file: A correlated classification of vaginal relaxation .

Clin Obstet Gynecol 1972 ; 15 (4) : 1048 – 1054 .

33 . Hall AF , Theofrastous JP , Cundiff GW , et-al. .

Interobserver and intraobserver reliability of the

proposed International Continence Society, Society

of Gynecologic Surgeons, and the American

Urogynecologic Society Pelvic Organ Prolapse

Classification System . Am J Obstet Gynecol 1996 ;

175 : 1467 – 1470 .

34 . Bump RC , Mattiasson A , Bo K , et-al. . The stand-

ardization of terminology of female pelvic organ

prolapse and pelvic floor dysfunction . Am J Obstet

Gynecol 1996 ; 175 : 10 – 17 .

35 . Wall LL , Delancey JOL . The politics of prolapse:

A revisionist approach to disorders of the pelvic

floor in women . Perspec Biol Med 1991 ; 34 : 486 –

496 .

313

Introduction

Traditional methods of treatment for pelvic organ

prolapse (POP) and stress incontinence have varied

over time. From the ancient use of pomegranates as

pessaries to the modern use of synthetic pessaries,

or surgical techniques utilizing native tissue, these

treatment modalities may not provide durable

results. Cystoceles conventionally are repaired

by anterior colporrhaphy, but recurrence in up to

40% of patients is reported [1] . Data from a large

managed care population in Oregon estimate the

lifetime risk for a woman to undergo surgery for

POP or incontinence by age 80 is 11.1%, with

reoperation occurring in 29.2% of cases [2] .

As POP affects up to half of all women over age

50, population projections of women aged 65 and

over are estimated to double to 35 million by 2030

[3, 4] . With approximately one third of patients

undergoing reoperation and the eventual rise in

incidence, surgical repair techniques need to evolve

to meet these challenges. Along with restoration of

anatomy and preservation of sexual function, repair

techniques need to incorporate durability as a goal

for success. Biomaterials assist in the attainment of

these goals; use of biomaterials will not, of course,

replace sound surgical practice, but may augment it

for long-term efficacy.

Biomaterial refers to any biocompatible sub-

stance that integrates into host tissue during treat-

ment and, in the case of grafts, can be natural or

synthetic. Biological grafts are further divided into

autologous grafts (patient's native tissue), allografts

(cadaveric tissue), and xenografts (animal tissue).

Synthetic grafts are either absorbable, nonabsorb-

able, or a combination of the two. Synthetic grafts

also are identified by woven structure (monofila-

ment vs. multifilament) and pore size (macroporous

vs. microporous or both). Selection of biomaterial

is dependent on the inherent characteristics of the

graft, individualized patient need, and surgeon

preference. Biomaterial use, however, is not free

from controversy. Potential complications such as

erosion and infection are present and limited data

exist for long-term outcomes [5] . Comprehension

of biomaterial qualities and indications, though,

will undoubtedly limit these complications and

maximize efficacy.

Use of Biomaterials:

A Biochemical and Genetic

Raison d'Être

Alterations of Collagen Metabolism:

Hernia Investigations

Some of the notable risk factors for prolapse

include increasing age, menopausal status, high

parity, and history of hysterectomy [6] . Other

proposed causes of prolapse include denervation

or direct injury of the pelvic floor musculature.

A common link between these factors is the disrup-

tion of normal endopelvic fascia and ligamentary

support; integrity of the muscles and connective tis-

sue of the pelvic floor is the key for continence and

Chapter 23

Biomaterials: Natural and Synthetic Grafts

Kaytan V. Amrute and Gopal H. Badlani

314 K.V. Amrute and G.H. Badlani

pelvic organ support. Alterations of collagen and

elastin metabolism have been suggested as another

underlying mechanism of pelvic organ support loss

and incontinence: previous research on individuals

with connective tissue disorders or with hernias

demonstrates credence to this premise.

It is well recognized that persons with connec-

tive tissue disorders such as Ehlers–Danlos and

Marfans syndrome have a higher rate of urinary

incontinence and pelvic prolapse. Initial studies

conducted in a female population with Ehlers–

Danlos diagnosis showed a 20% higher incidence

of stress urinary incontinence than those without

any known connective tissue disorder [7] . Likewise,

Carley et al. confirmed these data in a population

of women afflicted with either Ehlers–Danlos or

Marfans syndrome. A comparison between these

two groups demonstrated a higher rate of prolapse

in those with Ehlers–Danlos [8] .

In normal individuals, collagen is made up of

mainly type I and type III collagen, in a 4:1 ratio

[9] . Types I and III collagen are produced primarily

by connective tissue fibroblasts and enable flex-

ibility and tensile strength. Stability of the collagen

fibers is a result of cross-linking between proline

and hydroxyproline amino acids within collagen.

Elastin, another component of connective tissue,

facilitates compliance and stretching [10] . Hernia

patients demonstrate a different fibroblast pheno-

type, and consequently, produce abnormal collagen

systemically [9, 11] .

Individuals with hernias have an overexpres-

sion of type III collagen, leading to abnormal

cross-linking with type I collagen and, ultimately,

production of tenuous fibers [11] . Klinge et al. [12]

demonstrated a significant decrease in collagen

type I/III ratio in the skin of patients with indirect

or direct hernia compared to controls. The authors

concluded that hernias could be isolated manifesta-

tions of a systemic problem of collagen metabolism

and this could delineate the high recurrence rates

with repeated suture repair. Enhanced elastolytic

activity and decreased antiprotease action has been

illustrated as well [13] . Matrix metalloproteinases

(MMP) are proteases involved in collagen degra-

dation and remodeling and are regulated by tissue

inhibitors of metalloproteinases (TIMP). A certain

type of MMP, MMP-2, was noted to be significantly

overactive in the fibroblasts of the tranversalis fascia

in patients with direct inguinal hernia [14] .

Other factors, such as aging or smoking, may

contribute to the formation of hernias. Nicotine has

an inhibitory effect on fibroblasts and decreased

oxygen levels obviate normal collagen metabolism

[9] . Muscle wasting, inherent changes in connective

tissue, and increased MMP activity may possibly

explain the effects of the aging process on hernia for-

mation. These comorbidities along with others, such

as obesity and genetic predispositions, may be addi-

tive and lead to symptomatic hernia formation [9] .

Parallels to Pelvic Prolapse

and Incontinence

Research findings of abnormal collagen metabolism

in patients with inguinal hernias have been applied

to those with pelvic support loss and incontinence.

Jackson et al. [15] compared the vaginal–epithelial

tissue of premenopausal women with genitourinary

prolapse to a control group. Significant reduc-

tion of total collagen content and solubility was

associated with the afflicted group, attributable to

increased collagenolytic activity. Chen et al. [16]

noted increased collagen degradation in the vaginal

wall tissue of women with stress incontinence or

severe prolapse, demonstrated by an increase in the

expression of mRNA of MMP-1 ( P = 0.05) and in

MMP-1/TIMP-1 ratio ( P = 0.04) compared to con-

trols. Vaginal connective tissue in individuals with

prolapse also demonstrates an increased expression

of collagen type III fibers [17] . Gabriel et al. recently

performed a histological and immunohistochemical

comparison of uterosacral ligaments of patients with

and without prolapse [18] . While there was no dif-

ference between collagen type I and smooth muscle

content between the two groups, the prolapse group

had a significantly higher expression of collagen

type III ( P < 0.001).

As with individuals with hernias, a systemic

process of abnormal collagen metabolism may

exist. Collagen content in nonsupportive tissue

such as the uterine cervix in women with prolapse

is significantly lower compared to a control group

[19] . Ulmsten et al. demonstrated that the skin and

ligamentum rotundum of women with stress incon-

tinence had 25–40% less hydroxyproline than that

of unaffected women in a similar age group, indi-

cating lower collagen content [20] . Concentration

of helical peptide α1 (I) 620–633, a urinary col-

lagen degradation product, is significantly higher in

23. Biomaterials 315

patients with stress incontinence compared to those

without stress incontinence [21] . Histopathological

differences of skin and endopelvic fascia biopsies

in stress-incontinent women and unaffected women

show reduced collagen content in the incontinent

group [22] . Elastin metabolism also may be affected

as significantly decreased levels of α -1 antitrypsin

mRNA, a serine protease inhibitor, were noted in

women with stress incontinence and/or prolapse

[23] . Elevated elastase activity is evident in plasma

of patients with stress incontinence and provides

further evidence of systemic process [24] .

Genetic predisposition plays a significant role

in laxity of the pelvic floor as well. Bladder neck

and urethral hypermobility is partly determined

genetically, as demonstrated in a translabial ultra-

sound study with nulligravid twin sister pairs

with approximately 59% of bladder neck descent

variance due to genetic factors [25] . Bushbaum et

al. [26] quantitatively compared the degree of pro-

lapse using the pelvic organ prolapse quantification

(POP-Q) exam in 101 pairs of nulliparous and their

parous postmenopausal sisters. While a major-

ity of patients had no significant prolapse, a high

concordance in prolapse stage was evident among

sister pairs. In discordant sister pairs, ie, prolapse

in one sister greater than two or more stages of pro-

lapse compared to the other, the parous sister dem-

onstrated advanced stages of prolapse in more than

80% of the cases [26] . A recent case series reported

on ten patients with early-onset prolapse (average

age 37 years old) and family history of prolapse

[27] . Genetic analysis on this small population of

patients revealed an autosomal inheritance pattern

with incomplete penetrance, with both maternal

and paternal transmissions. Furthermore, the rela-

tive risk of prolapse to the siblings of the affected

patients was five times greater than the risk for the

general population [27] . A genome-wide linkage

scan performed on one family with a generational

history of prolapse suggests a polymorphic variant

in the promoter of laminin gamma1 (LAMC 1)

gene in vaginal tissue may increase the susceptibil-

ity of early-onset POP [28] .

Clinical Translation

Abnormal collagen and elastin metabolism,

together with inciting factors such as childbirth,

may lead to symptomatic pelvic floor defects and

incontinence. After repair of such defects, failure

of surgical therapy and recurrence of prolapse may

be explicated by this biochemical phenomenon. As

certain patients may have a genetic predisposition,

use of biomaterial grafts may offer a solution to

recurrence of pelvic support loss.

The “Ideal” Biomaterial and Host

Remodeling

Biomaterial Paradigm

The ideal biomaterial should represent the follow-

ing characteristics: inert, sterile, noncarcinogenic,

noninflammatory, nonimmunogenic, mechani-

cally durable, ability to withstand modification or

enzymatic degradation by host tissue, inexpensive,

accessible, convenient, and easy to use. Current

biomaterials do not meet all of these criteria, but

come close to this paradigm [29] . Ultimately, selec-

tion of graft material is tailored according to patient

need and surgeon preference. The requirements for

the mechanical properties of grafts used in pelvic

prolapse have not yet been defined and insights have

been extrapolated from abdominal hernia repair [9] .

Synthetic mesh implants used in hernia repairs have

a minimum tensile strength that far exceeds the

increased intra-abdominal pressures noted during

Valsalva maneuvers. “Dry” laboratory conditions

demonstrate that most meshes are stronger than

what is physiologically required. Consequently,

implants with lesser tensile strength or more elastic-

ity may result in better clinical outcomes [9] .

Host Response of Remodeling

Although biomaterials strive to be biologically inert

and nonimmunogenic, all invariably cause a foreign

body response, with the synthetic grafts inducing a

more vigorous response compared to natural grafts

[9] . Initially, after implantation, the host reacts to

the injury and covers the material with a biofilm.

Low-molecular-weight proteins, such as albumin,

and later more complex proteins such as fibrinogen,

immunoglobulins, extracellular matrix proteins are

incorporated onto the graft. If bacteria are present,

alterations in the biofilm may occur to cause future

clinical consequences, such as erosion. The biofilm

becomes immunogenic through structural changes

316 K.V. Amrute and G.H. Badlani

of the adsorbed proteins, thereby triggering a typical

acute inflammatory response, involving the comple-

ment system, binding of antibodies, and blood clot-

ting and fibrinolysis activation [9] .

A chronic inflammatory reaction then ensues: for-

mation of granulation tissue with fibroblasts, macro-

phages, and ultimately foreign body giant cells (see

Fig. 23.1 [30] ). Neovascularization also occurs fol-

lowed by fibrosis. Macrophages, differentiated from

extravascular monocytes, are the critical cell type

in the clinical response of the biological acceptance

or rejection of the graft. Roles include interaction

with lymphocytes and production of mediators that

induce protein synthesis and cell proliferation, ie,

fibroblasts [9] . Fibroblasts eventually predominate

as capillaries and inflammatory decrease in number.

Consequently, collagen and other matrix proteins

are deposited, resulting in fibrous tissue formation.

The host response of fibrosis and scarring eventu-

ally should engender a successful clinical outcome.

Yet, the remodeling process itself can be responsi-

ble for failure of graft material and recurrence of

symptoms. The inflammatory reaction, requisite for

fibrosis, may cause some adverse effects such as

erosion, adhesion formation, and graft shrinkage.

Another consideration is the deposition of abnormal

collagen, as the process occurs in an individual with

inherent defective collagen production and metabo-

lism [9] . Ideally, biological acceptance of the graft

should demonstrate little inflammatory response

with early infiltration of fibroblasts [30] .

Natural Biomaterials

Biological grafts may be harvested from a patient's

own fascia (autologous graft), from cadaveric tissue

(allograft), or from animal tissue (xenografts). Each in

turn have particular strengths and may be used when

synthetic grafts are contraindicated (see Table 23.1 ).

Advantages include in vivo tissue remodeling, histo-

logical similarity, and reduced erosion rates. Potential

shortcomings are limited supply, cost, unpredictable

host tissue integration, inconsistent strength, lack of

long-term data, and possible infectivity with allo-

grafts and xenografts [31] .

Autologous Biomaterial

Autologous grafts traditionally are harvested from

two sites: rectus abdominis fascia or tensor fascia

lata. Due to size restrictions, autologous grafts are

used mainly in sling procedures and rarely in POP

repair. Alridge first described the use of bilateral

strips of rectus fascia, passed through the rectus

muscles, and ligated together posterior to the ure-

thra [32] . Beck et al. [33] reported the use of fascia

lata as a suburethral sling for recurrent stress incon-

tinence treatment. Current surgical techniques are

described in detail elsewhere in this book.

The rectus abdominis fascia is obtained usually

through a Pfannenstiel incision, and unlike the fas-

cia lata harvest, repositioning of the patient is not

required. Transmission of infectious agents is mini-

mal. While the harvest may be straightforward,

potential complications include a limited length

of fascia obtained, increased morbidity secondary

to incision pain or wound infection, risk of future

Table 23.1. Indications for biological grafts .

• Poor vaginal healing

• Pelvic bone trauma

• History of pelvic radiation

• Urethral reconstruction

• Known allergic reaction to synthetic biomaterial

• Surgeon preference

Fig. 23.1. Host remodeling: initial histological reaction. Adapted from [30]

Stage 1: (ﬁ rst 7 days): intense inﬂ ammation with capillary proliferation, granular tissue, and giant cell

Stage 2: (after 14 days): granular tissue remains with more giant cells

Stage 3: (after 28 days): the acute inﬂ ammation has disappeared and number of histiocytes and giant cells has

increased

Stage 4: presence of giant cells on the external cells on the external surface of the implant with dense ﬁ brous

tissue

23. Biomaterials 317

abdominal hernia, and added procedure and recov-

ery times. Previous surgery or radiation therapy at

the harvest site also may preclude the acquirement

of good tissue of sufficient length and quality.

Recent studies on rectus fascia have demon-

strated high success rates with minimal complica-

tions. Morgan et al. [34] reported on 247 women

with type II or III stress incontinence treated with

pubovaginal slings, composed of rectus fascia.

At a mean follow-up of 51 months, continence

rates were 88% overall, 91% for type II and 84%

for type III. Secondary procedures, consisting of

transurethral collagen injections or repeat slings,

were performed in 14 patients. A complication rate

of 4% was noted and included pelvic hematoma,

incisional hernia, deep venous thrombosis, and

pulmonary embolus. However, no erosions or

extrusions were evident [34] . Another retrospec-

tive study showed a 92% overall success rate with

a minimum of 1 year follow-up (median 3.1 years,

range 1–15) in 251 patients; permanent urinary

retention occurred in only four patients, while de

novo urge incontinence occurred in 3% of patients

and persistent urge incontinence in 23% [35] .

Tensor fascia lata may offer several advantages

over rectus fascia. Fascia lata, with dimensions

of approximately 20 × 2 cm, is obtained laterally

from the upper thigh from the ileotibial band,

with the aid of a device such as the Masson fas-

cial stripper (Marina Masson Fasicalata Stripper,

Marina Medical, Hollywood, Florida, USA) or the

Crawford fascia stripper (Bausch & Lomb Storz

Instrument Company, San Dimas, CA, USA) (see

Fig. 23.2 ). Fascia lata has greater tensile strength

than rectus fascia [36] . Concerns of length, his-

tory of previous abdominal surgery, and future

complication of abdominal hernia are irrelevant.

Disadvantages include increased operating time,

repositioning of the patient, and possible cos-

metic issues. Potential complications include acute

hematoma, seroma requiring serial aspiration or

drainage, prolonged postoperative pain, muscle

herniation, and infection.

Success rates with autologous fascia lata grafts

by and large have been similar to rectus fascia. In

170 patients, Beck et al. demonstrated a 92% suc-

cess rate with minimal de novo urgency rates and

no erosions [37] . Another retrospective review,

supplemented by the urogential distress inventory

(UDI)-6 questionnaire with a mean follow-up

period of 4.4 years, demonstrated 85% of 100

patients reported being dry or improved and 93%

being pain-free at the harvest site by the seventh

day postoperatively. No infections at the harvest

site or lower extremity thrombotic events were

noted [38] . The same authors also retrospectively

evaluated use of fascia lata in abdominal sacrocol-

popexy in ten patients and noted POP-Q stage II or

lower in all patients with a follow-up range of 19

to 42 months [39] .

Allograft Biomaterial

As with autologous grafts, cadaveric grafts are

associated with a low risk of infectivity and ero-

sion. Use of allografts also confers the advantages

of absence of donor site morbidity, shorter operat-

ing times, more rapid recovery time, and similar

efficacy to autologous grafts [40] . Furthermore,

size restrictions are not applicable; in addition to

use in pubovaginal slings, allografts may be used

in other reconstructive procedures, such as abdomi-

nal sacrocolpopexy or anterior colporrhaphies.

Processing techniques, however, potentially may

compromise biomechanical properties of cadaveric

fascia, thereby contributing to an unpredictable

resorption and integration process [40] .

Donor cadaveric grafts, usually harvested from

the tensor fascia lata, undergo several processing

techniques to decrease infectivity and antigenicity,

thereby reducing a host immune response. Donors

usually are screened first with a thorough medical

and social history and serological testing for HIV,

Hep B, Hep C, and HTLV-1. After completion of

the screening process, harvest of tissue then should

occur under strict aseptic conditions. Removal of

infectious and antigenic material varies accord-

ing to manufacturer [40] . Tissue processing of

cadaveric fascia may include freeze-drying, after

a wash to remove various bacterial, viral, and fun-

gal organisms. Suspend Tutoplast

® by Coloplast

(Marietta, GA, USA) undergoes a multistep solvent

Fig. 23.2. Crawford fascia stripper

318 K.V. Amrute and G.H. Badlani

dehydration method with various organic solvents

which has the added benefit of eliminating prions,

the agent responsible for Creutzfeldt–Jakob disease.

Suspend Tutoplast

® also is further sterilized with

gamma-irradiation to decrease infection transmis-

sion risk [40] .

Although infectivity and antigenicity is lessened,

allograft quality may be affected by the various

processing methods. Lemer et al. [41] noted a

significantly lower tensile strength and stiffness

in freeze-dried fascia compared to autologous

grafts and solvent-dehydrated cadaveric fascia.

Independent of freeze-drying, incomplete rehydra-

tion of allograft of less than 1 h also can affect

quality. This may trap water between collagen fib-

ers as they expand, thereby creating a decrease in

structural integrity [40] . While irradiation at high

levels (over 30 kGy) may be virucidal, damage

to the tertiary structure of collagen can occur and

affect the tensile strength and graft stiffness. To

preserve collagen structure and achieve sterility,

along with other processing methods, cadaveric

fascia usually is exposed to 20–25 kGy of radia-

tion. In addition, donor factors may play a role

in graft quality. Instead of well-developed, well-

nourished, athletic individuals, allograft donors

usually consist of an elderly population that may

be sedentary, malnourished, and have age-related

attenuated fascia [40] .

Clinically, tissue-processing techniques and

donor factors may explicate the reduced func-

tional outcomes of allografts noted in pubovaginal

sling surgery. Success rates of cadaveric fascia

used for midurethral slings range from 65 to 98%

[42] . McBride et al. performed a retrospective

comparison of autologous slings against Suspend

Tutoplast

® , the solvent-dehydrated and gamma-

radiated cadaveric fascia [43] . Overall, 92.3% of

the autologous patients ( n = 39) and 90.5% of

the allograft patients ( n = 32) reported subjective

stress continence at 24 months. No differences

were noted in subjective quality-of-life measures,

maximum urethral closure pressures, and blad-

der neck mobility. However, 41.7% of allograft

patients demonstrated urodynamic stress inconti-

nence compared to 0% of autologous patients

( P = 0.007) [43] .

Poor outcomes also were noted in a recent study

of 303 patients with a median overall follow-up

time of 5.6 years comparing autologous rectus

fascia ( n = 153) to freeze-dried cadaveric fascia

( n = 150) [44] . Recurrent stress incontinence

symptoms (39.6% vs. 28.3%, P = 0.04) and reop-

eration (12.7% vs. 3.3%, P = 0.003) occurred

more in the cadaveric versus the autologous group,

respectively. Adjusting for differences in follow-up

time, the cadaveric group revealed higher rates

of incontinence (16 vs. 5 per 100 women-years,

P < 0.0001) and higher rates of reoperation

(4 vs. 1 per 100 women-years, P <0.0003) [44] .

FitzGerald et al. performed a histopathological

analysis of retrieved freeze-dried, irradiated graft

material on 7 of 12 patients who underwent

reoperation for recurrence of prolapse or stress

incontinence symptoms [45] . The results revealed

that most of the graft remnants demonstrated areas

of disorganized remodeling patterns and graft

degeneration. Unpredictable host integration of the

allograft may be related to several factors such as

rate of tissue remodeling, antigenicity of the graft

material, and high levels of stress placed on the

graft during remodeling [45] .

For use in prolapse surgery, Culligan and col-

leagues performed a randomized controlled trial in

100 patients who underwent abdominal sacrocol-

popexy, where 54 patients received polypropylene

mesh and 46 Suspend Tutoplast

® [46] . Objective

anatomic failure was defined as POP-Q stage 2

or more at any time during the follow-up period.

At 1-year follow-up, a significant difference in

objective cure rates was noted: 91% in the mesh

group and 68% in the solvent dehydrated, gamma-

radiated fascia group ( P = 0.007) [46] . A prospec-

tive randomized trial of 154 patients by Gandhi

et al. compared standard anterior colporrhaphy

with or without solvent-dehydrated graft [47] .

Sixteen women in the graft group (21%; n = 76)

and 23 in the control group (29%; n = 78) experi-

enced recurrent anterior vaginal wall prolapse ( P

= 0.229). While the difference was not statistically

significant, the authors concluded use of cadaveric

fascia will not decrease prolapse recurrence rates.

In brief, data suggest autologous grafts may be

superior to allografts in clinical results of pub-

ovaginal sling procedures. If cadaveric fascia is

considered for use, solvent dehydration processing

appears to be superior to freeze-dried methods.

Unpredictable host remodeling of the allografts

after placement possibly explains the difference in

clinical outcomes [40] .

23. Biomaterials 319

Xenograft Biomaterial

Xenografts are derived from other species, mainly

porcine or bovine sources, and act as acellular

collagen-based scaffolds. Collagen sources include

porcine small intestine submucosa, porcine der-

mis, fetal bovine skin, and bovine pericardium.

Production is governed strictly by Food and Drug

Administration (FDA) guidelines, which encom-

pass information of the animal herd, vaccina-

tion status, feed source, and bovine spongiform

encephalopathy clearance. Furthermore, the col-

lagen-based implants can be cross-linked or not;

cross-linking between the collagen fibrils protects

against host collagenase degradation, rendering the

implant relatively nonabsorbable [9] .

Pelvicol® (Bard Urological Division, Covington,

GA, USA) is a porcine dermal collagen implant

composed of a flexible sheet of fibrous, acellular

collagen and elastin fibers cross-linked by hexam-

ethylene-di-isocyanate (HMDI). The implant also

is terminally sterilized by gamma irradiation. In

addition to providing stability against enzymatic

degradation, HMDI cross-linking also may cause

less of an immune response. However, a host

cytotoxic effect may not be completely absent

[48] . In a rat model comparing the inflammatory

responses of Pelvicol® with Prolene synthetic

graft, a lesser inflammatory response was dem-

onstrated in the former group, where decreased

granulocytes and macrophages were noted [49] .

Pelvicol® induced a slower, but more orderly

collagen deposition paralleling the surface of the

implant and fewer adhesions were apparent. In lieu

of tissue ingrowth, encapsulation occurred, thereby

challenging mechanical strength and causing pos-

sible seroma formation [49] . To promote tissue

infiltration and vascularization, a porous version of

Pelvicol® is available (Pelvisoft®, Bard Urological

Division, Covington, GA, USA).

Gandhi et al. [50] , performing a retrospective

histological study on cross-linked porcine dermis

in 7 of 12 patients who underwent reoperation sec-

ondary to pubovaginal sling complications, showed

variable tissue reaction. In patients who were

reoperated for urinary retention at a time period

of 6–42 weeks later, explanted specimens showed

a trend toward graft preservation, with minimal

tissue ingrowth and remodeling. In two patients

who reoperated for stress incontinence recurrence,

with a longer time frame from initial surgery, the

grafts appeared to be replaced with dense fibro-

connective tissue and moderate neovascularization

without any inflammatory response [50] . Although

histological comparison was not performed with

biopsies from successful operations and the sample

size is small, the study raises questions concerning

predictability of host tissue reaction to cross-linked

porcine dermis. The cross-linking process may pre-

vent cellular infiltration by the host, consequently

affecting the remodeling process and eventually

leading to graft failure.

Wheeler et al. [51] analyzed outcomes of use

of cross-linked porcine dermis in 36 women who

underwent high vaginal uterosacral suspension

and cystocele repair. Dissection in the anterior

compartment was performed laterally for expo-

sure of sufficient paravaginal tissue capable of

graft attachment. Postoperatively, with a median

follow-up time of 17 months, significant improve-

ment was demonstrated in mean scores of the

Incontinence Impact Questionnaires-7 (IIQ-7) and

Urogential Distress Inventory-6 (UDI-6) ( P < 0.01).

Overall postoperative mean POP-Q measurements

also showed significant improvement, but approxi-

mately 50% of patients had a stage II or greater

anterior compartment prolapse; 28.6% of patients

had point Ba beyond the hymen. Complications

included graft resorption in one patient and reoper-

ation in a total of four patients. Although the study

was not a randomized, controlled trial and graft

attachment was not as far lateral as to the arcus

tendineous, use of porcine dermis did not produce

any significant advantages [51] .

Gomelsky and colleagues recently retrospec-

tively evaluated the incidence of vaginal extrusion

and management in 270 women who underwent

pubovaginal sling placement or prolapse repair

with Pelvicol

® over a 5-year period [52] . Nineteen

women (7%) had complete or partial vaginal

extrusion. Of the 13 patients who underwent

pubovaginal sling surgery, 11 patients healed by

re-epitheliazation and two required operative deb-

ridement. Two of the six patients who underwent

prolapse repair required reoperation for extensive

extrusion and had reoccurrence of prolapse while

the remaining patients healed with minimal inci-

sional separations. Statistical analysis revealed

that vaginal extrusion was significantly associated

320 K.V. Amrute and G.H. Badlani

with concomitant urethral diverticulectomy and

pubovaginal sling surgery [52] .

Non-cross-linked porcine dermis (InteXen™

and InteXen LP™, American Medical Systems,

Minnetonka, MN, USA) was introduced to address

the limitations of the cross-linked dermis. It is an

acellular material that should minimize risk of

rejection and decrease inflammatory response. The

lack of cross-linked collagen fibrils theoretically

should facilitate host tissue integration. InteXen LP

differs from InteXen in that it is not irradiated but

terminally sterilized by ethylene oxide then lyophi-

lized. A histological comparison of three implanted

porcine dermis biomaterials (InteXen, InteXen LP,

and Pelvisoft) was reported using Sprague-Dawley

male rat models [48] . At day 84, the endpoint

of the study, InteXen LP had significantly more

vascularization ( P <0.03) and the most even distri-

bution of cellular infiltration within the material.

A higher capillary count and cellular infiltration

was noted in the pores of Pelvisoft compared to

within the graft material. Pelvisoft and InteXen LP

had a higher degree of surface area persistence, or

material integrity, at the end of the study period.

Also, at day 84, tensile strength was similar in all

groups as well as fibroblast count. In this model,

non-cross-linked porcine dermis and porous cross-

linked dermis seem to facilitate vascularization and

remodeling [48] .

Gomelsky et al. [53] retrospectively reviewed

outcomes in 70 women who underwent repair of

high-grade cystocele with porcine dermis graft

interposition with InteXen. The graft was secured

to three points on the arcus tendineous bilater-

ally with delayed absorbable suture after proper

dissection. Concomitant repairs of stress inconti-

nence and prolapse occurred in 65 patients (with

pubovaginal sling) and 50 patients (iliococcygeous

vault suspension), respectively. After 24 months

of follow-up, 59 (91%) of patients were dry while

10 (14%) patients had recurrent prolapse: one

with vaginal vault prolapse (POP-Q value of C =

−2) repaired with abdominal sacrocolpopexy, six

with grade II asymptomatic cystocele (Ba = 0),

and three with grade III (Ba = + 2) cystocele who

elected no surgical intervention [53] .

Porcine small intestinal submucosa (SIS)

(Surgisis®, Cook Medical, Bloomington, IN, USA),

is composed of non-cross-linked collagen proc-

essed such that immunogenic cells are removed

while the complex extracellular matrix and natural

growth factors are left intact. It is obtained from

the tunica submucosa of the small intestine and is

the layer of connective tissue arrange immediately

under the mucosa layer. SIS contains collagen types

I, III, and V and growth factors TGF- b and FGF-2

and exists as vacuum-pressed or freeze-dried two-,

four-, and eight-layer implants [9] . Acting as a

biological scaffold, SIS is usually degraded in

4–12 weeks by an active remodeling process that

replaces the graft gradually by host connective

tissue. Specifically, SIS enables the ingrowth of

fibroblasts, rapid angiogenesis, differentiation of

myofibroblasts, and resurfacing of epithelial cells

[9, 54] . Weidemann and Otto [55] in their series of

15 patients performed a histopathological analysis

of SIS graft in three patients who underwent reop-

eration for failed pubovaginal sling procedures

after a mean of 12.7 months. The biopsies revealed

minimal focal residue and absence of a foreign

body or chronic inflammatory reaction. Compared

to other biomaterials, SIS produces the highest

stimulus for the formation of collagen fibers sur-

rounding the graft [56] .

Clinically, SIS has demonstrated good short-

term results in some studies. In one series of 152

pubovaginal sling patients, a 93% cure rate for

stress incontinence was noted at 4 years, but 50.7%

of patients showed urge incontinence [57] . A more

recent retrospective study of 34 patients showed

27 (79%) cured of stress incontinence at 2-year

follow-up. One patient developed de novo urgency

while three patients (9%) developed suprapubic

inflammation at 10, 21, and 45 days after surgery,

resolved with antibiotics. No prolonged urinary

retention, erosions, or other complications were

noted [58] . Ho et al. also noted in six of ten patients

receiving eight-ply SIS pubovaginal slings sympto-

matic postoperative inflammation. Pain and indura-

tion at the abdominal incision site occurred in this

series 10–39 days after surgery and all patients

were treated conservatively, with an exception of

one patient who required abscess drainage [59] .

For prolapse repair, a case-control study of 14

patients undergoing traditional anterior repair and

14 patients with SIS graft anterior repair demon-

strated significant improvements in quality-of-life

parameters such as role and physical limitations

at 6-month follow-up in the latter group [60] . SIS

graft repair improved all POP-Q measurements

23. Biomaterials 321

significantly except for total vaginal length. At

2-year follow-up, no significant difference was

noted in quality-of-issues or POP severity between

both groups; in terms of long-term efficacy, the ini-

tial greater improvement of POP-Q measurements

in the SIS graft group was not evident [60] .

Synthetic Biomaterials

Classification and Host Remodeling

Synthetic grafts are classified according several

parameters; mainly pore size, nature of fiber fila-

ments, and durability. Other important character-

istics include flexibility and mechanical strength.

Amid [61] established a classification system for

synthetic grafts used in abdominal herniorrhaphy

based on pore size and fiber type (see Table 23.2 ).

Synthetic mesh is usually created from knitted

single-fiber filaments (monofilament) or braided

with monofilament yarns into multifilament fibers

and the tensile strength will vary with fiber type,

the weight-to-area ratio, and the weave [62] . The

fibers may be absorbable or nonabsorbable mate-

rial, or a combination of both. Flexibility is deter-

mined by the individual stiffness of its yarns, the

knitting procedure, the pore size, and the amount of

material per unit of surface. Multifilament implants

generally are more supple [9] .

Pore size is the diameter of the open spaces while

interstitial distance is measured between the fibers

(see Fig. 23.3 ). Greater flexibility is noted in grafts

with a larger pore size, while grafts that are more

interlooped have smaller pores and a higher degree

of stiffness [9] . Pore size and interstitial distance

also are the most important characteristics that

determine whether host inflammatory cells, fibrob-

lasts, and collagen can infiltrate the mesh structure

[62] . Pore size >75 m m, defined as macroporous,

enable rapid ingrowth of fibroblasts and capillar-

ies necessary to integrate the implant with native

tissue. Interstices, in multifilament implants, are

smaller than the actual pores and increase the con-

tact surface with the host tissue. Although better

integration occurs, a stronger inflammatory reac-

tion can result. Yet, there seems to be an absolute

lower limit for filament size: when filament size is

less than 4/0, a constant granulomatous reaction

was demonstrated irrespective of the fiber type or

number of filaments [63] .

Pore sizes or interstices of less than 10 m m

hypothetically allow passage of bacteria (2 m m

or less) but not leukocytes (9–15 m m) and mac-

rophages (16–20 m m) (see Fig. 23.4 ). These cell

Table 23.2. Amid classification and types of synthetic mesh .

Type Pore size and filament number Material (trade names)

1 Macroporous a , Monofilament Polypropylene (Prolene, Marlex, Atrium),

Polypropylene/Polyglactin 910 (Vypro I and II),

Polyglactin 910 (Vicryl)

2 Microporous a , Multifilament Expanded Polytetrafluoroethylene (PTFE) (Gore-tex)

3 Macroporous/Microporous,

Multifilament

Polytetrafluoroethylene (PTFE) (Teflon),

Polyethylene tetraphthalate (Mersilene),

Braided polypropylene (Surgipro)

4 Submicronic b , Monofilament Polypropylene sheet (Cellgard)

a Macroporous: defined as >75 m m, Microporous ≤75 m m

b <1 m m, not used in pelvic reconstructive surgery

Fig. 23.3. Definition of terms for synthetic mesh

322 K.V. Amrute and G.H. Badlani

populations are necessary for clearance of infection

and play a vital role in the remodeling process [9] .

Peak ingrowth occurs at a pore size approximately

at 400–500 m m. Large pores limit the remodeling

process to the perifilament region, as the pores

are occupied by adipose cells [63] . A mesh with

smaller pores (<50 m m) or a solid product will be

encapsulated or induce an increased foreign body

reaction, consequently filling the pores by bridging

from one filament to another [9] . Bobyn et al. [64]

reported that the best mechanical anchorage occurs

when the pore size was between 50 and 200 m m

with an average of 90 m m. Furthermore, elasticity

in the range of 20–35% has been reported to match

the compliance of the surrounding tissues to avoid

both extrusion and patient discomfort [65] .

Types of Synthetic Mesh

A variety of synthetic mesh is available for use,

differing in porosity, fiber materials, weight, stiff-

ness, and resistance to degradation. Polypropylene

is commonly used as a nonabsorbable, type 1

macroporous, monofilament mesh and available

in different weaves and weights. Examples of

heavier mesh are Prolene (85 g m

−2 ) and Marlex

(95 g m

−2 ), while Gynemesh PS (43 g m

−2 ) is sig-

nificantly lighter (see Fig. 23.5 ). An example of

an absorbable product is polyglactin 910 (Vicryl,

Ethicon, Summerville, NJ, USA) while Vypro I

and II are examples of combination absorbable and

nonabsorbable mesh (50% polyglactin 910/50%

polypropylene).

Julian [66] first described the use of synthetic

mesh in anterior vaginal colporrhaphy in a prospec-

tive randomized study of 24 patients. Marlex (CR

Bard, Branston, RI, USA), a type 1 monofilament

polypropylene mesh, was placed proximally to the

vaginal apex and laterally to the levator fascia in 12

patients after routine colporrhaphy. At 24 months'

follow-up, the success rate in the Marlex group

was 100% compared to 66% in the control group

undergoing colporrhaphy alone. However, a high

rate of erosion was noted in four patients (25%)

[66] . Flood et al. [67] retrospectively analyzed 142

patients who similarly underwent anterior repair

with Marlex augmentation. In this series, the suc-

cess rate, defined as prolapse less than grade 1, was

100% with no mesh-related complications.

Short-term efficacy of polyglactin 910 has been

evaluated in two randomized controlled trials. In

one, 114 patients with stage 2 or 3 cystoceles were

randomly allocated into three groups: standard

anterior repair, standard plus polyglactin 910 mesh,

and ultralateral anterior repair [68] . At the median

follow-up time of 23.3 months, 83 patients were

available for evaluation: success rates (defined

stage 0 or stage 1 at points Aa and Ba) were noted

in 10 of 33 (30%) in the standard group, 11 of 26

(42%) in the standard and mesh group, and 11 of

24 (46%) in the ultralateral group. The results were

not statistically significant, and as such the addition

of polyglactin did not seem to improve surgical

outcome [68] . Sand et al. [69] prospectively rand-

omized 161 patients in need of anterior and poste-

rior colporrhaphy into a control group of standard

repair ( n = 80) and a group with mesh augmenta-

tion ( n = 80). Of those available for follow-up

( n = 143), at 1 year, 43% (30/70) of the control

group and 25% (18/73) with polyglactin 910 mesh

had recurrent cystoceles beyond the midvaginal

plane ( P = 0.02). Recurrent cystoceles to the hyme-

nal ring occurred in eight patients (11.4%) in the

control group and in two patients (2.7%) with mesh

Fig. 23.4 . ( a ) Small pore sizes (<10 m m) enable the

passage of bacteria and block the components for tissue

ingrowth, such as macrophages and fibroblasts while,

( b ) larger pore sizes (>75 m m) allow for the remodeling

process and neovascularization to occur

Fiber Cross

Section

Macrophage Protein

< 10 Micron

a

Fiber Cross

Section

b

Fibroblast

Capillaries

> 80 Micron

23. Biomaterials 323

( P = 0.04). No recurrent rectoceles to the hymenal

ring occurred in either groups [69] .

Great efficacy may be achieved with use of

polypropylene mesh along with a higher risk of

erosion. Compared to other materials, polypropyl-

ene induces a far less intense inflammatory reac-

tion [56] . Using a lightweight polypropylene mesh

(Gynemesh; Gynecare, Johnson & Johnson, NJ,

USA), de Tayrac et al. [70] performed transvaginal

repair of the anterior compartment with mesh aug-

mentation in 87 consecutive cases. The polypropyl-

ene mesh was placed in a tension-free fashion from

the retropubic space to the inferior portion of the

bladder. Cure in this series was defined according

to the POP-Q staging system with point Ba in stage

0 (optimal) or stage 1 (satisfactory). At the median

follow-up time of 24.3 months, 91.6% (77/84

patients) were cured, 5.9% patients had asympto-

matic stage 2 anterior vaginal wall prolapse, and

2.4% had recurrent stage 3 prolapse. Mesh erosion

was noted in 8.3% of patients, and four patients

required reoperation for partial excision. De novo

dyspareunia was noted in 16.7% of 30 sexually

active patients and de novo urgency was noted in

6.8% of patients [70] .

Synthetic biomaterials can be fashioned accord-

ing to specific patient anatomical defects and pelvic

dimensions. A soft polypropylene 5 × 5 cm circu-

lar mesh is used in a new transvaginal technique

described by Rodriguez and colleagues [71] . After

placement of a distal urethral sling and vaginal dis-

section, the mesh is situated to correct the central

and lateral defects of high grade cystoceles (POP-Q

stages 3 and 4); points of attachment include the

obturator fascia laterally, the bladder neck distally,

and sacrouterine/cardinal ligament complex proxi-

mally. In 98 patients who had the procedure, with

minimum 1-year follow-up, post-operative POP-Q

Fig. 23.5. Examples of synthetic mesh knits and weaves. ( a ) Marlex, ( b ) Mersilene, ( c ) Prolene, ( d ) Gore-tex

ab

cd

324 K.V. Amrute and G.H. Badlani

scores showed 85% of patients with stage 0–1, 13%

with stage 2, and 2% with stage 3 anterior vaginal

wall prolapse. De novo urge and stress incontinence

were seen in three and three patients, respectively.

No erosions were reported [71] .

At our institution, a 6- × 8-cm polypropylene

mesh is specially fashioned into an “H” shape and

fixed to four points in a tension-free manner to

repair anterior compartment defects and provide

vaginal vault support. After proper vaginal dis-

section, the anterior arms of the mesh are passed

retropubically to provide midurethral and blad-

der neck support, the middle portion addresses

anterior vaginal wall defects, and the posterior

arms aid in vaginal vault suspension via bilateral

sacrospinous ligament fixation. A retrospective

analysis on 96 patients with Baden-Walker stage

3 or 4 who had the procedure from January

2000 to June 2005 recently was performed [72] .

Seventy-six patients (79%) were available with a

mean follow-up time of 31 months. Four patients

(5.2%) reported recurrence of prolapse. Sixty-

eight patients (89%) were completely dry or

almost dry, defined as an occasional leak. For

those with preoperative incontinence ( n = 36),

average pad use per day decreased significantly

from 2.1 ± 0.4 to 0.8 ± 0.2 ( P < 0.005) postop-

eratively. Twelve patients (15.7%) reported of

de novo urgency. Other complications included

vaginal erosions in two patients (2.1%), urinary

retention secondary to obstruction in one patient

(1.1%), palpable vaginal suture in one patient

(1.1%), and recurrent stress incontinence in two

patients (2.1%). Among those who were sexually

active ( n = 21), 90.4% denied any dyspareunia

and patient satisfaction overall was high [72] .

Diagnosis and Management of Erosion

and Extrusion

Inherent risks to the use of biomaterials are the

complications of erosion and extrusion. Although

not universally applied as of yet, newer studies are

differentiating the inherently similar two terms:

“erosion” generally is defined as the presence of

graft material in the lumen of the urinary tract,

while “extrusion” is defined as the presence of

exposed graft in the vagina [73] . Erosion and extru-

sion rates mainly are extrapolated from pubovagi-

nal sling or abdominal sacrocolpopexy procedures;

limited data exist for the newer synthetic graft kits

used in pelvic reconstructive surgery.

The first reported incidence of vaginal extru-

sion from sling placement ranged from 0.3 to

23%, with decreased rates with the use of biologi-

cal grafts [74] . More recently, reported extrusion

rates range from 0.4 to 4.8% for TVT (Gynecare,

Johnson & Johnson, NJ, USA), 1–10.5% for

SPARC (American Medical Systems, Minnetonka,

MN, USA), and 0–6.7% for MONARC (American

Medical Systems, Minnetonka, MN, USA) [75– 79] .

Several theories have been postulated as to etiol-

ogy, ranging from operative techniques to specific

properties of the sling material to patient charac-

teristics (see Table 23.3 ). Although type II and III

meshes are multifilamentous and may allow bac-

teria to pass through, the small pore size (<10 m m)

may not allow the passage of macrophages and

leukocytes, important for the remodeling process

(see above). Type IV mesh rarely is used in pelvic

reconstructive surgery secondary to the small pore

size as well. Operative techniques such as inad-

equate plane of dissection, poor tissue irrigation,

excessive tension, and bacterial infection second-

ary to draining hematoma or nonsterile mesh are

other factors. Finally, patient comorbidities such as

diabetes or menopausal status and early resumption

of sexual activity may play a role [73, 80] .

Patient presentation ranges from asymptomatic

to a variety of symptoms such as vaginal discharge,

vaginal or groin pain, dyspareunia, de novo urgency,

stress incontinence, hematuria, recurrent urinary

tract infection, obstruction, or partner discomfort

during intercourse. Careful pelvic examination

Table 23.3. Possible etiologies for erosion/extrusion .

• Implant characteristics

– Small pore size, poor elasticity, basic tissue compat-

ibility

• Operative technique

– Plane too close to urethra, inadequate vaginal tissue

coverage, excessive tension, rolled edges of mesh

• Unrecognized complications

– Urethral/ bladder injury, poor vaginal tissue vascularity,

bacterial infection, hematoma formation and drainage,

placement of nonsterile mesh

• Patient factors

– Uncontrolled diabetes mellitus, tobacco use, prior his-

tory of pelvic irradiation, vaginal estrogen status, repeat

procedures, early resumption of sexual intercourse

23. Biomaterials 325

may reveal granuloma formation, anterior vaginal

tenderness, eroded tape, or suture. An examina-

tion under anesthesia may be requisite to evaluate

the full extent of extrusion. Cystourethroscopy is

also of paramount importance to exclude bladder/

urtheral erosion, particularly if the patient presents

with irritative or obstructive symptoms, hematuria,

de novo urgency, recurrent urinary tract infections,

or bladder stones. Pelvic magnetic resonance imag-

ing (MRI) may be needed when clinical signs of

pelvic or perineal abscess are noted [80] .

Management depends on type of material, pres-

ence of infection, size, and location [73] . Vaginal

extrusion of type I polypropylene mesh can be

managed conservatively: if less than 1–2 cm in

size, use of local estrogen replacement therapy,

antibiotics if infection is present, and abstinence

from sexual intercourse is recommended. If the

vaginal mucosa fails to re-epithelialize after 6–8

weeks, transvaginal excision of exposed mesh with

debridement and reapproximation of surrounding

tissue is performed. Persistent infection or failure

to heal mandates complete mesh excision. Vaginal

extrusion of types II, III, and IV require complete

excision, since these are prone to higher infection

rates and poor healing [73] .

Erosion into the urethra or bladder mandates

complete mesh excision, regardless of mesh

type. Bladder erosion is rare and traditionally

has been excised using a transvesical approach

[73] . Cystoscopic removal has been described but

maximal removal of exposed mesh is required to

avoid further erosion and continual symptoms. For

urethral erosions, Clemens et al. [74] recommends

removal of all synthetic material (sutures and sling),

since a distinct plane of scar and old synthetic

material usually is present and can be removed

in a piecemeal fashion. The synthetic material in

that review was a bovine collagen-injected poly-

ester sling (Protogen, Boston Scientific, Natick,

Massachusetts, USA) which has been removed

from the market. If a defect in the urethra is iden-

tified, it should be closed; if not visualized, pro-

longed urethral catheterization (2 weeks) should

result in closure, followed by a pullout cystoure-

throgram at time of catheter removal. In a study of

57 patients who underwent urethrolysis for urtheral

obstruction after pubovaginal sling placement, nine

patients were identified with erosion [81] . Three

patients with synthetic mesh underwent removal of

whole sling, multilayer closure of urtheral defect,

and use of Martius flap, if necessary. The remain-

ing patients, with allografts or autologous graft,

underwent sling incision and multilayer closure of

the defect. At mean follow-up of 30 months, there

was no recurrence of urethral erosions or fistulas

in either group, while two patients had persistent

stress incontinence, two with urge incontinence,

and one with urinary retention [81] .

Conclusions

Because a high rate of recurrence of prolapse

exists, traditional methods of repair may need

augmentation with the use of biomaterials. Certain

patient populations may need biomaterials due a

variety of risk and host factors, such as abnormal

collagen metabolism. However, choice of biomate-

rial depends on several factors, ie, surgeon prefer-

ence, patient need, and inherent characteristics

of the graft. Several key points should be kept in

consideration [82] :

• Graft integration into host tissue is vital for suc-

cessful outcomes. Collagen ingrowth and neovas-

cularization should occur without the occurrence

of infection or significant inflammatory reac-

tion. Poorly integrated grafts include synthetic

micorporous grafts and xenografts treated with

chemical cross-linking. As such, these types of

grafts may become encapsulated, leading to hard-

ening or shrinkage. Clinical manifestations then

may include recurrence of prolapse, dyspareunia,

or alteration of normal anatomy. Examples of

well-integrated biomaterials are non-cross-linked

biological grafts, and in terms of synthetics,

low-weight, large-pore, monofilament mesh with

an elasticity between 20 and 35%. A possible

disadvantage of non-cross-linked grafts is rapid

host degradation before proper integration, lead-

ing to failure in a small percentage of patients.

Processing methods such as freeze-drying also

may compromise biological graft quality.

• More randomized trials are needed: abdominal

sacrocolpopexy and pubovaginal slings are the

only procedures where prospective randomized

trials and clinical outcomes have demonstrated

the need for graft material and the greater efficacy

of synthetics compared to biological material.

Currently, published data on graft material are lim-

326 K.V. Amrute and G.H. Badlani

ited and do not completely delineate indications

and contraindications for graft use. Long-term

efficacy data of synthetic mesh for pelvic prolapse

repair isarelacking. Future clinical research must

involve standardized outcomes, including pre-

and postoperative POP-Q evaluations and use of

validated questionnaires for quality-of-life issues,

sexual function, and incontinence.

• With lack of evidence-based medicine, use of bio-

materials needs to be judicious and individualized.

Complications of biomaterials such as erosion and

dyspareunia, especially with synthetic grafts, can

alter patient lifestyle and may present as clinical

challenges. Ultimately, the goals of surgical resto-

ration must include patient satisfaction.

References

1 . Weber AM , Walters MD , Piedmonte MR , et al.

Anterior colporrhaphy: A randomized trial of three

surgical techniques . Am J Obstet Gynecol 2001 ;

185 : 1299 – 1306 .

2 . Olsen AL , Smith VJ , Bergstrom JO , et al.

Epidemiology of surgically managed pelvic organ

prolapse and urinary incontinence . Obstet Gynecol

1997 ; 89 : 501 – 506 .

3 . Samuelsson EC , Arne Victor FT , Tibblin G , et al.

Signs of genital prolapse in a Swedish population

of women 20 to 59 years of age and possible related

factors . Am J Obstet Gynecol 1999 ; 180 : 299 – 305 .

5 . Davila GW , Drutz H , Deprest J . Clinical implica-

tions of the biology of grafts: Conclusions of the

2005 IUGA grafts roundtable . Int Urogynecol J

Pelvic Floor Dysfunct 2006 ; 17 (Suppl 7) : S51 – 55 .

6 . Weber AM , Richter HE . Pelvic organ prolapse .

Obstet Gynecol 2005 ; 106 : 615 – 634 .

7 . McIntosh LJ , Mallett VT , Frahm JD , et al.

Gynecologic disorders in women with Ehlers–Danlos

syndrome . J Soc Gynecol Investig 1995 ; 2 : 559 – 564 .

8 . Carley ME , Schaffer J . Urinary incontinence and

pelvic organ prolapse in women with Marfan or

Ehlers–Danlos syndrome . Am J Obstet Gynecol

2000 ; 182 : 1021 – 1023 .

9 . Deprest J , Zheng F , Konstantinovic M , et al. The biol-

ogy behind fascial defects and the use of implants in

pelvic organ prolapse repair . Int Urogynecol J Pelvic

Floor Dysfunct 2006 ; 17 (Suppl 7) : S16 – 25 .

10 . Karlovsky ME , Thakre AA , Rastinehad A , et al.

Biomaterials for pelvic floor reconstruction . Urology

2005 ; 66 : 469 – 475 .

11 . Wagh PV , Read RC . Collagen deficiency in rectus

sheath of patients with inguinal herniation . Proc Soc

Exp Biol Med 1971 ; 137 : 382 – 384 .

12 . Klinge U , Zheng H , Si ZY , et al. Expression of the

extracellular matrix proteins of collagen I, collagen

III, fibronectin, and matrix metalloproteinases 1 and

13 in the skin of patients with inguinal hernia . Eur

Surg Res 1999 ; 31 : 480 – 490 .

13 . Cannon DJ , Read RC . Metastatic emphysema: A

mechanism for acquiring inguinal herniation . Ann

Surg 1981 ; 194 : 270 – 278 .

14 . Bellón JM , Bajo A , Ga-Honduvilla N , et al.

Fibroblasts from the transversalis fascia of young

patients with direct inguinal hernias show constitu-

tive MMP-2 overexpression . Ann Surg 2001 ; 233 :

287 – 291 .

15 . Jackson SR , Avery NC , Tarlton JF . Changes in

metabolism of collagen in genitourinary prolapse .

Lancet 1996 ; 347 : 1658 – 1651 .

16 . Chen B , Wen Y , Li H , Polan ML . Collagen metabo-

lism and turnover in women with stress urinary

incontinence and pelvic prolapse . Int Urogynecol J

Pelvic Floor Dysfunct 2002 ; 13 : 80 – 87 .

17 . Moalli PA , Shand SH , Zyczynski HM , et al.

Remodeling of vaginal connective tissue in patients

with prolapse . Obstet Gynecol 2005 ; 106 : 953 – 963 .

18 . Gabriel B , Denschlag D , Gobel H , et al. Uterosacral

ligament in postmenopausal women with or without

pelvic organ prolapse . Int Urogynecol J Pelvic Floor

Dysfunct 2005 ; 16 : 475 – 479.

19 . Wong MY , Harmanli , OH , Agar M , et al. Collagen

content of nonsupport tissue in pelvic organ pro-

lapse and stress urinary incontinence . Am J Obstet

Gynecol . 2003 ; 189 : 1597 – 1599 .

20 . Ulmsten U , Ekman G , Giertz G , et al. Different

biochemical composition of connective tissue in

continent and stress incontinent women . Acta Obstet

Gynecol Scand 1987 ; 66 : 455 – 457 .

21 . Kushner L , Mathrubutham M , Burney T , et al.

Excretion of collagen derived peptides is increased in

women with stress urinary incontinence . Neurourol

Urodyn 2004 ; 23 : 198 – 203.

22 . Chen Y , DeSautel , M , Anderson , A , et al. Collagen

synthesis is not altered in women with stress uri-

nary incontinence . Neurourol Urodyn 2004 ; 23 :

367 – 373 .

23 . Chen B , Wen Y , Polan ML . Elastolytic activity in

women with stress urinary incontinence and pelvic

organ prolapse . Neurourol Urodyn 2004 ; 23 : 119 – 126 .

24 . Shah DK , Kushner , L , Rao , SK , et al. Elastase

activity in plasma: Screening tool for stress urinary

incontinence . Abstract presented at AUA Meeting ,

Orlando, FL , 2002 .

25 . Dietz HP , Hansell NK , Grace ME , et al. Bladder

neck mobility is a heritable trait . BJOG 2005 ; 112 :

334 – 339 .

26 . Buchsbaum GM Duecy EE , Kerr LA , et al. Pelvic

organ prolapse in nulliparous women and their

23. Biomaterials 327

parous sisters . Obstet Gynecol 2006 ; 108 (6) :

1388 – 1393

27 . Jack GS , Nikolova G , Vilain E , et al. Familial trans-

mission of genitovaginal prolapse . Int Urogynecol J

Pelvic Floor Dysfunct 2006 ; 17 (5) : 498 – 501 .

28 . Nikolova G , Lee H , Berkovitz S , et al. Sequence

variant in the laminin gamma 1 (LAMC1) gene

associated with familial pelvic organ prolapse . Hum

Genet 2007 ; 120 (6) : 847 – 856 .

29 . Karlovsky ME , Kushner L , Badlani GH . Synthetic

biomaterials for pelvic floor reconstruction . Curr

Urol Rep 2005 ; 6 : 376 – 384 .

30 . Birch C . The use of prosthetics in pelvic reconstruc-

tive surgery . Best Pract Res Clin Obstet Gynaecol

2005 ; 19 : 979 – 991 .

31 . Silva WA , Karram MM . Scientific basis of use of

grafts during vaginal reconstructive procedures .

Curr Opin Obstet Gynecol 2005 ; 17 : 519 – 529 .

32 . Alridge AH . Transplantation of fascia for relief of

urinary stress incontinence . Am J Obstet Gynecol

1942 ; 44 : 398 – 411 .

33 . Beck RP , Grove D , Arnusch , D , et al. Recurrent

urinary stress incontinence treated by the fascia

lata sling procedure . Am J Obstet Gynecol 1974 ;

120 : 613 – 621 .

34 . Morgan TO , Westney OL , McGuire EJ . Pubovaginal

sling: 4-Year outcome analysis and quality of life

assessment . J Urol 2000 ; 163 : 1845 – 1848 .

35 . Chaikin DC , Rosenthal J , Blaivas JG . Pubovaginal

fascial sling for all types of stress urinary incontinence:

Long-term analysis . J Urol 1998 ; 160 : 1312 – 1316 .

36 . Haab F , Zimmern , PE , Leach GE . Diagnosis and

treatment of intrisinic sphincter deficiency in

females. AUA Update Series. Lesoon 35, Vol. XV .

American Urological Association : Baltimore, MD ,

1996 : 282 – 287 .

37 . Beck RP , McCormick S , Nordstrom L . The fascia lata

sling procedure for treating genuine stress inconti-

nence of urine . Obstet Gynecol 1988 ; 72 : 699 – 703 .

38 . Latini JM , Luxx MM , Kreder KJ . Efficacy and

morbidity of autologous fascia lata sling cystoure-

thropexy . J Urol 2004 ; 171 : 1180 – 1184 .

39 . Latini JM , Brown JA , Kreder KJ . Abdominal sacral

colpopexy using autologous fascia lata . J Urol 2004 ;

171 : 1176 – 1179 .

40 . Moalli PA . Cadaveric fascia lata . Int Urogynecol J

2006 ; 17 : S48 – 50 .

41 . Lemer ML , Chaikin DC , Blaivas JG . Tissue strength

analysis of autologous and cadaveric allografts for

the pubovaginal sling . Neurourol Urodyn 1999;

18:497–5 03 .

42 . Kobashi KC , Hsaio KC , Grovier FE . Suitability of

different sling materials for the treatment of female

stress urinary incontinence . Nat Clin Pract Urol

2005 ; 2 : 84 – 91 .

43 . McBride AW , Ellerkmann RM , Bent AE , et al.

Comparsion of long-term outcomes of autologous

fascia lata slings with Suspend Tutoplast fascia lata

allograft slings for stress incontinence . Am J Obstet

Gynecol 2005 ; 192 : 1677 – 1681 .

44 . Howden NS , Zyczynski HM , Moalli PA , et al.

Comparison of autologous rectus fascia and cadav-

eric fascia in pubovaginal sling continence outcomes .

Am J Obstet Gynecol 2006 ; 194 : 1444 – 1449 .

45 . FitzGerald MP , Mollenhauer J , Bitterman P , et al.

Functional failure of fascia lata allografts . Am J

Obstet Gynecol 1999 ; 181 : 1339 – 1346 .

46 . Culligan , PJ , Blackwell L , Goldsmith LJ , et al. A

randomized controlled trial comparing fascia lata

and synthetic mesh for sacral colpopexy . Obstet

Gynecol 2005 ; 106 : 9 – 37 .

47 . Gandhi S , Goldberg RP , Kwon C , et al. A prospec-

tive randomized trial using solvent dehydrated fascia

lata for the prevention of recurrent anterior vaginal

wall prolapse . Am J Obstet Gynecol 2005 ; 192 :

1649 – 1654 .

48 . Winter JC . InteXen tissue processing and laboratory

study . Int Urogynecol J 2006 ; 17 : S34 – 38 .

49 . Zheng F , Lin Y , Verbeken E , et al. Host response

after reconstruction of abdominal wall defects with

porcine dermal collagen in a rat model . J Obstet

Gynecol 2004 ; 191 (6) : 1961 – 1970 .

50 . Gandhi S , Kubba L , Abramov Y , et al. Histopathologic

changes of porcine dermis xenografts for transvagi-

nal suburethral slings . Am J Obstet Gynecol 2005 ;

192 : 1643 – 1648 .

51 . Wheeler TL 2nd , Richter HE , Duke AG , et al.

Outcomes with porcine graft placement in the

anterior vaginal compartment in patients who

undergo high vaginal uterosacral suspension and

cystocele repair . Am J Obstet Gynecol 2006 ; 194 (5) :

1486 – 1491 .

52 . Gomelsky A , Haverkorn RM , Simoneaux WJ ,

et al. Incidence and management of vaginal extru-

sion of acellular porcine dermis after incontinence

and prolapse surgery . Int Urogynecol J Pelvic Floor

Dysfunct 2007 ; 18 : 1337 – 1341 .

53 . Gomelsky A , Rudy DC , Dmochowski RR . Porcine

dermis interposition graft for repair of high-grade

anterior compartment defects with or without con-

comitant pelvic organ prolapse procedures . Urol

2004 ; 171 (4) : 1581 – 1584 .

54 . Hiles M , Hodde J . Tissue engineering a clini-

cally useful extracellular matrix biomaterial . Int

Urogynecol J 2006 ; 17 : S39 – 43 .

55 . Wiedemann A , Otto M . Small intestine sub-

mucosa for pubourethral sling suspension for

the treatment of stress incontinence: First his-

topathological results in humans . J Urol 2004 ;

172 (1) : 215 – 218 .

328 K.V. Amrute and G.H. Badlani

56 . Thiel M , Rodrigues PPC , Riccetto LZ , et al. A

stereological analysis of fibrosis and inflammatory

reaction induced by four different synthetic slings .

BJU Int 2005 ; 95 : 833 – 837 .

57 . Rutner AB , Levine SR , Schmaelzle JF . Processed

porcine small intestine submucosa as a graft mate-

rial for pubovaginal slings: Durability and results .

Urology 2003 ; 62 : 805 – 809 .

58 . Jones JS , Rackley RR , Berglund R , et al. Porcine small

intestinal submucosa as a percutaneous mid-urethral

sling: 2-Year results . BJU Int 2005 ; 96 : 103 – 106 .

59 . Ho KL , Witte MN , Bird ET . 8-Ply small intestinal

submucosa tension-free sling: Spectrum of postop-

erative inflammation . J Urol 2004 ; 171 : 268 – 271 .

60 . Chaliha C , Khalid U , Campagna L , et al. SIS graft

for anterior vaginal wall prolapse repair – a case-

controlled study . Int Urogynecol J Pelvic Floor

Dysfunct 2006 ; 17 (5) : 492 – 497 .

61 . Amid P . Classification of biomaterials and their

relative complications in an abdominal wall hernia

surgery . Hernia 1997 ; 1 : 15 – 21 .

62 . Dwyer PL . Evolution of biological and synthetic grafts

in reconstructive pelvic surgery . Int Urogynecol J

Pelvic Floor Dysfunct 2006 ; 17 (Supple 7) : S10 – 15 .

63 . Klinge U , Losterhalfe B , Birkenhaure V , et al. Impact

of polymer pore size on the interface scar formation in

a rat model . J Surg Res 2002 ; 103 : 208 – 214 .

64 . Bobyn JD , Wilson GJ , Macgregor DC , et al. Effect

of pore size on the peel strength of attachment of

fibrous tissue to porous-surfaced implants . Biomed

Mater Res 1982 ; 16 : 517 – 584 .

65 . Barbolt TA . Biology of polypropylene/polyglactin

910 grafts . Int Urogynecol J Pelvic Floor Dysfunct

2006 ; 17 (Supple 7) : S26 – 30 .

66 . Julian TM . The efficacy of Marlex mesh in the repair

of severe recurrent vaginal prolapse of the anterior

mid vaginal wall . Am J Obstet Gynecol 1996 ; 175 :

1472 – 1475 .

67 . Flood CG , Drutz HP , Waja L . Anterior colporrhaphy

reinforced with Marlex mesh for the treatment of

cystoceles . Int J Urogynecol 1998 ; 9 : 200 – 204 .

68 . Weber AM , Walters MD , Piedmonte MR , et al.

Anterior colporrhaphy: A randomized trial of three

surgical techniques . Am J Obstet Gynecol 2001 ;

185 : 1299 – 1304 .

69 . Sand PK , Koduri S , Lobel RW , et al. Prospective

randomized trial of polyglactin 910 mesh to prevent

recurrence of cystoceles and rectoceles . Am J Obstet

Gynecol 2001 ; 184 : 1357 – 1362 .

70 . de Tayrac R , Gervaise A , Chauveaud A , et al.

Tension-free polypropylene mesh for vaginal repair

of anterior vaginal wall prolapse . J Reprod Med

2005 ; 50 (2) : 75 – 80 .

71 . Rodriguez LV , Bukkapatnam R , Shah SM , et al.

Transvaginal paravaginal repair of high-grade

cystocele central and lateral defects with con-

cominant suburethral sling: Report of early results,

outcomes, and patient satisfaction with a new tech-

nique . Urology 2005 ; 66 (Suppl 5A) : 57 – 65 .

72 . Amrute KV , Eisenberg ER , Rastinehad AR , et al.

Analysis of outcomes of single polypropylene mesh

in total pelvic floor reconstruction . Neurourol Urodyn

2007 ; 26 (1) : 53 – 58 .

73 . Nazemi TM , Kobashi KC . Complications of

grafts used in female pelvic floor reconstruction:

Mesh erosion and extrusion . Ind J Urol 2007 ;

23 (2) : 153 – 160 .

74 . Clemens JQ , DeLancey JO , Faerber GJ , et al.

Urinary tract erosions after synthetic pubovaginal

slings: Diagnosis and management strategy . Urol

2000 ; 56 : 589 – 595 .

75 . Abouassaly R , Steinberg JR , Lemieux M , et al.

Complications of tension-free vaginal tape: A multi-

institutional review . BJU Int 2004 ; 94 : 110 – 113 .

76 . Huang KH , Kung FT , Liang HM , et al. Management

of polypropylene mesh erosion after intravaginal

midurethral sling operation for female stress uri-

nary incontinence . Int Urogynecol J Pelvic Floor

Dysfunct 2005 ; 16 : 437 – 440 .

77 . Lord HE , Finn JC , Tsokos N , et al. A randomized

controlled equivalence trial of short-term complica-

tions and efficacy of tension-free vaginal tape and

suprapubic urethral support sling for treating stress

incontinence . BJU Int 2006 ; 98 : 367 – 376 .

78 . Yamada BS , Govier FE , Stefanovic KB , et al. High

rate of vaginal erosions associated with mentor

ObTape . J Urol 2006 ; 176 : 651 – 654 .

79 . But I . Vaginal wall erosion after transobturator tape

procedure . Int Urogynecol J Pelvic Floor Dysfunct

2005 ; 16 : 506 – 508 .

81 . Amundsen CL , Flynn BJ , Webster GD . Urethral ero-

sion after synthetic and nonsynthetic pubovaginal

slings: Differences in management and continence

outcome . J Urol 2003 ; 170 : 134 – 137 .

82 . Davila GW , Drutz H , Deprest J . Clinical implica-

tions of the biology of grafts: Conclusions of the

2005 IUGA Grafts Roundtable . Int Urogynecol J

2006 ; 17 (Suppl 7) : 51 – 53 .

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329

Introduction

The goals for surgical correction of pelvic support

defects include normalizing support of all anatomic

compartments, alleviating clinical symptoms, and

optimizing sexual, bowel, and bladder function.

Care must be taken to restore normal anatomy and

function to all compartments, without precipitating

new support or functional problems. A thorough

evaluation of the apical, anterior, and posterior

compartments as described in previous chapters is

necessary prior to surgical correction.

The importance of an accurate pelvic exam

cannot be overemphasized. In addition to assess-

ing the degree and type of prolapse present, it is

important to perform the vaginal examination with

a surgical planning point of view, especially if the

patient is considering surgical therapy. The pres-

ence of any fascial tears or defects usually can be

predicted during careful vaginal examination, since

they are visualized as areas of sudden change in

vaginal wall thickness or rugations. By the end of

the pelvic examination, the surgeon should have

developed a surgical plan for repair of the prolapse.

Urodynamic assessment will help determine the

type of a concomitant anti-incontinence procedure

to be performed, if necessary.

The choice of surgical approach should be based

on what is best for the patient’s individual variables

[1] . The greatest advantage of the vaginal approach

is that all compartment defects (resulting in apical

prolapse, cystocele, rectocele, enterocele, and

perineal body defects) may be repaired concomi-

tantly, frequently through the same incision. The

following factors are particularly important when

planning a surgical approach for vaginal prolapse:

1. Importance of sexual function. If the patient

reports that vaginal sexual function is of great

importance to her (age may be an unrelated issue

here), a sacrocolpopexy may be considered pri-

marily.

2. Vaginal length. If the vaginal apex (dimples)

reaches the ischial spines with ease, the patient

will do well with a vaginal procedure, while those

whose apex does not reach the ischial spines may

be better served by an abdominal procedure or an

obliterative procedure, if appropriate.

3. Previous reconstructive procedures. The degree

of existent scarring and fibrosis must be kept in

mind, as the area around the sacral promontory

or sacrospinous ligaments may be difficult or

risky to reach. This is especially important in

this age of commonplace graft use.

4. Presence of large paravaginal defects. Although

paravaginal defect repairs can be performed vag-

inally, they can be technically difficult and their

long-term outcomes have not been reported.

Thus, an abdominal paravaginal approach or a

grafted repair may be preferable if significant

paravaginal defects are present.

5. Medical comorbidities. In the face of a medically

delicate or advanced-age patient, a vaginal, often

obliterative, procedure under regional anesthesia

is preferable.

Chapter 24

Pelvic Reconstructive Surgery:

Vaginal Approach

Daniel Biller and G. Willy Davila

330 D. Biller and G.W. Davila

BookID 124810_ChapID 24_Proof# 1 - <Date>

6. Tissue quality and presence of large fascial

defects. Tissue quality usually will improve with

preoperative local estrogen therapy, but large

fascial defects adjacent to the cuff may require

graft reinforcement, which can be accomplished

during surgical repair.

7. Associated colorectal problems. The fre-

quent coexistence of colorectal dysfunction

in women with vaginal prolapse requires that

these problems be kept in mind during surgi-

cal planning. As such, a woman with extensive

rectal prolapse may best undergo a concomitant

rectopexy and sacrocolpopexy or a perineal

proctosigmoidectomy and vaginal-approach

vaginal repair.

Optimizing Surgical Outcomes

The success rate of any surgical procedure is in

great part based on appropriate patient prepa-

ration. A clear understanding of the present

anatomic defects and voiding dysfunction as

diagnosed by urodynamics will help identify the

most appropriate procedures to be performed.

Tissue preparation with low-dose estrogen cream

(ie, 1 gm two nights per week) is crucial for

most postmenopausal women. Medical clearance

should be obtained and perioperative safety is

optimized by appropriate DVT prophylaxis (SC

Heparin or pneumatic compression device per

surgeon's preference), and prophylactic antibiot-

ics. Postoperatively, vaginal packing is placed for

24 h to prevent stress on suture lines secondary

to coughing or vomiting. For 6 weeks postopera-

tively, patients are instructed to lift no more than

5 pounds or exert themselves to any significant

degree. Estrogen cream is restarted and the patient

is instructed to perform Kegel exercises as a part

of her daily routine after the 6-week postopera-

tive visit.

Vaginal Apical Suspension

The vaginal approaches to surgical repair of api-

cal prolapse include McCall–Mayo culdoplasty,

uterosacral ligament suspension, iliococcygeal

suspension, sacrospinous ligament fixation, and

the new grafted “minimally invasive” vault pro-

cedures.

McCall–Mayo Suldoplasty

The technique of plicating the uterosacral liga-

ments in the midline while reefing the peritoneum

in the cul-de-sac combined with a posterior cul-

doplasty was introduced by McCall in 1957 [2] .

The importance of this technique for prevention of

posthysterectomy vaginal vault prolapse cannot be

overemphasized, especially in cases where vaginal

hysterectomy is performed for pre-existing vaginal

vault prolapse. The goal is the restoration of the

integrity and attachment of the apical endopelvic

fascia to the cardinal–uterosacral ligament com-

plex at the apex.

Nonabsorbable sutures incorporate both ute-

rosacral ligaments, intervening cul-de-sac peri-

toneum, and full thickness apical vaginal wall

(Fig. 24.1 ). Multiple sutures may be required if

extensive prolapse is present. As a general rule, the

uppermost suture is placed on the uterosacral liga-

ments a distance from the cuff equal to the amount

of vault prolapse that is present (ie, POP-Q: TVL

minus point D, or C if uterus is absent).

Care must be taken not to injure or kink the

ureters when placing the suture through the ute-

rosacral ligaments, since the ureters lay 1–2 cm

lateral at the level of the cervix. We recommend

cytoscopy with visualization of ureteral patency

following the procedure. Reported success rates

are high, but objective long-term data are limited.

Most pelvic surgeons would recommend that a

Fig. 24.1. McCall culdoplasty with placement of perma-

nent sutures through the uterosacral ligaments, cul-de-

sac peritoneum and full thickness vaginal wall

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24. Pelvic Reconstructive Surgery 331

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McCall culdoplasty be performed whenever a

vaginal hysterectomy is performed, especially for

uterine prolapse.

Uterosacral Ligament Suspension

Excellent anatomic outcomes have been described

with reattachment of the uterosacral ligaments to

the vaginal apex, similar to the McCall technique

(Table 24.1 ). The physiological nature of this

technique makes it very attractive. This technique

involves opening the vaginal wall from the ante-

rior to the posterior over the apical defect and

identifying the pubocervical fascia, rectovaginal

fascia, and uterosacral ligaments. One permanent

1–0 suture and one delayed absorbable 1–0 suture

are placed in the posterior-medial aspect of each

uterosacral ligament 1–2 cm proximal and medial

to each ischial spine. One arm of each permanent

suture then is placed through the pubocervical and

rectovaginal fascia, and one arm of each delayed

absorbable suture is placed in a similar fashion but

also incorporates the vaginal epithelium. After all

additional defects are repaired, the sutures are tied,

suspending the vault.

Potential pitfalls include ureteral injury and

difficulty identifying the uterosacral ligaments in

cases of extensive prolapse secondary to redundant

peritoneum and preexisting weak and attenuated

ligaments. Reported ureteral injury rates range

from 0 to 11% [3– 8] . Therefore, cystoscopy to

confirm ureteral patency is essential.

Success rates range from 82 to 96% over a fol-

low up of 6 months to 3 years. The largest study

was performed by Shull et al., who reported on 289

patients undergoing uterosacral ligament suspen-

sion [3] . Eighty-seven percent (251/289) had no

postoperative support defects at any site. Karram

et al. recently reported 5-year outcome data on

72 patients, who underwent high uterosacral vag-

inal vault suspension. Concomitant procedures

included vaginal hysterectomy (37.5%), poste-

rior colporrhaphy (87.5%), anterior colporrhaphy

(58.3%), and suburethral sling (31.9%). Failure

was defined as symptomatic recurrent prolapse of

stage 2 or greater in one or more segments, and was

reported in 11 of 72 patients (15.3%), specifically

apical recurrent prolapse of stage 2 or greater in 2

of 72 patients (2.8%). The authors concluded this

procedure seemed to be durable for repair of vagi-

nal enterocele and vault prolapse [4] .

It must be emphasized that uterosacral ligament

vault suspension at a time of vaginal hysterectomy

(when the ligaments are readily identifiable) is

vastly different from the procedure when performed

for posthysterectomy vault prolapse. Higher suc-

cess rates and decreased morbidity are likely

associated with the greater ease at identifying the

ligaments at their attachment site to the uterus.

Iliococcygeus Suspension

Originally described by Inmon in 1963, elevation

of the vaginal apex to the iliococcygeus muscles

along the lateral pelvic sidewall is a safe and

simple procedure [9] . It can be performed without

a vaginal incision by placing a monofilament per-

manent suture (ie, polypropylene) full thickness

through the apical vaginal wall into the muscle

and fascia unilaterally or bilaterally in nonsexually

active women where a suture knot in the vagina

will not be problematic. It thus is useful in elderly

patients where complete restoration of vaginal

anatomy is not necessary or as a salvage operation

Table 24.1. Uterosacral ligament suspension results .

Patients Follow-up mean

months (range) Number cured (rate) Ureteral injury

number (%)

Silva et al. [4] 72 5.1 (3.5–7.1) a 61/72 (84%) 5 (2.4)

Amundsen et al. [5] 33 28 (6–43) 27/33 (82%) NR b

Shull et al. [3] 289 48 251/289 (87%) 1 (1)

Barber et al. [6] 46 15.5 median (3.5–40.8) 90% (symptoms) 5 (11)

Jenkins [7] 50 33 (6–48) 48/50 (96%) 0 (0%)

a Years

b Not reported

332 D. Biller and G.W. Davila

BookID 124810_ChapID 24_Proof# 1 - <Date>

for someone with suboptimal vault support and

good distal vaginal anatomy, such as after a unilat-

eral sacrospinous fixation.

It also can be performed in an open fashion

following a posterior vaginal wall dissection and

entering the pararectal space. The sutures are

placed into the fascia overlying the iliococcygeus

muscle, anterior to the ischial spine inferior to the

arcus tendineus fascia pelvis, and incorporated

into the pubocervical fascia anteriorly and the rec-

tovaginal fascia posteriorly.

Shull reported a 95% cure rate of the apical com-

partment with a follow-up of 6 weeks to 5 years of

42 women. He did, however, note a 14% occur-

rence rate of prolapse at other sites [10] . Other

long-term data for this procedure are scant.

Sacrospinous Ligament Fixation

Fixation of the apex to the sacrospinous ligaments

is likely the most common currently performed

apical suspension procedure from the vaginal

approach. It was first described by Sederl in 1958

and has undergone multiple modifications [11] .

Indications for this procedure are correction of

complete procidentia, posthysterectomy vault pro-

lapse, and vaginal enterocele [12– 17] .

The sacrospinous ligaments are identified after

entering the pararectal space through a posterior

vaginal wall dissection, and two nonabsorbable

sutures are placed through the ligament, rather

than around it, as the pudendal neurovascular

bundle passes behind the ligament. The first suture

is placed 2 cm medial to the ischial spine and the

second 1 cm medial to the first. Each suture is then

secured to the underside of the vaginal apex, short

and long term results are overall acceptable (Table

24.2). Surgical approach will be based on the

proper identification of these support defects.

Although most surgeons perform the procedure

unilaterally, on the right side, as originally described

by right-handed surgeons, a bilateral procedure

results in more physiological suspension of the apex

(Fig. 24.2 ). It does not appear that reinforcement of

the apex with a graft improves surgical outcome, as

we noted in a retrospective review.

Overall, transvaginal vault suspension is asso-

ciated with excellent results. Improvements still

can be made in long-term cure of subsequent

anterior compartment prolapse and associated

morbidity [18] .

Anterior Wall Repairs

Anterior wall prolapse remains the most chal-

lenging aspect of vaginal prolapse repair. Despite

advancements in surgical technique, recurrence

rates after a traditional repair remain quite high

(40–60%). Anatomic concepts have guided sur-

geons through a progression from central fascial

plication (for a midline fascial stretching defect),

to paravaginal detachment correction (for separa-

tion of the vaginal sidewall sulcus from the arcus

tendineus fascia pelvis along the lateral pelvic side-

wall), to identification and correction of specific

fascial tears (for site-specific hernia-type tears)

without a significant reduction in recurrence rates

when analyzed on a long-term basis. It is likely

that most patients have a combination of fascial

stretch defects, apical paravaginal separation, and

site-specific fascial tears. Thus, one technique may

not be sufficient for a satisfactory repair in a given

patient.

Table 24.2. Sacrospinous ligament fixation .

Investigator Duration of

follow-up No. available

for follow-up No. cured (rate)

Richter/Albright, 1981 1–10 years 81 37 (70%)

Nichols, 1982 ≥ 2 years 163 158 (97%)

Morley and DeLancey, 1988 1 year 11 months 92 75 (82%)

Kettel and Herbertson, 1989 31 25 (81%)

Shull, 1992 2–3 years 81 53 (65%)

Adapted from [18]

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24. Pelvic Reconstructive Surgery 333

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Anterior Colporrhaphy

The anterior colporrhaphy was popularized by

Howard Kelly in 1912, and is a commonly used

technique for transvaginal correction of anterior

vaginal prolapse secondary to midline support

defects. A midline incision is made in the vaginal

epithelium from the bladder neck to approximately

2 cm from the uterine cervix or vaginal cuff. Sharp

and blunt dissection then is performed bilaterally

to separate the vaginal epithelium from the vagi-

nal muscularis (fascia) to the lateral sulcus. After

completing the dissection, the pubocervical fascia

is plicated in the midline in one or more layers with

interrupted stitches of delayed absorbable or per-

manent suture, thereby repairing the central defect

and elevating the bladder base and anterior vagina

toward the apex. The fascia then must be incorpo-

rated into the cervix (nonhysterectomized patient)

or the cardinal–uterosacral ligament complex (hys-

terectomized patient) at the apex (Fig. 24.3 ). Apical

support must be addressed to ensure durability of

the repair, especially when anterior enterocele is

present. Concomitant anti-incontinence procedures

may be done through the same incision or a dif-

ferent incision depending on surgeon preference.

Excess vaginal epithelium trimmed with care taken

not to excise too much vaginal wall to avoid stric-

ture formation. The incision is then closed with a

2–0 absorbable suture. Cystoscopy is then should

be performed to ensure bladder and ureteral integ-

rity. A vaginal pack is placed for postoperative

hemostasis.

Reported failure rates range from 0 to 60% for

traditional anterior colporrhaphy for the treatment

of anterior compartment prolapse [19– 22] . Degree

of lateral dissection may be important in achieving

Fig. 24.2. Bilateral sacrospinous fixation is a

more physiologic approach than the unilateral

approach, a graft does not appear to improve

outcomes

Fig. 24.3. An anterior colporrhaphy must include placa-

tion of healthy fascia in the midline and reattachment to

the vaginal cuff/cervix to achieve a satisfactory result

334 D. Biller and G.W. Davila

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an improved result, since a wide dissection to the

lateral vaginal sulcus was reported to be superior to

a limited anterior wall dissection [23] . Many stud-

ies focus on prolapse of the anterior compartment

after sacrospinous fixation and/or in conjunction

with Kelly plication for stress urinary incontinence,

which may not fully evaluate the effectiveness of a

midline plication procedure. Graft usage as rein-

forcement or as primary repair has been studied

and success rates range from 75 to 100%.

Paravaginal Defect Repair

In 1909, White described the paravaginal repair

as an anatomic correction of cystoceles [24] .

Richardson, in 1976, reintroduced the concept of

repairing anterior compartment prolapse with the

site-specific repair by way of paravaginal repair

[25] . The goal of the paravaginal defect repair is to

correct anterior vaginal wall prolapse that results

from loss of lateral support by reattaching the lat-

eral vaginal sulcus and the associated pubocervical

fascia to its normal lateral attachment site. The lat-

eral vagina attaches to the levator ani muscle bilat-

erally along a line from the anterior pubic ramus

to the ischial spine known as the “white line” or

arcus tendineus fasciae pelvis (ATFP). The ATFP

is formed from a condensation of the obturator

internus and levator ani fascia and is composed of

organized fibrous collagen connective tissue. When

the pubocervical fascia separates laterally from the

ATFP, a paravaginal defect results. As mentioned

previously this defect is identified on careful vaginal

physical examination and most commonly presents

as a right-sided unilateral defect, although certainly

bilateral defects and left-sided defects occur.

Paravaginal defect repair using the transvaginal

approach can be challenging, but it enables the

surgeon to repair concurrent central defects for

those women with loss of midline as well as lateral

anterior vaginal support. Initial dissection of the

pubocervical fascia from the vaginal epithelium is

identical to colporrhaphy. Entrance is gained into

the paravaginal space as the fascia is separated

to the lateral vaginal sulcus and urogenital dia-

phragm. Once a paravaginal defect is identified,

the normal site of lateral attachment of the vagina

should be clearly visualized. A Briesky-Navratil

retractor then can be used to retract the bladder

medially, exposing the levator ani muscle and

the course of the ATFP from the ischial spine to

the inferior aspect of the pubic ramus. Four to

six interrupted nonabsorbable sutures are placed

through the ATFP and the aponeurosis of the leva-

tor ani muscle from the level of the ischial spine

to the pubic symphysis at 1-cm intervals. Each

suture then is placed through the lateral edge of the

detached pubocervical fascia at its corresponding

level along the lateral vaginal wall sulcus and tied.

The vaginal epithelium then is trimmed and closed.

Cystoscopy is performed to confirm ureteral pat-

ency and absence of intravesical sutures.

Results of the vaginal paravaginal repair for

cystocele have ranged from 67 to 100% [26– 29] .

Shull reported a 93% success rate of less than grade

2 recurrent prolapse (to the hymen) with follow up

of 1.6 years in 56 patients who underwent vaginal

paravaginal repair [26] . Elkins reported a 92%

(23/25) cure rate [27] , and Young et al. reported a

98% objective cure rate in 55 patients followed for

1 year. However, 22 patients had recurrent midline

cystocele and 21 major complications occurred with

a 16% rate of transfusion [28] . Karram reported a

97% cure rate in 35 patients with mean follow-up

of 20.2 months. He did note, however, recurrent

enterocele in 20% (seven patients) and recurrent

rectocele in 14% (five patients). Serious complica-

tions did occur including retropubic hematoma,

abscess, and ureteral obstruction [29] . To date there

are no randomized controlled studies on vaginal

paravaginal repair.

Posterior Compartment

Reconstruction

Herniation of the rectum or posterior vaginal wall

into the vaginal canal resulting in a vaginal bulge

is commonly termed a “rectocele.” Symptoms

consist of perineal and vaginal pressure, obstruc-

tive defecation, constipation, and the need to splint

or digitally reduce the vagina in order to defecate.

Defects in the integrity and attachments of the pos-

terior vaginal wall and rectovaginal septum may

result in posterior wall defects.

The normal posterior vaginal wall is lined

by squamous epithelium overlying the lamina

propria, which is a layer of loose connective

tissue and a fibromuscular layer referred to as

the rectovaginal fascia. Defects in this support

structure result in posterior wall defects. When

the defect occurs superiorly as a tear off the apex

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24. Pelvic Reconstructive Surgery 335

BookID 124810_ChapID 24_Proof# 1 - <Date>

or cervix, traditional anatomic concepts term it

an “enterocele.” Tears from the perineal body are

thought to result in rectocele and perineocele.

Recent anatomic studies have shown that many

rectoceles actually are due to an apical fascial

separation which can readily be identified when

the dissection is carried up to the vaginal apex

(Fig. 24.4b ). A rectocele typically develops at or

below the levator plate along the vertical vagina

as an attenuation of the perineal body integrity

(Fig. 24.4a )

Transvaginal repair of posterior wall pro-

lapse allows for correction of vaginal as well

as rectal symptomatic dysfunction. Posterior

colporrhaphy in conjunction with perineoplasty

is commonly performed to address a rectocele

or relaxed perineum and widened genital hia-

tus. A midline incision then is made along the

length of the vagina to the superior edge of the

rectocele. Dissection then is carried laterally to

the lateral vaginal sulcus to separate the poste-

rior vaginal epithelium from the underlying rec-

tovaginal fascia. If an apical fascial separation

is noted, the fascial edges should be reattached

to the apex–cervix prior to repairing the lower

vagina. The rectovaginal fascia overlying the

levator ani muscles is plicated with interrupted

delayed absorbable sutures. In the presence of

a large rectocele, multiple suture layers may be

necessary. Concomitant perineoplasty is per-

formed by plicating the bulbocavernosus and

transverse perineii muscles. This reinforces the

perineal body and provides enhanced support to

the anterior rectal wall–corrected rectocele.

Discrete site-specific repair has been popular-

ized secondary to the high rate of dyspareunia after

posterior colporrhaphy likely secondary to plica-

tion of the levator ani muscles [30– 32] . The intent

of the site-specific repair of rectoceles is to identify

the fascial tears and reapproximate the edges with

interrupted absorbable sutures. Further discussion

of posterior compartment repair and results are

discussed in Chap. 27.

Mesh and Grafts in Vaginal Surgery

Adopting the principles of hernia repair by general

surgeons, reconstructive pelvic surgeons have begun

adopting reinforcement of transvaginal repairs with

synthetic and biological prostheses. Synthetic mesh

such as polypropylene (PP) has been demonstrated

to be useful for anti-incontinence surgery (slings)

and abdominal sacrocolpopexy (ASC) for repair

of vaginal vault prolapse. Although high success

rates have been reported for ASC, erosion of the

mesh and infection have been reported [33] . As

such, only monofilament, macroporous (PP type 1)

mesh should be used in order to minimize the risk

of erosion. Biological grafts used in reconstructive

surgery include autologous grafts (from another

body part, ie, fascia lata) and allografts including

cadaveric fascia lata, rectus sheath, and dermal

grafts. Xenograft materials used include porcine

dermis, bovine pericardium, and small intestinal

mucosa. There are scant long-term outcome data

on these materials in the literature. Although grafts

appear to improve short-term success rates, lack of

Fig. 24.4. ( a ) A rectocele develops as an anterior weak-

ness of the perineal body, and ( b ) is frequently associated

with a fascial separation from the vaginal apex or cervix

336 D. Biller and G.W. Davila

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long-term data leads to concerns of regarding graft

exposure/erosion, long-term integrity, and conse-

quences especially in sexually active women.

Grafted Apical Procedures

Minimally invasive techniques for apical suspension

have relied on placement of synthetic tapes from

the apex to strong pelvic structures. Introduced as

the infracoccygeal sacropexy, the posterior intrav-

aginal slingplasty (posterior IVS, Tyco/US Surgical,

Norwak, CT, USA) was the initial apical suspension

“kit” procedure [34] . Concerns regarding resultant

vaginal length and healing abnormalities due to the

multifilament nature of the tape used led to its poor

acceptance. However, the concept of placing a tape to

provide apical support was attractive to many, and the

approach was modified to allow placement of the tape

from ischial spine to ischial spine in an analogous

position to endogenous cardinal ligaments in order to

restore apical support. Entry into the pararectal space,

as for sacrospinous fixation, is needed, and the needle

tunneler device is used to appropriately place the tape.

Early results were quite promising with apical sup-

port restoration resulting in over 90% of patients and

vaginal lengths of approximately 8 cm [35, 36] .

Vaginal Wall Graft Use

Drutz reported on 142 women who underwent

anterior colporrhaphy reinforced with Marlex mesh

with mean follow-up of 3.2 years. Symptomatic

recurrence was reported at 5.7%, and objective

recurrence greater than stage II (descent less than

halfway to hymen) was not detected (0 of 142).

Mesh erosion was observed in 3 (2.1%) [37] .

Sand reported on 132 women undergoing either

standard rectocele repair or repair plus reinforce-

ment with polyglactin mesh (absorbable). He found

no difference in recurrence rates. However, placing

a piece of polyglactin 910 mesh within the suture

line of an anterior colporrhaphy was demonstrated

to reduce recurrence rates in a prospective, rand-

omized design [38] .

Even fewer studies demonstrate the use of a

biological graft to enhance longevity of a repair.

Porcine dermis implantation improved the outcome

of anterior colporrhaphy results in a 1-year follow-

up study [39] . Using bovine pericardium, we

demonstrated an improvement in outcomes over a

standard plication cystocele repair, which became

apparent after 6 months [40] . A summary of find-

ings is found in Table 24.3 .

No definitive study has yet been performed to

demonstrate the benefit of a graft for anterior or

posterior wall repairs. Until the literature provides

more conclusive evidence, surgeons must weigh

the potential benefit of reduced prolapse recurrence

rates versus the risk of vaginal wall erosion (syn-

thetic grafts), premature graft breakdown (non-cross-

linked biological grafts) and graft encapsulation and

distortion/hardening (cross-linked biological grafts)

when deciding whether to use an implanted graft.

Prolapse Repair Kits

The growing awareness of prolapse as a surgically

treatable condition has led to an increased volume

of reconstructive procedures. As a natural con-

sequence of increased surgical volume, surgeons

have teamed up with surgical device companies

to produce standardized, mesh-based surgical kits

to simplify the treatment of genital prolapse. This

process followed in the footsteps of midurethral

slings for stress incontinence, such as TVT, which

revolutionized urogynecologic surgery. However,

Table 24.3. Review of prosthetic surgical grafts in the management of cystoceles .

Author Type of mesh No. of patients Duration of follow-up Success rate

cystocele (%)

Julian Marlex, Control 12, 12 2 years, 2 years 100, 66

Flood Marlex 142 3.2 years 100

Sand Polyglactin, AC (no mesh) 73, 70 1 year, 1 year 75, 57

Weber Polyglactin, AC (no mesh) 26, 57 23 months, 23 months 42, 37

Gomelsky [39] Porcine dermis 70 2 years 91

Guerette [40] Bovine pericardium (no graft) 47, 47 1 year 83

Adapted from: Table 2 of [44]

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24. Pelvic Reconstructive Surgery 337

BookID 124810_ChapID 24_Proof# 1 - <Date>

Fig. 24.5. Kits currently available for comprehensive prolapse repair include: (a) Prolift, (b) Avaulta anterior, (c)

Avaulta posterior, (d) Apogee, and (e) Perigee

much controversy has resulted due to the lack of

sufficient long-term data prior to commercializa-

tion to satisfy more conservative surgeons.

Currently available commercial prolapse repair

kits include Prolift (Gynecare/Ethicon) for compre-

hensive repairs, Avaulta (Bard) in anterior and pos-

terior versions, and Apogee and Perigee (American

Medical Systems) for apical–posterior and anterior

wall repairs (Fig. 24.5 ). Apogee and Perigee are

available in PP synthetic and biological graft for-

mulations, while Prolift and Avaulta are available

only in synthetic PP versions.

338 D. Biller and G.W. Davila

BookID 124810_ChapID 24_Proof# 1 - <Date>

Available data to date on the use of the new kits

are limited to short- and medium-term single- or

multicenter case series. The largest use case series

has been collected by a group of seven French

surgeons reporting on a series of over 600 patients

undergoing Prolift procedures of a period of over

5 years. Their sequential reports of outcomes have

been invaluable in guiding pelvic surgeons in the

use of grafts in the pelvis. They have reported

a prolapse recurrence rate of 6.3% [41] . Most

importantly, they have shed light on means of

minimizing the risk of mesh erosions: appropriate

tissue preparation preoperatively, subfascial tissue

dissection, minimizing of mucosal trimming prior

to vaginal wall closure, and avoiding performance

of vaginal hysterectomy if not medically indicated.

They clearly demonstrated that avoidance of a “T”

incision along the anterior apical vagina reduced

the rate of erosion from 16 to 5%. Uterine pres-

ervation also greatly reduces operative time and

provides a strong structure (the cervix) to attach

the mesh to apically. American surgeons also have

demonstrated promising outcomes with the same

technique [42] .

Early outcomes demonstrated that apical support

requires a synthetic graft rather than a degradable

biological graft, as has been found with sacrocol-

popexy. Thus, current Apogee kits have a synthetic

apical tape to recreate cardinal ligaments. Repair of

the posterior and anterior vaginal walls with a syn-

thetic or biological graft demonstrated restoration

of normal anatomy with 1-year follow-up in 100%

of anterior wall repair kits, 91.2% of posterior–

apical repair kits, and 95.5% when a combination

of both is used [43] .

Summary

Advancements in the vaginal repair of genital pro-

lapse have been aimed at achieving similar results

to the abdominal approach, without the associated

higher morbidity and longer recovery. All com-

partments can be addressed simultaneously, and

selective use of grafts may enhance longevity and

optimize operation room time utilization.

References

1 . Biller DH , Davila GW . Vaginal vault prolapse:

Identification and surgical options . Clev Clin J Med

2005 ; 72 : S12 – S19 .

2 . McCall ML . Posterior culdoplasty: Surgical correc-

tion of enterocele during vaginal hysterectomy. A pre-

liminary report . Obstet Gynecol 1957 ; 10 : 595 – 602 .

Fig. 24.5. (continued)

e>

24. Pelvic Reconstructive Surgery 339

BookID 124810_ChapID 24_Proof# 1 - <Date>

3 . Shull BL , Bachofen C , et al. A transvaginal approach

to repair of apical and other associated sites of pel-

vic organ prolapse with uterosacral ligaments . Am J

Obstet Gynecol 2000 ; 183 : 1365 – 1373 .

4 . Silva WA , Pauls RN , Segal JL , et al. Uterosacral

ligament vault suspension: Five year outcomes .

Obstet Gynecol 2006 ; 108 (2) : 255 – 263 .

5 . Amundsen CL , Flynn BJ , Webster GD . Anatomical

correction of vaginal vault prolapse by uterosacral

ligament fixation in women who also require a pub-

ovaginal sling . J Urol 2003 ; 169 : 1770 – 1774 .

6 . Barber MD , Visco AG , et al. Bilateral uterosacral

ligament vaginal vault suspension with site spe-

cific endopelvic fascia defect repair for treatment

of pelvic organ prolapse . Am J Obstet Gynecol

2000 ; 183 : 1402 – 1411 .

7 . Jenkins VR II . Uterosacral ligament fixation for

vaginal vault suspension in uterine and vaginal

vault prolapse . Am J Obstet Gynecol 1997 ; 177 :

1337 – 1343 .

8 . Aronson MP , Aronson PK , Howard AE , et al. Low

risk of ureteral obstruction with “deep” (dorsal/

posterior) uterosacral ligament suture placement

for transvaginal apical suspension . Am J Obstet

Gynecol 2005 ; 192 : 1530 – 1536 .

9 . Inmon WB . Pelvic relaxation and repair including

prolapse of vagina following hysterectomy . South

Med J. 1963 ; 56 : 577 – 582 .

10 . Shull BL , Capen CV , Riggs MW , Kuehl TJ . Bilateral

attachment of the vaginal cuff to iliococcygeus fas-

cia: An effective method of cuff suspension . Am J

Obstet Gynecol 1993 ; 168 (6) : 1669 – 1677 .

11 . Sederl J . Zur operation des prolpases der blind

endigenden sheiden . Geburtshilfe Frauenheilkd

1958 ; 18 : 824 – 828 .

12 . Richter K , Albright W . Long term results follow-

ing fixation of the vagina on the sacrospinous

ligament by the vaginal route . Am J Obstet Gynecol

1981 ; 141 : 811 – 816 .

13. Kettel LM, Herbertson RM. An anatomic evalua-

tion of the sacrospinous ligament colpopexy. Surg

Gynecol Obstet 1989:1–45.

14 . Morley G , DeLancey JO . Sacrospinous ligament

fixation for eversion of the vagina . Am J Obstet

Gynecol 1988 ; 158 : 872 .

15 . Randall C , Nichols D . Surgical treatment of vaginal

inversion . Obstet Gynecol 1971 ; 38 : 327 – 332 .

16 . Nichols D . Sacrospinous fixation for massive

eversion of the vagina . Am J Obstet Gynecol

1982 ; 142 : 901 – 904 .

17 . Shull BL , Capen CV , et al. Preoperative and post-

operative analysis of site-specific pelvic support

defects in 81 women treated with sacrospinous liga-

ment suspension and pelvic reconstruction . Am J

Obstet Gynecol 1992 ; 166 : 1764 – 1771 .

18 . Sze EH , Karram MM . Transvaginal repair of vault

prolapse: A review . Obstet Gynecol 1997 ; 89 :

466 – 475 .

19 . Porges RF , Smilen SW . Long term analysis of the

surgical management of pelvic support defects . Am

J Obstet Gynecol 1994 ; 171 : 1518 – 1526 .

20 . Stanton SL , Hilton P , Norton C , Cardozo L . Clinical

and urodynamics effects of anterior colporrhaphy

and vaginal hysterectomy for prolapse with and

without incontinence . Br J Obstet Gynaecol

1982 ; 89 : 459 – 463 .

21 . Walter S , Olesen KP , Hald T , et al. Urodynamic

evaluation after vaginal repair and colposuspension .

Br J Urol 1982 ; 54 : 377 – 380 .

22 . Weber AM , Walters MD . Anterior vaginal prolapse:

Review of anatomy and techniques for surgical

repair . Obstet Gynecol 1997 ; 89 (2) : 311 – 318 .

23 . Weber AM , Walters MD , Piedmonte MR . Anterior

colporraphy: A randomized trial of three surgi-

cal techniques . Am J Obstet Gynecol 2001 ; 185 :

1299 – 1306 .

24 . White GR . Cystocele: A radical cure by suturing

lateral sulci of vagina to white line of pelvic fascia .

JAMA 1909 ; 853 : 1707 – 1710 .

25 . Richardson AC , Lyon JB , Williams NL . A new

look at pelvic relaxation . Am J Obstet Gynecol

1976 ; 126 : 568 – 573 .

26 . Shull BL , Benn SJ , Kuehl TJ . Surgical manage-

ment of prolpase of the anterior vaginal segment:

An analysis of support defects, operative morbid-

ity, and anatomic outcome . Am J Obstet Gynecol

1994 ; 171 (6) : 1429 – 1439 .

27 . Elkins TE , Chesson RR , Videla F . Transvaginal

paravaginal repair: A useful adjunctive procedure

in pelvic relaxation surgery . J Pelvic Surg 2000 ; 6 :

11 – 15 .

28 . Young SB , Daman JJ , Bony LG . Vaginal parav-

aginal repair: One-year outcomes . Am J Obstet

Gynecol 2001 ; 185 (6) : 1360 – 1366 .

29 . Mallipeddi PK , Steele AC , Kohli N , Karram MM .

Anatomic and functional outcome of vaginal parav-

aginal repair in correction of anterior vaginal wall

prolapse . Int Urogynecol J 2001 ; 12 : 83 – 88 .

30 . Mellgren A , Anzen B , Nilsson BY , et al. Results

of rectocele repair: A prospective study . Dis Colon

Rectum 1995 ; 38 : 7 – 13 .

31 . Francis W , Jeffcoate T . Dyspareunia following

vaginal operations . J Obstet Gynecol Br Comnwlth

1961 ; 68 : 1 – 10 .

32 . Kahn M , Stanton S . Posterior colporrhaphy: Its

effects on bowel and sexual function . Br J Gynecol

1997 ; 104 : 82 – 86 .

33 . Iglesia CB , Fenner DE , Brubaker L . The use of

mesh in gynecologic surgery . Int Urogynecol J

1997 ; 8 : 105 – 115 .

340 D. Biller and G.W. Davila

BookID 124810_ChapID 24_Proof# 1 - <Date>

34 . Vardy MD , Brodman M , et al. Anterior IVS tun-

neller device for stress incontinence and posterior

IVS tunneller for apical vault prolapse—A 2 year

prospective multicenter study . Int Urogynecol J

2006 ; 17 (S3) : S400 (abstract) .

35 . Davila G . Restoration of vaginal apical and poste-

rior wall support with the Apogee system . J Minim

Invasive Gynecol 2005 ; 12 (5) : S42 (abstract) .

36 . Biller DH , Jean-Michel M , Davila GW . Apical pro-

lapse repair using the Apogee system . Int Urogynecol

J 2007 ; 18 (Suppl) : S41 (abstract) .

37 . Flood CG , Drutz HP , Waja L . Anterior colporraphy

reinforced with Marlex mesh for the treatment of

cystocele . Int Urogynecol J 1998 ; 9 : 200 – 204 .

38 . Sand PK , Koduri S , Lobel RW . Prospective ran-

domized trial of polyglactin 910 mesh to prevent

recurrences of cystoceles and rectoceles . Am J

Obstet Gynecol 2001 ; 184 : 1357 – 1364 .

39 . Gomelsky A , Rudy DC , Dmochowski RR . Porcine

dermis interposition graft for repair of high ante-

rior compartment defects with or without con-

current pelvic organ prolapse procedures . J Urol

2004 ; 171 : 1581 .

40 . Guerette N , Aguirre O , VanDrie D , et al. Multi-center

randomized prospective trial comparing anterior

colporrhaphy alone to bovine pericardium colla-

gen matrix graft reinforced anterior colporrhaphy:

12-Month analysis . Int Urogynecol J 2006 ; 17 (Suppl

3) : S384 – S385 .

41 . Collinet P , Bilot F , Debodinance P , et al. Transvaginal

mesh technique for pelvic organ prolpase repair:

Mesh exposure management and risk factors . Int

Urogynecol J 2006 ; 17 (4) : 315 – 320 .

42 . Miller DP , Lucente V , Robinson D , Babin E .

Prospective clinical assessment of the total vaginal

mesh (TVM) technique for treatment of pelvic organ

prolapse: 6 and 12 month results . Int Urogynecol J

2006 ; 17 (S3) : S402 (abstract) .

43 . Davila GW , Flaherty JF , Lukban JC , et al.

Retrospective analysis of efficacy and safety of

Perigee ™ and Apogee ™ in patients undergoing

repair for pelvic organ prolapse . J Min Invast Surg

2006 ; 13 (5 Suppl) : S27 .

44 . Maher C , Baessler K . Surgical management of ante-

rior vaginal wall prolapse: an evidence based litera-

ture review . Int Urogynecol J 2006 ; 17 : 195 – 201 .

341

Surgical repair of pelvic organ prolapse can be

accomplished via a laparoscopic approach, abdom-

inal approach, vaginal approach, robotically, or a

combination of routes. In some instances, medical

necessity requires a patient to have a laparotomy

for nonreconstructive indications, and in such

instances it makes sense to take advantage of

the abdominal incision which provides generous

access to pelvic support structures and good avail-

ability of anchoring sites to accomplish the desired

reconstructive surgery. In other instances, surgeons

choose an abdominal approach because data have

shown excellent, long-lasting results through the

abdominal approach and because the surgeon

believes that the patient's severity of prolapse and/

or the life expectancy of the patient mandates the

more invasive abdominal approach in order to

obtain lasting results [1] .

The main objectives of pelvic reconstructive

surgery are the restoration of normal vaginal anat-

omy, relief of symptoms presumed to be caused

by abnormal pelvic floor anatomy, restoration or

maintenance of normal bladder and bowel func-

tion, and restoration and/or maintenance of normal

sexual function. Abdominal repairs for pelvic

reconstructive surgery include paravaginal repair

for cystocele, methods for vaginal apex suspen-

sion (ligament suspensions of the vaginal apex,

and abdominal sacral colpopexy (ASC). Pelvic

cul-de-sac closure techniques also are used for

prevention or treatment of enterocele. With some

modifications, the ASC also can be used to repair

a wide spectrum of defects including cystocele,

rectocele, as well as vaginal apex prolapse. Each

of the procedures performed through an abdominal

approach can be accomplished via a laparoscopic

approach; however, technical skills to accomplish

these procedures are advanced, and in general,

only surgeons with advanced laparoscopic skills

and previous experience with open reconstructive

surgeries can execute laparoscopic repairs with

safety and efficacy.

Abdominal Sacral Colpopexy

ASC is performed primarily for advanced pro-

lapse of the vaginal apex. With modifications,

it also can be very effective for anterior and

posterior vaginal wall relaxation. This procedure

is appealing to many surgeons because it repairs

defects in multiple compartments with a single

procedure; there is a large body of data support-

ing the long-term efficacy of the procedure [1– 4] .

In performing an ASC, graft material (either

synthetic or biological) is attached to the vaginal

apex. Depending on the individual anatomy, the

graft may be extended to varying lengths along

the anterior and posterior vaginal walls to correct

additional defects. The other end of the graft is

attached to the longitudinal ligament overlying

the sacrum just distal to the sacral promontory.

The anatomic goals of ASC include restoring

normal midline vaginal position, correction of

vaginal apex prolapse, and correction of high

cystocele and rectocele.

Chapter 25

Pelvic Reconstruction: Abdominal

Approach

Lawrence R. Lind and Harvey A. Winkler

342 L.R. Lind and H.A. Winkler

Pelvic Anatomy in Consideration of

Abdominal Sacral Suspension

Figure 25.1 demonstrates a lateral view of advanced

vaginal vault prolapse. The surgical principles of

ASC are based on repairing the deficient support

tissues that allow this level of herniation. The fas-

cial planes and support structures of the anterior

vaginal wall and vaginal apex are demonstrated in

Figs. 25.2 and 25.3 . Note the pubocervical fascia

between the bladder and the vagina and the rec-

tovaginal fascia between the vagina and the rectum

converge at the level of the cervix to form a pericer-

vical ring. The supporting fascia is then in continu-

ity with the uterosacral ligaments providing natural

attachment of the vaginal walls to the sacrum. In

an ASC, mesh is typically configured to run in the

same plane as the pubocervical fascia, rectovaginal

fascia, or both; to recreate a strong suspension for

the vaginal walls, bladder, and rectum, and uterus

(if retained).

The selection of materials (biological vs. syn-

thetic) is subject to much debate. There have been

studies documenting disappointing results with

donor fascia [5] . A few prospective studies compar-

ing the various graft materials currently available

reveal improved outcomes when using permanent

synthetic polypropylene graft materials.

Surgical Technique

ASC can be performed in a patient with a previ-

ous hysterectomy, at time of total abdominal hys-

terectomy, or in conjunction with a supracervical

hysterectomy. A few studies have demonstrated

that the risk of mesh erosion into the vagina is sig-

nificantly increased by the presence of the vaginal

cuff incision required to complete a total abdominal

hysterectomy [6] . In an attempt to reduce the risk of

erosions, therefore, increasing numbers of suprac-

ervical hysterectomies are performed at the time

of ASC. This trend mandates increased attention to

screening a patient's risk factors for subsequent cer-

vical malignancy and creates surgical challenges if a

trachelectomy is required subsequent to an ASC.

Fig. 25.1. A lateral view of the pelvis demonstrates

advanced pelvic organ prolapse

Fig. 25.2. A lateral view of the pelvis dem-

onstrates the support structures of the vaginal

vault and gynecologic organs. Note the pub-

ocervical and rectovaginal fascias fusing at

the level of the pericervical ring. These fibers

are then in continuity with the uterosacral

ligaments which provide proximal attachment

to the sacrum

25. Pelvic Reconstruction: Abdominal Approach 343

There are many variations in technique; how-

ever, a few general principles are followed by the

majority of experienced surgeons. A broad surface

area of attachment to the vagina allows enhanced

correction of anatomic defects. Volume of material

is concerning for erosion; however, a focal or “pin-

point” attachment site is felt to be more vulnerable

to failure and erosions. Attachment of graft to both

the anterior and posterior vaginal walls and respec-

tive fascias allows symmetric elevation of the apex

as well as allowing customized correction of the

anterior and posterior defects.

There is no comparative scientific evidence to

guide the choice of permanent versus absorbable

sutures to attach to the vaginal apex to the mesh.

We have observed that erosions (our own and those

referred to us) almost always have a permanent

surgical knot at the center focus of the erosion.

Mesh configurations have taken a trend toward

having wider pores; theoretically to allow for

rapid ingrowth, to permit macrophage entry, and to

decrease the total mass of foreign material. At any

point on the mesh where a permanent suture has

been attached, the mesh no longer retains the wide

pore configuration at that site. Instead, it represents

permanent synthetic mesh material gathered into a

central location at the base of three to five knots.

For these reasons, we use delayed absorbable

monofilament suture for attachment of the mesh to

the vagina.

Surgical Steps

After the abdomen is entered, nonreconstructive

surgery is performed first. The bladder is dis-

sected down off of the anterior vaginal wall and

the rectosigmoid reflection off of the posterior

vaginal wall. The patient typically is in low adjust-

able stirrups in the supine position, allowing both

abdominal and vaginal access to the vagina. An

EEA sizer is used to distend the vaginal apex and

assists in creating countertraction during dissection

(Fig. 25. 4 ). The end point for dissection is based

on preoperative examination, extent of prolapse,

and operative assessment. We typically end our

dissection when a clamp placed at the distal limit

of the dissection is able to pull the vaginal wall to

a horizontal plane (based on the sensations of a

vaginal examining hand).

Figure 25.5a–c demonstrate mesh configurations

customized for three different patients: the first with

somewhat pure, symmetric vaginal apex prolapse;

the second with a dominant cystocele; and the

third with dominant posterior vaginal relaxation.

Multiple delayed absorbable sutures are used to

attach the mesh to the vaginal walls and fascia.

Fig. 25.3. An oblique view of the pelvis

demonstrates the pubocervical fascia fibers

traversing laterally to their insertion point at

the arcus tendineus fascia pelvis or “white

line.” This view also demonstrates the concept

of the fusion of the fascias at the pericervical

ring and the continuity of those fibers with

the uterosacral ligaments

344 L.R. Lind and H.A. Winkler

Sacral Dissection

The peritoneum is entered overlying the sacrum

and the presacral fatty tissue is dissected until the

sacrum and fine vasculature overlying the sacrum

are clearly visualized. It is essential at this point

to note the bifurcation of the aorta, the middle

sacral vessels, the right ureter, and the sigmoid

colon. Failure to complete this dissection can

result in passing of sutures somewhat blindly and

may result in catastrophic sacral venous bleeding

[7] . The exact point of attachment distal to the

promontory is not critical. Surgeons typically

select an area in the midline that appears to be

the safest based on the location of small veins.

Three ascending sutures, typically permanent,

are placed in a horizontal fashion. Each suture

is tested with tension to confirm a good pass

through the supportive ligament (Fig. 25. 6 ). A

vaginal examining hand is used to judge the eleva-

tion of the anterior wall, posterior wall, and vaginal

apex. The goal is replacement to normal position

without additional tension. One must avoid the

temptation to pull the repair tight since experience

has demonstrated that pain, erosions, and possible

urinary incontinence are potential complications.

There are different configurations of the mesh

used for ASC including one piece of mesh, two

pieces of mesh, or one piece of mesh that is folded

over the anterior and the posterior vaginal walls.

It is our preference to use two separate pieces

of mesh. This allows the support of the anterior

vaginal wall and posterior vaginal wall to be

customized based on the patient's pre-operative

anatomy. After tension adjustment of each mesh,

the sacral promontory sutures are passed through

the mesh at the appropriate location and tied down.

A final result in a patient who retained the cervix

is demonstrated in Fig. 25. 7 . Peritoneum is used to

cover as much of the mesh as is possible. There is

no agreement as to whether or not the mesh should

be fully covered in a retroperitoneal position.

Advocates of covering the mesh completely sug-

gest that there is a decreased chance of adhesion

formation and bowel obstruction.

Fig. 25.4. Abdominal sacral colpopexy: An EEA sizer

is placed in the vagina to allow surgical countertraction

while dissecting the bladder reflection off the anterior

vaginal wall in preparation for graft placement

Fig. 25.5. Three variations of abdominal sacral colpopexy: ( a ) symmetric anterior and posterior defect support, ( b )

apical support and dominant anterior vaginal support with elongated anterior mesh segment, and ( c ) apical support

and dominant posterior vaginal support with elongated posterior mesh segment

25. Pelvic Reconstruction: Abdominal Approach 345

Closure of the Cul-de-Sac

Surgeon preference and operative findings guide

decisions regarding whether or not the cul-de-sac

should be closed posterior to the mesh. The goal

of this maneuver is to obliterate the anatomic deep

cul-de-sac, preventing enterocele and avoiding

bowel entrapment posterior to the mesh [3, 8] .

Figure 25.8 shows the hollow cul-de-sac and the

vulnerable entrapment space behind the mesh and

Fig. 25. 9 demonstrates bowel that has moved into

this space. There is no consensus regarding closure

of this space and there are a variety of methods

incorporated to obliterate the space.

A more radical modification of the ASC has

been described to treat patients with vaginal vault

prolapse combined with full-length posterior vagi-

nal wall relaxation including perineal mobility.

The “abdominal sacral colpoperineorrhaphy” incorpo-

rates a mesh that runs the full distance of the posterior

vaginal wall and retrieval of such mesh via a posterior

vaginal wall incision to enable suturing of the mesh at

the level of the perineum (Fig. 25. 5c ) [9] .

Concomitant Procedures

The goal of all pelvic reconstructive surgery is to

restore normal anatomy of all surgical compart-

ments, anterior, apical and posterior. Some surgeons

feel that the length of mesh applied to the anterior

and posterior vaginal walls can alleviate most

anterior and posterior defects, while others are of

the opinion that a dedicated paravaginal cystocele

repair is required for significant anterior vaginal

relaxation. Training and experience dictate which

methods are necessary for each individual patient.

If the posterior mesh is not extended enough to cor-

rect a sizeable rectocele, then a dedicated vaginal

rectocele repair is indicated.

There are data indicating that a reasonable

number of patients who were continent before an

ASC may become incontinent after the procedure

[10] . There also are randomized, prospective data

indicating that a Burch bladder suspension at the

time of ASC significantly reduces the chances

of urinary incontinence after the procedure [10] .

Based on this study, many (but not all) surgeons

feel that a Burch procedure should be performed

with all ASC regardless of preoperative inconti-

nence testing results.

Fig. 25.6. Abdominal sacral colpopexy. Placement of

sacral sutures into the longitudinal ligament distal to the

sacral promontory

Fig. 25.7. Abdominal sacral colpopexy. A completed

repair in a patient following supracervical hysterectomy

346 L.R. Lind and H.A. Winkler

Efficacy of Abdominal Sacral Colpopexy

Success rates as defined by absence of recur-

rent prolapse tend to be between 85 and 100%

for ASC, with most success rates 90% or higher

[1, 9, 11– 14] . The tools used to measure objec-

tive and subjective results vary between studies;

however, what is compelling is the consistent good

efficacy in most studies. There are only a few

randomized trials that compare ASC to vaginal

methods. Benson and Lucente found a higher suc-

cess rate for the abdominal group as compared to

the sacrospinous vaginal group to such an extent

that the study was terminated early [15] . Lowe and

Wang compared unilateral sacrospinous suspen-

sion to ASC and found optimal effectiveness in

80% of women in the vaginal group and in 94%

of the abdominal group [16] . Maher and others

did a similar comparison; however, they found no

statistical difference between the groups, but the

trend once again was favoring better results with

the abdominal approach [17] .

Complications

The most concerning complications of ASC include

bleeding, bowel injury, bowel obstruction, bladder

injury, dyspareunia, and infection or erosion of the

graft material. Fortunately, most of these complica-

tions occur in 5% or less of cases [1] . In general the

rate of mesh erosion varies between 0 and 5.5%,

with an average of 3.4% [1, 18– 26] . There are no

comparative data to definitively prove one mesh

material causes less erosion than another. The intui-

tive thought that a biological mesh might cause less

erosion than a synthetic mesh has not been proven

and some studies have created concern regarding the

long-term reliability of the biological materials.

ASC is an excellent option for advanced pelvic

prolapse, has stood the test of time, and is sup-

ported extensively in the literature. While this

abdominal procedure is the most invasive method

for repair of pelvic floor defects, long-lasting

results and the ability to correct multiple anatomic

defects with one procedure have made it one of the

more common and desirable procedures used to

treat advanced pelvic prolapse.

Ligament Suspensions

of the Vaginal Apex and Closure

of the Cul-de-Sac

There are several modifications of vaginal apex

suspensions performed through the abdomen that

use one or more existing pelvic ligaments to

suspend the vaginal apex. The advantages of

“autologous” procedures include elimination of a

Fig. 25.8. Abdominal sacral colpopexy. The posterior

cul-de-sac is a potential anatomic site for enterocele

formation or bowel entrapment

Fig. 25.9. Abdominal sacral colpopexy. Artistic rep-

resentation of small bowel which has moved poste-

rior to the graft representing the potential for bowel

obstruction

25. Pelvic Reconstruction: Abdominal Approach 347

foreign body (graft), elimination of the sacral dis-

section required for ASC, and time efficiency. The

uterosacral and cardinal ligaments are most com-

monly used for this purpose. Some surgeons use

only one pair of ligaments while others use both

pairs. In general, it is felt that ligament suspen-

sions may not have as reliable long-term success

compared to the ASC; however, randomized com-

parative objective data do not exist to definitively

quantify an advantage. Decisions for ligament

procedures versus ASC are based on surgeon

preference, severity of prolapse, life expectancy of

the patient, and anticipated patient activity level.

Some surgeons use these techniques for prevention

of prolapse at the conclusion of an abdominal hys-

terectomy to prevent prolapse at a later time, while

other surgeons use these techniques to directly treat

vaginal apex prolapse.

Uterosacral Ligament Vaginal Apex

Suspension

After removal of the uterus, the uterosacral liga-

ments are placed on traction to allow tracking of

the ligament several centimeters cephalad from

the distal attachment point to the uterus. As the

strength of the ligament is variable at its distal limit

it is essential to track it back to a point where good

strong support fibers can be palpated. As shown in

Fig. 25. 10 , the uterosacral ligament on each side

is encircled and pierced. The suture then passes

through the vaginal cuff on each side. The tied

sutures bring the vaginal apex to the supporting liga-

ments as shown in Fig. 25. 11 . In some variations of

technique, the pair of ligaments are pulled toward

the midline incorporating the anterior rectal serosa

and the posterior of the vaginal wall (Fig. 25. 12a,

b ). In all of these techniques, identification of the

ureters is essential to avoid inadvertent suturing or

kinking of the ureters, which are in close proximity

to the uterosacral ligaments.

Prevention of Enterocele Formation

In conjunction with vaginal apex suspensions and in

cases with isolated enteroceles, the deep cul-de-sac

can be obliterated to prevent abdominal contents

from herniating between the vagina and rectum.

While surgeons differ in their understanding of

enteroceles, there is agreement that bowel contents

herniating into the deep cul-de-sac can cause signifi-

cant clinical symptoms. Therefore, addressing this

potential hernia site is an important component of

comprehensive pelvic reconstructive surgery.

Fig. 25.10. Ipsilateral suspension of the vaginal apex to

the uterosacral ligments: Sutures are passed through the

uterosacral ligament on each side and then through the

vaginal apex

Fig. 25.11. Ipsilateral suspension of the vaginal apex to

the uterosacral ligments: The vaginal vault is pulled up

to the strong supporting uterosacral ligaments. Note that

the distal limits of the uterosacral ligaments which have

been tied after the hysterectomy are not the final attach-

ment points. A position proximal to the previous uterine

attachment point is selected to obtain a strong portion of

the ligament

348 L.R. Lind and H.A. Winkler

One technique for cul-de-sac closure incorpo-

rates sutures that run anterior to posterior along the

posterior vaginal wall, along the peritoneum of the

deep cul-de-sac, then along the anterior serosa of

the rectum (Fig. 25. 13a ). An alternative method runs

concentric circles of suture through the uterosacral

ligaments and (in a superficial plane) through the

vaginal and rectal walls (Fig. 25. 13b ).

Fig. 25.12. ( a, b ) An alternative method for uterosacral vaginal vault suspension brings the uterosacral ligaments

toward the midline and incorporates the anterior rectal serosa to close the cul-de-sac and support the vaginal apex in

one maneuver

Fig. 25.13. Two variations in technique for closure of the cul-de-sac. Both techniques incorporate the uterosacral liga-

ments, rectal serosa, posterior vaginal wall, and peritoneum of the deep cul-de-sac: ( a ) demonstrates sutures placed

in a vertical orientation and ( b ) demonstrates sutures placed in concentric circles

25. Pelvic Reconstruction: Abdominal Approach 349

Paravaginal Repair

The concept that cystoceles may result from the

separation of the pubocervical fascia from its lat-

eral attachment to the pelvic sidewall has been con-

sidered as early as 1909 [27] . In the 1960s, Burch

developed one of the most popular procedures for

urinary incontinence [28] . While searching for the

ideal anchoring point for his paraurethral sutures

(for what would become the ”Burch urethropexy”),

he originally chose the lateral pelvic sidewall

for his first few patients. He eventually favored

Cooper's ligament as an attachment point, but the

lateral pelvic sidewall was considered initially.

Most of the anatomic dissections for paravagi-

nal defects and the subsequent translation into an

established procedure for paravaginal repair of

cystocele are credited to Cullen Richardson. After

he observed the anterior–lateral vaginal sulcus

evert in a patient with a cystocele (with Valsalva),

he began several years of cadaver dissections

and formally brought paravaginal repair into the

reconstructive armamentarium of pelvic surgeons

[29, 30] . More recent clinical studies have sup-

ported the effectiveness of this procedure for

repair of cystocele [31] . While some have advo-

cated this repair for stress incontinence, the

preponderance of data relating to this procedure

support its use for cystocele repair and not for

urinary incontinence.

In order to select proper patients for paravaginal

cystocele repair, the distinction between “midline”

cystoceles and “lateral detachment” cystoceles must

be established preoperatively. A lateral detachment

cystocele is suggested by asymmetric eversion of

the anterior vaginal wall with straining and resolu-

tion of the cystocele with support of the anterior

lateral vaginal sulci. This can be accomplished

in an office assessment with ring forceps. Classic

teaching was that all cystoceles were the result of

midline weakening or stretching of support tis-

sues. Standard repair was an anterior repair that

brought lateral tissues across the midline to elevate

the bladder in the midline. Richardson's cadaver

dissections and clinical experience suggested that

the majority of cystoceles were the result of lateral

defects. Intact paravaginal fascia is demonstrated

in Fig. 25. 14a , a unilateral left paravaginal defect

in Fig. 25. 14b , and a bilateral defect in Fig. 25. 14c .

The fascia defect allows movement of the anterior

Fig. 25.14. Paravaginal fascia support and paravaginal

defects: ( a ) demonstrates intact pubocervical fascia,

( b ) depicts a left-sided paravaginal defect, and ( c )

depicts bilateral paravaginal defects (courtesy of Boston

Scientific Corp, Massachussetts)

350 L.R. Lind and H.A. Winkler

Fig. 25.15. Paravaginal repair: ( a ) The surgeon's nondominant hand is within the vagina guiding suture placement

into the anterior lateral vaginal wall incorporating the pubocervical fascia and the anterior lateral vaginal wall. ( b )

Placement of the suture through the arcus tendineus fascia pelvis ( white line ) (courtesy of Boston Scientific Corp.,

Massachusets)

vaginal wall and bladder toward the vaginal outlet,

resulting in a clinical cystocele.

Surgical Technique: Abdominal

Paravaginal Repair

A Pfannensteil incision is made and any neces-

sary intraperitoneal procedures are performed

first. If there is no requirement for surgery within

the peritoneum, then this procedure is performed

without entering the peritoneum. The retropubic

space is developed with blunt dissection between

the bladder and the superior pubic ramus. The

nondominant hand is placed in the vagina and one

or two fingers are used to explore the lateral vagi-

nal sulci. The goal is to attach the anterior lateral

vaginal wall to its original anatomic support site—

the arcus tendineus fascia pelvis—or “white line.”

The white line runs from the posterior–inferior

edge of the pubic symphysis to the ischial spine.

This linear density should be palpated and visual-

ized before placing sutures. If a Burch procedure

is necessary for stress incontinence, typically the

Burch sutures are placed first and paravaginal

sutures continue along the lateral vaginal wall

about a centimeter apart starting a centimeter or

two above the higher pair of Burch sutures. Figure

25.15a, b demonstrate the placement of the vagi-

nal (pubocervical) sutures and the lateral “white

line” sutures. A unilateral paravaginal repair is

demonstrated in Fig. 25. 16a and a bilateral repair

in Fig. 25. 16b . A Burch suspension and bilateral

paravaginal repair is demonstrated in Fig. 25. 16c .

If a Burch is not indicated, the paravaginal repair

25. Pelvic Reconstruction: Abdominal Approach 351

Fig. 25.16. Three variations of completed paravaginal repairs: ( a ) unilateral left paravaginal repair, ( b ) bilateral par-

avaginal repair, and ( c ) bilateral paravaginal repair with concomitant Burch procedure

typically starts lower with the first two vaginal

sutures very similar in location to those that

would have been used for a Burch procedure. The

only difference on the distal sutures is that they

are attached laterally to the white line rather than

to Cooper's ligament. The highest stitch is about

1 cm in front of the ischial spine. Each suture is

placed first through the anterior lateral vaginal

wall and overlying fascia, then through the corre-

sponding (slightly cephalad) location on the white

line. Cystoscopy is recommended. Most surgeons

prefer permanent suture. Some surgeons advo-

cate bilateral repairs on all patients regardless of

preoperative findings while others feel that if a

defect is purely unilateral that a unilateral repair

is indicated.

Conclusion

Abdominal repairs for female pelvic organ pro-

lapse have a variety of techniques. Selection of

techniques is guided by surgeon experience and

patient characteristics. The popularity of the ASC

352 L.R. Lind and H.A. Winkler

is due to excellent long-term results. Abdominal

repairs include suspension of the vaginal apex,

cystocele repair, high rectocele repair, and pre-

vention of enterocele.

References

1 . Nygaard IE , McCreery R , Brubaker L , et al.

Abdominal sacrocolpopexy: A comprehen-

sive review . Obstet Gynecol (United States)

2004 ; 104 (4) : 805 – 823 .

2 . Addison WA , Livengood CH III , Sutton GP , Parker

RT . Abdominal sacral colpopexy with Mersilene

mesh in the retroperitoneal position in the manage-

ment of posthysterectomy vaginal vault prolapse

and enterocele . Am J Obstet Gynecol 1985 ; 153 :

140 – 146 .

3 . Addison WA , Gundiff GW , Bump RC , Harris RI .

Sacral colpopexy is the preferred treatment for

vaginal vault prolapse . J Gynecol Technol 1996 ; 2 :

69 – 74 .

4 . Hendee AE , Berry CM . Abdominal sacropexy

for vaginal vault prolapse . Clin Obstet Gynecol

1981 ; 24 : 1217 – 1226 .

5. FitzGerald MP, Mollenhauer J, Bitterman P, Brubaker

L. Functional failure of fascia lata allografts. Am J

Obstet Gynecol 1999;1339–1346.

6 . Bensinger G , Lind L , Lesser M , et al. Abdominal

sacral suspensions: Analysis of complications

using permanent mesh . Am J Obstet Gynecol

2005 ; 193 : 2094 – 2098 .

7 . Sutton GP , Addison WA , Livengood CH III ,

Hammond CB . Life-threatening hemorrhage com-

plicating sacral colpopexy . Am J Obstet Gynecol

1981 ; 140 : 836 – 837 .

8 . Addison WA , Timmons MC , Wall LI , Livengood

CH III . Failed abdominal sacral colpopexy:

Observations and recommendations . Obstet Gynecol

1989 ; 74 : 480 – 483 .

9 . Cundiff GW , Harris RL , Coates K , et al. Abdominal

sacral colpoperineopexy: A new approach for cor-

rection of posterior compartment defects and peri-

neal descent associated with vaginal vault prolapse .

Am J Obstet Gynecol 1997 ; 177 : 1345 – 1355 .

10 . Brubacker L , Cundiff GW , Fine P , et-al. Abdominal

sacrocolpopexy with Burch colposuspension to

reduce urinary stress incontinence . N Engl J Med

2006 ; 354 (15) : 1557 – 1566 .

11 . Arthure HG , Savage D . Uterine prolapse and prolapse

of the vaginal vault treated by sacral hysteropexy . J.

Obstet Gynaecol Br Emp 1957 ; 64 : 355 – 360 .

12 . Lane FE . Repair of posthysterectomy vaginal vault

prolapse . Obstet Gynecol 1962 ; 20 : 72 – 77 .

13 . Birnbaum SJ . Rational therapy for the prolapsed

vagina . Am J Obstet Gynecol 1973 ; 115 : 411419 .

14 . Culligan PJ , Murphy M , Blackwell L , et al. Long-

term success of abdominal sacral colpopexy

using synthetic mesh . Am J Obstet Gynecol

2002 ; 187 : 1473 – 80 ; discussion 14811482 .

15 . Benson JT , Lucente V , McClellan E . Vaginal versus

abdominal reconstructive surgery for the treatment

of pelvic support defects: A prospective randomized

study with long-term outcome evaluation . Am J

Obstet Gynecol 1996 ; 175 : 14181422 .

16 . Lo T-S , Wang AC . Abdominal colposacropexy and

sacrospinous ligament suspension for severe uter-

ovaginal prolapse: A comparison . J Gynecol Surg

1998 ; 14 : 5964 .

17 . Maher CF , Qatawneh AM , Dwyer PL , et al.

Abdominal sacrocolpopexy or vaginal sacros-

pinous colpopexy for vaginal vault prolapse: A

prospective randomized study . Am J Obstet Gynecol

2004 ; 190 : 20 – 26 .

18 . Cundiff GW , Addison WA . Management of pelvic

organ prolapse . Obstet Gynecol Clin North Am

1998 ; 25 : 907921 .

19 . Visco AG , Weidner AC , Barber MD , et al. Vaginal

mesh erosion after abdominalsacral colpopexy . Am

J Obsete Gynecol, 2001 ; 184 : 297 – 302

20 . Pilsgaard K , Mouritsen L . Follow-up after repair

of vaginal vault prolaspse with abdominal col-

posacropexy . Acta Obstet Gynecol Scand 1999 ; 78 :

66 – 70 .

21 . Brizzolara S , Pillai-Allen A . Risk of mesh erosion

with sacral colpoexy and concurrent hysterectomy .

Obstet Gynecol 2003 ; 102 : 301 – 310 .

22 . Virtanen H , Hirvonen T , Makinen J , Kiihloma P .

Outcome of thirty patients who underwent repair

of posthysterectomy prolapse of the vaginal vault

with abdominal sacral colpopexy . J Am Coll Surg

1994 ; 178 : 283 – 287 .

23 . Baker KR , Beresford JM , Campbell C .

Colposacropexy with Prolene mesh . Surg Gynecol

Obstet 1990 ; 170 : 51 – 54 .

24 . Scettini M , Fortunato P , Gallucci M . Abdominal

sacral colpopexy with Prolene mesh . Int Urogynecol

J Pelvic Floor Dysfunct 1999 ; 10 : 295 – 299 .

25 . Diana M , Zoppe C , Mastrangeli B . Treatment of vag-

inal vault prolapse with abdominal sacral colpopexy

using Prolene mesh . Am J Surg 2000 ; 179 : 126 – 128 .

26 . Van Lindert AC , Groenendijk AG , Scholten PC ,

Heintz AP . Surgical support and the suspension of

genital prolapse, including preservation of the uterus,

using Gore-Tex soft patch (a preliminary report) . Eur

J Obstet Gynecol Reprod Biol 1993 ; 50 : 133 – 139 .

27 . White GR . Cystocele, a radical cure by suturing

lateral sulci of vagina to white line of pelvic fascia .

J Am Med Assoc 1909 ; 53 : 1707 – 1711 .

25. Pelvic Reconstruction: Abdominal Approach 353

28 . Burch JC . Urethrovaginal fixation to Cooper's liga-

ment for the correction of stress incontinence,

cystocele, recotcele, and prolapse . Am J Obstet

Gynecol 1961 ; 82 : 281 – 290 .

29. Richardon AC.Paravaginal repair. In: Glenn Hurt W,

ed. Urogynecologic surgery. Gaithersburg: Aspen

Publication, 1992:73–80.

30 . Richardson AC , Lyon JB , Williams NL . A new

look at pelvic relaxation . Am J Obstet Gynecol

1976 ; 65 : 586 .

31. Shull BL, Baden WF. A six year experience with

paravaginal defect repair for stress urinary incon-

tinence. Am J Obstet Gynecol. 198;160:1432–

1436.

355

Introduction

The introduction of the pelvic lymph node dis-

section by Schuessler in 1991 represented a mile-

stone for urological laparoscopy [1] . Within the

last 15 years, this minimally invasive technique

experienced an enormous technical development.

Initially, urological laparoscopy was limited by

technical problems such as subtle hemostasis or the

difficulties with endoscopic suturing [2] . However,

following the successful introduction of laparoscopic

radical prostatectomy by Gaston, Guillonneau,

and Vallancien in 1999, a significant increase of

interest was observed [3– 5] . In 2001, Binder and

Kramer performed the first robot-assisted laparo-

scopic radical prostatectomy using the da Vinci

device [6] . However, in 2003, Menon and Ahlering

showed the easy transfer of robotic-assisted from

open radical prostatectomy, which thereafter revo-

lutionized the management of localized prostate

cancer in the United States [7, 8] . In 2007, almost

60% of all radical prostatectomies are performed

with the da Vinci system. Interestingly, all these

developments based on extensive experience with

laparoscopic sacrocolpopexy by Gaston [5] .

The technique of sacral fixation of the vagina for

correction of genital prolapse (promontofixation)

was first described in the year 1889, respectively,

1892, by Freund and Zweifel using a transperito-

neal as well as a transvaginal approach [9] , but it

was Ameilen Hugier who in 1957 presented a more

detailed description of open sacral colpopexy [10] .

Miller described in 1927 a transvaginal colpopexy

to the sacrospinal ligaments [11] , which was fur-

ther modified by various authors including Richter

and Albrich [12] .

Scali in 1974 proposed the suspension by place-

ment of prosthetic slings between the vagina and

the bladder, which was anchored to the sacral

promontory [13] . In the early 1990s, the gynecolo-

gists Dorsey and Nezhat described a laparoscopic

sacropexy [14, 15] . In contrast to the technique

of laparoscopic bladder neck suspension or col-

posuspension, which has not been performed fre-

quently after its introduction due to worse results,

respectively, recent less invasive techniques such as

tension-free vaginal tape (TVT) or (TOT) [16, 17] ,

laparoscopic sacrocolpopexy is used increasingly

for pelvic floor repair [10, 18– 22] . In 2004, Di

Marco reported the successful use of the da Vinci

robot for a robotic-assisted laparoscopic sacrocol-

popexy for the treatment of vaginal vault prolapse

[23] followed by others [24].

In this chapter, we want to outline the indications

and technical approach of laparoscopic sacrocol-

popexy together with an analysis of results reported

by other authors, particularly in comparison to

new techniques, such as tension-free vaginal mesh

(TVM) for repair of pelvic organ prolapse (POP).

Indication

POP affects millions of women around the world.

American data suggest that 10% of all women need

surgery for prolapse or stress incontinence, with

Chapter 26

Laparoscopic Sacrocolpopexy:

Indications, Technique and Results

Jens J. Rassweiler , Ali S. Goezen , Walter Scheitlin , Christian Stock, and Dogu Teber

356 J.J. Rassweiler et al.

30% of those patients requiring repeated surgical

repair for recurrent prolapse [25] . These figures are

predicted to rise by 45% in the next 30 years due

to the increased life expectancy of women in the

Western world and increasing prevalence of pelvic

floor dysfunction with age [26] .

Genital prolapse can involve the anterior vaginal

wall, the apical vagina, the posterior vaginal wall,

or a combination of these sites [27] . It can be clas-

sified as anterior if it compromises cystocele with

or without urethral hypermobility; posterior, when

rectal herniation occurs; and apical if it involves

an enterocele, uterine, or vault prolapse [28] . This

is further defined by the degree of descent through

the introitus in the DeLancey classification utiliz-

ing four grades [29] .

There are a variety of symptoms, affecting the

pelvic floor, the lower urinary tract, as well as

producing bowel or sexual dysfunction. The opti-

mal treatment depends on several issues, such as

patient’s general health status, symptoms, quality of

life impairment, and prolapse type and grade. There

is a large number of open, vaginal, laparoscopic and

robot-assisted laparoscopic techniques described

Fig. 26.1. Cystogram before and after laparoscopic sacrocolpopexy: ( a ) massive vaginal vault prolapse and ( b ) com-

plete correction of POP after laparoscopic sacrocolpopexy with and without Valsalva (Ruhe and Press)

26. Laparoscopic Sacrocolpopexy 357

in the literature [27, 29– 32] . Their common goal is

to restore the vagina and descended pelvic organs

to their correct anatomical position in order to

improve or relieve symptoms and restore their nor-

mal physiological function [27, 30– 32] .

Diagnostic Work-Up

The preoperative workup involves a detailed uro-

gynecologic history and physical examination to

determine the type and degree of genital prolapse

as well as to determine the presence of any concur-

rent stress urinary incontinence. The latter must

be further assessed by performing the Bonney and

Ulmsten maneuver or even by a urodynamic study.

Urine analysis, Pap smear, and pelvic ultrasound

must be performed routinely in order to exclude

malignancy or large uterine volume (ie, indication

for a simultaneous hysterectomy). For a better

classification of the degree of the pelvic prolapse,

all patients should have a cystogram with and

without Valsalva maneuver (Fig. 26.1 ). In case of

a enterocele, real-time dynamic MRI studies might

be helpful (Fig. 26.2 ). All patients with a posterior

prolapse require a gastroenterological consultation.

All patients with concomitant anal incontinence are

presented to the surgical department of our certi-

fied continence center.

Technique

Trocar Placement

Based on adequate preoperative diagnosis, the pro-

cedure can be performed also with an intact uterus .

Prior to the operation, we place a Foley catheter

under sterile conditions.

In a 30° Trendelenburg and lithotomy position,

a transperitoneal access is performed (Verress-

needle, 15 mm Hg max. pressure of CO

2 ) using

five trocars:

• 3 × 10 mm (telescope, midright port for sutur-

ing (Fig. 26.3 ) and introduction of the meshes,

midleft port for dissecting tools and retracting

peanut holder)

• 2 × 5 mm (left and right lateral port)

Optionally, the camera can be moved by use of

the AESOP 3000 robot (Intuitive Surgical, Menlo

Park, USA). The procedure is performed by one

surgeon on the left side of the patient and two

assistants, one of them sitting between the patient’s

legs to manipulate the surgical blade retractor, which

Fig. 26.2. Dynamic MRI imaging of severe enterocele following hysterectomy: ( a ) without Valsvalva: normal posi-

tion of the bladder and bowel and ( b ) with Valsalva: massive vaginal vault prolapse with enterocele

358 J.J. Rassweiler et al.

is introduced into the vagina at the beginning of the

operation. We are using only bipolar coagulation

during the entire procedure. Once all trocars are

placed, the uterus (if present) is fixed to the abdomi-

nal wall with a 0-Prolene-suture on a straight needle

passed through the skin (Fig. 26.4 ).

Surgical Principle

The transperitoneal laparoscopic sacrocolpopexy is

based on the anterior and posterior fixation of the

vaginal wall to the sacral promontory using non-

resorbable meshes (ie, polypropylene, polytetraflu-

orethylene, polyester single side covered silicone)

(Fig. 26.5a ). The two meshes are fashioned from

two 6 × 11 cm sheets (ie, Prolene-mesh, Ethicon,

Norderstedt, Germany), measuring 11 cm in length

and tapering from a width of 5 cm at the vaginal end

to 3 cm at the sacral end (Fig. 26.5b ). If indicated,

simultaneous (prophylactic) correction of associated

urinary stress continence can be accomplished using

either a TVT or a laparoscopic Burch procedure

using three suspension sutures on either side.

Posterior Dissection

Pulling on the transcutaneous stay suture of the

uterus provides an excellent exposure of the

Douglas pouch (Fig. 26.4 ). We now incise the peri-

toneum horizontally at the line between the ute-

rosacral ligaments to enter the rectovaginal space

for dissection of the posterior vaginal wall down

to both levator ani muscles (Fig. 26.6a ). Following

adequate dissection we fix the posterior mesh to

the vaginal wall either by interrupted or continu-

ous sutures (2/0 prolene, 15 cm). A broad fixation

including lateral parts of the levator ani muscle is

of upmost importance (Fig. 26.6b ).

Anterior Dissection

This step includes the opening of the Retzius space

with exposure of the bladder and dissection of the

anterior vaginal wall by adequate exposure of the

intervesicovaginal space (Fig. 26.7a ). If the uterus

is present, a window through the broad ligament

Fig. 26.3. Arrangement of trocars for laparo-

scopic sacrocolpopexy. The midright port is

used for suturing to provide an adequate angle

between the instruments (i.e., >25°)

Fig. 26.4. Fixation of the uterus by a transcutaneous stay

suture with straight needle (Prolene 2/0)

26. Laparoscopic Sacrocolpopexy 359

on the right side must be created (Fig. 26.7c ). For

this purpose, the uterine stay suture is released.

Subsequently, we introduce the anterior mesh and

fix it to the anterior vaginal wall using either inter-

rupted of continues sutures (2/0 prolene; 15 cm)

(Fig. 26.7b ).

Presacral Dissection and Sacropexy

Finally, we expose the sacral promontory medial

to the sigmoid following transsection of the

uterosacral ligaments and suture both meshes to

the periosteum using two interrupted sutures (2/0

prolene 12 cm). We start with the posterior mesh.

During the fixation, the vagina is pushed cranially

by use of the retractor blade and the knot is secured

by the assistant (Fig. 26.8 ). If the mesh is too long,

we trim it endoscopically. The anterior mesh is

put through the window of the broad ligament

(Figs. 26.7c and 26.8b ). Finally, the peritoneum is

closed over both meshes by use of continuous 2—0

–Vicryl sutures (Fig. 26.9 ).

Incontinence Procedure

In case of a pronounced cystocele (anterior pro-

lapse), we prefer to perform a Burch colposuspen-

sion using three suspension sutures (1/0 Ethibond)

on either side. All other cases with verified stress

incontinence are treated by a transvaginal TVT

placed under laparoscopic control.

Fig. 26.5. Principle of sacral colpopexy. ( a ) Placement of two meshes sutured to the anterior and posterior vaginal

anchored to the sacral promontory. ( b ) Tapering of the two meshes (modified from Rozet et al. [13])

Fig. 26.6. Posterior dissection between vagina and rectum.

( a ) Endoscopic view at the end of dissection. ( b ) Fixation

of the mesh to the levator ani muscle on the right side

360 J.J. Rassweiler et al.

Results

Operating room times range between 97 and 276

min with a conversion rate to open surgery between

2 and 7%. Postoperative complications in experi-

enced centers vary between 6 and 16%, including

bowel lesions, mesh infections, spondylicitis, and

vaginal erosions. The overall success rates depend

on definition and technical considerations (ie,

anterior mesh vs. anterior plus posterior mesh) and

range between 66 and 94%. Compared to recently

published open transabdominal [30, 33, 34] and

transvaginal series [33, 35] , these results are com-

parable (

Table 26.1 )

Discussion

Sacral colpopexy is the most commonly performed

abdominal procedure to restore support to the

vaginal apex [36, 37] . It has several advantages

when approaching the complex problem of vaginal

Fig. 26.7. Anterior dissection between vagina and bladder distal to the uterus. ( a ) Endoscopic view at the end of dis-

section. ( b ) Endoscopic suturing to fix the anterior mesh at the vaginal wall. ( c ) Transposition of the mesh through

the window created at the right broad ligament

26. Laparoscopic Sacrocolpopexy 361

vault prolapse, namely, consistent anatomy, the

most definitive enterocele repair, and culdeplasty.

This procedure maintains a functional vagina and

restores maximal vaginal length by securing the

vaginal apex to the periosteum of the sacrum.

Sacrospinous fixation is the most commonly per-

formed transvaginal suspension procedure [12, 35,

38] . Its advantages include achieving a functional

vagina, avoiding the morbidity of an abdominal

incision and the ability to repair coexisting anterior

and posterior compartment defects using a single

surgical site. Because the technique displaces the

vaginal axis posteriorly, it leads to the develop-

ment of new anterior compartment defects. Other

reported complications include intraoperative hem-

orrhage due to pudendal artery laceration, vaginal

shortening, sexual dysfunction, pudendal nerve

injury, and postoperative pain.

In this scenario, the laparoscopic sacrocolpopexy

may combine the advantages of both traditional

techniques offering excellent anatomical correc-

tion with minimal invasiveness and morbidtity.

However, there are several issues to be taken into

consideration.

Fig. 26.8. Promontofixation. ( a ) Endoscopic suturing of

the posterior mesh to the sacral promotory. The assistant

pulls on the mesh to provide a tension-free knotting. ( b )

Fixation of the anterior mesh which was guided through

the window at the right broad ligament

Fig. 26.9. Closure of the peritoneum to retroperitoneal-

ize both meshed. ( a ) Starting the suture anteriorly. ( b )

Final view at the sacral promontory with complete clo-

sure of the peritoneum

362 J.J. Rassweiler et al.

Definition of Success

Blanchard et al. emphasized the varying definition

of success following correction of pelvic organ

prolapse studies [34] . Many investigators define

success as the absence of recurrent vault prolapse,

but the incidence of site-specific pelvic organ

defects after sacrocolpopexy has not been clearly

reported. However, it always has to be taken into

consideration which type of defect exists and

whether the patients had undergone only an ante-

rior repair [22] .

Important Technical Issues

There is still a controversy as to whether an ante-

rior and posterior mesh repair should be performed

routinely during laparoscopic and open sacrocol-

popexy. Antiphon et al. clearly demonstrated a sig-

nificantly lower posterior compartment failure rate

(5.9% vs. 31.3%) following a double, anterior, and

posterior, mesh [22] . However, it also increased the

postoperative complication rate (ie, constipation

rate 75% vs. 31%). In accordance with the huge

experience of Rozet and colleagues [13] , we prefer

the systematic placement of two prosthetic meshes,

which directly impacts on a lower rectocele relapse

(only 4%). Moreover, one should take into consid-

eration that laparoscopic sacrcocolpopexy mainly

is indicated in case of severe pelvic organ prolapse

in patients predisposed to develop recurrencies in

untreated compartments of the pelvic floor.

Another issue might be the type of mesh used

[20] . Based on long-term experiences with bladder

neck suspension, transvaginal sling procedures,

and laparoscopic hernia repair, we prefer the use

of polypropylene, which provides larger pore and

interstices size (type 1 synthetic graft). In our

hands, the risk of erosion is minimal. However, the

retroperitonealization of the implant is mandatory

to avoid any bowel lesion (Fig. 26.9 ).

Comparison with Other Techniques

To our knowledge, there is only a single study [39]

comparing laparoscopic transabdominal sacropexy

with either open abdominal approach, but none

comparing it to the vaginal approach or even those

using the new total mesh techniques. Paraiso et

al. found 50 min longer operative time for laparo-

scopic sacrocolpopexy (269 vs. 281 min), but a sig-

nificantly shorter hospital stay (1.8 vs. 4.0 days),

with similar complication and success rates [39] .

However, there are studies showing better cure

rates (ie, 95.6% vs. 79.7%) when comparing open

abdominal sacrocolpopexy with vaginal sacros-

pinous ligament fixation [33] ( Table 26.1 ). In this

Table 26.1. Results of laparoscopic and robotic-assisted sacrocolpopexy compared to open series.

OR-time Conversion Complication Success rate

Author N (min.) (%) (%) (%) Fixation

Laparosocpic

Cosson19 2002 83 276 (120–360) 7 16 94 ant + post

Antiphon22 2004 108 261 (120–450) 3 6 84 ant + post

66 anterior

Rozet13 2005 363 97 (45–156) 2 9 94 ant + post

Rassweiler + 2008 21 216 (157–263) – 8 92 ant + post

Robot-assisted

Di Marco23 2004 30 186 (120–241) 3 7 95 ant + post

Abdominal

Ng36 2004* 113 133 (32–227) n.a. 11 96 ant + post

Limb30 2005 61 260 (135–420) n.a. 4 91 ant + post

Blanchard37 2006 40 162 (90–270) n.a. 20 80 anterior

Transvaginal

Lantzsch38 2001 200 n.a. n.a. 16 87 posterior

Ng36 2004* 64 78 (28–156) n.a. 11 80 posterior

+ present study; * comparative study; n.a. = not applicable

26. Laparoscopic Sacrocolpopexy 363

study, however, the postoperative morbidity was

high after the transabdominal approach, including

pyrexia (52% vs. 28%) and hematuria (25% vs.

4%). One may argue that such complications could

be significantly diminished by the laparoscopic

approach without deterioration of the success rates.

Until now, there have been no peer-reviewed

studies published comparing the new total vaginal

mesh techniques with other established proce-

dures. Novara et al. [37] recently analyzed the data

regarding such minimally invasive total prosthetic

implant techniques in the literature (i.e., Prolift,

Apogee, Perigee) and emphasizing the relatively

high rate of mesh erosion (max 12%), mesh shrink-

age (max 17%), and de novo voiding symptoms

(max 12%).

Advantages of Laparoscopic Prolapse

Repair

There are several newer treatments in addition to

the classic abdominal sacrocolpopexy and vaginal

sacrospinous ligament fixation in the management

of severe uterovaginal or vault prolapses, including

less invasive methods such as laparoscopic pelvic

floor repair [31, 32] . The laparoscopic route offers

superior vision and less traumatic access compared

with the traditional techniques. This could be

translated into a better assessment, more precise

and correct anatomical repair, the use of strong and

acceptable material as a substitute for weak tis-

sues, faster recovery, and excellent anatomical and

functional results.

Problems of Laparoscopic Technique

There is no doubt that the laparoscopic approach

requires a high degree of skill and expertise based

on a specialized training. The learning curve takes

a longer time and as a result not every surgeon may

achieve competence in this methods [39, 40] . On

the other hand, urologists focusing on laparoscopic

or robotic-assisted techniques are well trained with

endoscopic dissection and suturing techniques

based on their daily practice. There already are

well-established training programs [41– 43] . Such

trained surgeons have to be only instructed in the

assessment of the specific pathologies of vaginal

vault prolapse. This is underlined by our own

experience: despite significantly fewer numbers

of cases, our operative time and follow-up results

do not differ from other experienced groups ( Table

26.1 ). We therefore would like to motivate urologi-

cal laparoscopists to include this procedure in their

list of indications.

Perspectives

Despite a significant number of patients who

already have undergone laparoscopic sacrocol-

popexy, there are no phase III trials comparing the

approach with the traditional open techniques or

with the newer total vaginal mesh techniques. Such

studies should be realized by high-volume cent-

ers or as a multi-institutional trial to really define

the role of the procedure. Based on a significant

experience with pelvic laparoscopy and pelvic

floor reconstruction, we believe that laparoscopic

placement of two meshes (anterior and posterior)

together with an anti-incontinence procedure if

indicated represents a highly effective technique

with minimal morbidity for the patients. Other

options seem to work, too, but are associated with

a higher complication rate (ie, erosion of TVM

tchniques), higher morbidity (ie, open abdominal

sacral colpopexy), or lower success rates (ie, trans-

vaginal sacrofixation). Finally, as we already expe-

rienced with the example of radical prostatectomy,

the use of the da Vinci robot may further allow

the technique to result in a significant increase of

laparoscopic sacrocolpopexy [23, 24, 44] .

References

1 . Schuessler WW , Vancaille RG , Reich H , Griffith

DP . Transperitoneal endosurgical lymphadenectomy

in patients with localized prostate cancer . J Urol

1991 ; 145 : 988 – 991 .

2 . Rassweiler J , Janetschek G , Griffith DP . Laparoscopic

surgery in urology . Thieme Stuttgart , New York

1996 .

3 . Guillonneau B , Cathelineau X , Barret E , et-al. .

Laparoscopic radical prostatectomy: Technical and

early oncological assessment of 40 operations . Eur

Urol 1999 ; 36 : 14 – 20 .

4 . De la Rosette JJMCH , Abbou CC , et-al. . Laparoscopic

radical prostatectomy: A European virus with global

potential . Arch Esp Urol 2002 ; 55 : 603 – 609 .

5 . Rassweiler J , Hruza M , Teber D , Su L-M .

Laparoscopic and robotic assisted radical prosta-

tectomy—critical analysis of the results . Eur Urol

2006 ; 49 : 612 – 624 .

364 J.J. Rassweiler et al.

6 . Binder J , Kramer W . Robotically assisted laparoscopic

radical prostatectomy . BJU Int 2001 ; 87 : 408 – 410 .

7 . Menon M , Shrisvastava A , Tewari A , et-al. .

Laparoscopic and robot assisted radical prostatec-

tomy: Establishment of a structured program and

preliminary analysis of outcomes . J Urol 2002 ;

168 : 945 – 949 .

8 . Ahlering TE , Skarecky D , Lee D , Clayman RV .

Successful transfer of open surgical skills to a

laparoscopic environment using a robotic interface:

Initial experience with laparoscopic radical prostate-

ctomy . J Urol 2003 ; 170 : 1738 – 1741 .

9 . Zweifel P . Vorlesungen über klinische Gynäkologie ,

Hirschwald , Berlin , 1892 .

10 . Hugier A . Sacral colpopexy . Gynecol Obstetrique

1957 ; 56 : 114 – 117 .

11 . Miller NF . A new method of correcting complete

inversion of the vagina with or without complete

prolapse, two cases . Surg Gynecol Obstet 1927 ;

44 : 550 – 554 .

12 . Richter K , Albrich W . Long-term results following

fixation of the vagina on the sacrospinal ligament

by the vaginal route . Am J Obstet Gynecol 1981 ;

141 : 811 – 816 .

13 . Rozet F , Mandron E , Arroyo C , et-al. . Laparoscopic

sacral colpopexy approach for genito-urinary pro-

lapse: Experience with 363 cases . Eur Urol 2005 ;

47 : 230 – 236 .

14 . Dorsey JH , Cundiff G . Laparosopic procedures for

incontinence and prolapse . Curr Opin Obst Gynecol

1994 ; 6 : 223 – 231 .

15 . Nezhat CH , Nezhat C , Nezhat F . Laparoscopic

sacral colpopexy for vaginal vault prolapse . Obstet

Gynecol 1994 ; 84 : 885 – 888 .

16 . Rassweiler J , Frede T , Seemann O , Jaeger T .

Laparoscopic colposuspension with the Burch tech-

nique—fact or fiction . Urologe B 2000; 40 : 330 –

332 (Engl. Abstract) .

17 . El-Toukhy , Davies AE . The efficacy of laparoscopic

mesh colposuspension: Results of a prospective

controlled . BJU Int 2001; 88 : 361 – 366 .

18 . Paraiso MFR , Falcone T , Walters MD . Laparoscopic

surgery for enterocele, vaginal apex prolapse and

rectocele . Int Urogynecol J 1999 ; 10 : 223 – 229 .

19 . Cosson M , Rajabally R , Bogaert E , et-al. . Laparoscopic

sacrocolpopexy, hysterectomy, and Burch colposus-

pension : Feasibility and short-term complications of

77 procedures . 2002 ; JSLS 6 : 115 – 119 .

20 . Deval B , Haab F . What's new in prolapse surgery ?

Curr Opin Urol 2003 ; 13 : 315 – 323 .

21 . Sundaram CP , Ramakrishna V , Landman J , Klutke

CG . Laparosopic sacrocolpopexy for correction of

vaginal vault prolapse . J Endourol 2004 ; 18 : 620 – 624 .

22 . Antiphon P , Elard S , Benyoussef A , et-al. .

Laparoscopic promontory sacral colpopexy: Is the

posterior, recto-vaginal mesh mandatory? Eur Urol

2004 ; 45 : 655 – 661 .

23 . Di Marco DS , Chow GK , Gettman MT , Elliott DS .

Robotic-assisted laparoscopic sacrocolpopexy for

treatment of vaginl vault prolapse . Urology 2004 ;

63 : 373 – 376 .

24 . Daneshgari F , Paraiso MF , Kaouk J , et-al. . Robotic

and laparoscopic female pelvic floor reconstrction .

BJU Int 2006; 98 (Suppl 1) : 62 – 68 .

25 . Boyles S , Weber A , Meyn L . Procedures for pelvic

organ prolapse in the United States . Am J Obstet

Gynecol 1997; 186 : 712 – 716 .

26 . Luber KM , Boero S , Choe JY . The demographics of

pelvic floor disorders: Current observations and futures

perspectives . Curr Opin Urol 2005 ; 15 : 256 – 262 .

27 . Novara G , Galfano A , Secco S , et-al. . Prolapse surgery:

An update . Curr Opin Urol 2007 ; 17 : 237 – 241 .

28 . Baden WF , Walker TA . Genesis of the vaginal pro-

file: A correlated classification of vaginal relaxation .

Clin Obstet Gynecol 1972; 15 : 1048 – 1054 .

29 . DeLancey JOL . Anatomic aspects of vaginal ever-

sion after hysterectomy . Am J Obstet Gynecol 1992 ;

166 : 1717 – 1728 .

30 . Limb J , Wood K , Weinberger M , et-al. . Sacral col-

popexy using mersilene mesh in the treatment of vagi-

nal vault prolapse . World J Urol 2005 ; 23 : 55 – 60 .

31 . Palma P , Riccetto C , Dambros M , Rodrigues Netto

N . New trends in the transobturator management of

cystoceles . BJU Int 2006 ; 97 : 201 – 210 .

32 . Reisenauer C , Kirschniak A , Drews U , Wallwiener

D . Anatomical conditions for pelvic floor reconstruc-

tion with polypropylene implant and its application

for the treatment of vaginal prolapse . Eur J Obstet

Gynecol Reprod Biol 2007 ; 131 (2) : 214 – 225 .

33 . Ng CCM , Han WHC . Comparison of effectiveness

of vaginal abdominal routes in treating severe uter-

ovaginal or vault prolapse . Singapore Med J 2004 ;

45 : 475 – 481 .

34 . Blanchard KA , Vanlangendonck R , Winters JC .

Recurrent pelvic floor defects after abdominal sacral

colpopexy . J Urol 2006 ; 175 : 1010 – 1013 .

35 . Lantzsch T , Goepel C , Wolters M , Koelbl H ,

Methfessel . Sacrospinous ligament fixation for vagi-

nal vault prolapse . Arch Gynecol Obstet 2001;

265 : 21 – 25 .

36 . Wattiez A , Canis M , Mage G , et-al. . Promontofixation

for the treatment of prolapse . Urol Clin N Am

2001; 28 : 151 – 157

37 . Novara G , Artibani W . Surgery for pelvic organ

prolapse: current status and future perspectives . Curr

Opin Urol 2005 ; 15 : 256 – 262 .

26. Laparoscopic Sacrocolpopexy 365

38 . Flynn BJ , Webster G . Surgical management of

the apical vaginal defect . Curr Opin Urol 2002 ;

12 : 353 – 358 .

39 . Paraiso MF , Walters M , Rackley R , et-al. .

Laparoscopic and abdominal sacropexies. A com-

parative cohort study . Am J Obstet Gynecol 2005;

192 : 1752 – 1758 .

40 . Ross JW , Preston M . Laparoscopic sacrocol-

popexy for severe vaginal vault prolapse: Five

year outcome . J Minim Invasive Gynecol 2005 ; 12 :

221 – 226 .

41 . Teber D , Dekel Y , Frede T , et-al. . The Heilbronn

laparoscopic training programm for laparoscopic

suturing: Concept and validation . J Endourol 2005;

19 : 230 – 238

42 . Frede T , Erdogru T , Zukosky D , et-al. . Comparison

of training modalities for performing laparoscopic

radical prostatectomy: Experience with 1,000

patients . J Urol 2005 ; 174 : 673 – 678

43 . Stolzenburg J , Schwaibold H , Bhanot SM , et-al. .

Modular surgical training for endoscopic extra-

peritoneal radical prostatectomy . BJU Int 2005; 96 :

1022 – 1027 .

44 . Nezhat C , Saberi NS , Shahmohamady B , Nezhat

F . Robotic-assisted laparoscopy in gynecological

surgery . JSLS 2006 ; 10 : 317 – 320

367

Introduction

Women with lower urinary tract symptoms

and pelvic organ prolapse frequently report

coexistent problems with the posterior pelvic

compartment. This may include fecal urgency

or incontinence, constipation, rectal pain syn-

dromes, and rectal prolapse. Functional bowel

disorders are the most understudied of all pelvic

floor disorders. Little evidence exists regard-

ing accepted definitions, treatments, and the

relationship between anatomical findings and

function [1] . We believe that understanding

the complexity of the relationship between the

pelvic floor organs, support system, and rectal

function requires a multidisciplinary approach

that addresses the posterior compartment as a

functional unit in the pelvic floor.

This chapter will encompass the most common

functional bowel disorders, the challenges involved

in evaluating patients with posterior compartment

disorders, and the relevant surgical anatomy and

physiology. Furthermore, we will provide a multi-

disciplinary approach to the evaluation of patients

with bowel symptoms, the use of anorectal testing,

and the various treatment concepts for posterior

compartment disorders.

Posterior Compartment

Dysfunction: Definitions

and Challenges

The prevalence of functional bowel disorders in

patients with urinary incontinence and pelvic organ

prolapse using standardized definitions (Table 27.1 )

is reported as 19% of patients with fecal incon-

tinence and 36% with constipation [2] . Patients

with constipation are further categorized into 19%

of patients with outlet constipation, 5% functional

constipation, 5–7% irritable bowel syndrome (IBS)

and its subtypes, and 25% of patients with anorec-

tal pain disorders. Rectal prolapse is reported in

only 2% of the population; however, concomitant

pelvic floor disorders have been reported in 8–27%

of these patients [3, 4] . Case-control studies reveal

that patients with rectal prolapse undergo genital

prolapse surgery more frequently and at a signifi-

cantly younger age than age-matched controls [5] .

Fecal incontinence is thought to coexist with

urinary incontinence and pelvic organ prolapse as a

result of direct sphincter trauma or neuropathic inju-

ries from vaginal deliveries [6] . In otherwise healthy

younger women, obstetric anal sphincter injury is

the principal causative factor in the development

Chapter 27

Posterior Compartment Repair

and Fecal Incontinence

Gil Levy and Brooke H. Gurland

368 G. Levy and B.H. Gurland

of fecal incontinence [7] . In women over the age

of 65 years old fecal incontinence is significantly

associated with chronic health conditions, liquid

stool consistency, and bowel surgery [8] .

Outlet type constipation is most common in

women with pelvic organ prolapse as a result of the

loss of pelvic floor support. Childbirth, hysterec-

tomy, and chronic straining can damage the pelvic

diaphragm and rectal vaginal supports, resulting

in abnormal perineal descent of the distal rectum,

sigmoid colon, or small bowel causing obstructive

symptoms.

Rectal pain syndromes are the least well under-

stood. Proctalgia fugax and levator spasm may

occur in patients with prolapse, a result of stretching

of the pelvic floor supports or muscular spasm.

Rectal prolapse is associated with chronic strain-

ing and a loss of fixation of the rectal attachments .

Fecal incontinence is reported in 50–70% of these

patients [9, 10] . Possible etiologies include stretch-

ing of the anal muscles, inhibition of the internal

anal sphincter due to rectal reflexes, impairment of

rectal sensation, or denervation of the pelvic floor

muscles. Outlet constipation is reported in 72% of

patients with rectal prolapse due to a mechanical-

like obstruction [11] .

Surgical repair of prolapse is based on the

premise that correction of anatomical defects will

improve symptoms. Thus, it is important to under-

stand which symptoms are directly related to pelvic

organ prolapse and which symptoms are associated

with other disorders. Weber et al. reports 79.7% of

women with posterior vaginal wall prolapse had

one or more bowel complaints, but the authors

could not correlate the bowel symptoms to the

degree of posterior vaginal wall prolapse [12] .

Several other studies report similar findings with

the exception of a significant correlation between

perineal descent and outlet constipation [13, 14] .

Furthermore, da Silva et al. reveals that bowel

symptoms correlate with abnormal anal physiol-

ogy testing and primary anorectal pathology, but

symptoms do not correlate with advanced posterior

vaginal wall prolapse [15] .

The literature that discusses surgical treatment

can be difficult to interpret because of the use of

broad, nonstandardized definitions and paucity of

adequate outcome tools to evaluate function. The

ROME II criteria (Table 27.1 ) are a set of criteria

agreed upon by gastroenterologists and colorectal

surgeons to describe functional bowel disorders,

but these definitions and their relationships have

not been validated in patients with prolapse or

incontinence.

The Pelvic Organ Quantification Score (POP-

Q), which is the accepted tool to evaluate pelvic

organ prolapse, does not correlate with radiological

findings [16, 17] . Its posterior compartment meas-

uring points do not allow the determination among

rectocele, sigmoidocele, enterocele, or intussus-

ception during physical examination. Although

defecography will differentiate these findings and

is considered the “gold standard” to evaluate evac-

uation disorders, there is no consensus in the gyne-

cology literature to its recommended use [18] .

These are some of the challenges confronting

physicians who are managing patients with poste-

rior compartment dysfunction. We will begin this

chapter by highlighting the surgical anatomy and

physiology of the posterior compartment, which

is essential in approaching patients with these

disorders.

Anatomy and Physiology

The posterior pelvic compartment has the follow-

ing borders: (1) posterior: the anterior surface of

the sacrum and the levator muscles; (2) anterior:

the posterior vaginal wall and the posterior vaginal

fornix; (3) inferior: the perineum, anal muscles,

and perineal body; and (4) superior: the peritoneal

reflection and pouch of Douglas. The compartment

contains the rectum and anus (Fig. 27.1 ).

Sacrum

The sacrum and coccyx comprise the posterior

border of this compartment. These structures

are covered by a thick layer of fascia, known as

Waldeyer's fascia, which fuses with the fascia

propria of the rectum above the anorectal ring.

A lack of fixation of the fascial support of the

rectum against the sacrum can lead to internal

rectal prolapse, intussusception, and ultimately

full thickness rectal prolapse. The coccyx, ischial

spine, and sacrospinous ligaments can be palpated

during clinical examination or accessed through

27. Posterior Compartment Repair and Fecal Incontinence 369

the pararectal space during surgical dissection.

The sacrospinous ligament originates on the ischial

spine and inserts onto the sacrum. The sacral

plexus lies immediately next to the sacrospinous

ligament on its cephalic border and passes through

the greater sciatic foramen. Just before its exit,

the plexus gives off the pudendal nerve, which,

with its accompanying vessels, passes posterior

to the sacrospinous ligament at its attachment to

the ischial spine. Entrapment of these nerve fibers

can cause gluteal pain. The levator ani muscles,

iliococcygeus, and pubococcygeus arise from the

ischial spine and pubic bone, respectively, and

insert on S3, S4, and the coccyx and anococcygeal

ligament. The puborectalis muscle is the most

medial portion of the levator muscle. The levator

ani is supplied by S4 root on the pelvic surface

and by the perineal branch of the pudendal nerve

on its inner surface. The genital hiatus allows for

passage of the lower rectum, vagina, and urethra.

Posterior Vaginal Wall

The rectovaginal septum is an elastic fibromuscu-

lar tissue layer that invests the posterior vaginal

wall and is covered by mucosa up to the level of

the cervix [19] . Superiorly, it is an extension of

the endopelvic fascia and attaches to the cervix

and the cardinal uterosacral complex, which sup-

ports the vaginal apex. Laterally, it attaches to the

Table 27.1. Definitions of common posterior compartment terminology .

Fecal urgency is a symptom rather than a condition and is defined as “the patient's statement of the overwhelming desire to def-

ecate accompanied by fear of leakage of bowel contents”

Fecal incontinence is defined as recurring episodes of involuntary loss of gas, solid, or liquid stool that are a social or hygienic

problem. The time frame and the character of loss should be specified

Functional constipation/ROME II criteria

a

The presence of at least 12 weeks (which do not need to be consecutive) in the previous year of two or more of the following

symptoms:

•<3 Bowel movements (BMs) per week

• Hard or lumpy stools for more than 25% of BMs

• Straining with defecation for more than 25% of BMs

• A sensation of incomplete evacuation for more than 25% of BMs

• The use of manual maneuvers to assist defecation for more than 25% of BMs

Outlet constipation is a subtype of functional constipation. Patients also must report one of the following: a sensation that stool

cannot be passed, a need to press on the perineum to complete the bowel movement, or difficulty relaxing and allowing the

stool to come out

Dyssnergia constipation involves similar symptoms as above with EMG evidence of nonrelaxing puborectalis

Irritable bowel syndrome/ROME II criteria a

The presence of at least 12 weeks (which do not need to be consecutive) in the previous year, of two or more of the following

symptoms:

• Intermittent loose stools or constipation

• Abdominal pain or cramping

• Pain relieved with defecation

Rectal pain syndromes/ROME II criteria a

Proctalgia fugax is defined as having more than 1 episode of aching pain or pressure in the anal canal over the last year that lasts

for seconds to minutes and disappears completely

Levator ani syndrome includes the same pain which can last more than 20min up to several days or longer and has occurred

frequently or continuously over the last 3 months

Rectal prolapse is a true intussusception of the rectum with protrusion of the full thickness of the rectum through the anal

opening

a Source: Thompson WG, Longstreth G, Drossman DA, Heaton K, Irvine EJ, Muller-Lissner S. Functional bowel disorders and

functional abdominal pain, pages 351–432. Whitehead WE, Wald A, Diamant NE, Enck P, Pemberton JH, Rao SSC. Functional

disorders of the anus and rectum, pages 483–532. In: Drossman DA, Corazziari E, Talley NJ, Thompson WG, Whitehead WE,

eds. ROME II The functional gastrointestinal disorders, diagnosis, pathophysiology and treatment: A multinational consensus.

2nd edn. Allen Press, Lawrence, KS

370 G. Levy and B.H. Gurland

pelvic sidewalls and fuses with the aponeurosis of

the levator ani muscle along a line referred to as

the arcus-tendineus-fascia-rectovaginalis [20] . The

rectovaginal septum fuses with the perineal body at

its inferior portion.

Proximal injuries to the rectovaginal septum

will permit the peritoneum to come into direct

contact with the vaginal epithelium, resulting in

small bowel or sigmoid protrusion, enterocele

or sigmoidocele, respectively. Defects that are

more distal will lead to bulging of the rectum

into the posterior vaginal wall causing rectocele

(Fig. 27.2 ). The site-specific surgical repair of

rectocele and enterocele is geared toward iden-

tifying and repairing defects in the rectovaginal

septum [21] .

Perineal Body

The perineal body is a pyramidal structure located

between the vaginal introitus and anus with its base

along the perineum. It is an attachment of the infe-

rior central tendon, bulbocavernosus, transverse

perineii muscles, and external sphincter muscles

(Fig. 27.2 ). The perineal body also is connected

to the rectovaginal septum, causing the retraction

of the intergluteal cleavage. This cleavage disap-

pears when the attachment of the perineal body

is injured, causing perineal descent. Detachments

of the rectal vaginal fascia from the perineal body

can lead to distal rectocele in patients with normal

posterior vaginal wall support. Richardson reported

this as a “perineal rectocele” and a possible etiology

Fig. 27.2. Anatomical relationship of the

perineal body and the rectovaginal septum

(reprinted with permission from Cleveland

Clinic Foundation: Pollack J, Davila

GW. Rectocele Repair: The Gynecologic

Approach. Clinics in Colon and Rectal

Surg 2003; 16:61–69)

Fig. 27.1. Anatomical structures of the pelvic compartments

27. Posterior Compartment Repair and Fecal Incontinence 371

for persistent difficult rectal evacuation in patients

who underwent rectocele repair [21] .

Pouch of Douglas

The peritoneal pocket located between the vaginal

apex and the rectum is called the cul-de sac or

pouch of Douglas. This space can be stretched

deep in between the vagina and rectum allowing

the peritoneum, small bowel, or redundant sigmoid

colon to interpose those structures, causing perito-

neocele, enterocele, or sigmoidocele.

Anal Sphincter Muscles/Anal Canal

The external anal sphincter (EAS) is fused to the

perineal body anteriorly and is attached to the

coccyx posteriorly by the anoccygeal ligament.

The EAS is an elliptical cylinder of striated muscle that

surrounds an inner tube of smooth muscle, the inter-

nal sphincter muscle (IAS), but ends slightly distal

to it. The deepest part of the EAS is intimately

related to, but embryologically distinct from, the

puborectalis muscle. The puborectalis muscle is

a U-shaped strong loop of striated muscle, which

slings the anorectum junction to the back of the

pubis, maintaining an acute anorectal angle [22] .

The inferior rectal branch of the pudendal nerve

innervates the EAS.

The IAS represents the distal 2.5- to 4-cm long

condensation of the inner circular layer of the

rectum. The anal opening or lower-most edge of

the anus, also known as the anal verge, is closed

at rest due to tonic circumferential contractions of

the sphincters and the anal cushions. As a smooth

muscle, the IAS is at a state of constant contraction

due to intrinsic myogenic and extrinsic autonomic

properties and represents a natural barrier to the

involuntary loss of stool. The IAS is responsible

for 50–85% of the resting tone, the EAS accounts

for 25–30%, and the remaining 15% is attributed to

expansion of the anal cushions [23, 24] .

The surgical anal canal extends from the sulcus

between the IAS and EAS for approximately 4cm

to the anorectal ring. The anorectal ring, the upper

end of the puborectalis muscle and IAS, is an easily

recognizable boundary of the anal canal on physi-

cal examination. Vaginal delivery, perineal lacera-

tion, and instrumental deliveries can lead to anal

sphincter injury and fecal incontinence.

Rectum

The rectum is a 12- to –15-cm long segment of

large intestine that occupies the sacral concavity

and ends 2–3cm inferior to the tip of the coccyx.

At the tip of the coccyx, the rectum ungulates back-

ward, passing through the levators and becomes the

anal canal. The rectum is a very compliant organ

that accommodates stool contents and acts as a

reservoir so that defecation can be delayed.

Defecation

Regulated bowel habits rely on the interaction of

complex neurological and muscular features under

the influence of the central nervous system. Stool

consistency, intestinal motility, delivery of stool

to the rectum, rectal capacity and compliance,

anorectal sensation, integrity of the anal sphincter

mechanism, neurological function of the pelvic

floor muscles and nerves all contribute to “normal”

bowel activity.

The sigmoid colon fills the rectum and trig-

gers defecation. Rectal distention is interpreted

as a desire to defecate. Following the rectal fill,

the IAS relaxes by opening the upper anal canal

and allowing sampling of contents. The EAS

contraction reflex maintains continence during

this phase . If the call to stool is answered, then

sitting or squatting positions are assumed and

increased abdominal pressure and rectal contrac-

tions squeezes the part of the rectum that lies

above the pelvic diaphragm. The EAS and pub-

orectalis relax and the anorectal angle becomes

more obtuse and defecation occurs. If defecation

is to be deferred, conscious contraction of the EAS

occurs with rectal compliance and contractions of

the puborectalis pull the distal vagina and anorec-

tal junction toward the pubic symphysis, creating

a near 90 angle, anorectal angle, which facilitates

fecal continence. In diarrheal states high volumes

of liquid stool empty rapidly into the rectum,

overwhelming the sphincter mechanism, leading

to fecal urgency and incontinence.Disorders that

relate to poor rectal compliance or loss of rectal

reservoir can result in fecal urgency or inconti-

nence. Sensory neuropathy (diabetes) or altered

mental status (stroke or dementia) may selectively

reduce conscious sensation and awareness of rectal

fullness. In these patients relaxation occurs before

372 G. Levy and B.H. Gurland

the sensation of rectal distention, which results in

fecal impaction and overflow incontinence. Anal

sphincter injuries can result in the inability to

maintain adequate resting and squeeze pressures

and a noncompliant rectum.

For patients with motility disorders, markedly

delayed intestinal transit may result in nonfilling

of the sigmoid colon, thus delaying the defecation

process. Patients with outlet-type constipation can

have nonrelaxation of the puborectalsis (anismus).

Thus, the anorectal angle remains abnormally con-

tracted at the time of defecation.

Furthermore, chronic straining can lead to

stretching of the pudendal nerves and denervation

of the external sphincter muscle and fecal inconti-

nence. Denervation of the pelvic diaphragm results

in opening of the genital hiatus and laxity of the

endopelvic fascia, which then is prone to attenua-

tion and tearing. In this pathological state of exces-

sive perineal descent, the pelvic organs are allowed

to pass through the genital hiatus.

Patient Evaluation

Medical Intake

Women with posterior compartment prolapse may

complain of urinary dysfunction, bowel disorders,

or hernia-like symptoms. Urinary urgency, fre-

quency, and incontinence frequently are identified

concomitantly with posterior compartment disor-

ders and are discussed in detail in prior chapters. In

order to create a systematic evaluation of posterior

compartment complaints we grouped the symptoms

into two categories: (1) bowel complaints including

fecal incontinence, constipation, rectal pain, and

rectal prolapse; and (2) vaginal complaints includ-

ing vaginal pressure, a feeling of a bulge, visible

prolapse, vaginal pain or bleeding,, and sexually

related symptoms.

When evaluating patients with bowel disorders

the consistency and frequency of bowel move-

ments and the use of enemas and laxatives needs

to be documented. The inability to control gas,

liquid, or solid stool and the frequency of loss

are reported as well as the presence of passive,

urgent, or mixed incontinence. Passive loss of

stool, without the patient knowing until the acci-

dent has occurred, implies that there is a rectal

sensory deficit. Urgency incontinence implies that

the patient has the sensation to move her bowels

but cannot control the movement. This may occur

with chronic diarrheal states, irritable bowel, or

anal sphincter injuries. Soiling, a streak of stool

on the underwear, may be related to liquid stool

consistency or seepage of stool from fecal impac-

tion and overflow incontinence. A number of fecal

incontinence scoring systems have been proposed

and validated to assist in clinical decision-making.

We use the Wexner fecal incontinence score (FICS)

to evaluate the degree of fecal incontinence (Table

27.2 ). Prior validations report a FICS ³ 9 correlate

with significant fecal incontinence [25] .

To evaluate patients with complaints of consti-

pation we use the ROME II criteria (Table 27.1 ).

Patients with rectal pain are asked to describe the

quality and duration of their symptoms and its

association with bowel movements. Prolapse of

tissue from the anus, the presence of rectal bleed-

ing, and the quantity and frequency of blood loss

are documented.

Underlying medical and surgical conditions and

medications, which may alter bowel habits, need

be investigated. Patients who fit the criteria for

IBS should be referred for the appropriate workup

(Table 27.1 ). The risk of malignancy also should

be considered, specifically where there has been

a change in bowel habits or bleeding, and appro-

priate evaluation with colonoscopy initiated. The

conditions associated with fecal incontinence are

summarized in Table 27.3 . Medical conditions

associated with constipation are reported in Table

27.4 . Outlet obstruction constipation can be further

categorized by the mechanism of action (Table

27.5 ). Patients with internal intussusception or full

thickness rectal prolapse also may complain of

fecal urgency or incontinence, mucus discharge or

soiling, outlet constipation, rectal pressure, rectal

bleeding, or pain. Rectal bleeding may be associ-

ated with internal intussusception, full thickness

rectal prolapse, and solitary rectal ulcer syndrome.

The common vaginal symptoms associated with

posterior compartment disorders include feeling of

a bulge, heaviness, or pain. Pain can be reported

as pelvic, abdominal, lower back, or perineal. In

cases of advanced genital prolapse the patient may

describe visible prolapse of the vagina.

Symptoms may relate to sexual dysfunction

and include dyspareunia or decreased sensation.

27. Posterior Compartment Repair and Fecal Incontinence 373

Dyspareunia should be documented in various parts

of penetration or intercourse positions. Lack of

sensation needs to be differentiated from decreased

libido and documented in the various parts of the

sexual stages.

We use validated multicompartment scoring sys-

tems and quality of life questionnaires to address

the severity of symptoms. We repeat the assess-

ment following intervention to measure the success

of treatment [26, 27] .

Physical Examination

Perineal, vaginal, anal, and rectal evaluations are

important components of the physical examination.

Inspection may reveal previous scars and atrophic

changes, dermatologic conditions, a gaping introi-

tus or prior episiotomy scars. A short, distorted

perineal body associated with the “dovetail sign”

is suspicious of an anterior anal sphincter defect.

A gaping patulous anus may indicate neurological

injury or full thickness rectal prolapse. Palpation

of the external genitalia can reveal localized ten-

derness and irritation. Neurological examination

to sharp and soft stimuli and sensory, motoric, and

reflex functions should be evaluated. The bulbocav-

ernosus reflex or anal wink reflex refers to contrac-

tions of the external sphincter with gentle touching

of the clitoris or anus. Flattening of the perineum

during Valsalva beyond the ischial tuborosities is

suggestive of excessive perineal descent and can be

Table 27.2. Wexner fecal incontinence .

Solid stool Liquid stool Gas Wears pad Lifestyle change

Frequency of accidents

Never 0 0 0 0 0

Rarely <1 month 1 1 1 1 1

Sometimes <1/week, >1/month 2 2 2 2 2

Usually >1/week 3 3 3 3 3

Always >1/day 4 4 4 4 4

Score (0 = perfect continence and 20 = complete incontinence)

Source: Jorge J, Wexner S. Ethiology and management of fecal incontinence. Dis Colon Rectum 1993; 36:77–97

Table 27.3. Etiologies of fecal incontinence .

I Altered stool consistency — diarrheal states

A. Irritable bowel syndrome

B. Inflammatory bowel disease

C. Infectious diarrhea

D. Laxative abuse

II Inadequate reservoir capacity or compliance

A. Inflammatory bowel disease

B. Surgical removal of the rectum

C. Collagen vascular disease

III Inadequate rectal sensation

A. Neurological conditions

i. Dementia/cerebrovascular accident

ii. Multiple sclerosis

B. Central nervous system injuries or neoplasms

C. Sensory neuropathy

i. Diabetes

D. Overflow incontinence

i. Fecal impaction

ii. Psychotropic drugs

IV Abnormal sphincter mechanism or pelvic floor

A. Anatomic sphincter defect

i. Traumatic

a. Obstetric injury

b. Anorectal surgery

B. Pelvic floor denervation

i. Pudendal neuropathy

ii. Chronic straining of stool

iii. Descending perineal syndrome

iv. Aging

v. Vaginal deliveries

vi. Rectal prolapse

Table 27.4. Conditions associated with constipation.

Organic disorders Diabetes

Amyloidosis

Hypokalemia

Hypocalcemia

Hyperparathyroidism

Parkinson's disease

Cerebral vascular disease

Autonomic neuropathy

Medications Anticholinergics

Opiates

Antihypertensives

374 G. Levy and B.H. Gurland

felt with the patient sitting on the examiner's hand

palpating the perineum.

Internal vaginal examination may reveal tender-

ness over the levator muscles, which is suggestive

of levator spasm as a possible etiology for pelvic

pain and dyspareunia. During speculum examina-

tion atrophic changes and posterior vaginal wall

support are reported. Evaluation of the posterior

vaginal wall is routinely performed using single-

blade speculum to retract the anterior wall and

allow direct visualization of the posterior wall

and fornix during rest and Valsalva maneuver.

The Pelvic Organ Prolapse Quantification score

(POP-Q) is used to report the degree of prolapse

[16] . Bimanual vaginal and rectal examination

may be performed in the standing position to elicit

the maximal prolapse of the pelvic organs as they

descend through the pouch of Douglas.

During anorectal examination, sphincter coordi-

nation is noted when patients are asked to squeeze,

relax, and push. Valsalva maneuver usually is

required to elicit full thickness rectal prolapse.

Digital examination reveals resting and squeeze

anal tone and a large rectocele or sphincter defect

frequently may be palpated. If rectal prolapse is

suspected, then we have the patient sit on the com-

mode and attempt evacuation in order to visualize

the rectal prolapse. Physical examination finding

are summarized in Table 27.6 .

Anoscopy is performed to evaluate patients for

mucosal abnormalities and rectoanal intussuscep-

tion. Colonoscopy is recommended to rule out

anatomic lesions and inflammatory conditions.

Diagnostic Studies

Anorectal physiology permits objective measures

of subjective functional colorectal problems and

helps to distinguish between among pathophysi-

ological mechanisms that would not otherwise be

detected on clinical examination [28] (Table 27.7 ) .

Anorectal Manometry

Anorectal manometry measures intra-anal and

intrarectal pressures at rest and during squeeze and

Valsalva to measure internal and external sphincter

function. We use a system that can accommodate

both urodynamic and anorectal testing. A thin

catheter with a balloon secured to the end is intro-

duced into the anus and pressure measurements are

reordered along the length of the anal canal (Fig.

27.3 ). There is a graduated increase in pressure

Table 27.6. Physical examination findings.

Inspection

• Vaginal skin integrity

• Posterior vaginal wall descent

• Perineal body thickness and integrity

• Stool particles around the anus

• Anus closed or open (patulous)

• Scars or muscular defect

• Anal skin reflex to palpation (anal wink)

• Mucosal versus full thickness prolapse with Valsalva

• Perineal descent with Valsalva below the ischial tuborosities

Palpation

• Pain/tenderness at the introitus

• Vaginal/uterine prolapse

• Masses

• Resting pressures

• Squeeze pressure

• Sphincter defects

• Rectal content

• Relaxation of the puborectalis

• Tenderness over the levators

• Rectocele

Endoscopy

• Rectoanal intussusception

• Mucosal lining/colitis

• Malignancy

Table 27.5. Etiologies of outlet type constipation .

Mechanism

1. Impaired rectal sensation 1. Megarectum

2. Functional outlet obstruction 1. Inefficient inhibition

of the IAS

a. Hirschsprung's

b. Chagas

2. Inefficient relaxation

of the pelvic floor

muscles

a. Anismus

b. Spinal cord lesions

c. Multiple sclerosis

3. Mechanical obstruction 1. Full thickness rectal

prolapse

2. Internal intussusception

to the anal verge

3. Large enterocele

4. Redirection of expulsion

force

1. Rectocele

2. Descending perineum

syndrome

3. Total rectal prolapse

27. Posterior Compartment Repair and Fecal Incontinence 375

proceeding distally and the highest resting pres-

sures are generally recorded from 1 to 2cm from

the anal verge. The mean anal canal resting pres-

sure in healthy adults ranges from 40 to 60 (cm/

H

2 0) and is lower in elderly patients. During nor-

mal squeeze effort intra-anal pressures double or

triple their baseline resting pressures (80 –180cm/

H

2 O) (Fig. 27.4 ) [29] . Low anal pressures are seen

in patients with incontinence from anal sphincter

defects, neurogenic incontinence, rectal prolapse,

and perineal descent.

The rectal anal inhibitory reflex (RAIR) and rectal

sensation are measured by injecting air into an intra-

rectal balloon at the end of the catheter. Rectal dis-

tention causes reflex transient IAS relaxation and

EAS contraction, thus permitting rectal sampling

of fecal contents. Patients with Hirschsprungs and

Chagas disease have an absent RAIR.

The first rectal sensation usually is between 10

and 20ml of air. As more air is introduced, the

rectum distends and the patient reports the urge to

move her bowels. Viscous and elastic properties

intrinsic to the rectum allow it to maintain a low

intraluminal pressure despite a large volume [30] .

Through this mechanism of rectal compliance, stool

contents can be accommodated so that defecation

can be delayed. Low rectal compliance is identified

in patients with inflammation to the rectum such

as proctitis and inflammatory bowel disease and in

patients with anal sphincter injuries. Some believe

that the development and maintenance of a com-

pliant rectum is related to a competent sphincter

[31] . It is unclear whether poor rectal compliance

is a cause or a consequence of fecal incontinence.

High sensory thresholds have been associated with

diabetes, peripheral neuropathy, perineal descent

syndrome, fecal impaction, encopresis, spina bifida,

and meningeocele and may be related to overflow

fecal incontinence or difficult evacuation [32] .

Neurological Studies: Electromyography/

Pudendal Nerve Latency

Electromyography (EMG) is used to investigate

the electrical activity of the EAS and pelvic floor

muscles. Concentric needle, monopolar, and single-

fiber electrodes are techniques that require insertion

of a needle into the EAS or puborectalis to measure

motor unit potentials (MUP). Muscular defects can

be demonstrated by assessing reinervation patterns.

Surface EMG using patch electrode on the

external sphincter muscles or a sponge electrode

in the anal canal is noninvasive and well tolerated

by the patient. During squeezing, the amplitude

of the MUP will increase, while pushing or simu-

lated defecation appears very similar to the resting

pattern. Nonrelaxation of the puborectalis can be

diagnosed by an abnormal pattern during Valsalva

(Fig. 27.5 ).

Table 27.7. Diagnostic studies.

Test Purpose

Anorectal manometry To measure resting and squeeze

anal pressures

Rectal sensation/compliance

and RAIR

Electromyography

Needle EMG To measure sphincter injuries by

assessing reinervation pat-

terns

Surface EMG To measure relaxation of the

puborectalis

Pudendal nerve terminal

latency studies

To measure the integrity of the

pudendal nerve

Endorectal ultrasound Anatomic mapping of the

internal and external anal

sphincter

Cinedefecography To evaluate for incomplete or

delayed rectal evacuation and

possible etiologies: rectocele,

intussusception, rectal pro-

lapse,

enterocele, perineal descent

MRI Anatomic view of all pelvic

floor

compartments

Fig. 27.3. Anal manometry catheter

376 G. Levy and B.H. Gurland

Pudendal nerve terminal latencies (PNTML) are

measured by stimulating the pudendal nerve intra-

rectally with the St. Mark's electrode on a gloved

finger to assess pudendal neuropathy. Prolongation

of the PNTML indicates pathology to the pudendal

nerve; however, the nature and the site of the lesion

remain uncertain. Moreover, the conduction velocity

of a nerve may have little bearing on its functional

integrity. The prevalence of prolonged PNTML in

patients presenting for anorectal physiology studies

is reported at 20–28% with unilateral neuropathy

and 11–12% with bilateral neuropathy [33, 34] .

Bilateral, not unilateral pudendal neuropathy is

associated with diminished sphincter function and

higher incontinence scores. In some studies, pro-

longed pudendal nerve latencies have been shown

to be an important prognostic factor in patients

undergoing anal sphincter repair [35] . Figure 27.6

demonstrates normal and abnormal PNTML.

Imaging Studies

Ultrasound

Anal endosonography requires an ultrasound scan-

ner, a 360 endoprobe at 7 or 10mHz with a rigid

cap for evaluation of the anal canal musculature

(Fig. 27.7 ). The probe is moved in or out of the

anal canal and images are taken at the upper, mid-

dle, and distal anal canal. At the upper anal canal

the puborectalis is visualized as a hyperechoic

U-shaped structure. At the middle anal canal the

external and internal sphincter muscles form a

complete ring and outer hyperechoic and inner

Fig. 27.4. Normal manometry measurements during rest and squeeze cycle

Fig. 27.5. EMG of the pelvic floor muscles demonstrating nonrelaxing puborectalis

27. Posterior Compartment Repair and Fecal Incontinence 377

hypoechoic circles are visualized. At the distal

anal canal only the subcutaneous EAS is visual-

ized as a hyperechoic ring. Anal sphincter injuries

are detected by a break in the muscular ring.

Defects may be reported as EAS, IAS, or com-

bined injuries (Fig. 27.8 ). Ultrasound measure-

ments of the perineal body increase the sensitivity

of detecting anal sphincter injuries [36] . A finger

is placed into the vaginal introitus at the level of

the middle anal canal and the distance between

the tip of the finger to the IAS is measured and

perineal body measurements less than 10mm are

Fig. 27.6. Measurements of pudendal nerve latency (normal <2.2 ms). Left 2.1 ms, Right 3.1 ms. The bottom curves

demonstrate slow conduction consistent with unilateral neuropathy

Fig. 27.7. Anal ultrasound probe

Fig. 27.8 . Anal ultrasound demonstrating anterior anal

sphincter defect

378 G. Levy and B.H. Gurland

suspicious for sphincter injuries [37] . Ultrasound

measurements of perineal body do not correlate

with POP-Q measurements [38] .

In most practices, endoanal ultrasound has

become the preferred modality for evaluation of

sphincter defects. It provides an anatomic view

but is not helpful in assessment of neuromuscu-

lar activity. Although needle EMG can be very

uncomfortable for the patient, endoanal ultrasound

and needle EMG may be complementary when the

presence of a defect is uncertain.

Three-dimensional anorectal endosonography takes

the data from a series of closely spaced two-dimen-

sional images combined with a three-dimensional

image. Improved visualization of the anal muscula-

ture is an exciting prospect. The clinical significance

of this modality has yet to be proven.

Cinedefecography

Cinedefecography is a dynamic study that requires

opacification of the pelvic floor structures with

contrast and simulation of defecation [39] . It is

performed on patients with difficult evacuation

or selectively on patients with fecal incontinence

to identify internal or full thickness rectal pro-

lapse. Oral contrast is given to opacify the small

bowel, liquid barium to opacify the sigmoid colon,

and barium paste is inserted into the rectum and

vagina. Opacification of the bladder or the peri-

toneum will enhance visualization of cystoceles

and enteroceles. Cinedefecography is performed in

the fluoroscopy suite with the aid of videorecord-

ing and freeze-framing with the patient sitting on

a specialized water-filled commode. Images are

taken at rest, squeeze, and pushing, and evacuation

is recorded. We look for delayed or incomplete

rectal emptying, changes in the anorectal angle, the

presence and size of an anterior or posterior rec-

tocele and evacuation of the rectocele, sigmoid or

small bowel descent below the pubococcygeal line

(sigmoidocele or enterocele, respectively), perineal

descent, internal intussusception, and full thickness

rectal prolapse (Fig. 27.9 ). Cinedefecography is

able to identify pathology not visualized on clini-

cal examination [17] . There is a 33% incidence of

internal rectoanal intussusception in patients with

clinical rectoceles and defecatory dysfunction [40] .

Although internal prolapse is unlikely to progress

into overt prolapse, it may contribute to the evacuation

symptoms. Furthermore, enterocele diagnosed by

defecography is associated with a high likelihood of

other pelvic floor findings [41] (Fig. 27.10 ).

Magnetic Resonance Imaging Systems

The development of fast sequence magnetic res-

onance imaging (MRI) provides a quick, effi-

cient, detailed, and reproducible evaluation of

pelvic organ prolapse and pelvic floor relaxa-

tion. Evaluation of all three pelvic compartments

can be performed with high-resolution capability

and no radiation. Disadvantages to MRI are the

cost, supine position, and the lack of correlation

between videoproctography and MRI [42] . Upright

open-configuration dynamic MRI has significant

advantages over the supine position, allowing the

patient to simulate defecation and prolapse associ-

ated with the upright position [43] . Investment into

open-configuration MRI and a combined interest

between the pelvic floor surgeon and radiologist

will promote the use of this exciting technology.

Treatment Concepts and Surgical

Techniques

Surgical Treatment of Symptomatic

Posterior Vaginal Wall Prolapse

The surgical treatment of symptomatic poste-

rior wall prolapse is based on the concept that

the restoration of anatomy will alleviate pelvic

Fig. 27.9. Large rectocele marked on defecography

(reprinted with permission Lahr, C. Why Can't I Go,

Charleston: Sunburst Press, 2004)

27. Posterior Compartment Repair and Fecal Incontinence 379

floor symptoms. In order to compare the various

surgical techniques discussed in the literature, suc-

cess needs to be evaluated from anatomical and

functional perspective. The National Institutes of

Health have established criteria to evaluate ana-

tomical repair of the posterior compartment (Table

27.8 ) using POP-Q scoring, but have failed to pro-

vide a validated and standardized tool to evaluate

postoperative functional results and their effects on

quality of life. Other difficulties in the analysis of

the relevant surgical literature include:

1. Variability in inclusion and exclusion criteria

2. Multiple modifications of the surgical techniques

3. Short-term published follow-up

4. Lack of independent postoperative reviewers

5. Combination with other reconstructive procedures

6. Lack of validated symptom scales

The surgical approach for the treatment of

posterior vaginal wall prolapse can be divided

into transvaginal, transanal, transperineal, and

abdominal, and open or laparoscopic procedures.

Fig. 27.10. Enterocele demonstrated during defacography. Series of frames prior and during valsalva maneuver

demonstrating small bowel loop descent deep into the perineum (reprinted with permission Lahr, C. Why Can't I Go

Charleston: Sunburst Press, 2004)

Table 27.8. NIH criteria for posterior compartment surgical outcome.

Optimal

anatomical outcome

Cure No prolapse of the posterior

vagina is demonstrated

Stage 0 by ICS staging, with

points Ap and Bp at −3cm

Satisfactory

anatomical outcome

Improvement Descent of the posterior vagina to

within 1cm above the hymen

Stage 1 by ICS staging, with

point Ap or Bp at −2cm

Unsatisfactory

anatomical outcome

Persistence or recurrence,

failed treatment

Descent of the posterior vagina to

1cm proximal to the hymen or

lower, or no change or worsen-

ing from pretreatment stage

Stage 2 or worse by ICS staging,

with points Ap or Bp at −1cm

or lower, or no change or

worsening from pretreatment

position

380 G. Levy and B.H. Gurland

Independent of the surgical technique, chronic

increased abdominal pressure can cause recurrence

of the anatomical defect. High intraperitoneal pres-

sure is associated with body mass index (BMI)

>35; heavy smokers; chronic heavy lifters, such

as nurses or impact sports players; and chronic

constipation. Established risk assessment scales to

improve success rate predictions of these high-risk

patients do not exist.

The transvaginal approach to posterior vaginal

wall repair is preferred by gynecologists and can be

divided into four surgical techniques: (1) midline

plication of the levator ani muscles [44] ; (2) plica-

tion of the rectovaginal septum [45] ; (3) site-specific

repair of the discrete tears in the rectovaginal sep-

tum [46] ; and (4) posterior colporrhaphy using graft

material. Overall, all of these techniques provide

adequate anatomic repair of the posterior vaginal

wall, but they vary in regard to functional success

and complications. Midline levator ani plication

has been criticized due to reports of postoperative

constipation and dyspareunia in 19–41% of patients

[44, 47– 49] . The midline plication of the rectovagi-

nal fascia was reported to improve obstructed def-

ecation in over 80% of patients [50, 51] . Patients

who underwent the site-specific repair had a higher

anatomical failure rate compared to those who

underwent rectovaginal septum plication. However,

patients who underwent site-specific repair denied

significant dyspareunia, but they failed to document

an improvement in fecal symptoms.The literature

describing the use of graft material for posterior

vaginal wall repair is limited to case series reports

that lack level I evidence. Graft material initially

was used to augment the site-specific repair using

the graft as a buttress. As the techniques evolved,

grafts were used to replace the rectovaginal septum

with the assumption that the defect not only is a

physical tear and/or detachment but is due to an

intrinsic weakness of the tissue from decreased col-

lagen quality secondary to genetic, hormonal, and

aging factors. It was theorized that the grafts would

provide scaffolding for regeneration of collagen.

This premise was based on laboratory evidence of

fibroblast migration into the biomaterial as early as

a few weeks after surgery [52– 55] . However, further

studies failed to document histological evidence of

an increased endogenous collagen production at the

posterior compartment implant site 6 months after

surgery [56] .

There are many variations of graft materials and

anchoring techniques. Both biological and synthetic

graft materials have been used to repair posterior vag-

inal wall prolapse. The biological materials include

allografts and xenografts. Allografts are harvested

from cadaveric fascia or dermis. Chemical cross-

linking of cadaveric products increases durability

but also can result in an inflammatory reaction,

fibrosis, or scar formation. However, allografts are

at an extremely low risk for erosion. Xenografts

include porcine dermis or small intestine and

bovine pericardium. Xenografts also can be chemi-

cally cross-linked or minimally processed. The

synthetic materials used are either absorbable

(Polyglactine 910 = Vicryl) or permanent [poly-

propylene (Prolene), polytetrafluoroethylene

(Gore-Tex), polyester fiber (Mersilene), or knitted

polyesther (Dacron)]. The synthetic materials are

fenestrated with holes of at least 100 m m to allow

fibroblasts migration and tissue regeneration.

Kohli and Miklos [57] reported 93% anatomic

success rate, at 12-month follow-up, using porcine

dermis as a buttress following site-specific poste-

rior colporrhaphy. Altman et al. [58] reported 41%

success rate using the same biomaterial anchored

to the levator muscles, perineal body, and the

upper rectovaginal septum without performing

the site-specific repair. Furthermore, he reported

a dramatic drop in success rate with long-term

follow-up. Symptoms of incomplete emptying and

a decreased need for hand-assisted defecation sig-

nificantly improved, but overall the improvement

was reported in less than 50% of patients.

There are few reports that describe the use of

synthetic graft material for posterior vaginal wall

repair. The synthetic grafts usually are anchored

to strong anatomical structures such as the sacros-

pinous ligaments, arcus tendineous, obturator fas-

cia, and muscle. An alternative to graft fixation was

described by Petros, who introduced the concept of

a neoligament as an anchoring technique using the

IVS tunneler in an infracoccygeal approach [59] .

Short-term follow-up for patients undergoing

posterior repair with synthetic mesh reveals an

anatomic success rate of 85% and a subjective cure

rate of 60–80%. The main complications reported

after synthetic graft use are postoperative dyspare-

unia and mesh erosion in 69 and 13%, respectively

[60] . However, de Tayrac et al. reported their series

of patients undergoing posterior colporraphy with

27. Posterior Compartment Repair and Fecal Incontinence 381

synthetic graft material anchored to the sacros-

pinous ligaments and perineal body without

site-specific repair [61] . He reported significant

improvement in bowel symptoms and sexual func-

tion using validated questionnaires and quality of

life tools.

The transanal or transperineal approaches are

preferred by colorectal surgeons who have limited

training operating on the vagina. The indications

for surgery are complaints of difficult evacuation,

manual digitation, rectocele >4cm, and residual

contrast in the rectocele by defecography [62] .

Evidence of nonrelaxing puborectalis is associated

with poor functional results [63] .

Most studies reveal improvement of rectal symp-

toms with transanal rectocele repair [64, 65] .

However, there is level I evidence that transvaginal

repair is superior to transanal because of better

anatomic repair with equivalent functional results

reporting cure rates approaching 75%, independent

of the approach [66, 67] .

The transperineal approach involves the same

surgical techniques used in the transvaginal route

except the approach to the surgical space is made

through a perineal incision, avoiding incision of

the vaginal mucosa [68] . Insertion of the mesh

for the reconstruction of the rectovaginal septum

through the perineum provides comparable suc-

cess rates but lacks long-term follow-up [69] .

The transperineal approach may be the preferred

technique when rectocele repair is performed in

combination with overlapping sphincteroplasty

and perineoplasty.

Abdominal open or laparoscopic procedures

usually are performed for a combination of apical

and posterior wall prolapse and are based on the

sacrocolpopexy techniques with the use of graft

material. Lyons and Winer [70] report a laparo-

scopic approach using absorbable material with

80% resolution of prolapse symptoms and digital-

assisted defecation at 1-year follow-up. Other

authors have suggested additional modifications

to the abdominal sacrocolpopexy by extension and

fixation of the mesh down to the level of the leva-

tor ani or perineal body. In addition to correcting

apical prolapse and posterior compartment defects,

these procedures are designed to improve exces-

sive perineal descent [71] . Fox and Stanton [72]

reported 93% success rate using a Teflon mesh,

but functional symptoms did not improve. On the

other hand, Sullivan et al. describe their experience

with a total Marlex pelvic mesh repair achieving

excellent anatomical results and 75% improvement

in bowel symptoms [73] .

Classic teachings have included obliteration

of the pouch of Douglas, enterocele repair, as an

integral part to the success of apical and posterior

compartment reconstruction. Procedures such as

the Moschcowitz and Hallban culdoplasty involved

obliteration of the cul-de-sac by approximating the

peritoneum [74, 75] . The Mayo-modified McCall

technique with reconstruction of level one support

was reported to provide an anatomical success

rates of 82% [76– 78] .However, it is impossible to

analyze the contribution of the enterocele resec-

tion to the final anatomical or functional success,

because enterocele repair usually performed in

conjunction with other prolapse procedures. It is

interesting to note that current surgical techniques

using graft material for the repair of vaginal apex

do not emphasize enterocele resection as a manda-

tory step to avoid recurrence.

Richardson proposed that an enterocele resulted

from a defect in the integrity of the endopelvic

fascia at the vaginal apex [79] . He described

enterocele repair in combination with site-specific

rectocele repair by reapproximation of the upper

edge of the rectovaginal septum to the pubocervi-

cal fascial edge and uterosacral ligament. High

anatomic success rates were reported using this

site-specific approach but functional results were

not discussed [80] .

Treatment Options for Fecal Incontinence

The initial management of patients with fecal

incontinence focuses on improving stool consist-

ency and decreasing the overall number of bowel

movements with a high-fiber diet, bulking agents,

and constipating medications. Most medical thera-

pies reported are geared toward the treatment of

diarrhea rather than fecal incontinence and lit-

tle evidence exists to guide the physician in the

selection of drug therapies [81] . For patients with

leakage of stool secondary to fecal impaction or

decreased rectal sensation, fiber therapy, laxa-

tives, and a daily enemas help to empty the rectal

vault and minimize fecal accidents. Noninvasive

modalities such as intra-anal and pelvic floor

muscle strengthening exercises (biofeedback) for

382 G. Levy and B.H. Gurland

the treatment of fecal incontinence are reported to

improve continence scores [82] . Due to a limited

number of studies and methodological weaknesses,

the Cochrane Incontinence Group Trials Register

failed to identify a major difference in outcome

between any method of biofeedback or exercises

for fecal incontinence or an improvement compared

to conservative measures [83] . We offer intra-anal

biofeedback for fecal incontinence to patients with

normal sphincter anatomy or to patients who refuse

or are poor candidates for surgical repair.

Bulking agents injected into the anal sphincter

such as those approved for use in patients with

urinary stress incontinence also have been tried to

treat passive fecal leakage for patients with normal

sphincter anatomy or patients with isolated internal

sphincter injuries. Different materials and injection

techniques have been reported but are confined to

small pilot studies and presently are not available

for widespread use [84] . The SECCA procedure

is an additional option for patients with normal

sphincter anatomy and fecal incontinence. This

involves radio frequency energy delivery into the

anal canal and has been proven to be well tolerated

and efficacious [85] .

Anterior anal sphincter injuries frequently are

identified in patients who complain of fecal incon-

tinence in addition to other pelvic floor disorders

such as urinary incontinence or advanced pelvic

organ prolapse [86] . Surgical repair can be per-

formed concomitantly with other pelvic floor pro-

cedures with good outcomes and cost effectiveness

[87] . Furthermore, Steele et al. reports that patients

who underwent anterior overlapping sphincter

repair in conjunction with total pelvic floor repair

had better functional results than patients with

sphincteroplasty alone [88] . Other authors have not

corroborated these findings. We offer these patients

combined urinary, prolapse, and anorectal surgical

procedures. The additional benefits to the patient

include a single anesthesia and recovery time and

overall decreased disability.

There are several techniques described for anal

sphincteroplasty. Obstetricians most commonly

perform apposition of the external anal sphincter

with an end-to-end technique. Overlapping sphinc-

teroplasty is preferred by colorectal surgeons for

external or external and internal anal sphincter

injuries. For immediate primary repair following

obstetric injury overlap repair is associated with

less fecal urgency and lower incontinence scores

at 1 year compared to end-to-end approxima-

tion [89, 90] . Although fecal incontinence scores

are improved following sphincteroplasty, complete

continence is difficult to achieve and tends to dete-

riorate over time [91, 92] . Pudendal neuropathy has

been implicated as a poor prognostic indicator in

patients undergoing overlapping sphincter repair,

but it is not a contraindication to surgery [35, 93] .

Postanal repair involves posterior levatorplasty

and is thought to improve continence by lengthen-

ing the anal canal and making the anorectal angle

more acute. Postanal repair can be considered in

patients without a sphincter defect and low resting

pressures who failed or do not wish to undergo

biofeedback. It also is an option for patients for

whom overlapping sphincter repair has achieved

anatomical but not functional improvement.

Reports of poor long-term success rates and the

introduction of newer, less invasive techniques

have discouraged many surgeons from offering

postanal repair [94] .

Sacral nerve stimulation (SNS) is geared

toward neuromodulation instead of anatomic

repair. It has been proven beneficial for the treat-

ment of voiding disorders, and European studies

document up to 80% success rate using SNS

in the treatment for patients with fecal incon-

tinence, an intact sphincter, and normal sacral

plexus [95– 97] . The most common technique

includes a two-phase procedure. An electrically

stimulated spinal needle is placed percutaneously

under fluoroscopic guidance in the S3 foramina.

The electrode is connected to an external pulse

generator for the testing period of 10–14 days

and the patient is asked to complete a symptom

diary. Patients that demonstrate at least 50%

improvement are offered the second phase dur-

ing which a permanent stimulator is implanted

subcutaneously in the upper part of the gluteal

area. SNS was thought to increase the anal canal

closure pressure resulting from contraction of

the puborectalis and sphincter muscles and trans-

formation of fast twitch, fatigable muscle fibers

(type 2) to slow twitch, fatigue-resistant fibers

(type 1) [98] . However, changes in anal resting

and squeeze pressure have not been consist-

ently reported. Other authors propose that SNS

improves rectal sensation and compliance, thus

decreasing fecal urgency [99, 100] .

27. Posterior Compartment Repair and Fecal Incontinence 383

Neosphincter procedures are an option for

patients with congenital abnormalities, neurogenic

incontinence, or those who have failed other repairs.

These procedures control continence by mimicking

the natural action of the sphincter muscles using a

muscle interposition, dynamic graciloplasty, or an

inflatable plastic cuff around the anus [artificial

bowel sphincter (ABS)]. Controlled clinical trials

reveal that either procedure improves continence

or quality of life. However, adverse events such

as infection, erosion, or ulceration are common

[101– 103] . The neurotransmitter used to stimulate

the gracilis muscle is no longer available in the

United States leaving the ABS as the procedure of

choice for patients considering a neosphincter.

It is difficult to make comparisons among the

procedures listed above. Presently, there are no

randomized trials comparing the techniques,

identifying one procedure as superior to another.

Furthermore, for patients who have intractable

fecal incontinence and who have failed other meas-

ures permanently, colostomy is a viable option.

Treatment of Outlet Type Constipation

The initial management of patients with complaints

of constipation is to exclude organic and ana-

tomic causes, colonic dysmotility, and extraintes-

tinal processes. First-line therapies include bulking

agents, laxatives, enemas, and enterokinetic agents.

Increased dietary fiber (bulking agents) increases

stool weight and frequency of defecation and

decreases intestinal transit time in nonconstipated

patients. Most symptoms associated with func-

tional constipation can be improved by increasing

dietary fiber to 20–30g per day. In some situa-

tions, increasing dietary fiber may make symptoms

worse, resulting in cramping and flatulence.

Laxatives liquefy stool and increase the propul-

sive activity, thus overcoming abnormal expulsive

forces. Osmotic laxatives include magnesium-

containing products, polyethelyene glycol, and

nonabsorbable sugars such as lactulose and sorbi-

tol. Through different mechanisms these products

increase intraluminal water content and promote

bowel activity. Stimulant laxative—senna and

bisacodyl—are metabolized by intestinal flora and

then increased fluid and electrolyte accumulation

in the distal ileum and colon. There are concerns

that long-term use of stimulant laxatives harm the

colon and promote dependency and habituation.

However, these products may be useful in patients

with occasional constipation [104] . Enema use

may consist of tap water, saline, or commercially

available sodium phosphate combinations. These

may be helpful in patients with diminished rectal

sensation or megarectum.

Enterokinetic agents increase intestinal motil-

ity through various mechanisms. Presently, there

are only two commercially available medications:

tegaserod and lubiprostone. Tegaserod (Zelnorm)

is a 5-hydroxytryptamine agonist that stimulates

intestinal motility by facilitating enteric choliner-

gic transmission. It is FDA approved for women

with constipation-predominant IBS and in some

studies shows modest effectiveness for chronic

constipation in men and women younger than 65

years old [105] . Lubiprostone, a selective type

2 chloride channel activator, accelerates small

bowel and colonic transit by activating intestinal

chloride channels and increases intestinal fluid

secretion without altering serum electrolyte levels.

It is approved for patients of all ages with chronic

constipation. These medications are fairly new and

trials are needed to assess their role in outlet type

constipation.

Pelvic floor biofeedback aims at retraining the

pelvic floor muscles to relax, strengthening, and

sensory training. Uncontrolled studies suggest

that approximately 70% of patients with pelvic

floor dyssynergia type constipation (paradoxical

contraction of the puborectalis) benefit from bio-

feedback to learn to effectively relax the pelvic

floor during defecation [106] . A randomized, con-

trolled trial of biofeedback compared to laxative

treatment revealed that five biofeedback sessions

are more effective than continuous polyethylene

glycol for treating pelvic floor dyssynergia [107] .

For patients with dysynergia who fail conserva-

tive measures and biofeedback, there is anecdotal

evidence that botulinum toxin injected intramus-

cularly into the puborectalis provides sympto-

matic relief [108] .

Biofeedback and diet modification for patients

with large rectoanal intussusception (occult rectal

prolapse) reveal 30% improvement of evacuation

symptoms with these noninvasive modalities [109] .

Despite the low success rate, biofeedback fre-

quently is offered as first-line therapy for patients

with rectoanal intussusception because there is

384 G. Levy and B.H. Gurland

no consensus in the literature as to the benefit of

surgical repair. Johnson et al. reports improvement

of evacuation symptoms following rectopexy or

sigmoid resection and rectopexy [110] . However,

other authors report that abdominal rectopexy or

mucosal resection are associated with high recur-

rence rate for constipation [111, 112] .

Stapled transanal rectal resection (STARR) is

a promising technique specifically for patients

with outlet-type constipation and clinical findings

of rectal intussusception, rectocele, and mucosal

prolapse. STARR is based on the stapled hemor-

rhoidopexy procedure frequently used by color-

ectal surgeon for the treatment of hemorrhoids.

It employs a double-stapled circumferential full

thickness resection of the lower rectum using

two proximate PPH-01 stapling guns (Ethicon

Endosurgery, Ohio USA). The first staple line is

placed anteriorly and reduces the intussusception

and the bulging rectocele, correcting the anterior

wall defect, and the second staple line is placed

posteriorly and is aimed at correcting the intus-

susception.

Boccasanta et al. report a prospective multicenter

trial of 90 patients who underwent the STARR with

100% improvement of constipation symptoms and

no complaints of worsening fecal incontinence or

dyspareunia. The outcome at 1 year was excellent

in 53%, good in 37%, fairly good in 6%, and poor

in 4% [113] . Renzi et al. report their results on 14

patients who underwent STARR and a successful

outcome was achieved in 90% [114] . At this time

there is only limited objective analysis available

for the STARR. Contraindications to this procedure

include full thickness rectal prolapse, enterocele at

rest, the presence of mesh or foreign material adja-

cent to the rectum, anal incontinence, and proctitis

[115] .

Rectocele repair for symptomatic outlet-type

constipation is discussed in detail earlier in this

chapter with a mean improvement of difficult

evacuation of 75–80% regardless of transanal or

transvaginal techniques [66, 67] . At our institution

rectocele repair is performed through the transvagi-

nal route by the urogynecologist, but concomitant

rectal pathologies are identified preoperatively and

combined procedures are performed if needed.

Sacral nerve stimulation presently is under

investigation for use in constipation. As a coinci-

dental finding in patients undergoing sacral nerve

stimulation for lower urinary tract dysfunction,

many patients experienced an increase in bowel

frequency and improved defecation. Ongoing

trials suggest modest symptomatic improvement

[116, 117] .

Treatment of Rectal Prolapse and

Combined Pelvic Organ Prolapse

Correction of rectal prolapse can be performed

through a perineal, abdominal, or laparoscopic

technique. Narrowing the anal canal with encir-

cling devices, Thiersch wire, or its modifications

can prevent the prolapse from emerging but does

not repair the process and is reserved for patients

whose comorbid status is too high for other options

[118] . For elderly women, we prefer the perineal

approach, while younger, healthier patients are

offered abdominal and laparoscopic procedures.

The perineal approach can be performed under

regional anesthesia and is associated with minimal

postoperative pain and avoids the complications

and disabilities associated with abdominal surgery.

There are two widely used perineal procedures:

mucosal resection (Delorme procedure) and peri-

neal rectosigmoidectomy (Altemeier procedure).

The Delorme procedure involves resection of the

redundant rectal mucosa and plication of the mus-

cular layer. Perineal rectosigmoidectomy entails

full thickness rectal and sigmoid resection through a

transanal approach. The addition of levatorplasty is

associated with improved fecal continence. Agachan

et al. compared the Delorme procedure, perineal

rectosigmoidectomy, and perineal rectosigmoidec-

tomy with levatorplasty and found recurrence rates

of 38, 13, and 5%, respectively [119] . Postoperative

continence was improved in all three procedures,

but incontinence scores were lowest for patients

who underwent perineal rectosigmoidectomy with

levatorplasty. We prefer this procedure for elderly

patients with extensive rectal prolapse. However,

this is difficult to perform on patients with minimal

prolapse or in those whose prolapse is not full thick-

ness in its entire circumference and a modification

of the Delorme procedure is offered [120] .

Overall, recurrence rates are the lowest with

an abdominal procedure at 0–4% [121, 122] .

Abdominal rectopexy involves fixation of the rec-

tum to the sacrum with sutures or mesh. Equivalent

27. Posterior Compartment Repair and Fecal Incontinence 385

recurrence and functional improvement rates are

reported between open and laparoscopic tech-

niques [123] . There are three major procedures

discussed: posterior suture fixation, posterior mesh

rectal fixation (Wells or Ripstein), or ventral

rectal fixation (Orr-Loygue). Rectopexy alone is

preferred for patients with fecal incontinence and

rectal prolapse. Sigmoid resection performed in

conjunction with sutured rectopexy (Frykman-

Goldberg) is frequently performed for patients

with preoperative constipation and rectal prolapse

[124] . Postoperative constipation is a complication

reported with rectopexy and is thought to be asso-

ciated with denervation injuries caused by division

of the lateral rectal ligaments [125] . Portier et al.

reports that limited rectal dissection and preser-

vation of the lateral ligaments seems to prevent

postoperative constipation without increasing the

risk of prolapse recurrence [126] . There is no clear

predominant treatment of choice and the results of

all abdominal procedures are comparable. Surgeon

experience and training dictate the technique pref-

erence. There are few reports in the literature

discussing combined surgical procedures for rectal

and genital prolapse and advocating its effective-

ness [127, 128] . In our institution, we perform

multicompartment prolapse procedures with a sur-

gical team of both a gynecologist/urogynecologist

and colorectal surgeon. Preoperative symptoms,

patient comorbidites, and established prolapse

recurrence rates factor into the decision-making

process. The choice of procedure is individualized

for each patient.

References

1. Weber A, Abrams P, Brubaker L, et al. The stand-

ardization of terminology for researchers in female

pelvic floor disorders. Int Urogynecol J Pelvic Floor

Dysfunct 2001; 12(3):178–186.

2. Jelovsek J, Barber M, Paraiso M, Walters M.

Functional bowel and anorectal disorders in patients

with pelvic organ prolapse and incontinence. Am J

Obstet Gynecol 2005; 193(6):2105–2111.

3. Kupfer C, Goligher J. One hundred consecutive

cases of complete prolapse of the rectum treated by

operation. Br J Surg 1970; 57(7):482–487.

4. Peters W, Smith M, Drescher C. Rectal prolapse in

women with other defects of pelvic floor support.

Am J Obstet Gynecol 2001; 184(7):1488–1494;

discussion 1494–1495.

5. Altman D, Zetterstrom J, Schultz I, et al. Pelvic

organ prolapse and urinary incontinence in women

with surgically managed rectal prolapse prolapse:

A population-based case-control study. Dis Colon

Rectum 2005; 49:28–35.

6. Nichols C, Ramakrishnan V, Gill E, Hurt W. Anal

incontinence in women with and those without

pelvic floor disorders. Obstet Gynecol 2005;

106(6):1266–1271.

7. Sultan AH, Kamm MA, Hudson CN et al. Anal

sphincter disruption during vaginal delivery. N Engl

J Med 1993;329:64–70.

8. Bliss DZ, Fischer LR, Savik K et al. Severity of

fecal incontinence in community-living elderly in a

health maintenance organization. Res Nurs Health.

2004; 27:162–173.

9. Siproudhis L, Bellisant E, Juguet F, et al. Rectal

adaptation to distension in patients with overt rectal

prolapse. Br J Surg 1998; 85:1527–1532.

10. Hiltunen KM, Matikainen MJ, Auvinen O, Hietanen

P. Clinical and manometric evaluation of anal

sphincter function in patients with rectal prolapse.

Am J Surg 1986; 151:489–492.

11. Kairaluoma MV, Kellokumpu IH. Epidemiologic

aspects of complete rectal prolapse. Scand J Surg

2005; 94:207–210.

12. Weber A, Walters M, Ballard L, et al. Posterior vagi-

nal wall prolapse and bowel function. Am J Obstet

Gynecol 1998; 179:1446–1450.

13. Ellerkmann R, Cundiff G, Melik C, et al. Correlation

of symptoms with location and severity of pel-

vic organ prolapse. Am J Obstet Gynecol 2001;

185:1332–1338.

14. Kahn M, Breitkopf C, Valley M, et al. Pelvic organ

support study and bowel symptoms: Straining at

stool is associated with perineal and anterior vaginal

descent in a general gynecologic populations. Am J

Obstet Gynecol 2002; 192:1516–1522.

15. da Silva G, Gurland B, Sleemi A, Levy G. Posterior

vaginal wall prolapse does not correlate with

fecal symptoms or objective measures of anorec-

tal function. Am J Obstet Gynecol 2006; 195(6):

1742–1747.

16. Bump R, Mattiasson A, Bo K, et al. The stand-

ardization of terminology of female pelvic organ

prolapse and pelvic floor dysfunction. Am J Obstet

Gynecol 1996; 175:10–17.

17. Altman D, Lopez A, Kierkegaard J, et al. Assessment

of posterior vaginal wall prolapse: Comparison of

physical findings to cystodefecoperitoneography. Int

Urogynecol J 2005; 16:96–103.

18. Brubaker L, Baker R, Jacquentin B, et al. Pelvic

organ prolapse. In: Abrams P, Cardozo L, Khoury

S, Wein AJ, eds. 2nd International consultation on

386 G. Levy and B.H. Gurland

incontinence. Plymouth, UK: Health Publication,

2002:243–265.

19. Strohbelm K. Normal pelvic floor anatomy. Obstet

Gynecol Clin North Am 1998; 25:683–705.

20. Leffler KS, Thompson JR, et al. Attachment of the

rectal vaginal septum to the pelvic sidewalls Am J

Gynecol 2001; 185:41–43.

21. Richardson AC. The anatomic defects in rectocele

and enterocele. J Pelvic Surg 1995; 4:214–221.

22. Levi A, Borghi F, Garavoglia M. Development of

the anal canal muscles. Dis Colon Rectum 1990;

34:262–266.

23. Lester B, Penninckx F, Kerremans R. The com-

position of anal basal pressure. An in vivo and in

vitro study in man. Int J Colorectal Dis 1989; 4:

118–122.

24. Gibbons CP, Trowbridge EA, Bannister JJ, Read

NW. Role of anal cushions in maintaining conti-

nence. Lancet 1986; 1:886–887.

25. Rothbarth J, Bemelman W, Meijerink W, et al. What

is the impact of fecal incontinence on quality of life?

Dis Colon Rectum 2001; 44:67–71.

26. Barber MD, Walters MD, Bump RC. Short forms of

two condition-specific quality of life questionnaires

for women with pelvic floor disorders (PFDI-20

and PFISQ-7). Am J Obstet Gynecol 2005; 193:

103–113.

27. Rogers RG, Coates KW, Kammerer-Doak DN,

et al. A short form of the pelvic organ prolapse/

urinary incontinence sexual questionnaire (PISQ-

12). Int Urogynecol J Pelvic Floor Dysfunct 14(3):

164–168.

28. Rao SS, Patel RS. How useful are manometric

tests of anorectal functions in the management of

defecation disorders? Am J Gastroenterol 1997;

92:469–475.

29. Jorge J, Wexner S. A practical guide to basic anorec-

tal physiology investigations. Contemp Surg 1996;

43:214–224.

30. Ahran P, Faverdin C, Persoz B, et al. Relationship

between viscoelastic properties of the rectum and anal

pressures in man. J Appl Physio 1976;41:677–704.

31. Rasmussen O. Anorectal function. Dis Colon

Rectum 1994; 37:386–403.

32. Hancke E, Schurholz M. Impaired rectal sensation

in idiopathic fecal incontinence. Int J Colorectal Dis

1987; 2:146–148.

33. Hill J, Hosker G, Kiff E. Pudendal nerve terminal

motor latency measurements: What they do and do

not tell us. Br J Surg 2002; 89:1268–1269.

34. Ricciardi R, Mellgren AF, Madoff RD, et al. The

utility of pudendal nerve terminal latencies in idi-

opathic incontinence. Dis Colon Rectum 2006;

49:852–857.

35. Gilliland R, Altomare D, Moreira H, et al. Pudendal

neuropathy is predictive of failure following anterior

overlapping sphincteroplasty. Dis Colon Rectum

1998; 41:1516–1522.

36. Zetterstrom J, Mellgren A, Madoff R, et al. Perineal

body measurements improves evaluation of anterior

sphincter lesions during endoanal ultrasonography.

Dis Colon Rectum 1998; 41:705–713.

37. Oberwalder M, Thaler K, Baig M, et al. Anal

ultrasound and endosonographic measurements of

perineal body thickness: A new evaluation for

fecal incontinence in females. Surg Endosc 2004;

18:650–654.

38. Sleemi A, Levy G, Gurland B. Correlation between

perineal body measurements and anal sphincter

defect in patients with fecal Incontinence. Abstract

presented at the Society for Gynecologic Surgeons

(SGS), 31st Scientific Meeting, California, April

2005.

39. Jorge J, Habr-Gama A, Wexner S. Clinical applica-

tions and techniques of cinedefecography. Am J

Surg 2001; 182:93–101.

40. Thompson J, Chen A, Pettit P, Bridges M. Incidence

of occult rectal prolapse in patients with clinical

rectoceles and defecatory dysfunction. Am J Obstet

Gynecol 2002; 187:1494–1500.

41. Mellgren A, Johansson C, Dolk A, et al. Enterocele

demonstrated by defaecography is associated with

other pelvic floor disorders. Int J Colorect Dis 1994;

9:121–124.

42. Matsuoka H, Wexner SD, Desai MB, et al. A com-

parison between dynamic pelvic magnetic resonance

imaging and videoproctography in patients with

constipation. Dis Colon Rectum 2001; 44:571–576.

43. Roos F, Weishaupt D, Wildermuth S, et al.

Experience of four years with open MR defecog-

raphy: Pictorial review of anorectal anatomy and

disease. RadioGraphics 2002; 22:817–832.

44. Mellgren A, Anzen B, Nilsson BY, et al. Results

of rectocele repair: A prospective study. Dis Colon

Rectum 1995; 38:7–13.

45. Milley S, Nichols D. A correlative investigation of

the human rectovaginal septum. Anat Rec 1969;

163:443–451.

46. Richardson AC. The rectovaginal septum revisited:

Its relationship to rectocele and its importance in

rectocele repair. Clin Obstet Gynecol 1993; 36:

976–983.

47. Kahn M, Stanton S. Posterior colporrhaphy: Its

effects on bowel and sexual function. Br J Gynecol

1997; 104:82–86.

48. Lopez A, Anzen B, Bremmer S, et al. Durability

of success after rectocele repair. Int Urogynecol J

2001; 12:97–103.

27. Posterior Compartment Repair and Fecal Incontinence 387

49. Francis W, Jeffcoate T. Dyspareunia following

vaginal operations. J Obstet Gynecol Br Comnwlth

1961; 68:1–10.

50. Singh K, Cortes E, Reid W. Evaluation of the fas-

cial technique for surgical repair of isolated poste-

rior vaginal wall prolapse. Obstet Gynecol 2003;

101:320–324.

51. Maher C, Qatawneh A, Baessler K, Schluter P.

Midline rectovaginal fascia plication for repair of

rectocele and obstructed defecation. Obstet Gynecol

2004; 104:685–689.

52. Bartolami C, Shetty V, Milavec J, et al. Preparation

and evaluation of nonproprietary bilayer skin substi-

tute. Plast Reconstr Surg 1991; 87:1089–1098.

53. Ruiz-Torres A. Cross-linking of collagen depending

on age. Gerontology 1978; 24:337–342.

54. Hayflick L. The cell biology of aging. Clin Geriatr

Med 1985; 1:15–27.

55. Mays P, McAnulty R, Campa J, et al. Similar age

related alterations in collagen metabolism in rat tis-

sues in vivo and fibroblasts in vitro. Biochem Soc

Trans 1990; 18:957.

56. Altman D, Mellgren A, Blomgren B, et al. Clinical

and histological safety assessment of rectocele

repair using collagen mesh. Acta Obstet Gynecol

Scand 2004; 83:995–1000.

57. Kohli N, Miklos JR. Dermal graft- augmented rec-

tocele repair. Int Urogynecol J (2003) 14:146–149.

58. Altman D, Zetterstrom J, Mellgren A, et al. A three

year prospective assessment of rectocele repair

using porcine xenograft. Obstet Gynecol 2006;

107:59–65.

59. Petros P. Vault prolapse11: restoration of dynamic

vaginal support by infracoccygeal sacropexy: An

axial day case vaginal procedure. Int Urogynecol J

2001; 12:296–303.

60. Salvatore S, Soligo M, Meschia M, et al. Prosthetic

surgery for genital prolapse: Functional outcome.

Neurourol Urodyn 2002; 21:296–297.

61. de Tayrac R, Picone O, Chauveaud-Lambling A,

Fernandez H. A 2 year anatomical and functional

assessment of transvaginal rectocele repair using

a polypropylene mesh. Int Urogynecol J 2006;

17:100–105.

62. Rosato GO. Rectocele and perineal hernias. In: Beck

DE, Wexner SD, eds. Fundamentals of anorectal sur-

gery, Second ed. London: W.B. Saunders Company.

1998:187–197.

63. Tjandra JJ, Ooi BS, Tang CL, et al. Transanal repair

of rectocele corrects obstructed defecation if it is not

associated with anismus. Dis Colon Rectum 1999;

42:1544–1549.

64. Altomare D, Rinaldi M, Veglia A, et al. Combined

perineal and endorectal repair of rectocele by circu-

lar stapler: A novel surgical technique. Dis Colon

Rectum 2002; 45:1549–1552.

65. Stojkovic S, Balfour L, Burke D, et al. Does the

need to self-digitate or the presence of a large or

nonemptying rectocele on proctography influence

the outcome of transanal rectocele repair? Colorectal

Disease 2003; 5:169–172.

66. Nieminen K, Hiltunen K, Laitinen J, et al. Transanal

or vaginal approach to rectocele repair; results of

prospective randomized study. Neurourol Urodyn

2003; 22:547–548.

67. Kahn M, Stanton S, Kumar D, Fox SD. Posterior

colporrhaphy is superior to the transanal repair

for treatment of posterior vaginal wall prolapse.

Neurourol Urodyn 1999; 18:70–71.

68. Watson S, Loder P, Halligan S, et al. Transperineal

repair of symptomatic rectocele with Marlex mesh:

A clinical, physiological and radiologic assessment

of treatment. J Am Coll Surg 183:257–261.

69. Parker M, Phillips R. Repair of rectocele using

Marlex mesh. Ann R Coll Surg Engl 75:193–194.

70. Lyons T, Winer W. Laproscopic rectocele repair

using polyglactin mesh. J Am AssocGynecol

Laparosc 1997; 4:381–384.

71. Cundiff GW, Harris RL, Coates K, et al. Abdominal

sacral colpoperineopexy: A new approach for cor-

rection of posterior compartment defects and peri-

neal descent associated with vaginal vault prolapse.

Am J Obstet Gynecol 1997; 177:1345–1355.

72. Fox SD, Stanton SL. Vault prolapse and rectocele:

Assessment of repair using sacrocolpopexy with

mesh interposition. BJOG 2000; 107:1371–1375.

73. Sullivan E, Longaker C, Lee P. Total pelvic mesh

repair: A ten-year experience. Dis Colon Rectum

2001; 44:857–863.

74. Hallban J. Operative gynecology. Berlin, Urban and

Schwarzenberg, 1932:172.

75. Moschcowitz A. The pathogenesis, anatomy and

cure of prolapse of the rectum. Surg Gynecol Obstet

1912; 15:7–14.

76. Webb M, Aronson M, Ferguson L, et al.

Posthysterectomy vaginal vault prolapse: Primary

repair in 693 patients. Obstet Gynecol 1998; 92:

281–285.

77. Shull B, Bachofen C, Coates K, Kuehl T. A trans-

vaginal approach to repair of apical and other

associated sites of pelvic organ prolapse with utero-

sacral ligaments. Am J Obstet Gynecol 2000; 183:

1365–1374.

78. Karram M, Goldwasser S, Kleeman S, et al. High

uterosacral vaginal vault suspension with fascial

reconstruction for vaginal repair of enterocele and

vaginal vault prolapse. Am J Obstet Gynecol 2001;

185:1339–1343.

388 G. Levy and B.H. Gurland

79. Richardson A. The anatomic defects in rectocele

and enterocele. J Pelvic Surg 1995; 1:214–221.

80. Miklos J, Kohli N, Lucente V, Saye W. Site-specific

fascial defects in the diagnosis and surgical man-

agement of enterocele. Am J Obstet Gynecol 1998;

179:1418–1423.

81. Cheetham M, Brazzelli M, Norton C, Glazener C.

Drug treatment for faecal incontinence in adults.

Cochrane Database Syst Rev 2003; 3:1–67.

82. Guillemot F, Bouche B, Gower-Rousseau C, et al.

Biofeedback for the treatment of fecal incontinence.

Dis Colon Rectum 1994; 38:393–397.

83. Norton C, Cody J, Hosker G. Biofeedback and/or

sphincter exercises for the treatment of faecal incon-

tinence in adults. Cochran Database Syst Rev 2006;

3:CD002111.

84. Vaizey C, Kamm M. Injectable bulking agents

for treating faecal incontinence. Br J Surg 2005;

92:521–527.

85. Efron J, Corman M, Fleshman J., et al. Safety and

effectiveness of temperature controlled radiofre-

quency delivery to the anal canal (SECCA proce-

dure) for the treatment of fecal incontinence. Dis

Colon Rectum 2003; 46:1606–1618.

86. F Nichols C, Gill E, Nguyen T, et al. Anal sphincter

injury in women with pelvic floor disorders. Obstet

Gynecol. 2004; 104:690–696.

87. Halverson A, Hull T, Paraiso M, Floruta C. Outcome

of sphincteroplasty combined with surgery for uri-

nary incontinence and pelvic organ prolapse. Dis

Colon Rectum 2001; 44:1421–1426.

88. Steele S, Lee P, Mullenix P, et al. Is there a role

for concomitant pelvic floor repair in patients with

sphincter defects in the treatment of fecal inconti-

nence. Int J Colorectal Dis 2006; 21:508–514.

89. Fernando R, Sultan A, Kettle C, et al. Methods of

repair for obstetric anal sphincter injury. Cochrane

Database Syst Rev 2006; 3:CD002866.

90. Fernando R, Sultan A, Kettle C, et al. Repair

techniques for obstetric anal sphincter injuries: A

randomized controlled trial. Obstet Gynecol 2006;

107(6):1261–1268.

91. Zorcolo L, Covotta L, Bartolo C. Outcome of anterior

sphincter repair for obstetric injury: Comparison of early

and late results. Dis Colon Rectum 2005; 48:524–531.

92. L Halverson A, Hull T. Long-term outcome of over-

lapping anal sphincter repair. Dis Colon Rectum

2002; 45:345–348.

93. Chen A, Luchtefeld, Senagore A, et al. Pudendal

nerve latency: Does it predict outcome of anal

sphincter repair? Dis Colon Rectum 1998; 41:

1005–1009.

94. Matsuoka H, Mavrantonis C, Wexner S, et al.

Postanal repair for fecal incontinence—Is it worth-

while? Dis Colon Rectum 2000; 43:1561–1567.

95. Rosen HR, Urbarz C, Holzer B, et al. Sacral nerve

stimulation as a treatment for fecal incontinence.

Gastroenterology 2001; 121:536–541.

96. Malouf AJ, Vaizey CJ, Nicholls RJ et al. Permanent

sacral nerve stimulation for fecal incontinence.

Ann Surg 2000; 232:143–148.

97. Ganio E, Ratto C, Masin A, et al. Neuromodulation

for fecal incontinence: Outcome in 16 patients with

definitive implant. The initial Italian sacral neu-

rostimulation group(GINS) experience. Dis Colon

Rectum 2001; 44:965–970.

98. Matzel K, Stadelmaier U, Hohenfellner M, et al.

Electrical stimulation of sacral spinal nerves for

treatment of fecal incontinence. Lancet 1995;

346:1124–1127.

99. Leroi A, Parc Y, Lehur P, et al. Efficacy of sacral

nerve stimulation for fecal incontinence Ann Surg

2005; 242:662.

100. Kenefick NJ, Vaizey CJ, Cohen RC, et al. Medium

term results of permanent sacral nerve stimulation

for fecal incontinence. Br J Surg 2002; 89:896–901.

101. Baeten C, Bailey R, Bakka A, et al. Safety and

efficacy of dynamic graciloplasty for fecal inconti-

nence. Dis Colon Rectum 2000; 43:743–751.

102. O'Brien P, Dixon J, Skinner S, et al. A prospective,

randomized, controlled clinical trial of placement

of the artificial bowel sphincter (acticon neosphinc-

ter) for the control of fecal incontinence. Dis Colon

Rectum 2004; 47:1852–1860.

103. Mundy L, Merlin T, Maddern G, Hiller J. Systematic

review of safety and effectiveness of an artificial

bowel sphincter for faecal incontinence. BJS 2004;

91:665–672.

104. Wald A. Outlet dysfunction constipation.

Gastroenterology 2001; 4:293–297.

105. Johanson J, Wald A, Tougas G, et al. Effect of

tegaserod in chronic constipation: A randomized,

double blind, controlled trial. Clin Gastroenterol

Hepatol 2004; 2:796–805.

106. Heyman S, Jones K, Scarlett Y, Whitehead W.

Biofeedback treatment of constipation a critical

review. Dis Colon Rectum 2003; 46:1208–1217.

107. Chiarioni G, Whitehead W, Pezza V, et al.

Biofeedback is superior to laxatives for normal

transit constipation due to pelvic floor dyssynergia.

Gastroenterology 2006; 130:657–664.

108. Hallan R, Williams N, Melling J, et al. Treatment

of anismus in intractable constipation with botuli-

num toxin. Lancet 1988; 24:714–717.

109. Mimura T, Roy AJ, Storrie JB, Kamm MA.

Treatment of impaired defecation associated with

rectocele by behavioral retraining (biofeedback)

DCR 2000; 43:1267–1272.

110. Johnson E, Carlsen E, Mjaland O, Drolsum A.

Resection rectopexy for internal rectal intussuscep-

27. Posterior Compartment Repair and Fecal Incontinence 389

tion reduces constipation and incomplete evacua-

tion of stool. Eur J Surg 2002; 588 (Suppl):51–56.

111. Brown A, Anderson J, McKee R, Finlay I. Surgery

for occult rectal prolapse. Colorect Dis 2004; 6:

176–179.

112. Pescatori M, Boffi F, Russo A, Zbar AP.

Complication and recurrence after excision of

rectal internal mucosal prolapse for obstructed def-

ecation (oral presentation). EACP Annual Meeting,

September 17, 2004.

113. Boccasanta P, Venturi M, Stuto A, et al. Stapled

transanal rectal resection for outlet obstruction: A

prospective, multicenter trial. Dis Colon Rectum

2004; 47:1285–1297.

114. Renzi A, Izzo D, Di Sarno G, et al. Stapled

transanal rectal resection to treat obstructed defeca-

tion caused by rectal intussusception and rectocele.

Int J Colorectal Dis 2006; 21:661–667.

115. L Corman M, Carriero A, Hager T, et al. Consensus

conference on stapled transanal rectal resection

(STARR) for disordered defaecation. Colorectal

Dis 2006; 8:98–101.

116. Ganio E, Masin A, Ratto C, et al. Short term sac-

ral nerve stimulation for functional anorectal and

urinary disturbances: Results in 40 patients. Dis

Colon Rectum 2001; 44:1261–1267.

117. Keneflick NJ, Nichols RJ, Cohen RG, Kamm MA.

Permanent sacral nerve stimulation for treatment of

idiopathic constipation. Br J Surg 2002; 89:882–888.

118. Khanduja K, Hardy T, Aguilar P, et al. A new sili-

cone prosthesis in the modified Thiersch operation.

Dis Colon Rectum 198; 31:380–383.

119. Agachan F, Reissman P, Pfeifer J, et al.

Comparison of three perineal procedures for the

treatment of rectal prolapse. South Med J 1997;

90:925–932.

120. Madiba T, Maig M, Wexner S. Surgical manage-

ment of rectal prolapse. Arch Surg 2005; 140:

63–73.

121. Briel JW, Chouten WR, Boerma MO. Long term

results of suture rectopexy in patients with fecal

incontinence associated with incomplete rectal

prolapse. Dis Colon Rectum 1997; 40:1228–1232.

122. Khanna AK, Misra MK, Kumar K. Simplified

sutured sacral rectopexy for complete rectal pro-

lapse in adults. Eur J Surg 1996; 162:143–146.

123. Kariv Y, Delaney C, Casillas S, et al. Long-term

outcome after laparoscopic and open surgery for

rectal prolapse. Surg Endosc 2006; 20:35–42.

124. Frykman HM, Goldberg SM. The surgical treat-

ment of rectal procidentia. Surg Gynecol Obstet

1969; 129:1225–1230.

125. Mollen RM, Kuijupers HC, van Hoek. Effects of

rectal mobilization and lateral ligament division on

colonic and anorectal function. Dis Colon Rectum

2000; 43:1283–1287.

126. Portier G, Iovino F, Lazorthes F. Surgery for rec-

tal prolapse: Orr-Loygue ventral rectopexy with

limited dissection prevents postoperative induced

constipation without increasing recurrence. Dis

Colon Rectum 2006; 49:1136–1140.

127. Ayav A, Bresler L, Brunaud L, et al. Surgical man-

agement of combined rectal and genital prolapse

in young patients: Transabdominal approach. Int J

Colorectal Dis 2005; 20:173–179.

128. Dekel A, Rabinerson D, Ben Rafael Z, et al. Concurrent

genital and rectal prolapse: Two pathologies-one joint

operation. BJOG 2000; 107(1):125–129.

391

Part VI

Management of Male Incontinence

393

Introduction

Urinary incontinence affects up to 30% of commu-

nity-dwelling individuals over the age of 65 and

up to 50% of nursing home residents [1, 2] . This

morbid and costly condition is often responsible

for the institutionalization of the frail elderly, as

incontinence predisposes to skin breakdown, uri-

nary tract infections, falls, and hip fractures [3] .

Furthermore, the patient often succumbs to embar-

rassment, leading to social isolation and depres-

sion [4, 5] . While urgency incontinence (UI) may

affect only one third of patients who suffer from

the overactive bladder (OAB) syndrome, it is the

most common type of incontinence in adults and

has an even greater negative impact on quality of

life than does stress urinary incontinence (SUI) and

OAB [6, 7] .

With SUI, there is no effective pharmacotherapy,

yet surgical intervention often is minimally invasive,

efficacious, and with low morbidity. In contrast, the

ideal therapy for UI is not agreed upon. Behavioral

modification and biofeedback can be efficacious in

mild to moderate cases but are labor-intensive with

unproven durability. Multiple pharmacotherapeutic

agents are available and approved for OAB and UI,

but their expense, limited efficacy, and substantial

side effect profile limit their utility, especially in

older men on fixed incomes.

UI in older adults involves more than simply the

presence of an OAB. Physical function, cognitive

function, and medications are important for con-

tinence. A substantial proportion of men with UI

have a combination of both “storage” and “void-

ing” symptoms. Although voiding symptoms are

most common in older men, storage symptoms are

most bothersome (especially UI) and interfere the

most with activities of daily life. UI in males, just

as in females, usually is related to an inability to

store urine due to bladder dysfunction. However,

the presence of a potentially obstructing prostate

confounds the situation. In women, OAB can be

diagnosed based on history, physical examination,

and urinalysis, and treatment usually can be initi-

ated with a trial of behavioral modification, pelvic

floor exercises, and anitmuscarinic medications. In

men with UI, however, consideration must be given

to the possibility of an obstructed outlet, which can

have a substantial effect on the evaluation and the

treatment of UI. Regardless of the etiology, how-

ever, the goal of treatment is to alleviate symptoms,

prevent clinical deterioration, and improve quality

of life.

Nomenclature

In order to best discuss the prevalence, evaluation,

treatment, and complications associated with vari-

ous urinary disorders of storage and emptying, it

is important to categorize and properly label the

various symptoms, signs, and diagnoses associ-

ated with voiding dysfunction. This is best done

by utilizing the nomenclature provided by the

International Continence Society standardization

subcommittee [8] .

Chapter 28

Primary Urge Incontinence

Craig V. Comiter

394 C.V. Comiter

Symptoms

Storage symptoms are those symptoms experi-

enced during the storage phase of the bladder.

Examples of storage symptoms include daytime

frequency, nocturia, increased bladder sensation,

urgency and UI. Urinary incontinence has been

simplified and redefined as “the complaint of

any involuntary leakage of urine.” Urge urinary

incontinence is defined as “the complaint of

involuntary leakage (of urine) accompanied by

or immediately proceeded by urgency.” Urgency

is recognized by the International Continence

Society as “the complaint of a sudden compelling

desire to pass urine, which is difficult to defer.”

Voiding symptoms are experienced during the

voiding phase and include complaints of a slow

or intermittent stream, hesitancy, straining, split

stream, or terminal dribbling. These symptomatic

terms are descriptive, should be thought of as the

patient's complaints, and should not be used to

make a definitive diagnosis.

Signs

Signs are observed by the examiner and are useful

to verify and quantify the various lower urinary

tract symptoms (LUTS). Urodynamic observa-

tions (such as detrusor overactivity, increased

bladder sensation, and elevated voiding pressure)

are indicated to help explain LUTS, and similar to

symptoms do not represent a definitive diagnosis

or condition.

Urodynamic observations may help to explain

the symptoms but do not represent a definitive

diagnosis, disease, or condition. Whether these

observations are made during filling cystometry,

urethral pressure profilometry, voiding profilom-

etry, or pressure-flow studies, the urodynamics

are only useful if they reproduce the patients'

symptoms. For example, if a patient complains

of urgency and UI, a urodynamic evaluation that

reveals poor sensation and absent bladder contrac-

tion is not particularly useful in formulating a diag-

nosis to explain the patient's condition.

Increased bladder sensation is defined as “an

early desire to void and/or an early strong desire

to void, which occurs at low bladder volume and

persists.” Bladder compliance is the relationship

between changes in bladder volume per change

in detrusor pressure. While the International

Continence Society does not define normal val-

ues for bladder sensation and compliance, at the

author's institution the normal male usually toler-

ates at least 300 cc of water or saline without an

uncomfortable urge and demonstrates compliance

greater than 30 cc cm

−1 water pressure. Detrusor

overactivity (DO) is a urodynamic observation

characterized by involuntary detrusor contractions

(either spontaneous or provoked) during filling

cystometry and may or may not be associated

with incontinence. Although the specific change in

pressure may depend on the strength of the bladder

contraction and the resistance of the outlet, when

the change in detrusor pressure is equivocal, video

is often helpful to demonstrate a change in vesicu-

lar shape, thereby confirming the unstable bladder

contraction. Phasic DO is characterized by an

oscillating pressure wave during cystometry, while

terminal DO comprises a single involuntary detru-

sor contraction occurring at capacity, resulting in

incontinence. DO can be classified as “neurogenic”

when a neurological condition is thought to cause

the detrusor overactivity or idiopathic when invol-

untary detrusor contractions occur in the absence

of a defined neurological cause.

Detrusor hyperactivity with impaired contrac-

tility (DHIC) occurs when the bladder is overac-

tive (DO) but empties inefficiently. This impaired

emptying is associated with diminished detrusor

contractile function, of slow velocity, with little

detrusor reserve power, and a significant amount

of residual urine. DHIC may in fact represent a

more advanced stage in the natural history of DO,

characterized by deterioration of detrusor contrac-

tility [9] .

Diagnoses

Bladder outlet obstruction (BOO) is the generic

term for obstructed voiding, characterized on

urodynamics by increased detrusor pressure and

reduced urine flow rate. While no particular void-

ing pressure at maximum urinary flow rate defines

obstruction, various nomograms are useful to define

obstructed urination using a model of turbulent

flow through a collapsible tube. One must realize

that mathematical BOO is not identical to clinical

BOO. Since an obstructing prostate and a decom-

pensated bladder often may coexist, BOO should

28. Primary Urge Incontinence 395

be thought of as a term to describe the relationship

between the bladder and the outlet. For example, a

weak (decompensated) detrusor may be relatively

obstructed by a normal prostate, just as a normal

bladder may be obstructed by an overly restrictive

or compressive prostate.

Benign prostatic hyperplasia (BPH) often is

an inappropriately used term, which actually

describes the typical histopathological pattern of

increased glandular or stromal growth of the pros-

tate, and increases in prevalence with increasing

age (Fig. 28.1 ). Histology (often seen only fol-

lowing surgery or autopsy) does not correlate well

with symptoms, signs, or urodynamics. In fact,

only 25–50% of men with histological BPH have

bothersome LUTS [10] . Benign prostatic enlarge-

ment (BPE) refers to enlargement of the gland

due to histological benign prostatic hyperplasia.

Benign prostatic obstruction (BPO) is one type

of bladder outlet obstruction. BPO is diagnosed

when the cause of BOO is known to be related

to BPE, due to histological BPH. Urological lore

often recognizes these “presumptive diagnostic

terms” as definitive. However, proper use of ter-

minology can avoid significant confusion, and

along with accurate diagnostic tests can lead to

rational treatment of LUTS, potentially avoiding

unnecessary and often inefficacious pharmaco-

therapy and surgery.

Pathophysiology

Normal Storage and Voiding

The ability to eliminate metabolic toxins via liquid

waste has gone through millions of years of evolu-

tionary change. However, since passing urine can

leave a visual and olfactory footprint, thereby alert-

ing the predator to the recent position of the prey,

it is selectively advantageous to the organism to

store urine for prolonged periods of time and void

episodically [11] . In some species, coaptive evolu-

tion has linked micturition with the advantageous

behavior of marking a territory or even determining

social status and reproductive rights [11] .

As passing urine can leave the organism vulner-

able, it is necessary for the mature animal to store

urine for prolonged periods of time, while voiding

only episodically. Storage occurs at low pressure

in a compliant bladder (thus preserving renal func-

tion), without unstable bladder contractions and

without unpleasant sensations. Voiding normally

occurs via a reflex contraction of the bladder, coor-

dinated with a relaxed outlet, typically until the

bladder is empty.

Normal storage relies on the inhibitory input

to the bladder supplied by the sympathetic neu-

rons originating in the thoracic and lumbar spinal

segments and the excitatory input to the bladder

Fig. 28.1. Prevalence of histological BPH as a function of age. BPH is a histological diagnosis, and does not neces-

sarily equate with symptoms, signs, or urodynamic findings

0

10

20

30

40

50

60

70

80

90

100

1-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90+

Age (years)

% BPH

(histology)

396 C.V. Comiter

outlet. Together, these efferent pathways contribute

to normal storage. The “guarding reflex,” which

occurs during normal bladder filling, is triggered

by bladder afferent nerves that project to the sacral

cord, which synapse with interneurons, which in

turn activate the urethral external sphincter effer-

ents (via the pudendal nerve); this facilitates urine

storage [12] .

Normal voiding relies on excitatory efferent

input to the bladder. Sacral parasympathetic pre-

ganglionic fibers travel in the pelvic nerve and pro-

vide the bulk of the excitatory efferent input to the

bladder. Preganglionic neurons synapse within the

parasympathetic ganglion near the detrusor. The

postganglionic neurons (parasympathetic) provide

excitation to the smooth muscle of the bladder pri-

marily via acetylcholine release. Acetycholine then

attaches to the muscarinic receptors, mediating

bladder contraction. The two predominant mus-

carinic receptors responsible for bladder contrac-

tion are the M3 and M2 subtypes. It appears that in

the normal bladder, M3 receptor agonism is mostly

responsible for the bladder contraction, while M2

agonism plays a secondary role via reversal of

β-adrenergic mediated relaxation. However, in the

spinal cord-injured rodent [13] and in the rodent

with an obstructed bladder [14] , M2 activation has

been shown to play a more dominant role in medi-

ating bladder contraction.

What makes the bladder unique among the vis-

cera is the conscious control and inhibition over

urination. While the immature human relies on

reflex voiding, mediated by bladder tension recep-

tors triggering a reflex bladder contraction through

the sacral micturition center, the mature human

normally has the ability to consciously delay urina-

tion until socially appropriate.

Several reflexes assist complete evacuation in

the normal state: amplification, in which a weak

smooth muscle signal from the bladder can be

augmented to ensure an efficient contraction; coor-

dination, whereby the bladder contraction and

sphincteric relaxation occur concomitantly until

the bladder is empty; and timing, so that voli-

tional voiding can be initiated at different bladder

volumes under conditions of varying degrees of

urgency. Amplification occurs through a “blad-

der—bladder” reflex. Bladder afferents synapse

with the sacral cord interneurons, which in turn

synapse with bladder efferent parasympathetics.

Positive feedback then activates more afferent fir-

ing and more reflex efferent activity [15] . Bladder

afferents also influence urethral smooth muscle

relaxation (“bladder—urethra” reflex), via inhibi-

tory reflexes [16] . The pontine micturition center is

responsible for maintaining and coordinating outlet

relaxation with the bladder contraction. Taken

together, amplification and coordination permit

volitional voiding over a wide range of bladder

volumes, with varying degrees of urgency.

Urgency and Urge Incontinence

The complex excitatory and inhibitory reflex

mechanisms that regulate normal voiding also can

be a liability. Various disease processes can lead to

the emergence of bladder hyperactivity and incon-

tinence, with loss of volitional control over the

micturition reflex. Although most easily thought

of as an inability to store urine due to the blad-

der, it is useful to categorize this pathophysiology

according to neurogenic, myogenic, intravesical,

and extravesical.

Neurogenic

OAB can result from the loss of the central inhibi-

tory controls via injury/disorder of the brain or

suprasacral spinal cord. Examples of brain disor-

ders leading to UI include cerebrovascular acci-

dent, Parkinson's disease, and dementia. Disruption

of axonal pathways within the spinal cord includes

transverse myelitis, traumatic suprasacral myelop-

athy, cervical spondylosis, and multiple sclerosis

[17] (which can affect the brain as well). Other

neurological abnormalities include increased affer-

ent nerve input and loss of peripheral inhibition. An

example of an abnormal sensitization of bladder

afferent input is the emergence of abnormal C-fiber

activity. Normally, in the mature adult, bladder sen-

sation is mediated through tension receptors acting

via A-delta myelinated neurons. The unmyelinated

afferent C-fiber nociceptors are normally quiescent

during bladder filling. Various insults can lead

the nociceptors to become mechanosensitive with

decreased activation thresholds, such as inflam-

mation or outlet obstruction. Inappropriate C-fiber

activation can mediate increased neurotransmis-

sion to and within the sacral cord, thereby leading

to bladder muscle overactivity.

28. Primary Urge Incontinence 397

Recent evidence supports a neurogenic etiology

of UI due to DO in men with BOO. Nerve growth

factor (NGF) levels are elevated in bladders of

men with BOO and in men with OAB. It has been

demonstrated that specific blockade of NGF pre-

vents neural plasticity and bladder overactivity in

experimental models of BOO and OAB [18, 19] .

NGF mediates DO by altering the properties of

sodium and potassium channels in bladder afferent

neurons. Furthermore, NGF upregulates TRPV1

in sensory fibers and brings this receptor from an

inactive into an active configuration, further medi-

ating urgency and UI [20, 21] .

Myogenic

Changes in the bladder itself, including in the

detrusor muscle, also can contribute to UI, either

with or without BOO. Interstitial cells have long

been known to exist in the ureter, contributing to

automatic peristaltic activity, which helps to propel

the urine from the renal pelvic to the bladder. Such

pacemaker cells also are present in the suburothe-

lial urethra and bladder body. These are electrically

active cells, which can communicate via gap junc-

tions and appear to respond to ATP as the main

neurotransmitter [22] .

In addition, suburothelial spindle cells known

as myofibroblasts lie in close apposition with bare

nerve endings and communicate with detrusor

muscle cells via gap junctions, creating a “func-

tional syncytium.” These mechanoreceptors are

activated by stretch [23] . Alterations in these cells,

as well as increased abutment junctions among

detrusor muscle cells which can occur with normal

aging, can contribute to increased detrusor activity

and UI [24] .

Recent evidence supports a myogenic compo-

nent (in addition to the aforementioned neurogenic

component) of DO in men with BOO. Akari et al.

[25] demonstrated that epithelial sodium channels

(which are expressed in the bladder epithelium)

contribute to mechanosensory transduction in the

bladder afferent pathways. The expression of the

sodium channels is increased in men with BOO

and in fact correlates with storage symptoms in

men with BOO [26] . In addition, urinary levels

of PGE2 were shown to be elevated in men with

BOO and normal detrusor contractility compared

to those with BOO and detrusor underactivity;

it also was shown that PGE2 levels in the urine

were negatively correlated with maximum bladder

capacity. In addition, partial denervation of the

bladder smooth muscle leads to an increase in the

number of spontaneous action potentials [27] . Even

in the absence of BOO, normal aging is associated

with replacement of the normal intermediate cell

junctions with an increase in protrusion junctions

and abutment junctions, which allow these spon-

taneous action potentials to propagate from cell to

cell [28] .

Intravesical

Occasionally, the cause of UI may be due to

an intravesical reversible process. Bladder stones

often will present with both storage and voiding

symptoms. Stones may be associated with BOO

due to prostatic obstruction or may be secondary to

nonobstructive urinary stasis. The space-occupying

stone lies within the bladder lumen, thereby dimin-

ishing functional urinary capacity. In addition, the

contact between the stone and the bladder wall can

lead to increased afferent stimulation of the blad-

der, which can contribute to UI. Finally, the BOO

associated with bladder stones in turn can lead to

the neurogenic and myogenic changes outlined

above.

Carcinoma in situ may be associated with irrita-

tive storage symptoms, including UI. In men with

UI in the absence of voiding symptoms, especially

in the presence of microscopic or gross hematuria,

cystoscopy and bladder barbotage (and possible

bladder biopsy) are indicated to rule out carcinoma

in situ.

Acute urinary tract infection also can mediate

UI. This should be readily detected by urinalysis

and urine culture. One must be aware, however,

that bacteriuria is common in older adults and may

be coincidentally present in an individual with UI,

rather than directly causing the UI. That said, a trial

of antibiotics is indicated as an initial treatment in

patients with UI and bacteriuria.

Extravesical

There are some factors that may contribute to UI

which are separate from (yet often related to) blad-

der function. In the UUI patient, there often is a

component of pelvic floor dysfunction. Volitional

pelvic floor muscular contraction provides an

398 C.V. Comiter

inhibitory input (via a sacral cord reflex) to the

bladder, suppressing an involuntary detrusor con-

traction [29] . Thus one patient may be wet with an

unstable bladder contraction of 15 cm water, while

another may be dry despite an unstable bladder

contraction of 40 cm water. The former patient can-

not adequately recruit the pelvic floor muscles into

a coordinated contraction of appropriate magnitude

to suppress the unstable bladder activity. Thus, it is

logical that Kegel exercises (when correctly taught

and performed) can be so successful in treating

UUI. Strengthening the pelvic floor muscles and

reestablishing voluntary control over the pelvic

floor can help to suppress the detrusor overactiv-

ity, hence preventing UUI. SUI also can contribute

directly to UI. In patients with stress incontinence,

leakage of urine into the proximal urethra can

activate urethral afferents and facilitate voiding

reflexes, thereby contributing to DO and UI [30] .

Additional factors that may contribute to UI

in older men are those related to urine produc-

tion and toileting. Clearly, demented or delirious

patients may not have the cognitive faculties to be

aware of their environs and may engage in socially

inappropriate urination. Restricted mobility also

may contribute to UUI. While the man may be

aware of his urge to void and may even be able to

voluntarily contract his pelvic floor, slow move-

ment or the need for travel assistance can lead the

patient to succumb to the unstable bladder contrac-

tion. In addition, disorders of urine production

can “overwhelm” the bladder. Polydypsia clearly

causes polyuria, as may diabetes mellitus, diabetes

insipidus, renal concentration defects, and the use

of diuretics. If an uninhibited detrusor contrac-

tion regularly occurs at a certain bladder volume,

consistently challenging the bladder with excess

urinary volume will lead to urge incontinence.

Similarly, lower extremity edema and conges-

tive heart failure can lead to sudden increases in

urine production, especially with the patient in the

recumbent position.

Evaluation

The initial evaluation for a man with UI includes a

detailed medical history and focused physical exami-

nation. History should inquire about LUTS, includ-

ing both storage symptoms (frequency, nocturia,

urgency, incontinence) and voiding symptoms

(hesitancy, straining, double voiding, force of

stream). Duration, triggering factors, irritants (caf-

feine, alcohol), and any history of hematuria, dysu-

ria, urinary tract infections, or urinary retention are

relevant. Perhaps most important is the patient's

perception of his bladder condition and his goals

for improvement (eg, stop leaking versus reduce

frequency or nocturia, etc.). Associated medical

conditions such as heart failure, spinal or prostate

surgery, bowel function, and dementia also are

important. A detailed list of medications are neces-

sary, especially those medications that may have

urinary side effects, such as diuretics, antidepres-

sants, alpha-adrenergic antagonists, beta-adrener-

gic agonists and antagonists, sedatives, anxiolytics,

anticholinergics, and analgesics.

Physical examination should include a general

physical examination, with specific observation

of gait and mental status, with an evaluation of

the patient's mobility and his neurological status.

Digital rectal examination is indicated to assess for

prostate size (and masses) and to check pelvic floor

tone and voluntary squeeze of the pelvic floor mus-

cles. Notation should be made of lower extremity

edema (fluid overload) or decreased skin turgor

(fluid depletion).

Laboratory evaluation should include urinalysis,

looking for blood cells, pus cells, nitrates, crystal-

luria, and glucosuria. AUA guidelines recommend

measurement of serum prostate-specific antigen

[31] (coincidental prostate cancer treatment may

obviate or affect treatment of BPE), and the

Agency for Health Care Policy and Research

guidelines suggest gross evaluation of renal func-

tion via measurement of serum creatinine [32] .

Evaluation also should include measurement of

postvoid residual urine volume (PVR). An elevated

PVR (which must be considered in the context

of voided volume) simply means that the bladder

did not contract sufficiently enough during the

micturition cycle to overcome the urethral resist-

ance and empty efficiently. An elevated PVR is not

diagnostic of BOO, nor does a low PVR exclude

BOO. However, in a patient with a high PVR (low

voiding efficiency), one should be suspicious of

detrusor underactivity and/or BOO. Elevated PVR

is only weakly associated with BOO [33] . Similar

to measurement of PVR, uroflowmetry can be

measured noninvasively, has no risk, yet provides

28. Primary Urge Incontinence 399

invaluable information. Although low flow can

indicate BOO and/or detrusor underactivity, the

vast majority of men with a maximum urinary

flow rate <10 ml s

−1 have BOO (up to 88%) [34] .

Optional tests include cystoscopy and urine cytol-

ogy, and are appropriate if one suspects bladder

stone or transitional cell carcinoma in situ.

It is often difficult to differentiate patient with

BOO, OAB, and/or DHIC based on history and

physical examination alone. Only urodynamic

evaluation can precisely distinguish among these

potential diagnoses. While it may not be neces-

sary to make this distinction in order to introduce

behavioral treatment, initiation of pharmacother-

apy or surgical treatment is best done once a proper

diagnosis is established.

Urodynamics, if indicated, should start with

uroflowmetry, followed by measurement of PVR.

Filling cystometry is useful to measure bladder

sensation, compliance, capacity, and to identify

any uninhibited bladder contractions (either spon-

taneous or provoked). Measurement of abdomi-

nal leak point pressure is necessary to rule out

intrinsic sphincter deficiency. Pressure-flow study

or micturitional urethral pressure profilometry

[35] should then follow, in order to assess blad-

der contractility and to rule out bladder outlet

obstruction. Rectal monometry allows the exam-

iner to determine whether abdominal straining is

present. Furthermore, the presence of rectal con-

tractions may indicate a subtle neuropathy [36] .

Electromyography will help to rule out detrusor-

sphincter-dyssynergia, which may be associated

with multiple sclerosis or other suprasacral spinal

cord pathology, or poor voluntary control of the

striated sphincter, which may be present with

Parkinson's disease [37] . Finally, fluoroscopy is

helpful to assess for bladder trabeculation and to

help identify any anatomic abnormalities.

Symptoms and physical findings are not nec-

essarily predictive of urodynamic findings, and

therefore often are not sufficient to make a correct

diagnosis in and of themselves. DO and BOO are

both common in men with LUTS with or without

and UI [38] . However, while UI strongly correlates

with DO, other LUTS do not correlate well with

urodynamic findings, such as BOO [39, 40] . While

some investigations have shown that the incidence

of DO increases with the degree of BOO [40, 41] ,

others do not support such findings [42– 44] , instead

implying that DO and BOO are concomitant disor-

ders, perhaps each related independently to the

aging process. Neither the physical finding of an

enlarged prostate nor the sign of elevated PVR are

strongly associated with BOO. Approximately 50%

of unobstructed older men have an elevated PVR,

and 30% of men with BOO have normal PVR [45] .

Thus presence of UI with or without DO is not

diagnostic of BOO, nor is the presence of voiding

symptoms even with an elevated PVR predictive of

BOO. This lack of correlation among symptoms,

signs, and urodynamic findings also is the case for

younger men with LUTS and UUI, who may not be

at risk for prostatic obstruction but may be at risk

for congenital bladder neck obstruction or urethral

stricture disease [46] . Therefore, urodynamics are

necessary for the proper evaluation and treatment

of complex voiding dysfunction in men with UI

when there is diagnostic uncertainty.

In men with suspected neurogenic voiding

dysfunction, urodynamic evaluation is even more

important prior to instituting treatment. For exam-

ple, treating a patient with pure neurogenic DO in

the absence of BOO with deobstructive therapy

may clearly risk devastating UI. Similarly, in

men with Parkinson's disease and UI who dem-

onstrate a lack of voluntary sphincter control,

the risk of postoperative incontinence may be

as high as 80% [47] . However, the presence of

neurogenic DO should not be a contraindication

to deobstructing therapy when BOO is present.

Table 28.1 summarizes the suggested evaluation

of a man with UI.

Management

Behavioral Modification

Behavioral therapy should be offered as an initial

treatment, as it is nonmorbid, noninvasive, and

often efficacious. In general behavioral modifica-

tion is associated with a 50% decrease in UI [48] .

A trial fluid restriction, caffeine restriction, timed

voiding, and pelvic floor exercises poses minimal

risk. Behavioral modification requires that the

patient understand the basic pathophysiology of

UI, namely that the bladder is unable to store a

sufficient quantity of urine prior to the involuntary

evacuation of that urine. In such patients, fluid

intake often is greater than necessary and usually

400 C.V. Comiter

can be safely reduced to 1,000–1,500 ml per

day. Contraindications to fluid restriction include

recurrent nephrolithiasis, frequent urinary tract

infections, and severe constipation. Caffeinated

beverages should be eliminated but must be done

gradually to avoid precipitating rebound head-

aches. A trial of timed voiding whereby the patient

volitionally empties his bladder prior to a strong

sense of urgency (and UI) is recommended. If a

diuretic is being taken, it may be best to schedule

even more frequent voids (as often as every 30

min) during the time of active diuresis. The final

component of conservative management is pelvic

floor muscle physiotherapy. The patient's abil-

ity to contract the pelvic floor can be evaluated

during the rectal examination by prompting the

patient to squeeze the examiner's finger with his

anal sphincter. Another useful method is to ask

the patient to contract the anal sphincter as if he

were holding in gas, but should be reminded not to

contract the abdominal or gluteal muscles. For the

patient who cannot isolate the pelvic floor muscles,

a trial of physical therapy or biofeedback is use-

ful. The goal of physical therapy and biofeedback

should be to teach the patient proper pelvic floor

exercises, which then can be done on a regular

basis at home. Finally, it is useful to remind the

patient to contract the pelvic floor when a strong

sense of urgency arises, in order to suppress the

uninhibited bladder contraction and subsequent

internal sphincter relaxation that can mediate UI

[49] . When combined with pharmacotherapy, the

improvement in UI is greater than with behavioral

therapy alone [50] .

Pharmacotherapy

More than half of men with BPE also suffer from

OAB (urgency, often accompanied by frequency

and nocturia, occasionally associated with UI).

And it is the OAB symptoms that are often most

bothersome. In addition, the majority of men with

UI have DO, while the presence of concomitant

BOO is less than 50% [51] . Thus the use of phar-

macotherapy that targets the prostate in order to

treat presumed BOO (such as alpha-adrenergic

antagonists and 5-alpha reductase (5AR) inhibi-

tors) is appropriate in less than half of men with

UI, while the use of antimuscarinics would be

appropriate in the majority of patients.

The use of alpha-adrenergic inhibitors for the

treatment of men with LUTS associated with

BPE does not adequately treat the UI and other

storage symptoms in a substantial proportion of

the patients [52] . It is curious why the most com-

mon pharmacotherapy for men with UI directed at

treating the BOO rather than the UI and DO [53] .

Treating the prostate for a process that clearly can

be localized to the bladder should no longer serve

as first-line treatment. Newer safety and efficacy

data regarding the use of antimuscarinics in men

with DO even with BOO may help to shift current

practice patterns.

Alpha Blockers

UI clearly is related to an inability to store urine

due to the bladder and may or may not be associ-

ated with prostatic obstruction. However, the most

Table 28.1. Evaluation of male with urge incontinence

History

Storage symptoms

Voiding symptoms

Duration

Triggers

Associated symptoms (dysuria)

Medications

Physical examination

General

Digital rectal examination

Bulbocavernosis reflex

Pelvic floor muscle tone

Gait

Mental status

Mobility

Laboratory examination

Urinalysis

Serum prostate specific antigen

Serum creatinine (if concern regarding obstructive uropathy)

Postvoid residual urine volume

Uroflowmetry

Additional urodynamic evaluation (if considering surgical

treatment)

Cystometry

Pressure-flow study/micturitional urethral pressure profilometry

Rectal monometry

Electromyography

Abdominal leak point pressure

Cystoscopy/cytology (if suspicious of carcinoma, carcinoma

in situ, or bladder stone)

28. Primary Urge Incontinence 401

common practice among urologists, internists, and

family physicians is to treat the outlet with alpha-

adrenergic antagonists [53] . Inhibition of the alpha-

adrenergic receptors aims at treating the dynamic

component of the obstructing prostatic urethra,

by relaxing the smooth muscle of the prostate and

bladder neck. Prostatic and bladder neck smooth

muscle tone is mediated by alpha-adrenergic recep-

tors [54] . The predominant type of receptor in the

prostate and bladder neck (75%) is α 1a [54, 55] .

There is no doubt that α 1-receptor antagonists

are efficacious in reducing LUTS and the bother

from LUTS in men with BOO [56]. While phenoxy-

benzamine (nonselective, teratogenic) and prazosin

(short-acting, significant risk of hypotension) are

no longer recommended as first-line therapy for

LUTS associated with BPE, the efficacy of tera-

zosin, doxazosin, tamsulosin, and alfuzosin (long-

acting α 1 receptor antagonists) has been proven in

prospective, randomized, placebo-controlled trials,

mediating significant improvements in symptom

scores, QOL indexes, and uroflow. The efficacy of

these different medications is comparable among

the long-acting agents at appropriate therapeutic

doses [57] but are differentiated by their side-

effect profile and the requirement for dose titration

(Table 28.2 ). Although more expensive, alfuzosin

and tamsulosin are associated with a substantially

lower risk of dizziness and hypotension than are

doxazosin and terazosin.

Alpha-adrenergic inhibitors do not necessarily

deobstruct the obstructed outlet [58] and not all

men with LUTS and UUI have concomitant BOO.

Alpha-adrenergic antagonists are even successful

in symptomatic men without BOO [59] . This can

be explained by the presence of α - 1d receptors in

the spinal cord, brain, and bladder body, which,

if inhibited, can mediate a decrease in storage

LUTS [60].

5 Alpha Reductase Inhibitors

The static component of BOO can be treated suc-

cessfully with 5AR inhibitors, which reduce the

volume of the prostate stroma and epithelium by

inhibiting the formation of dihydrotestosterone

from testosterone. Treatment with this class of

medication has been shown to decrease the pro-

gression of and complications of LUTS associated

with BPE [61] . The incidence of urinary retention

and the likelihood of surgery are each reduced by

50% in men with prostate size >30–40 cc, and the

prostate volume is reduced by approximately one

third in men treated with finasteride (type-2 5AR

inhibitor) or dutasteride (type-1 and type-2 5AR

inhibitor). Symptomatic improvement is less dra-

matic and no studies have investigated the specific

change in UI in men treated with 5AR inhibitor

monotherapy. Certainly, there is no obvious mecha-

nism of action for 5AR inhibitors in men with UI

without BOO.

Antimuscarinics

A substantial proportion of men with LUTS have a

combination of both storage and voiding symptoms,

and accordingly urodynamic evaluation reveals

that many men have coexisting DO and BOO. In

women, storage symptoms and UI generally are

treated with antimuscarinics. However, guidelines

from the European Association of Urologists and

from the American Urological Association do

not mention the therapeutic role of anticholiner-

gic drugs for treating storage symptoms in men

[62] . Antimuscarinic therapy for men with LUTS

associated with BPE is perceived as a potential

risk for urinary retention. However, men with

LUTS associated with BPE demonstrate urody-

namic BOO only 50% of the time. Therefore, the

use of α -blockers and/or 5AR inhibitors may not

Table 28.2. Alpha adrenergic antagonists commonly used in men with UI

Agent Dosing (mg) Titration to effective dose Most common side effects (compared

to placebo)

Terazosin 1, 2, 5, 10, 20 Yes Dizziness

Doxazosin 1, 2, 4, 8, 16 Yes Dizziness

Tamsulosin 0.4, 0.8 No Ejaculatory dysfunction

Alfuzosin 10 No Dizziness

402 C.V. Comiter

be necessary in approximately half of the men to

whom they are prescribed! In addition, 50–75% of

men with BPH also have OAB, and it is the OAB

symptoms that often are most bothersome [53] .

Furthermore, despite the general efficacy of alpha-

adrenergic antagonism, the vast majority of men

with LUTS associated with BPE continue to have

bothersome storage symptoms (OAB) following

alpha-blocker treatment. Accordingly, the use of

antimuscarinics in men with LUTS and UI recently

has been investigated.

The rationale for the use of antimuscarinics in

patients with LUTS associated with BPE is consist-

ent with recent views on the mechanism of action

of antimuscarinics. No longer are antimuscarinics

believed to simply block muscarinic receptors on

the detrusor muscle thereby decreasing bladder

contractility. Rather, antimuscarinics likely act on

the storage phase, during which acetylcholine is

released from neuronal and nonneuronal sources,

and then act on afferent nerves in the suburothe-

lium and detrusor. Urinary retention should be

unlikely, as most antimuscarinic drugs are com-

petitive antagonists. During the (normal) massive

release of acetylcholine at the time of voiding, the

effects of the antimuscarinic medications decrease,

and therefore should not impair bladder contractil-

ity and should not lead to urinary retention [63] .

Abrams et al. evaluated the safety and efficacy

of tolterodine alone versus placebo in men with

OAB and BOO [64] . Not only did tolterodine

ameliorate the urodynamic storage dysfunction

(increase in capacity and increase in volume at

unstable contraction), but there were no instances

of urinary retention in the tolterodine arm, nor were

there important changes in urinary flow, voiding

pressure, or PVR. Lee et al. demonstrated that

a combination of the antimuscarinic medication

propiverine (not currently available in the United

States) plus doxazosin provided superior sympto-

matic relief of the storage symptoms in men with

OAB and BOO more than did doxazosin alone [65] .

Despite a statistically significant increase in PVR

in the group receiving the antimuscarinic medica-

tion, there were no instances of urinary retention,

and discontinuation rates were the same with or

without the antimuscarinic. Athanasopoulos et al.

evaluated the combination of tolterodine plus tam-

sulosin versus tamsulosin alone in men with urody-

namically documented DO and BOO [66] . While

both arms demonstrated significant improvement

in urinary flow rate and volume at first unstable

contraction, only the tolterodine arm demonstrated

improvement in QOL. Furthermore, addition of the

antimuscarinic did not lower uroflow or elevated

PVR. These results suggest that antimuscarinics

can be safely administered in men with BOO.

Despite this evidence documenting the safety

and efficacy of antimuscarinic medication in men

with urodynamically proven BOO, many opinion

leaders still recommend “pretreating” the outlet

prior to initiating antimuscarinic pharmacotherapy

[67, 68] . Based on the growing body of literature

documenting the safety and efficacy of antimus-

carinics in men with UI with or without BOO, the

use of antimuscarinics should become less contro-

versial and more mainstream.

Surgical

Transurethral resection of the prostate (TURP) or

other deobstructing surgical procedures such as

simple open prostatectomy or laser enucleation/

vaporization of the prostate as a therapy for UI

should be offered in selected cases when there is a

significant degree of prostatic urethral obstruction.

The urological literature is replete with studies

demonstrating substantially worse outcomes when

TURP is performed in patients without BOO who

suffer from incontinence due to DO [69] .

As DO is present in the majority of men with

UI, the purpose of urodynamics is not to demon-

strate DO, but rather to assess for the presence and

degree of BOO. While BOO is a relative indication

for TURP, DO is not a contraindication for TURP.

In fact, DO and UI are improved or reversed in

approximately two thirds of men following deob-

structing surgery [70, 71] . It should be noted,

however, that the greatest degree of improvement

occurs in the most severely obstructed men [72] ,

further strengthening the argument for detailed

urodynamic evaluation of men with UI. While

DO is necessary for UI, it often is not sufficient to

cause incontinence without a concomitant abnor-

mality of cognition or of pelvic floor muscular

control. Cognitive impairment should not be, how-

ever, a deterrent to surgery, especially in the patient

with significant BOO. In the cohort reported by

Gormely et al. those with the most improvement

also were cognitively impaired [72] .

28. Primary Urge Incontinence 403

Despite the common perception that most older

men with LUTS suffer from prostatic obstruc-

tion and that most older men benefit from TURP,

symptomatic improvement and overall outcome is

significantly worse in patients with DO and with-

out BOO [73] . Postoperatively, UI was more likely

to persist in men without clear BOO than in those

who were obstructed preoperatively. It appears that

persistent UI secondary to DO may be the principle

cause of unfavorable outcomes following TURP

[74] . In addition, the characterization of DO may

help to predict favorable versus unfavorable surgi-

cal outcome. Persistent UI after surgery is most

likely in those with low-volume DO (capacity <160

(c) and if the unstable bladder contractions are of

the phasic rather than the terminal variety [75] .

Despite the evidence demonstrating more favo-

rable outcomes for TURP in the setting of urethral

obstruction, urodynamic evaluation is recom-

mended as “optional” by the American Urological

Association and by the Agency for Health Care

Policy and Research guidelines prior to deobstruct-

ing surgery. While results are dramatically differ-

ent in patients with UI who suffer from obstruction

versus those without obstruction, TURP occasion-

ally can lead to symptomatic improvement in the

latter group through a mechanism of action inde-

pendent of deobstruction. It is possible that the heat

effect on periprostatic nerves secondary to TURP

or minimally invasive prostate therapy may medi-

ate improvement in the bladder overactivity [76] .

Neuromodulation

Neuromodulation treats UI primarily via afferent

nerve stimulation/modulation. Afferent stimulation

of the pelvic and pudendal nerve fibers results in

modulation of voiding and continence reflex path-

ways in the CNS [77, 78] .

Sacral nerve stimulation (SNS) with the InterStim

(Medtronic, Minneapolis, MN) relies on transfo-

raminal stimulation of the third sacral root, follow-

ing surgical implantation of a quadripolar lead and

an implantable pulse generator. What makes this a

particularly attractive option for the patient with UI

refractory to behavioral modification and pharma-

cotherapy is the minimally invasive nature and the

reversibility of the test procedure. Prior to implan-

tation of the pulse generator, the patient is given

a 1- to 4-week trial of neuromodulation, using

an external pulse generator and a percutaneously

implanted quadripolar electrode, which stimulates

the third sacral root. The patient may elect place-

ment of the permanent stimulation device only

following a successful test stimulation period. The

pulse generator is placed in the upper outer quad-

rant of the buttocks and connected to the preplaced

quadripolar lead. Stimulation settings are typically

frequency 14 HZ, pulse width 150 ms, and a vari-

able amplitude from 0.1 to 10.5 V. The patient is

able to control the amplitude of stimulation, thus

achieving an efficacious and comfortable level of

nerve stimulation. As the device has been FDA-

approved for approximately a decade, there is wide

experience with this treatment modality. Long-term

efficacy (defined as >50% reduction in inconti-

nence episodes) is generally 60–76% [79, 80] .

SNS is thought to work via inhibition of the

ascending (afferent) pathway in which the sensory

information from the bladder is transmitted via

the spinal tract neurons to the pontine micturition

center. Sacral nerve stimulation activates specific

inhibitory pathways, inhibiting involuntary reflex

voiding [78] . Low-stimulation current applied to

the A-delta myelinated sacral root fibers selectively

excites central inhibitory pathways. These central

inhibitory pathways in turn modulate the activity

of the somatic nerves traveling through the pelvic

nerve, innervating the external urethral sphincter

and pelvic floor. Thus, SNS indirectly inhibits the

afferent mediated excitatory reflexes by suppress-

ing interneuronal transmission within the sacral

cord. However, it does not inhibit the voluntary

voiding that occurs via direct descending supraspi-

nal excitatory input to the pelvic parasympathetic

neurons [81] . Furthermore, the low-stimulation

frequencies do not reach the threshold required

to activate the autonomic nerve fibers (ie, direct

motor responses), and thus a simultaneous bladder

contraction is avoided [82– 84] .

Alternative methods of neuromodulation include

posterior tibial nerve stimulation (PTNS) and puden-

dal nerve stimulation (PNS). PTNS has been shown

to help with both neurogenic and nonneurogenic

UI refractory to conservative management, with

cure rates of approximately 50% [85, 86] , and even

higher with the addition of an antimuscarinic medi-

cation. [87] . Advanced Bionics Corp. (Velerick, CA)

has introduced a leadless, rechargeable, implantable

microstimulator, which is percutaneously placed

404 C.V. Comiter

transperineally at the level of the pudendal nerve.

PNS is not yet FDA approved; however, the Bion®

pudendal nerve stimulator currently is being evalu-

ated in a prospective, randomized, sham-controlled

study for the chronic treatment of UI.

Augmentation Cystoplasty

Augmentation cystoplasty, whether performed

through a laparotomy or performed laparoscopi-

cally [88] , is more commonly offered to men

with neurogenic voiding dysfunction than to men

with nonneurogenic voiding dysfunction. The

usual indication is to protect the upper urinary

tracts in the setting of diminished bladder compli-

ance, hydronephrosis, recurrent nephrolithiasis,

vesicoureteral reflux, or recurrent pyelonephritis.

Although less common, augmentation cystoplasty

also is efficacious in nonneurogenic refractory UI.

Although the majority of men are cured of their UI

[89, 90] , in the author's experience, approximately

15% of patients have permanent postoperative

retention, and therefore must be able to perform

clean intermittent self-catheterization.

Intravesical

Botulinum Toxin

Intradetrusor injections of botulinum toxin (BTX)

recently have emerged as a viable treatment for UI

due to neurogenic and idiopathic DO. The heavy

chain of BTX binds to the presynaptic motor termi-

nal and enters the cell by endocytosis. The disulfide

bond linking the two BTX chains (heavy chain and

light chain) is broken, and the light chain is translo-

cated out of the endocytic vesicle into the cytoplasm.

Each serotype of the toxin works by enzymatic

cleavage of one or more of the proteins necessary

for normal acetylcholine exocytosis. The preferred

method of injection is via 5 Fr needle through a rigid

cystoscope. Thirty sites are each injected with 1 m

of 10 U m

−1 BTX-A, while the trigone is spared of

injection. BTX-A is associated with a cure/improved

rate of 85% for both neurogenic and nonneurogenic

DO [91, 92] . Improvement is realized immediately

following intradetrusor injection and lasts for up to

6 months. The risk of nausea, vomiting, dry mouth,

dysphagia, and respiratory muscle weakness appears

to be minimal when BTX is used for lower urinary

tract dysfunction. Side effects include impaired

bladder sensation and hesitancy and straining of

urination, and complications include urinary tract

infection and transient urinary retention requir-

ing intermittent catheterization [93] . BTX-B has a

shorter duration and higher side effect profile [94] .

C-Fiber Desensitization

RTX is a specific ligand of the vanilloid recep-

tor (TRPV1) receptor, a nonselective ion channel

abundantly expressed in type-C bladder affer-

ent nerve fibers and in urothelial cells [95– 99] .

Following RTX binding to TRPV1, bladder C

fibers become inactivated through a phenomenon

usually known as desensitization during which

bladder sensory input is prevented from reaching

the spinal cord [100] . Intravesical application of

RTX is followed by a prolonged disappearance of

TRPV1 immunoreactivity in the bladder [101] and

has been shown to reduce frequency, urgency, and

UI in patients with neurogenic and nonneurogenic

DO [102– 105] . In addition, the blockade of bladder

C fiber sensory input recently has been investigated

as a new strategy to treat storage LUTS (without

frank UI) in BPE patients. Dinis et al. demon-

strated the efficacy of 50-nM RTX solution in men

with BPH-associated storage LUTS, with four of

six patients cured of UI and the other two at least

50% improved [106] .

A recently published randomized study of RTX

versus BTX-A demonstrated efficacy for both

agents, but demonstrated superiority of BTX-A

over RTX in patients with neurogenic DO [107] .

Management of the Failed TURP

Approximately 15–20% of men following TURP

have persistent or recurrent voiding symptoms

requiring further therapy. Just as symptoms and

signs do not correlate well with urodynamic find-

ings prior to TURP, symptoms are unreliable in

predicting urodynamic findings (especially BOO

versus DO) following TURP. In men with bother-

some LUTS post-TURP, only 16–38% demonstrate

BOO, while 4–25% will have detrusor underactivity.

Sphincteric insufficiency is rare, with a prevalence

of only 8%. Approximately 50% of patient with

nonneurogenic voiding dysfunction will demon-

strate DO, while 76% of those with neurogenic

dysfunction will have uninhibited bladder contrac-

tions on urodynamics [108, 109] . As the etiology of

post-TURP voiding dysfunction varies, urodynamic

28. Primary Urge Incontinence 405

evaluation is vital for directing rational treatment in

the already dissatisfied patient. While surgical relief

of obstruction does indeed facilitate symptomatic

improvement in the majority of men with UI who

demonstrate BOO, persistent DO can be noted in

about 30–50% of the patients [52, 110] . The rate of

de novo DO has been reported to be at most 10% in

patients following prostatectomy [52] , thereby sug-

gesting that the prognostic value of DO with regard

to the treatment efficacy of TURP may be attributed

to the postoperative persistent DO. An additional

poor prognostic urodynamic indicator is diminished

vesical compliance with unstable contractions aris-

ing at small capacity (<160 cc ). On the other hand,

terminal DO at volumes >160 cc is likely to resolve

following TURP in the patient with BOO.

The urologist often is faced with the patient

who has had multiple deobstructing surgeries.

In a study of men who had failed two or more

TURPs, urodynamic evaluation revealed DO in

80%, BOO in only 27%, detrusor underactivity in

27%, and sphincteric incompetence in only 20%

[72] . Therefore, residual BOO occurs in a minority

of patient following TURP, and secondary TURP

or incision of a bladder neck contracture is usually

not indicated. As DO, BOO, and detrusor underac-

tivity are all common causes of post-TURP voiding

dysfunction and UI, urodynamics plays a central

role in the diagnostic workup of such patients.

Conclusions

The etiology of UI is substantially more complex

than the presence of DO, especially in the geriatric

male population. Unstable bladder contractions

represent only one of several contributing factors,

and therefore a full evaluation is necessary, includ-

ing history and physical examination, urinalysis,

and measurement of uroflow and PVR. Symptoms

and signs should not be confused with diagnoses,

and if suspicion of any confounding diagnoses,

such as BOO, DHIC, or detrusor underactivity

remain, then multichannel urodynamics are indi-

cated. Treatment should begin conservatively with

behavioral modification and pelvic floor exercises

and then should progress to pharmacotherapy.

Although treatment of presumed BOO with α 1 -

adrenergic antagonists with or without 5AR inhibi-

tors is the most common practice, newer data

support the safety and efficacy of antimuscarinic

medication, even in men with urodynamically

proven BOO.

Deobstructing surgery should be offered only to

patients with urodynamically proven BOO. Neither

cognitive impairment nor neurogenic voiding dys-

function is a contraindication to outlet surgery in the

obstructed patient. Nevertheless, surgery should be

undertaken cautiously, especially in the patient with

Parkinson's disease and a lack of sphincteric control.

The patient with refractory urge incontinence follow-

ing TURP should be reevaluated with urodynamics.

Secondary deobstructive surgery is indicated in only

25% of patients, so it should be offered only in the

setting of supportive urodynamic findings. Men with

persistent incontinence following surgery are much

more likely to suffer from DO than from sphincteric

incompetence, and they should be offered behav-

ioral modification, pelvic floor physiotherapy, and

pharmacotherapy, but may ultimately benefit from

neuromodulation, intradetrusor BTX injection, or

even augmentation cystoplasty.

References

1. Fantl JA, Newman DK, Colling J, et al. Urinary

incontinence in adults: Acute and chronic manage-

ment. In: Clinical practice guideline. Rockville,

Maryland: United States Department of Health and

Human Services, No. 2, 1996.

2. Hu TW, Wagner TH, Bentkover, JD, et al. Costs of

urinary incontinence and overactive bladder in the

United States: A comparative study. Urology 2004,

63:461-65.

3. Hu TW, Wagner TH, Bentkover JD, et al. Estimated

economic costs of overactive bladder in the United

States. Urology 2003, 61:1123-8.

4. Lukacz ES, Lawrence JM, Burchette RJ, et al.

The use of Visual Analog Scale in urogynecologic

research: A psychometric evaluation. Am J Obstet

Gynecol 2004, 191:165- 70.

5. Heidrich SM, Wells TJ. Effects of urinary incon-

tinence: Psychological well-being and distress in

older communitydwelling women. J Gerontol Nurs

2004, 30:47- 54.

6. Grimby A, Milsom I, Molander U, et al. The influ-

ence of urinary incontinence on the quality of life of

elderly women. Age Ageing 1993 22:82- 9.

7. Liberman JN, Hunt TL, Stewart WF, et al. Health-

related quality of life among adults with symptoms

of overactive bladder: Results from a U. S. commu-

nity-based survey. Urology 2001, 57:1044- 50.

406 C.V. Comiter

8. Abrams P, Cardozo L, Fall M, et al. The standardisa-

tion of terminology of lower urinary tract function:

Report from the standardisation sub-committee of

the International Continence Society. Neurourol

Urodyn 2002, 21:167-78.

9. Resnick NM, Yalla SV. Detrusor hyperactivity with

impaired contractile function. An unrecognized but

common cause of incontinence in elderly patients.

JAMA 1987, 257:3076-3081.

10. Ziada A, Rosenblum M, Crawford ED. Benign

prostatic hyperplasia: An overview. Urology 1999;

53:1-6.

11. Hinman Jr, F. The art and science of piddling: Voiding

habits of man and beast London: Vespasian

Pr, 1999.

12. de Groat WC, Vizzard MA, Araki I, et al. Spinal

interneurons and preganglionic neurons in sacral

autonomc reflex pathways. Prog Brain Res 1996;

107:97- 111.

13. Braverman AS, Ruggieri MR. Hypertrophy changes

the muscarinic receptor subtype mediating bladder

contraction from M3 toward M2. Am J Physiol

Regul Integr Comp Physiol 2003; 285: R701-8.

14. Braverman AS, Doumanian LR, Ruggieri MR.

M2 and M3 muscarinic receptor activation of uri-

nary bladder contractile signal transduction. II.

Denervated rat bladder. J Pharmacol Exp Ther 2006;

2:875-80.

15. Chancellor MB, Leng W: The mechanism of action

of sacral nerve stimulation in the treatment of detru-

sor overactivity and urinary retention. In: Jonas U,

Grunewald V, editors. New perspectives in sacral nerve

stimulation for control of lower urinary tract dysfunc-

tion. London: Martin Dunitz Ltd, 2002:17-28.

16. MaLossi J, Chai TC. Sacral neuromodulation for

the treatment of bladder dysfunction. Cur Urol Rep

2002; 3:61-66.

17. Araki I, Matsui M, Ozawa K, et al. Relationship of

bladder dysfunction to lesion site in multiple sclero-

sis. J Urol 2003; 169:1384-7.

18. Steers WD, Tuttle JB. Mechanism of Disease: The

role of nerve growth factor in the pathophysiology

of bladder disorders. Nat Clin Pract Urol 2006;

3:101-10.

19. Kim JC, Park EY, Hong SH, et al. Changes of uri-

nary nerve growth factor and prostaglandins in male

patients with overactive bladder symptom. Int J Urol

2005; 12:875-80.

20. JiRR, Samad TA, Jin SX, et al. P38 MAPK acti-

vation by NGF in primary sensory neurons after

inflammation increases TRPV1 levels and maintains

heat hyperalgesia. Neuron 2002; 36:57–68

21. Chuang HH, Prescott ED, Kong H, et al.. Bradykinin

and nerve growth factor release the capsaicin recep-

tor from PtdIns(4,5)P2-mediated inhibition. Nature

2001; 411:957–62.

22. LagouM, De Vente J, Kirkwood TB, et al. Location

of interstitial cells and neurotransmitters in the

mouse bladder. BJU Int 2006; 97:1332-7.

23. Kanai A, de Groat W, Birder L, et al. Symposium

report on urothelial dysfunction: Pathophysiology

and novel therapies. J Urol 2006; 175:1624-9.

24. Elbadawi A, Yalla SV, Resnick NM. Structural basis

of geriatric voiding dysfunction. III. Detrusor over-

activity. J Urol 1993; 150:1668-80.

25. Araki I, Du S, Kamiyama M, et al. Overexpression

of epithelial sodium channels in epithelium of

human urinary bladder with outlet obstruction.

Urology 2004; 64:1255-60.

26. Kim JC, Park EY, Hong SH, et al. Changes of uri-

nary nerve growth factor and prostaglandins in male

patients with overactive bladder symptom. Int J Urol

2005; 12:875-80.

27. Wein AJ, Rackley RR. Overactive bladder: A better

understanding of pathophysiology, diagnosis and

management. J Urol 2006; 175:S5-10.

28. Elbadawi A, Yalla SV, Resnick NM. Structural basis

of geriatric voiding dysfunction. III. Detrusor over-

activity. J Urol 1993; 150:1668-80.

29. Andersson KE, Wein AJ. Urethral afferent nerve

activity affects the micturition reflex; implication

for the relationship between stress incontinence

and detrusor instability. Pharmacol Rev 2004;

56:581-631.

30. Jung SY, Fraser MO, Ozawa H, et al. Urethral

afferent nerve activity affects the micturition reflex;

implication for the relationship between stress

incontinence and detrusor instability. J Urol 1999;

162:204-12.

31. Nickel JC, Herschorn S, Corcos J, et al. Canadian

guidelines for the management of benign prostatic

hyperplasia. Can J Urol 2005; 12:2677-83.

32. McConnell JD, Barry MJ, Bruskewitz RC, et al.

Benign prostatic hyperplasia: Diagnosis and treat-

ment. In: Clinical practice guideline. Rockville,

MD: Agency for Health Care Policy and Research,

1994.

33. de la Rosette JJ, Witjes WP, Schafer W, et al.

Relationships between lower urinary tract symptoms

and bladder outlet obstruction: results from the ICS

“BPH” study. Neurourol Urodyn 1998; 17:99-108.

34. Poulsen AL, Schou J, Puggaard L, et al. Prostatic

enlargement, symptomatology and pressure/flow

evaluation: Interrelations in patients with symptom-

atic BPH. Scand J Urol Neph 1994; 157:67-73

35. Sullivan MP, Comiter CV, Yalla SV. Micturitional

urethral pressure profilometry. Urol Clin North Am

1996; 23:263-78.

28. Primary Urge Incontinence 407

36. Combs AJ, Nitti VW. Significance of rectal contrac-

tions noted on multichannel urodynamics. Neurourol

Urodyn 1995; 14:73-80.

37. Staskin DS, Vardi Y, Siroky MB. Post-prostatectomy

continence in the Parkinsonian patient: The sig-

nificance of poor voluntary sphincter control. J Urol

1988; 140:117-8.

38. Diokno AC, Brown MB, Brock BM, et al. Clinical

and cystometric characteristics of continent and

incontinent noninstitutionalized elderly. J Urol 1988;

140:567-71.

39. Sakakibara R, Hamano S, Uchiyama T, et al. Do

BPH patients have neurogenic detrusor dysfunction?

A uroneuroloigcal assessment. Urol Int 2005; 74:44-

50.

40. Hyman MJ, Groutz A, Blaivas JG. Detrusor insta-

bility in men: Correlation of lower urinary tract

symptoms with urodynamic findings. J Urol 2001;

166:550-2.

41. Wadie BS, Ebrahim el-HE, Gomha MA. The rela-

tionship of detrusor instability and symptoms with

objective parameters used for diagnosing bladder

outlet obstruction: A prospective study. J Urol 2002;

168:132-4.

42. Rosier PF, de la Rosette JJ, Wikjkstra H, et al.

Is detrusor instability in elderly males related to

the grade of obstruction. Neurourol Urodyn 1995;

14:625-33.

43. Knutson T, Edlund C, Fall M, Dahlstrand C.BPH

with coexisting overactive bladder dysfunction--an

everyday urological dilemma. Neurourol Urodyn

2001; 20:237-47.

44. Comiter CV, Schacterle RS, Sullivan MP, et al.

Urodynamic risk factors for renal insufficiency in

adult men with obstructive and non-obstructive

voiding dysfunction. J Urol 1997; 158:181-5.

45. Chatelain C, Denis L, Foo KT, et al. Benign pros-

tatic hyperplasia. Paris, France; The International

Consultation on Benign Prosatatic Hyperplasia,

2000.

46. Nitti VW, Lefkowitz G, Ficazzola M, et al.

Lower urinary tract symptoms in young men:

Videourodynamic findings and correlation with

noninvasive measures. J Urol 2002; 168:135-8.

47. Abrams P, Cardozo L, Khoury S, et al. Incontinence:

3rd international consultation on incontinence.

Plymouth, United Kingdom: Health Publication

Ltd, 2005.

48. Fantl JA, Wyman JF, McClish DK, et al. Efficacy of

bladder training in older women with urinary incon-

tinence. JAMA 1991; 265:609-13.

49. Shafik A, Shafik IA. Overactive bladder inhibition

in response to pelvic floor muscle exercises. World

J Urol 2003; 20:374-7.

50. Burgio KL, Locher JL, Goode PS: Combined behav-

ioral and drug therapy for urge incontinence in older

women. J Am Geriatr Soc 2000; 48:370-4.

51. Eckardt MD, van Nenrooij GE, Boon TA. Interactions

between prostate volume, filling cystometric esti-

mated parameters, and data from pressure-flow

studies in 565 men with lower urinary tract symp-

toms suggestive of benign prostatic hyperplasia.

Neurourol Urodyn 2001; 20:579-90.

52. de Nunzio C, Franco G, Rocchegiani A, et al. The

evolution of detrusor overactivity after watchful

waiting, medical therapy and surgery in patients with

bladder outlet obstruction. J Urol 2003; 169:535-9.

53. Chapple CR, Roehrborn CG. A shifted paradigm for

the further understanding, evaluation, and treatment

of lower urinary tract symptoms in men: Focus on

the bladder. Eur Urol 2006; 49:651-9.

54. Narayan P, Tewari A. A second phase III multicenter

placebo controlled study of 2 dosages of modified

release tamsulosin in patients with symptoms of

benign prostatic hyperplasia. United States 93-01

Study Group. J Urol 1998; 160:1701-6.

55. Goepel M, Wittmann A, Rubben H, et al. Comparison of

adrenoceptor subtype expression in procine and human

bladder and prostate. Urol Res 1997; 25:199-206.

56. Tiwari A, Krishna NS, Nanda K, et al. Benign pros-

tatic hyperplaisia: An insight into current investiga-

tional medical therapies. Expert Opin Investig Drugs

2005; 14:1359-72.

57. Vallancien G. Alpha-blockers in benign prostatic

hyperplasia. Urology 1999; 54:773-775.

58. Gleason DM, Bottaccini MR. Effect of terazosin on

urine storage and voiding in the aging male with

prostatism. Neurourol Urodyn 1994; 13:1-12.

59. Gerber GS, Kim JH, Contreras BA, et al. An obser-

vational urodynamic evaluation of men with lower

urinary tract symptoms treated with doxazosin.

Urology 1996; 47:840-4.

60. Schwinn DA. The role of alpha1-adrenergic receptor

subtypes in lower urinary tract symptoms. BJU Int

2001; 88 Suppl 2:27-34.

61. TarterTH, Vaughan ED Jr. Inhibitors of 5alpha-

reductase in the treatment of benign prostatic hyper-

plasia. Curr Pharm Des 2006; 12:775-83.

62. Reynard JM. Does anticholinergic medication have

a role for men with lower urinary tract symptoms/

benign prostatic hyperplasia either alone or in com-

bination with other agents? Curr Opin Urol 2004;

14:13-16.

63. Andersson KE, Yoshida M. Antimuscarinics and the

overactive detrusor—which is the main mechanism

of action? Eur Urol 2003; 43: 1-5.

64. Abrams P, Kaplan S, De Koning Gans HJ, et al. Safety

and tolerability of tolterodine for the treatment

408 C.V. Comiter

of overactive bladder in men with bladder outlet

obstruction. J Urol 2006; 175:999-1004.

65. Lee KS, Choo MS, Kim DY, et al. Combination

treatment with propiverine hydrochloride plus dox-

azosin controlled release gastrointestinal therapeutic

system formulation for overactive bladder and coex-

isting benign prostatic obstruction: A prospective,

randomized, controlled multicenter study. J Urol

2005; 174:1334-8.

66. Athanasopoulos A, Gyftopoulos K, Giannitsas K,

et al. Combination treatment with an alpha-blocker

plus an anticholinergic for bladder outlet obstruc-

tion: A prospective, randomized, controlled study. J

Urol 2003; 169:2253-6.

67. Gonzalez RR, Te AE. Overactive bladder and men:

Indications for anticholinergics. Curr Urol Rep

2003; 4:429-35.

68. Staskin DR, Dmochowski RR. Future studies of

overactive bladder: The need for standardization.

Urology 2002; 60(5 Suppl 1):90-3.

69. Machino R, Kakizaki H, Ameda K, et al. Detrusor

instability with equivocal obstruction: A predictor

of unfavorable symptomatic outcomes after tran-

surethral prostatectomy. Neurourol Urodyn 2002;

21:444-9.

70. Hebjorn S, Andersen JT, Walter S, et al. Detrusor

hyperreflexia. A survey on its etiology and treat-

ment. Scand J Urol Nephrol 1976; 10:103-9.

71. Akino H, Gobara M, Okada K. Bladder dysfunc-

tion in patients with benign prostatic hyperplasia:

Relevance of cystometry as prognostic indicator of

the outcome after prostatectomy. IntJ Urol 1996;

3:441-7.

72. Gormley EA, Griffiths DJ, McCracken PN, et al.

Effect of transurethral resection of the prostate on

detrusor instability and urge incontinence in elderly

males. Neurourol Urodyn 1993; 12:445-5373.

73. Abrams PH, Farrar DJ, Turner-Warwick RT, et al.

The results of prostatectomy: A symptomatic and

urodynamic evaluation analysis of 152 patients. J

Urol 1979; 121:640-5.

74. Ameda K, Koyanagi T, Nantani M, et al. The rel-

evance of preoperative cystometrography in patients

with benign prostatic hyperplasia: correlating the

findings with clinical features and coutcome after

prostatectomy. J Urol 1994; 152 :443-7.

75. Kageyama S, Watanabe T, Kurita Y, et al. Can we

predict persistent do after TURP? Neurourol and

Urodyn 2000; 19:223-240.

76. Sugiyama T, Park YC, Hanai T, et al. Why is transure-

thral microwave thermotherapy (TUMT) positively

effective? Int Urol Nephrol 1998; 30:293-300.

77. Lycklama A, Nijeholt AAB, Groenendijk PM, et al.

Clinical and urodynamic assessments of the mode

of action of sacral nerve stimulation. In: Jonas U,

Grunewald V, editors, New perspectives in sacral

nerve stimulation for control of lower urinary tract

dysfunction. London: Martin Dunitz Ltd, 2002:43-

54.

78. Chancellor MB, Chartier-Kastler EJ: Principles of

sacral nerve stimulation (SNS) for the treatment

of bladder and urethral sphincter dysfunctions.

Neuromodulation 2000; 3:15-26.

79. Abrams P, Blaivas JG, Fowler CJ, et al. The role of

neuromodulation in the management of urinary urge

incontinence. BJU Int 2003; 91:355-9.

80. Siegel SW, Catanzaro F, Dijkema HE, et al. Long-

term results of a multicenter study on sacral nerve

stimulation for treatment of urinary urge inconti-

nence, urgency-frequency, and retention. Urology

2000; 56:87-91.

81. Van Kerrebroeck, PEV: The role of electrical stim-

ulation in voiding dysfunction. Eur Urol 1998;

34(suppl 1):27-30.

82. MaLossi J, Chai TC: Sacral neuromodulation for

the treatment of bladder dysfunction. Curr Urol Rep

2002; 3:61-66.

83. Van Balken MR, Vergunst H, Bemelmans BLH: The

use of electrical devices for the treatment of bladder

dysfunction: A review of methods. J Urol 2004;

172:846-51.

84. Grunewald V, Hofner K, Thon WF, et al. Sacral elec-

trical neuromodulation as an alternative treatment

option for lower urinary tract dysfunction. Restor

Neurol Neurosci 1999; 14:189-193.

85. Vandoninck V, Van Balken MR, Finazzi Agro E, et

al. Posterior tibial nerve stimulation in the treatment

of urge incontinence. Neururol Urodyn 2003; 22:17-

23.

86. van der Pal F, van Balken MR, Heesakkers JP, et

al. Correlation between quality of life and voiding

variables in patients treated with percutaneous tibial

nerve stimulation. BJU Int 2006; 97:113-6.

87. Karademir K, Baykal K, Sen B, et al. A peripheric

neuromodulation technique for curing detrusor over-

activity: Stoller afferent neurostimulation. Scand J

Urol Nephrol 2005; 39:230-3.

88. Rackley RR, Abdelmalak JB. Laparoscopic aug-

mentation cystoplasty. Surgical technique. Urol Clin

North Am 2001; 28:663-70.

89. Herschorn S, Hewitt RJ. Patient perspective of

long-term outcome of augmentation cystoplasty for

neurogenic bladder. Urology 1998; 52:672-8.

90. Albo M, Raz S, Dupont MC. Anteiror flap extraperi-

toneal cystoplasty. J Urol 1997; 157:2095-8.

91. Schurch B, de Zeze M, Denys P, et al. Botulinum

toxin type A is a safe and effective treatment for

neurogenic urinary incontinence: Results of a single

treatment, randomized, placebo controlled 6-month

study. J Urol 2005; 174:196-200.

28. Primary Urge Incontinence 409

92. Kuo HC. Clinical effects of suburothelial injection

of botulinum A toxin on patients with nonneuro-

genic detrusor overactivity refractory to anticho-

linergics. Urology 2005; 66:94-8.

93. Patterson JM, Chapple CR. Botulinum toxin

in urinary incontinence. Curr Opin Urol 2006;

16:255-60.

94. Ghei M, Maraj BH, Miller R, et al. Effects of botu-

linum toxin B on refractory detrusor overactivity:

A randomized, double-blind, placebo controlled

crossover trial. J Urol 2005; 174:1873-7.

95. Szallasi A, Blumberg PM. Vanilloid (capsaicin)

receptors and mechanisms. Pharmacol Rev 1999;

51:159–211.

96. Caterina MJ, Schumacher MA, Tominaga M,

et al. The capsaicin receptor: A heat-activated

ion channel in the pain pathway. Science 1997;

389:816–24.

97. Yiangou Y, Facer P, Ford A, et al. Capsaicin

receptor VR1 and ATP-gated ion channel P2X3 in

humanurinary bladder. BJU Int 2001; 87:774–9.

98. Avelino A, Cruz C, Nagy I, et al. Vanilloid

receptor type 1expression in the rat urinary tract.

Neuroscience 2002; 109:787–98.

99. Birder LA, Kanai AJ, de Groat WC, et al. Vanilloid

receptor expression suggests a sensory role for

urinary bladder epithelial cells. Proc Natl Acad Sci

USA 2001; 98:13396–401.

100. Avelino A, Cruz F, Coimbra A. Intravesical

resiniferatoxin desensitizes rat bladder sensory

fibres without causing intense noxious excita-

tion. A c-fos study. Eur J Pharmacol 1999;

378:17–22.

101. Apostolidis AN, Brady C, Yiangou Y, et al. Parallel

changes in suburothelial vanilloid receptor TRPV1

(VR1) and pan-neuronal marker PGP9.5 immu-

noreactivity in patients with neurogenic detrusor

overactivity (NDO) following intravesical RTX.

Eur Urol Suppl 2003; 2:91.

102. Fowler CJ, Jewkes D, McDonald WI, et al.

Intravesical capsaicin for neurogenic bladder dys-

function. Lancet 1992; 339:1239.

103. Silva C, Rio ME, Cruz F. Desensitization of blad-

der sensory fibres by intravesical resiniferatoxin,

a capsaicin analogue: Long-term results for the

treatment of detrusor hyperreflexia. Eur Urol 2000;

38:444–52.

104. Silva C, Ribeiro MJ, Cruz F. The effect of intra-

vesical resiniferatoxin in patients with idiopathic

detrusor instability suggests that involuntary detru-

sor contractions are triggered by C-fiber input. J

Urol 2002; 168:575–9.

105. Kuo H. Effectiveness of intravesical resiniferatoxin

for anticholinergics treatment refractory detrusor

overactivity due to nonspinal cord lesions. J Urol

2003;170:835–9. 100

106. Dinisa P, Silvaa J, Ribeiroa MJ, et al. Bladder

C-fiber desensitization induces a long-lasting

improvement of BPH-associated storage LUTS: A

pilot study. Eur Urol 2004; 46:88–94.

107. Giannantoni A, Di Stasi SM, Stephen RL, et al.

Intravesical resiniferatoxin versus botulinum-A

toxin injections for neurogenic detrusor overactiv-

ity: A prospective randomized study. J Urol 2004;

172:240-3.

108. Seaman EK, Jacobs BZ, Blaivas JG, et al.

Persistence or recurrence of symptoms after

transurethral resection of the prostate: A urody-

namic assessment. J Urol 1994; 152:935-7.

109. Nitti VW, Kim Y, Combs AJ. Voiding dysfunction

following transurethral resection of the prostate:

Symptoms and urodynamic findings. J Urol 1997;

157:600-3.

110. Van Venrooij, GE, Van Melick HH, Eckhardt

MD, et al. Correlations of urodynamic changes

with changes in symptoms and well-being after

transurethral resection of the prostate. J Urol 2002;

168:605-9.

411

Introduction

According to EAU Guidelines on Urinary

Incontinence [1] , the clinical presentations of men

with symptoms and history of urinary incontinence

may be grouped into four subdivisions: post-

micturition dribbling, postprostatectomy inconti-

nence, incontinence with frequency/urgency, and

incontinence with a complex history (Fig. 29.1)

Postprostatectomy incontinence and incontinence

with urgency/frequency are symptoms that are

suggestive of stress urinary incontinence (SUI),

urgency urinary incontinence (UUI), mixed incon-

tinence, and “overflow” incontinence. The etiology

of these conditions mainly is sphincteric incompe-

tence, detrusor overactivity, bladder outlet obstruc-

tion (BOO), or detrusor underactivity .

Prevalence estimates of these subtypes vary

somewhat. The predominant type of urinary incon-

tinence in men is UUI, while in women it is SUI.

The distribution in men is 73% UUI, 19% mixed,

and only 8% SUI, as opposed to women where

49% of all cases are SUI [3] .

Because UI may cause social isolation, loss of

sexual function, or other psychosocial problems

[4, 5] , it could have significant impact on patients'

psychosocial well-being and quality of life (QOL).

Studies have shown that patients suffering with

UI are more depressed [6, 7] , psychologically

distressed, emotionally disturbed, and socially

isolated [8] . Moreover, compared with continent

individuals, those patients with UI also have higher

levels of anxiety, lower QOL, and poorer life

satisfaction [7] . The severity of UI also is correlated

with degrees of mental distress, social restrictions,

and restricted activities [4, 5] . As a result, UI has

an adverse effect on patients' daily lives and could

become a barrier for normal social function.

Current treatments for UI include behavioral

(e.g., bladder training, fluid manipulation, sched-

uled toileting, pelvic muscle exercises), pharma-

cological , and surgical interventions, used either

alone or in combination [9– 11] . Behavioral tech-

niques currently are recommended as first-line

therapy in the treatment of UI except for overflow

incontinence due to BOO. Behavioral interven-

tions usually are relatively inexpensive and easy to

implement, but the effectiveness chiefly depends

on the patient's adherence [12] . When nonpharma-

cological interventions have failed, drug therapy

can be an option [9] .

The goal of this chapter is to present the cur-

rent status in pharmacotherapy options of male

UI by looking into the four main subtypes of male

incontinence: urgency, stress, overflow, and post-

prostatectomy UI.

Urgency Urinary Incontinence

UUI involves a strong, sudden need to urinate

immediately followed by a bladder muscle contrac-

tion, resulting in an involuntary loss of urine. It is

basically a storage problem in which detrusor mus-

cle contracts involuntarily, and often these contrac-

tions occur regardless of the amount of urine that is

Chapter 29

Pharmacotherapy of Male Incontinence

Peter Tsakiris and Jean J.M.C.H. de la Rosette

412 P. Tsakiris and J.J.M.C.H. de la Rosette

in the bladder [1] . UUI is a clinical symptom of the

overactive bladder syndrome (OAB) characterized

by urgency, with or without incontinence, and usu-

ally is associated with frequency and nocturia.

UUI in men is most commonly associated with

neurogenic bladder or detrusor muscle instability.

What characterizes male UI with regard to female

is the greater possibility of BOO [due to benign

prostatic hyperplasia (BPH), urethral stricture,

bladder neck stenosis) in men. This difference

between the two genders when dealing with UI in

most of the cases causes an increased intravesi-

cal pressure, which subsequently causes detrusor

overactivity (DO) via partial neurological denerva-

tion of the bladder smooth muscle and consequent

supersensitivity of muscarinic acetylcholine recep-

tors [13] . Increased bladder outlet resistance also

may result in ischemia, increased detrusor collagen

content, changes in electrical properties of detrusor

smooth muscle cells [14] , and reorganization of

the spinal micturition reflex [15] , all of which are

associated with the development of DO in animal

models. However, comorbid BOO and DO are not

always evidence of a cause-and-effect relationship

between these two conditions. OAB symptoms can

be caused solely by bladder dysfunction that is

independent of prostatic pathology. The observa-

tion that many men with OAB symptoms do not

have BOO [16] underscores the potential role of

bladder dysfunction. The fact that OAB symptoms

are not limited to men provides further support for

this assertion, bearing in mind that female BOO is

extremely uncommon (Fig. 29.2 ) .

In one study of 160 men with lower urinary

tract symptoms (LUTS), including UI, urinary

frequency, nocturia, or difficulty in voiding, BOO

was confirmed in 109 (68%) [17] , while Laniado et

al. [18] reported that only 48% of men with LUTS

had urodynamically confirmed BOO. A study in

the United States suggested that 16% of men with

OAB symptoms have UUI [19] . It is a fact, however,

that men with UUI have been underrepresented in

trials of pharmacotherapy for OAB, although 84%

of men with UUI report some degree of symptom

bother [20] .On a theoretical basis, possible poten-

tial sites for pharmacological intervention in the

management of UI include the bladder smooth

muscle, efferent (motor) nerves, afferent (sensory)

nerves, and the central nervous system. The main-

stay oral drug class for the medical treatment of

incontinence is the antimuscarinics. These are anti-

cholinergic agents that act on motor receptors on

peripheral smooth muscle and perhaps on sensory

receptors as well. Due to the fact that females seek

medical care for UI much more often then males,

the vast majority of the studies on medical treat-

ment of incontinence with antimuscarinics have

been conducted in females or in mixed gender

populations dominated by females, ie, under condi-

tions where the data are driven by the overwhelm-

ing female population in those trials.

Since our knowledge on medical incontinence

treatment is largely driven by data from females,

the assumption that female data can be simply

extrapolated to males has been a field of quite

intensive investigation. Experimental studies have

Fig. 29.1. Male incontinence

post-micturition dribbing

post-prostatectomy incontinence

incontinence with freq/urgency

incontinence with a complex history

- stress UI

- urge UI

- mixed UI

- overflow UI

sphincteric incompetence

overactive detrusor

bladder outlet obstruction

underactive detrusor

Fig. 29.2. Disorders associated with neurogenic

bladder

29. Pharmacotherapy of Male Incontinence 413

been published addressing the question whether

any gender difference is to be expected for mus-

carinic antagonists. At the beginning of the past

decade, male and female rats were reported to

exhibit differential sensitivity to the analgesic

effects of the muscarinic agonist pilocarpine [21] .

Later on, in the context of overactive bladder, the

muscarinic antagonist tolterodine was reported

to exhibit markedly gender-dependent effects on

number of voids and volume voided per micturi-

tion in rats [22] . In line with these findings the

estrus cycle was reported to affect the sensitivity

of isolated rat bladder strips to muscarinic stimula-

tion [23] .

Evidence supporting the lack of gender differ-

ence for the sensitivity toward muscarinic stimu-

lation is suggested in studies conducted in mice

[24] and cats [25] in vitro. In a study exploring the

possibility of gender-based differential regulation

of M

2 and M

3 receptors in rats and human urinary

bladders [26] the authors reported that none of the

parameters of muscarinic responsiveness indicated

a differential regulation in male and female rat

bladder. Their patient data additionally indicated

that gender differences of a clinically relevant mag-

nitude also are absent in humans. They concluded

that neither the overall muscarinic responsiveness

nor the relative roles of M

2 and M

3 receptors are

regulated in a gender-specific manner in the rat

urinary bladder. These findings are in accordance

with the results from a study on about 2,000 OAB

patients in which tolterodine was similarly effec-

tive in both genders in vivo [27] .

A common concern of physicians in treating

male incontinence is that the inhibitory effect

of antimuscarinics on detrusor muscle contrac-

tion theoretically could aggravate the voiding

difficulties or cause urinary retention in men with

concomitant BOO. It therefore is evident that the

evaluation and management of men with symp-

toms consistent with OAB requires a thorough

and diligent evaluation of the lower urinary tract

in order to plan optimal therapeutic intervention.

Evaluation is predicated on a complete assessment

of voiding dynamics and is best accomplished with

urodynamic studies. These studies should provide

a complete measurement of filling characteristics,

pressure and flow criteria, sphincteric activity, and

postvoid residual determination in order to assess

the existence and degree of obstruction.

However, as it has been stated in a recent review

article, little evidence from clinical trials has sup-

ported the concern [28] . In a meta-analysis of rand-

omized controlled trials of antimuscarinics used to

treat OAB in female or mixed gender populations,

only oxybutynin IR significantly increased the risk

of urinary retention compared with placebo [29] .

Men with BOO and DO who received tolterodine

for 12 weeks demonstrated no change in Q max and a

reduction in detrusor pressure at Q max . Tolterodine-

treated men demonstrated a statistically significant

increase in postvoid residual (PVR) urine volume

compared with placebo, but whether this increase

was clinically relevant is unclear. In this study,

tolterodine was not associated with an increase

in acute urinary retention (AUR) which required

catheterization [30] . There also was no incidence

of AUR among 39 men with BPH and LUTS who

received open-label tolterodine extended-release

(ER) treatment for 6 months [31] . In a recently

published 12-week, randomized, double-blind,

active- and placebo-controlled trial conducted at

95 urology clinics in the United States [32] , 879

patients were randomly assigned to receive pla-

cebo, 4 mg of tolterodine ER, 0.4 mg of tamsulosin,

or tolterodine ER plus tamsulosin. Changes in PVR

volume, Q max , or incidence of AUR did not differ

significantly among the four treatment groups.

However, this study did not include patients with

PVR volume >200 ml and maximum urinary flow

rate <5 ml/s.

Although several antimuscarinics are used to

treat OAB, tolterodine has been most extensively

investigated for the treatment of male OAB symp-

toms. Abrams et al. [30] reported a 12-week trial

of tolterodine versus placebo in 222 men with

frequency, urgency with or without incontinence,

urodynamically confirmed DO, and mild to severe

obstruction. Exclusions included PVR >40% of

cystometric capacity and urinary retention within

the preceding 12 months. The typical patient was

moderately obstructed with proven DO. Only one

episode of AUR was seen in the placebo group,

with none in the tolterodine group. However, two

patients on tolterodine were withdrawn due to a

high PVR (320 ml in one, undefined in the other).

There was no difference in the overall incidence

of adverse events. Dry mouth was common among

the tolterodine-treated patients (24%), but only one

patient considered it severe. Urodynamic results

414 P. Tsakiris and J.J.M.C.H. de la Rosette

showed evidence of fairly small treatment differ-

ences due to tolterodine for residual urine +27 ml;

voiding efficiency −7%; and bladder contractility

index (BCII) −10%. Significant reductions due

to tolterodine were seen in detrusor pressure at

maximum flow, with a difference between groups

of −7 cm H

2 O.

In a post hoc analysis study, the researchers

assessed the efficacy and tolerability of tolterodine

ER for reducing UI episodes in 163 men with OAB

and urgency UI [33] . Key exclusion criteria of this

study were, among others, the existence of clini-

cally relevant BOO (judged by the investigator and

based on patient history) and patients with a mean

micturition (void) volume of < 200 ml. Reductions

in weekly UI episodes after 12 weeks of treat-

ment were significantly greater in the tolterodine

ER group than in the placebo group (median %

change, 71% vs. 40%, P < 0.05). A significantly

larger percentage of men receiving tolterodine ER

reported an overall benefit of treatment (63% vs.

46%, P = 0.04). Except for dry mouth, the inci-

dence of adverse events in men receiving toltero-

dine ER was low and similar to placebo. One man

receiving tolterodine ER had symptoms suggestive

of urinary retention, leading to his withdrawal from

the study. None of the men had AUR retention

requiring catheterization.

In accordance with these, significant reductions

in total micturitions and urgency-related micturi-

tions were observed in men with OAB symptoms

who received tolterodine ER treatment for a period

of 12 weeks [34] . However, all these reports are

secondary analyses of subpopulations and not pro-

spective clinical trials. Moreover, all of these stud-

ies were underpowered to detect clinically relevant

increases in the incidence of a relatively rare event

such as AUR, for example, to detect a doubling of

AUR incidence.

Combination of Antimuscarinics Plus a

1 -

Receptor Antagonists

Some small and short-term studies have proposed

that antimuscarinics can be safely combined with

a 1 -receptor antagonists to treat men with OAB

symptoms in the presence or absence of BOO. Fifty

men with urodynamically confirmed mild or mod-

erate BOO and DO received tamsulosin for 1 week

before being randomized to tamsulosin/tolterodine

combination therapy or tamsulosin alone [35] .

Group allocation was randomized, but there was

no blinding. Significant reductions in maximum

detrusor pressure during micturition and maximum

involuntary contraction pressure were observed

in men who received the combination treatment

for 3 months. These patients also demonstrated

significantly increased Q max and volume at first

involuntary contraction, as well as improvements

in a QOL measure. There was no incidence of uri-

nary retention in either treatment group; however,

it should be noted that men with severe obstruc-

tion (not defined) were specifically excluded.In

the randomized, controlled trial by Kaplan et al.

[32] , patients were treated with placebo, only tol-

terodine, only tamsulosin, or both tolterodine ER

plus tamsulosin for 12 weeks. Patients receiving

the combination treatment compared with placebo

experienced significant reductions in UUI (−0.88

vs. −0.31, P = 0.005), urgency episodes without

incontinence (−3.33 vs. −2.54, P = 0.03), micturi-

tions per 24 h (−2.54 vs. −1.41, P < 0.001), and

micturitions per night (−0.59 vs. −0.39, P = 0.02 ).

Patients receiving tolterodine ER plus tamsulosin

demonstrated significant improvements on the total

International Prostate Symptom Score (−8.02 vs.

placebo, −6.19, P = 0.003) and QOL item (−1.61

vs. −1.17, P = 0.003).

The efficacy and tolerability of oxybutynin ER

in combination with the a

1 -blocker tamsulosin in

reducing the irritative and obstructive components

of LUTS was evaluated in a multicenter, double-

blind trial [36] . Subjects of the trial were required

to demonstrate a Q max < 8 ml/s and a PVR < 150

ml on two occasions in order to qualify. A total of

418 men were randomized. Tamsulosin combined

with oxybutynin ER resulted in a significantly

greater improvement in total AUA symptom score

compared with tamsulosin and placebo after 8

( P = 0.033) and 12 ( P = 0.006) weeks of treat-

ment. Combining active treatments resulted in

greater decreases in AUA irritability scores after

4 ( P = 0.008), 8 ( P < 0.001), and 12 ( P < 0.001)

weeks. The incidence of an elevated PVR volume

>300 ml was 2.9% ( n = 6) in patients receiving

combination therapy and 0.5% ( n = 1) in patients

receiving tamsulosin alone. Incidence of reduced

Q max (<5 ml/s) was 3.8% ( n = 8) and 5.7% ( n = 12),

respectively. No patients developed AUR requiring

catheterization.

29. Pharmacotherapy of Male Incontinence 415

Lee et al. [37] studied 228 men with urodynami-

cally proven BOO and with frequency and urgency

episodes at least daily, in an 8-week, randomized,

double-blind, multicenter study. Patients were

excluded if the PVR was >30% of cystometric

capacity. Monotherapy with doxazosin was com-

pared to combined treatment using doxazosin and

propiverine. Symptoms were assessed by the IPSS.

The combined treatment group had significant

improvement rates with regard to urinary frequency

(23.5% vs. 14.3%, P = 0.004), average micturition

volume (32.3% vs. 19.2%, P = 0.004), and stor-

age (41.3% vs. 32.6%, P = 0.029. There were no

episodes of retention, but two patients in the com-

bined group were withdrawn due to a rise in PVR,

and the average PVR increased significantly in

the combined group. Dry mouth was significantly

more common in the combined group, although

less than a third of affected patients left the study.

It should be mentioned that the majority of patients

studied fell into the equivocal range of obstruc-

tion as defined by an AG number [now termed the

bladder outlet obstruction index (BOOI)] of 20–40.

Furthermore, only 35% of patients had DO. Thus,

the typical patient in this study was only mildly

obstructed and tended not to have DO.

To date, no studies have evaluated the efficacy

of combining antimuscarinics with 5 a -reductase

inhibitors, and there is no evidence to suggest

that this cannot be a safe combination for the

treatment of men with BPH and OAB symptoms.

When treating male patients with UI and OAB

syndromes in general, caution has to be exercised

in those with significant PVR, since there is

potential for increased risk of infection, further

bladder decompensation, or renal insufficiency

[38] . Close monitoring is recommended in these

patients. At present, we must conclude that the

literature is based on pilot studies that use uro-

dynamic criteria for patient selection that do not

necessarily represent real-life practice. Some of

these studies are not placebo-controlled or are

not adequately powered. Additionally, the short

duration of the treatment trials (8 and 12 weeks)

in the studies necessitates the investigation of

anticholinergic treatment for a longer period.

Combination therapy with an anticholinergic and

an a 1 -receptor antagonist in men with OAB and

with suspected BOO is an interesting potential

direction in pharmacotherapy that requires testing

in well-designed clinical trials before it can be

recommended for routine clinical use.

Stress Urinary Incontinence

SUI is defined as the involuntary leakage of urine

on effort or exertion or on sneezing or coughing

[1] and accounts for less than 8% of male urinary

incontinence. It is a condition caused by sphinc-

teric incompetence and usually occurs in women,

while the most cases in men occur after pelvic

surgery and especially prostatectomy. The etiol-

ogy of sphincteric incompetence in these cases is

lesions of autonomic parasympathetic nerves or the

urethral sphincter itself.

Progress is significantly slower in the develop-

ment of drugs for SUI compared to UUI. The

main aim of drug treatment of SUI is to increase

outflow resistance. Because SUI is a condition usu-

ally occurring in women, the studies investigating

the effectiveness of pharmacotherapy in men are

spare. Additionally, the anatomical differences of

the lower urinary tract between males and females

are responsible for the different underlying patho-

physiological mechanisms of SUI. Consequently,

the results from the use of drugs for treatment of

female SUI might differ on men (Fig. 29.3 ) .

Currently there is no pharmacological treatment

approved for SUI in men. Theoretically, an increase

in outflow resistance and therefore beneficial drug

effects can be obtained in some patients by use of

active a -adrenoceptor agonists and inhibitors of

reuptake of noradrenaline and serotonin in adren-

ergic nerve endings [41, 42] .

a -Adrenoceptor agonists have been used for SUI

because they are effective at increasing bladder

outlet resistance during bladder filling in animal

models [43] . They have been found to be effective

for SUI in both open-label and controlled clinical

trials [41] ; nevertheless there is a lack of long-term,

randomized, controlled clinical trials. Additionally,

the side effects observed where quite serious.

Phenylpropanolamine was withdrawn from the

US market by the Food and Drug Administration

(FDA) because of the risk of hemorrhagic stroke in

women [44] . Furthermore, a - adrenoceptor agonists

lack exclusive selectivity for urethral a - adrenocep-

tors and may cause elevated blood pressure, sleep

disturbances, nausea, dry mouth, headache, tremor,

416 P. Tsakiris and J.J.M.C.H. de la Rosette

palpitations, and exacerbation of abnormal cardiac

rhythms [45] . Interestingly, an agent that could

potentially be useful in managing stress incon-

tinence is clenbuterol, a b -adrenergic antagonist

[46] . Although one would expect that such an agent

would not be useful for SUI based on its mecha-

nism of action, limited controlled studies have

shown that the beneficial effects might result from

improvement of the striated or extrinsic sphincteric

mechanism. In a study of 72 incontinent men after

prostate resection (BPH), clenbuterol improved

76.3% of treated men [47] . However, no drug in

these categories has been subjected to rigorous

clinical trials, and therefore none has received FDA

approval for the treatment of SUI.

Imipramine, a tricyclic antidepressant, was among

the first drugs with serotonin [5-hydroxytryptamine

(5-HT)] and norepinephrine (NE) reuptake inhibi-

tory action to be investigated for the treatment of

SUI that showed some effectiveness in a few stud-

ies; however, side effects were considered serious

enough to preclude further investigation.

During the last years, new interest has been given

to drugs that stimulate sensomotor activity in the

external urethral sphincter. Duloxetine is another

combined 5-HT–NE reuptake inhibitor [48, 49] . In

different double-blind, randomized, placebo-control-

led clinical trials, a significant reduction of urinary

incontinence and significantly improved inconti-

nence quality of life (I-QOL) for women could be

demonstrated [50– 53] . Considering the proven effect

on the striated sphincter muscles in incontinent

women, it is plausible that a similar effect can be

reached in men if the nervous structure or the sphinc-

teric apparatus is not totally destroyed. By increasing

the neural input the sphincteric activity, it is expected

that continence will increase as well.

Data on the effect of duloxetine in men with

SUI are still sparse,, and these studies have been

published only during the last months [54– 56] .

Schlenker et al. presented their preliminary results

from a pilot study on the off-label use of duloxetine

for the treatment of SUI after radical prostatectomy

or cystectomy with orthotopic neobladder [54] .

Over a 2-year period, 18 patients with SUI pos-

tradical prostatectomy or radical cystectomy were

treated with 40 mg of duloxetine twice daily. The

average number of pads pretreatment was 8 a day.

After an average of 9.4 weeks of pharmacotherapy

with duloxetine, the average number of pads fell

to 4.2 pads/day ( P < 0.0001). Fifteen of the 18

patients (83.33%) reported improvement of SUI

after the use of duloxetine and 7 of 18 patients

(39%) were completely dry or used one pad per

day at the most for safety reasons. The mean pad

use in these patients before duloxetine was 3.9

pads/day. Six patients reported no side effects at

all; the majority reported mild side effects such as

fatigue ( n = 4), dry mouth ( n = 3), nausea ( n = 1),

or insomnia ( n = 1). Most of the side effects van-

ished within 4 weeks but six patients (33.3%) dis-

continued the medication due to adverse events.

In another study, the researchers investigated

the impact of duloxetine in urodynamic param-

eters of 18 men with SUI 12 months after radical

prostatectomy [55] . All underwent a pad test to

quantify the degree of urine loss and urodynamic

evaluation before and after a 3-month duloxetine-

treatment period. The intrinsic sphincter was eval-

uated by abdominal leak point pressure (ALPP)

Fig. 29.3. Pharmacotherapy for male SUI

Agent

Oxybutinin

Tolterodine

Solifenacin

Darifenacine

Trospium

Propiverine

Capsaicin analogue agents

Calcium channel blockers

Potassium channel openers

a-adrenergic antagonists

b-adrenergic agonists

Prostaglandin synthesis inhibitors

Antimuscarinic action

Target-specific antimuscarinic action rather than subtype-specific

M3 selective receptor antagonist

M1-3 antagonist. Does not cross normal blood brain barrier

Anticholinergic and calcium antagonistic actions

Block vanilloid receptors of c-fibers

Not encouraging results

Need further trial

Mechanism

29. Pharmacotherapy of Male Incontinence 417

and retrograde leak point pressure (RLPP), and

the striated sphincter by maximal urethral closure

pressure (MUCP). In their results, they reported an

increase in all three parameters and a significant

reduction in urine loss. Additionally, after HCl

duloxetine treatment there was significant correla-

tion between RLPP and ALPP, while before treat-

ment among all three urodynamic parameters.

Filocamo et al. [56] recently published a pro-

spective, randomized, single-blind study in which

they assessed the efficacy and safety of association

of duloxetine and rehabilitation compared with

rehabilitation alone in men with SUI after radi-

cal retropubic prostatectomy (RRP). From a total

of 112 men, 92 patients completed the study and

ten were removed due to adverse events (nine for

duloxetine and one for placebo, discontinuation

rates 15.2 and 1.8%, respectively). In their results,

there was a significant decrease in pad use in the

combined treatment group right after the comple-

tion of the 4-month treatment period, 39 patients

versus 27 were dry ( P = 0.007). However, 1 month

after planned interruption of duloxetine, they

observed a U-turn; 23 patients were completely dry

vs. 38 in the rehabilitation alone group ( P = 0.008).

This shift also was observed 2 months later. On

trying to explain these results, the authors stated

that probably patients treated with duloxetine had

less motivation than rehabilitation-only patients to

learn to reproduce an adequate pelvic floor muscle

precontraction during effort.

These studies suggest a beneficial effect of

duloxetine on men with SUI, with drug tolerabil-

ity, however, appearing to be an important issue.

It is evident that larger prospective studies with

adequate placebo control and a longer and stand-

ardized follow-up are recommended in order to

draw more representative conclusions for the effec-

tiveness of duloxetine in men with SUI.

Postprostatectomy Incontinence

The incidence of incontinence following pros-

tatectomy varies between 1 and 15% depending

mainly on the procedure used. In late life, preexist-

ing bladder problems may coexist, accounting for

the observed underlying pathology. The highest

incidence is associated with radical prostatectomy,

the incidence of stress incontinence requiring some

treatment varying between 5 and 15% [57] . After

transurethral prostatectomy(TURP) or transvesi-

cal prostatectomy (TVP), the risk of incontinence

is reported to be 0.4–1%. This might increase up

to 20–40% following radical retropubic prosta-

tectomy (RRP) [58, 59] . After being cured from

some major problems such as voiding difficulties

and malignancy, these patients are confronted with

the social and hygienic problems brought about by

incontinence. The integrity of the striated muscle

sphincter is compromised in approximately 25%

of incontinent patients [60] . Underlying detrusor

instability accounts for the majority of cases either

alone or in combination with sphincteric insuf-

ficiency. It therefore is evident that proper urody-

namic investigation should be followed in order to

properly diagnose the primary etiology of incon-

tinence and provide adequate treatment; detrusor

instability, sphincteric incompetence, or mixed.

Factors that have been associated with an

increased risk of incontinence following prostate-

ctomy are an increased age [61] , associated neuro-

logical disease, or cognitive impairment [62, 63] .

Evidence indicates that surgical technique can play

a role, as a decrease in the risk of urinary inconti-

nence is seen when manipulation of the lower uri-

nary tract structures and tissues is limited, stitches

in the smooth muscle of the urethra are avoided,

and urethral length of at least 2.5 cm is preserved

[64, 65] . The relationship between preoperative

urine leakage and postoperative continence is less

clear because baseline rates can be confounded by

the obstructive symptoms of the disease often seen

prior to surgery [66] . There is some debate about

the influence of prior surgery in more recent series

and it appears likely that there is no additional risk

attributable to a repeat procedure.

Treatment of postprostatectomy incontinence

should be targeted at the underlying pathology

where appropriate. The drug options for urge and

mixed incontinence are described previously in this

chapter. There is good evidence that the incidence

of detrusor instability will rise in association with

increasing age among the postoperative population

and that this will lead to an increase in lower uri-

nary tract symptoms which will require treatment

[67] . Periurethral injectable materials also have

been used in an attempt to treat stress incontinence

in men. The reported results of this intervention

have been contradictory and success in the short

418 P. Tsakiris and J.J.M.C.H. de la Rosette

term is followed by relapse [68, 69] . For patients

with persistent stress incontinence following medi-

cal management, the implantation of an artificial

urethral sphincter is a successful option; more than

70% of men will be either cured or significantly

improved following the procedure.

Overflow Incontinence

Overflow incontinence (OI) occurs more often in

men than women and it is characterized by large

postvoid residual volumes of urine. The underlying

pathology could be either an underactive (acon-

tractile) detrusor or BOO. These conditions very

often coexist, since BOO can lead to underactive

bladder.

Underactive detrusor also can result from

chronic urinary tract infection or overdistension

of the bladder which can damage stretch receptors

in the bladder wall. Radical pelvic surgery and

diabetic neuropathy may damage the nerves, caus-

ing the same to occur. Drugs like anticholinergics,

phenothiazines, antidepressants, narcotics, calcium

channel blockers, and antihistamines can give rise

to the same effects.

Urodynamic investigation is necessary in order

to assess the existence of BOO and treat it initially.

Surgery is the treatment of choice if obstruction

is present; however, pharmacotherapy treatment

with a -adrenergic blockers, eg, tamsulosin, tera-

zosin, or doxazosin, may be beneficial [70] . The

5 a -reductase inhibitor, finasteride, has been shown

to decrease the symptom score and prostatic vol-

ume and to increase the urinary flow rates [71,

72] . Combination of these two agents ( a -blocker

+5 a -reductase inhibitors) does not have additive

effects on symptoms but seems more effective than

either one as monotherapy in preventing a com-

bined endpoint of clinical progression [70] .

OI due to poor contraction of the bladder should

be managed by clean intermittent self-catheteriza-

tion (CISC) every 4 h or scheduled voiding train-

ing. If CISC is difficult or not possible for the

patient, pharmacotherapy treatment can be used.

However, little evidence exists suggesting that drug

therapy may be beneficial [73] . In general, detru-

sor contractility can be enhanced either with para-

sympathomimetics or with drugs that inactivate

cholinesterase, thus maintaining the cholinergic

simulation. Bethanechol chloride, a cholinergic

agonist, has been used to stimulate bladder contrac-

tions, but has not been proven to be effective over

the long term [74– 77] . In a prospective study, intra-

vesical prostaglandins were given to 36 patients

who had urinary symptoms associated with a

poorly functioning detrusor; 67% of these patients

were found to be in chronic retention. Using stand-

ard urodynamic techniques, 72% showed objective

evidence of an immediate improvement in detru-

sor function and there was prolonged therapeutic

benefit in 39%. The authors noted that the results

were encouraging for those already receiving oral

cholinergic stimulation, with a prolonged reduc-

tion in the PVR [78] . Based on that observation, a

prospective, randomized, double-blind study was

conducted recently, investigating the effectiveness

of combining intravesical prostaglandin E

2 (PGE 2 )

and oral bethanechol chloride in patients with

underactive bladder [79] . From the 19 patients

studied, 17 were men. Although there was evidence

of a pharmacological effect, bethanechol chloride

and PGE

2 had a limited therapeutic effect com-

pared with placebo.

Distigmine bromide, an anticholinesterase agent,

inactivates cholinesterase, leading to a sustained

action of acetylcholine on cholinergic nerve end-

ings, which results in improved detrusor contrac-

tions. Distigmine shows clinical efficacy in patients

with poor detrusor function, and therefore may be

used alternatively in selected cases, as was shown

in 14 patients after TURP [80] and in a mixed gen-

der study population [81] . In an interesting study

published recently, the authors compared the effec-

tiveness of a cholinergic drug, an a -blocker, and

combinations of the two for the treatment of under-

active detrusor [82] . One hundred-nineteen patients

with underactive bladder were assigned to three

groups: the cholinergic group, consisting of 40

patients taking bethanechol chloride (60 mg/day)

or distigmine bromide (15 mg/day); the a -blocker

group, consisting of 38 patients taking urapidil (60

mg/day); and the combination group, consisting of

41 patients taking both a cholinergic drug and an

a -blocker. The effectiveness of each therapy was

assessed 4 weeks after initialization of the therapy.

The results in average and maximum flow rates and

PVP showed a significant increase and decrease,

respectively, in the combination group ( P = 0.0004

and P = 0.0008, respectively).

29. Pharmacotherapy of Male Incontinence 419

General Conclusions

When pharmacotherapy is selected to treat male

UI, physicians must have in mind that there are

fewer medical treatment studies on males. Studies

of UI have been conducted mostly on female popu-

lations, while data from mixed gender studies are

clearly driven by the overwhelmingly female popu-

lation in those studies. This chapter presented the

medical treatment options for each type of male UI

based on published studies; however, much more

research is needed in order to allow evidence-based

treatment recommendations.

References

1. EAU Guidelines. Guidelines on urinary inconti-

nence. Update March 2005.

2. Abrams P, Cardozo L, Fall M, et al. Standardisation

Sub-Committee of the International Continence

Society. The standardisation of terminology in lower

urinary tract function: Report from the standardisa-

tion sub-committee of the International Continence

Society. Urology 2003; 61(1):37–49.

3. Jeffcoate TNA, Francis WJA. Urgency incontinence

in the female. Am J Obstet Gynecol 1996; 94:

604–618.

4. Shaw C. A review of the psychosocial predictors

of help-seeking behaviour and impact on quality of

life in people with urinary incontinence. J Clin Nurs

2001; 10:15–24.

5. Hunskaar S, Sandvik H. One hundred and fifty

men with urinary incontinence. III. Psychosocial

consequences. Scand J Prim Health Care 1993;

11:193–196.

6. Valvanne J, Juva K, Erkinjuntti T, Tilvis R. Major

depression in the elderly: A population study in

Helsinki. Int Psychogeriatr 1996; 8:437–443.

7. Herzog AR, Fultz NH, Brock BM, et al. Urinary

incontinence and psychological distress among

older adults. Psychol Aging 1988; 3:115–121.

8. Bogner HR, Gallo JJ, Sammel MD, et al. Urinary

incontinence and psychological distress in commu-

nity-dwelling older adults. J Am Geriatr Soc 2002;

50:489–495.

9. Couture JA, Valiquette L. Urinary incontinence.

Ann Pharmacother 2000; 34:646–655.

10. Wilson L, Brown JS, Shin GP, et al. Annual direct

cost of urinary incontinence. Obstet Gynecol 2001;

98:398–406.

11. Gormley EA. Biofeedback and behavioral therapy

for the management of female urinary incontinence.

Urol Clin North Am 2002; 29:551–557.

12. Vapnek JM. Urinary incontinence. Screening and

treatment of urinary dysfunction. Geriatrics 2001;

56:25–29.

13. Sibley GN. The physiological response of the detru-

sor muscle to experimental bladder outflow obstruc-

tion in the pig. Br J Urol 1987; 60:332–336.

14. Abdel-Aziz KF, Lemack GE. Overactive bladder in

the male patient: Bladder, outlet, or both? Curr Urol

Rep 2002; 3:445–451.

15. Steers W. Pathophysiology of overactive bladder

and urge urinary incontinence. Rev Urol 2002;

4:S7–18.

16. Hyman MJ, Groutz A, Blaivas JG. Detrusor insta-

bility in men: Correlation of lower urinary tract

symptoms with urodynamic findings. J Urol 2001;

166:550–552.

17. Hyman MJ, Groutz A, Blaivas JG. Detrusor insta-

bility in men: Correlation of lower urinary tract

symptoms with urodynamic findings. J Urol 2001;

166:550–553.

18. Laniado ME, Ockrim JL, Marronaro A, et al. Serum

prostate specific antigen to predict the presence

of bladder outlet obstruction in men with urinary

symptoms. BJU Int 2004; 94:1283–1286.

19. Stewart WF, van Rooyen JB, Cundiff GW, et al.

Prevalence and burden of overactive bladder in the

United States. World J Urol 2003; 20:327–336.

20. Peters TJ, Donovan JL, Kay HE, et al. The

International Continence Society “Benign Prostatic

Hyperplasia” Study: The bothersomeness of urinary

symptoms. J Urol 1997; 157:885–889.

21. Kiefel JM, Bodnar RJ. Roles of gender and gona-

dectomy in pilocarpine and clonidine analgesia in

rats. Pharmacol Biochem Behav 1992; 41:153–158.

22. Yoshimura Y, Schmidt F, Constantinou CE. Gender

specificity of tolterodine on micturition and the diur-

nal variation of urine production of the conscious

rat. BJU Int 2000; 87:879–885.

23. Longhurst PA, Levendusky M. Influence of gen-

der and the oestrous cycle on in vitro contractile

responses of the rat urinary bladder to cholinergic

stimulation. Br J Pharmacol 2000; 131:177–184.

24. Choppin A. Muscarinic receptors in isolated urinary

bladder smooth muscle from different mouse strains.

Br J Pharmacol 2002; 137:522–528.

25. An JY, Yun HS, Lee YP, et al. The intracellular

pathway of the acetylcholine-induced contraction

in cat detrusor muscle cells. Br J Pharmacol 2002;

137:1001–1010.

26. Kories C, Czyborra C, Fetscher C, et al. Gender

comparison of muscarinic receptor expression

and function in rat and human urinary bladder:

Differential regulation of M2 and M3 receptors?

Naunyn Schmiedebergs Arch Pharmacol 2003;

367(5):524–531.

420 P. Tsakiris and J.J.M.C.H. de la Rosette

27. Michel MC, Schneider T, Krege S, Goepel M. Do

gender or age affect the efficacy and safety of tol-

terodine? J Urol 2002; 168:1027–1031.

28. Chapple C, Roehrborn C. A shifted paradigm for the

further understanding, evaluation, and treatment of

lower urinary tract symptoms in men: Focus on the

bladder. Eur Urol 2006; 49(4):651–659.

29. Chapple C, Khullar V, Gabriel Z, Dooley JA. The

effects of antimuscarinic treatments in overactive

bladder: A systematic review and meta-analysis. Eur

Urol 2005; 48:5–26.

30. Abrams P, Kaplan SA, De Koning Gans HJ, Millard

R. Safety and tolerability of tolterodine for the

treatment of overactive bladder in men with bladder

outlet obstruction. J Urol 2006; 175:999–1004.

31. Kaplan SA, Walmsley K, Te AE. Tolterodine

extended release attenuates lower urinary tract

symptoms in men with benign prostatic hyperplasia.

J Urol 2005; 174:2273–2276.

32. Kaplan SA, Roehrborn CG, Rovner ES, et al.

Tolterodine and tamsulosin for treatment of men

with lower urinary tract symptoms and overactive

bladder: A randomized controlled trial. JAMA 2006;

296(19):2319–2328.

33. Roehrborn CG, Abrams P, Rovner ES, et al. Efficacy

and tolerability of tolterodine extended-release in

men with overactive bladder and urgency urinary

incontinence. BJU Int 2006; 97(5):1003–1006.

34. Marschall-Kehrel D, Abrams P, Guan Z, et al. Gender

analysis of data from two 12-week randomized con-

trolled trials of tolterodine: Tolterodine reduces over-

active bladder-related nocturnal frequency in men and

women with overactive bladder. Eur Urol 2005; 4:61.

35. Athanasopoulos A, Gyftopoulos K, Giannitsas K,

et al. Combination treatment with an alpha-blocker

plus an anticholinergic for bladder outlet obstruc-

tion: a prospective, randomized, controlled study. J

Urol 2003; 169:2253–2256.

36. MacDiarmid S, Chen A, Tu Nora et al. Effects of

tamsulosin and extended-release oxybutynin on

lower urinary tract symptoms in men. American

Urological Association Annual Meeting, May, 2006

(Abstract, podium presentation).

37. Lee KS, Choo MS, Kim DY, et al. Combination

treatment with propiverine hydrochloride plus doxa-

zosin controlled release gastrointestinal therapeutic

system formulation for overactive bladder and coex-

isting benign prostatic obstruction: A prospective,

randomized, controlled multicenter study. J Urol

2005; 174:1334–1338.

38. Larsson G, Hallen B, Nilvebrant L. Tolterodine in

the treatment of overactive bladder: Analysis of the

pooled phase II efficacy and safety data. Urology

1999; 53:990–998.

39. Diokno AC. Medical management of urinary

incontinence. Gastroenterology 2004; 126(1 Suppl

1):S77–81 (review).

40. Dinis P, Silva J, Ribeiro MJ, et al. Bladder C-fiber

desensitization induces a long—lasting improvement

of BPH-associated storage LUTS: A pilot study. Eur

Urol 2004; 46(1):88–93; discussion 93–94.

41. Diokno AC, Taub M. Ephedrine in treatment of uri-

nary incontinence. Urology 1975; 5:624–625.

42. Andersson KE. Current concepts in the treatment of

disorders of micturition. Drugs 1998; 35:477–494.

43. Brune ME, O'Neill AB, Gauvin DM, et al. Comparison

of alpha 1-adrenoreceptor agonists in canine urethral

pressure profilometry and abdominal leak point pres-

sure models. J Urol 2001; 166:1555–1559.

44. Fleming G. The FDA regulation and the risk of

stroke. N Engl J Med 2000; 343:1886–1887.

45. Anderson KW, Appell R, Awad S, et al.

Pharmacological treatment of urinary incontinence.

In: Abrams P, Khoury S, Wein A, eds. Incontinence.

Plymouth: Health Publications Ltd, 2002:418–511

46. Yasuda K, Kawabe K, Takimoto Y. Clenbuterol

Clinical Research Group. A double blind clinical

trial of a b 2-adrenergic agonist in stress inconti-

nence. Int Urogynecol J 1993; 4:146–151.

47. Zozikov B, Kunchev SI, Varlev C. Application of

clenbuterol in the treatment of urinary incontinence.

Int Urol Nephrol 2001; 33:413–416.

48. Wernicke JF, Gahimer J, Yalcin I, et al. Safety and

adverse event profile of duloxetine. Expert Opin

Drug Saf 2005; 4:987–993.

49. Wong DT, Bymaster FP, Mayle DA, et al. LY248686,

a new inhibitor of serotonin and norepinephrine

uptake. Neuropsychopharmacology 1993; 8:23–33.

50. Dmochowski RR, Miklos JR, Norton PA, Et al.

Duloxetine versus placebo for the treatment of

North American women with stress urinary inconti-

nence. J Urol 2003; 170:1259–1263.

51. Norton PA, Zinner NR, Yalcin I, Bump RC.

Duloxetine versus placebo in the treatment of stress

urinary incontinence. Am J Obstet Gynecol 2002;

187:40–48.

52. Kinchen KS, Obenchain R, Swindle R. Impact

of duloxetine on quality of life for women with

symptoms of urinary incontinence. Int Urogynecol J

Pelvic Floor Dysfunct 2005; 16:337–344.

53. van Kerrebroeck P, Abrams P, Lange R, et al.

Duloxetine versus placebo in the treatment of

European and Canadian women with stress urinary

incontinence. BJOG 2004; 111:249–257.

54. Schlenker B, Gratzke C, Reich O, et al. Preliminary

results on the off-label use of duloxetine for the treat-

ment of stress incontinence after radical prostatectomy

or cystectomy. Eur Urol 2006; 49(6):1075–1078.

29. Pharmacotherapy of Male Incontinence 421

55. Zahariou A, Papaioannou P, Kalogirou G. Is HCl

duloxetine effective in the management of urinary

stress incontinence after radical prostatectomy?

Urol Int 2006; 77:9–12.

56. Filocamo M, Li Marzi V, Del Popolo G, et al.

Pharmacologic treatment in postprostatectomy

stress urinary incontinence. Eur Urol 2007; 51(6):

1559–1564.

57. Catalona WJ, Basler WJ. Return of erections and

urinary continence following nerve sparing radical

prostatectomy. J Urol 1987; 138:574–578.

58. Fowler FJ Jr, Barry MJ, Lu-Yao G, et al. Patient

reported complications and follow-up treat-

ment after radical prostatectomy. The National

Medicare Experience: 1988–1990. Urology 1993;

42(6):622.

59. Murphy GP, Mettlin C, Menck H, et al. National

patterns of prostate cancer treatment by radical

prostatectomy: Result of a survey by the American

College of Surgeons Committee on Cancer. J Urol

1994; 152(5 Pt 2):1817.

60. Fitzpatrick JM, Gardina RA, Worth PHL. The evalu-

ation of 68 patients with post prostatectomy inconti-

nence. Br J Urol 1979; 51:552–555.

61. Steiner MS, Morton RA, Walsh PC. Impact of

anatomical radical prostatectomy on urinary incon-

tinence. J Urol 1991; 145:S12–15.

62. Hammerer P, Dieringer J, Schuler J, et al. Urodynamic

parameters to predict continence after radical prosta-

tectomy. J Urol 1991; 145:292A.

63. Barkin M, Dolfin D, Herschorn S, et al. Voiding

dysfunction in institutionalised elderly men: The

influence of previous prostatectomy. J Urol 1983;

130:258–259.

64. Moore K. A review of the anatomy of the male

continence mechanism and the cause of urinary

incontinence after prostatectomy. J WOCN 1999;

26:86–93.

65. Avant O, Jones J, Beck H, et al. New method to

improve treatment outcomes for radical prostatec-

tomy. Urology 2000; 56:658–662.

66. Potosky AL, Legler J, Albertsen PC, et al. Health

outcomes after radical prostatectomy or radiother-

apy for clinically localized prostate cancer: Results

from the Prostate Cancer Outcomes Study (PCOS).

J Natl Cancer Inst 2000; 92:1582–1592.

67. Thomas AW, Cannon A, Bartlett E, et al. The

natural history of voiding dysfunction in men: The

long term follow up of TURP. Br J Urol 1998; 81:

(Suppl 4)22.

68. Politano VA. Transurethral polytef injection for post

prostatectomy incontinence. Br J Urol 1992; 69:26–28.

69. Deane AM, English P, Hehir M, et al. Teflon injection

in stress incontinence. Br J Urol 1985; 57:78–80.

70. Hutchison A, Farmer R, Verhamme K, et al. The

efficacy of drugs for the treatment of LUTS/BPH.

A study in 6 European countries. Eur Urol 2007;

51(1):207–215.

71. Gormley GJ, Stoner E, Bruskewitz RC, et al. The

effect of finasteride in men with benign prostatic

hyperplasia: the Finasteride Study Group. N Engl J

Med 1992; 327:1185–1191.

72. Rittmaster RS. Finasteride. N Engl J Med 1994;

330:120–125.

73. Barendrecht MM, Oelke M, Laguna MP, Michel

MC. Is the use of parasympathomimetics for treat-

ing an underactive urinary bladder evidence-based?

BJU Int 2007; 99(4):749–752.

74. McDowell BJ, Burgio KL, Dombrowski M, et al.

An inter-disciplinary approach to the assessment and

behavioral treatment of urinary incontinence in geriat-

ric outpatients. J Am Geriatr Soc 1992; 40:370–374.

75. Light JK, Scott FB. Bethanechol chloride and the

traumatic cord bladder. J Urol 1982; 128:852,

76. Awad S. Clinical use of bethanechol. J Urol 1985;

134:523–524.

77. Sonda LP, Gershon C, Diokno AC, Lapides J.

Further observations on the cystometric and uro-

flowmetric effects of bethanechol chloride on the

human bladder. J Urol 1979; 122:775–777.

78. Desmond AD, Bultitude MI, Hills NH, Shuttleworth

KE. Clinical experience with intravesical prostag-

landin E2. A prospective study of 36 patients. Br J

Urol 1980; 52:357–366.

79. Hindley RG, Brierly RD, Thomas PJ. Prostaglandin

E2 and bethanechol in combination for treating

detrusor underactivity. BJU Int 2004; 93(1):89–92.

80. Tanaka Y, Masumori N, Itoh N, et al. Symptomatic

and urodynamic improvement by oral distigmine

bromide in poor voiders after transurethral resection

of the prostate. Urology 2001; 57(2):270–274.

81. Bougas DA, Mitsogiannis IC, Mitropoulos DN, et

al. Clinical efficacy of distigmine bromide in the

treatment of patients with underactive detrusor. Int

Urol Nephrol 2004; 36(4):507–512.

82. Yamanishi T, Yasuda K, Kamai T, et al. Combination

of a cholinergic drug and an alpha-blocker is more

effective than monotherapy for the treatment of

voiding difficulty in patients with underactive detru-

sor. Int J Urol 2004; 11(2):88–96.

423

Urinary incontinence is a dreaded complication

of prostatectomy affecting men in the prime

of their lives and causing considerable distress

[1] . Cooney and Horton in 1951 wrote: “It is

our impression that most urologists have an

attitude of resignation regarding urinary incon-

tinence and seldom attempt operative relief of

these patients. Many have called attention to the

tremendous increase in the sale of Cunningham

clamps since the advent of transurethral pros-

tatectomy, and the difficulty with sphincteric

control following perineal prostatectomy is also

well known. Even in suprapubic prostatectomy

there appears to be an irreducible minimum of

these embarrassing complications and probably

in due time the retropubic prostatectomist will

also ruefully acknowledge his guilt in a certain

number of cases” [2] . They describe a rectus fas-

cial bulbous urethral sling placed anterior to the

pubis which produced cure in two patients and

failed for technical reasons in a third.

For decades urologists struggled with the treat-

ment of postprostatectomy incontinence often

with disappointing and nondurable results. A

major advance in the treatment of male urinary

incontinence was the development of the artificial

urinary sphincter (AUS) in 1973 [3] . This review

of the history of the treatment of male urinary

incontinence will be divided into the preartificial

urinary sphincter era and the postartificial urinary

sphincter era.

Preartificial Urinary Sphincter Era

Foley Prosthesis

Foley in 1947 described “an artificial sphincter”

that consisted of a pneumatic or inflatable incon-

tinence clamp which he implanted around the

urethra just distal to the penoscrotal junction. This

was connected by tubing to a pump that the patient

carried in his “trouser’s pocket.” This pneumatic

device was inflated for continence and deflated

for voiding. In this 1947 article the author noted,

“Under the writer’s direct supervision the artificial

sphincter as here described has been used with sub-

stantial satisfaction in many cases of enuresis and

incontinence” [4] . No further results were given.

Male Slings

There is a long history of the use of slings for the

treatment of postprostatectomy urinary inconti-

nence. Because of the renaissance of the male sling

in recent years, early results with this treatment

modality will be discussed along with more recent

experience later in this chapter.

Berry Prosthesis

Berry in 1961 reported his preliminary results with

an acrylic or silicone prosthesis that was implanted

against the bulbous urethra and fixed with wire

Chapter 30

Treatment for Male Incontinence:

Historical Review

Drogo K. Montague

424 D.K. Montague

sutures to the ascending pubic rami in men who

had postprostatectomy urinary incontinence [5] .

In an update published 10 years later he reported

five major modifications of the original prosthesis:

H-type, balloon, rolling pin, spindle, and yolk [6] .

The report noted that 66 men underwent a total of

103 procedures. Complications included infection,

perineal pain, and sinus formation. The procedure

was unsuccessful in 80.6% of the cases. Many

early successes subsequently became failures due

to gradual loosening of the device.

Engle and Wad reported in 1969 on 15 opera-

tions for implantation of the Berry prosthesis [7] .

Only five achieved continence and at the time of

the report only two of those still had their pros-

thesis. The authors noted: “Our success rate with

the Berry prosthesis is considerably less than that

of other authors. Also our complication rate has

been high. These considerations have left consid-

erable doubt in our minds as to the real merit of

this procedure.”

Raney in 1969 also reported his experience with

the implantation of this device in eight men [8] .

Three patients became continent for a few days,

one was partially continent for 2 months, and four

never regained control. Raney concluded: “We

believe that correction of male urinary inconti-

nence with a prosthesis is perhaps a step in the right

direction. The Berry procedure has not fulfilled its

expectation, partially because the urinary sphinc-

ters and their actions are poorly understood.”

Kaufman Procedures and Prosthesis

In an effort to compress the bulbous urethra with-

out foreign bodies or prosthetic devices, Kaufman

described a procedure in which he detached both

crura along with the ischiocavernosus muscles,

crossed them over the bulbocavernosus muscles,

and attached them to the opposite pubic rami [9] .

In a later publication Kaufman reported that of

28 men treated with this procedure, 9 were cured,

7 were markedly improved, and 12 were failures

[10] . In the same paper he reported a modifi-

cation of this procedure where the crura were

mobilized but not detached. The mobilized crura

were approximated over the bulbous urethra with

a wad of Marlex being placed between the urethra

and the crura. He called the first operation the

Kaufman I with the modification being known as

the Kaufman II procedure. Using the Kaufman II

procedure cure or marked improvement was noted

in 7 of 11 men all of whom had been followed for

at least 5 months.

In 1973 the Kaufman III operation was described

[11] . In this procedure a silicone gel prosthesis was

placed against the bulbous urethra and anchored in

place by passing straps around the crura. In 30 men

with postprostatectomy incontinence who under-

went the Kaufman III operation as their first pro-

cedure, 14 were cured, 10 were greatly improved,

2 were moderately improved, and 4 were failures.

In 17 men who had previous unsuccessful opera-

tions for incontinence, the Kaufman III procedure

resulted in five cures, four with great improvement,

four with moderate improvement, and four failures.

In a later report Kaufman modified the Kaufman

III procedure by stapling the silicone gel prosthesis

straps to the pubic rami [12] .

Bladder Neck Reconstruction

Tanagho and Smith described a bladder neck recon-

struction in the male for treatment of urinary incon-

tinence [13] . In this procedure they completely

separated the bladder neck from the prostate. They

then created an anterior bladder wall flap 1 in.

wide and 1 in. long. This then was fashioned into

a tube over a 16–18F Foley catheter and this tube

was approximated to the proximal portion of the

prostatic urethra. They reported on the results of

15 operations in which the overall success rate was

50%. They noted that with proper patient selection

the success rate was about 80%.

Electronic Implants

Alexander and Rowan in 1968 noted: “It has been

shown … that the voluntary (sic) muscles of the

pelvic floor are in a state of tonic contraction at

rest. In patients with incontinence the function

of the pelvic-floor musculature is impaired and

the object of an electronic implant is restoration

of this function…Continuous electrical stimu-

lation by means of electrodes in proximity to

the pudendal nerves is effective in preventing

escape of fluid from the urinary bladder” [14] .

In this report they describe a passive electronic

30. Treatment for Male Incontinence 425

implant similar to that described by Bradley

et al. in 1963 [15] . Methods in use included an

implantable electronic implant [16, 17] , vaginal

pessary, and rectal plugs [18, 19] . Other methods

using electrical means were designed to induce

bladder evacuation and to enable bladder volume

sensing [20] .

None of these methods proved to be consist-

ently effective. Gerry W. Timm, PhD, a biomedical

engineer, wrote to me in March 2002: “The idea

for the sphincter (AUS) was first proposed to me in

October 1968 by Dr. Bradley (William E. Bradley,

MD, a neurologist) on our return from a discour-

aging visit to a number of international centers

studying electrical stimulation to produce bladder

evacuation.” Dr. Timm quoted Dr. Bradley as say-

ing, “Why not by-pass the need to know lower

urinary tract physiology which is required for

producing efficient bladder evacuation and instead

devise a mechanical device, such as an electro-

magnetic clothespin, to occlude the urethra for

patients with incontinence?” (personal communi-

cation, letter March 13, 2002). This led to not only

the description of the electromagnetic clothespin

type of occlusive device but also the first concept

of a totally implantable hydraulic AUS [21] . This

concept was defined further in subsequent publica-

tions [20, 22– 25] .

Postartificial Urinary Sphincter Era

American Medical Systems Artificial

Urinary Sphincter

Drs. Gerald W. Timm and William E. Bradley, both

from the University of Minnesota, joined F. Brantley

Scott, MD, a urologist from the Baylor College of

Medicine in Huston, to bring the AUS to the point in

its development where it was ready to be implanted

in humans [3] . To manufacture and market the AUS

along with an offshoot of this device, the inflat-

able penile prosthesis [26] , Drs. Scott, Bradley, and

Timm joined forces in 1972 with Robert Buuck, a

businessman, to form American Medical Systems

(AMS), Minnetonka, MN.

Between 1973 and 1983, the AUS underwent

several major design changes (Fig. 30.1 ) [27, 28] .

The first device, the AS 721, was introduced in

1973 (Fig. 30.2 ). This hydraulic device was con-

structed of medical-grade silicone elastomer and

stainless steel. It consisted of a circumferential

cuff that could be implanted around the male or

female bladder neck or around the bulbous urethra

in the adult male. This was connected by tubing to

inflation and deflation bulbs that were implanted

in the scrotum or labia majora. These bulbs were

connected to a fluid reservoir, which was implanted

behind the rectus muscle in the lower abdomen.

The device was filled with normal saline or isot-

onic contrast. Pressure in the sphincter was control-

led by a mechanical V4 valve above the deflation

pump.

Subsequent design changes led to the AS 742

(Fig. 30.3 ), which was introduced in 1974. This

device incorporated a pressure-regulating balloon

(PRB), which instead of the V4 valve determined

cuff pressure. The PRB also allowed fluid transfer

back into the cuff through a delayed filled resistor,

thus eliminating the need for the inflation pump.

PRBs were provided in three different pressure

ranges: 51–60, 61–70, and 71–80 cm H

2 0. Cuffs

also were provided in a variety of sizes for both the

bladder neck and bulbous urethra.

In 1976 the AS 761 (Fig. 30.4 ) was introduced.

In this model, which is similar to the original AS

721, a PRB was placed between the cuff and V4

pressure valve. With this device the PRB rather

than the less reliable V4 valve determined cuff

pressure.

In 1979 the AS 791 (Fig. 30.5 ) was introduced.

This device and a variant, the AS 792, were

streamlined versions of the AS 742. A problem

with the AS 742, AS 791, and AS 792 was that

once these devices were implanted and connec-

tions were made, the cuff remained inflated at

all times except when the patient deflated it for

voiding. There was no way to stop the automatic

refilling of the cuff.

The device used today (AMS Sphincter 800™)

(Fig. 30.6 ) was introduced in 1983. It works on

the same principle as the AS 742, AS 791, and

AS 792, but it incorporates a deactivation fea-

ture. Following surgical implantation, the surgeon

cycles the device to open the cuff; the deactivation

button is then pushed, and this prevents refilling

of the cuff. Usually 4–6 weeks later, when cuff

and pump site swelling have resolved, the device

426 D.K. Montague

Fig. 30.1. Time line for the five models of American Medical Systems’ artificial urinary sphincter (used by permission

of American Medical Systems, Minnetonka, MN, USA)

Fig. 30.2. The AS 721

is reactivated by forcibly squeezing the deflation

pump. Deactivation can be done again later when-

ever necessary, for example, if the patient needs an

indwelling urethral catheter. This device continues

in use today, although there have been numerous

modifications to the design of the various com-

ponents of this device in efforts to increase both

effectiveness and longevity. These include a narrow

back cuff for the urethra, a smaller 4.0-cm cuff,

surface coating for the cuff, kink-resistant tubing,

a sutureless connector system, and tubing collars

to relieve strain.

30. Treatment for Male Incontinence 427

Rosen Prosthesis

In 1976, 3 years after the introduction of the AUS,

Rosen described a three-pronged clamp with two

parallel arms on one side and a single arm carry-

ing a balloon that opposed them [29] . The balloon,

implanted against the bulbous urethra, was con-

nected by tubing to a scrotal reservoir that could

inflate the balloon for continence and deflate it for

voiding. Of 16 patients in whom this device was

implanted, ten were cured, one was improved, and

five failed. Rosen updated his results 2 years later

by stating: “Twenty-three patients have been oper-

ated on and 18 have been cured. The main compli-

cations are device failure and sepsis. The results so

far justify a limited optimism that the device has a

significant role to play in the management of male

urinary incontinence” [30] .

Fig. 30.3. The AS 742

Fig. 30.4. The AS 761

Fig. 30.5. The AS 791

Fig. 30.6. The AMS Sphincter 800™

428 D.K. Montague

Small, in 1980, reported 16 patients in whom

the Rosen prosthesis was implanted with follow-

up ranging from 2 to 36 months. Eleven of the 16

were reported as being “cured” [31] . Geisy and

Barry 1 year later reported less optimistic results

[32] . They reported 19 men who had the Rosen

device implanted. Follow-up ranged from 9 to 34

months. There were 26 additional operations for

balloon leakage, aneurysm, tubing kinks, reservoir

malfunction, and urethral erosion. Using life-table

actuarial analysis demonstrated that 44% had failed

by 6 months and 75% had failed by 12 months. The

authors concluded: “Although the simple concept

developed by Rosen is an intriguing one and excel-

lent continence can result, the multiple procedures

required to achieve satisfactory results leave a great

deal of room for product improvement.”

In a 1981 report entitled: “Pitfalls of the Rosen

anti-incontinence prosthesis,” Augspurger reported

on 17 male patients who had a Rosen prosthesis

implanted. Nine had a functioning device, four

had a nonfunctioning prosthesis and were awaiting

replacement, and four had had the device removed

[33] . Vereecken and associates in 1985 published

a paper entitled: “The Rosen prosthesis: A bad

experience.” In it they noted: “…we implanted 4

Rosen inflatable incontinence prostheses in 4 men

with urinary incontinence. Twelve operations were

necessary on these 4 patients to assure them to be

continent during a total of 43 months. Because of

the great number of complications we no longer

use the Rosen prostheis” [34] .

Collagen Injections

Injections of glutaraldehyde cross-lined bovine

collagen have been used to treat postprostatectomy

urinary incontinence. More than one injection usu-

ally is needed to obtain an initial result and periodic

reinjections often are necessary to maintain this

result. We summarized the literature concerning

collagen injections in the male (Table 30.1 ) [40] .

Male Slings

Uhle in 1957, referring to the earlier work of Cooney

and Horton [2] , wrote: “This presentation will sum-

marize my experience and thoughts pertaining to the

fascial sling placed anterior to the pubis and about

the bulbous urethra for the control on urinary incon-

tinence. Ten and one-half years have elapsed since

the first case was operated upon. A total of 8 cases

form the basis of this report. In 5 cases the aponeu-

rosis of the rectus muscle was used, in 2 cases the

fascia lata of the thigh was employed, while the

eighth case was subjected to the use of both at dif-

ferent intervals of time. The technique and results of

these anteropubic fascial slings which compress the

bulbous urethra have been presented….The results

were partially effective in fifty per cent of the cases”

[41] . The same eight cases and the surgical tech-

nique were presented in more detail in a somewhat

later publication [42] .

Servado in 1974 described six cases of rec-

tus fascial sling around the bulbous urethra and

passed retropubically for postprostatectomy uri-

nary incontinence. He noted: “…all regained full

continence immediately following the fascial-

sling operation. None of them has a residual urine

and, therefore, no urinary infection has occurred.

There is occasional mild stress incontinence in

one case only. The patients have now been fol-

lowed for one to six years and all continue to be

fully continent” [43] .

Table 30.1. Collagen injection for male incontinence a .

Publication Dry Improved Failed Mean injections ( n ) Mean follow-up

(months)

Griebling et al. [35] b 589 152 216 192 5.7–13.3

Martins et al. [36] 46 11 21 14 2.8 26

Sanchez-Ortiz et al. [37] 31 2 9 20 2.6 15

Smith et al. [38] 62 5 24 33 4 29

Klute et al. [39] 20 2 7 11 1 28

Total 748 172 (23) 277 (27) 270 (36)

Numbers in parentheses are percentages aUsed by permission by of Elsevier (Urol. 55: 1–4, 2000) bSummary of 13 studies

1989–1996

30. Treatment for Male Incontinence 429

Pettersson in 1975 reported eight men with

postprostatectomy urinary incontinence who were

treated with fascia lata bulbous urethral slings

passed retropubically. He noted: “Four patients

were continent 7–36 months postoperatively. Two

patients had stress incontinence and two patients

had recidivating incontinence” [44] .

There has been a renaissance recently in the use

of the male bulbous urethral sling for the treat-

ment of postprostatectomy urinary incontinence.

In a recent editorial, we reported that our litera-

ture review showed 20 publications from 1997 to

2005 [45] . Only four of these had 20 patients or

more with a mean follow-up of at least 1 year, and

these four publications are briefly summarized in

Table 30.2 .

A New Artificial Urinary Sphincter

While there have been numerous modifications

to the various components of the AMS Sphincter

800™, its basic design has remained unchanged

for more than 20 years. The first commercially

available alternative to the AMS Sphincter 800™

was recently announced [50] . This device consists

of a newly designed urethral cuff, a scrotal pump-

control assembly, and two PRBs. This new device

does not have the deactivation feature of the AMS

Sphincter 800™; however, it does have a self-

sealing port at the bottom of the pump which can

be used to add or remove fluid from the system.

This new device eliminates the need for tubing

connections. Possible advantages of this new AUS

are outlined in an accompanying editorial [51] .

Eleven patients received this new implant and

in two patients the device was removed. In the

remaining nine patients there was a reduction in

the mean daily leakage volume from 770.6 to 55.1

ml and an overall improvement in the continence

index from 54 to 97%.

References

1. Herr HW. Quality of life of incontinent men after

radical prostatectomy [see comments]. J Urol 1994;

151(3):652–654.

2. Cooney CJ, Horton GR. An operation for the cure

of urinary incontinence in the male. J Urol 1951;

66(4):586–592.

3. Scott FB, Bradley WE, Timm GW. Treatment

of urinary incontinence by implantable prosthetic

sphincter. Urol 1973; 1(3):252–259.

4. Foley FEB. An artificial sphincter: A new device

and operation for control of enuresis and urinary

incontinence. J Urol 1947; 58:250–259.

5. Berry JL. A new procedure for correction of uri-

nary incontinence: Preliminary report. J Urol 1961;

85:771.

6. Berry JL, Dahlen CP. Evaluation of a procedure for

correction of urinary incontinence in men. J Urol

1971; 105(1):105–106.

7. Engel RM, Wade JC. Experience with the Berry

prosthesis. J Urol 1969; 102(1):78–80.

8. Raney AM. Re-evaluation of post-prostatectomy

urinary incontinence with the Berry procedure. J

Urol 1969; 102(1):81–83.

9. Kaufman JJ. A new operation for male incontinence.

Surg Gynecol Obstet 1970; 131(2):295–299.

10. Kaufman JJ. Surgical treatment of post-prosta-

tectomy incontinence: Use of the penile crura

to compress the bulbous urethra. J Urol 1972;

107(2):293–297.

11. Kaufman JJ. Treatment of post-prostatectomy uri-

nary incontinence using a silicone gel prosthesis. Br

J Urol 1973; 45(6):646–653.

12. Kaufman JJ, Raz S. Passive urethral compression

with a silicone gel prosthesis for the treatment of

male urinary incontinence. Mayo Clin Proc 1976;

51(6):373.

Table 30.2. Summary of recent male sling publications

a .

Publication n Mean follow-up

(months) Results (pads per day) Comments

Castle et al. [46] 38 18 39% 1 pad or less Bone anchored

Rajpurkar et al. [47] 46 24 37% no pads, 37% 1–2 pads Bone anchored

Ulrich and Comiter [48] 36 24 67% no pads, 14% 1 pad, 11% 2 pads Bone anchored

Stern et al. [49] 71 48 Seven slings explanted; results for

remaining 64: 68% 1–2 pads, 39%

no pads

Three tetrafluoro-ethylene

bolster anchored to rectus

fascia

a From [45]

430 D.K. Montague

13. Tanagho EA, Smith DR. Clinical evaluation of a

surgical technique for the correction of complete

urinary incontinence. J Urol 1972; 107(3):402–411.

14. Alexander S, Rowan D. Electrical control of uri-

nary incontinence by radio implant. A report of 14

patients. Br J Surg 1968; 55(5):358–364.

15. Bradley WE, Chou SN, French LA. Further expe-

rience with the radio transmitter receiver unit

for the neurogenic bladder. J Neurosurg 1963;

20:953–960.

16. Caldwell KP. The treatment of incontinence by

electronic implants. Hunterian lecture delivered

at the Royal College of Surgeons of England on

8th December 1966. Ann R Coll Surg Engl 1967;

41(6):447–459.

17. Caldwell KP, Cook PJ, Flack FC, James D. Treatment

of post-prostatectomy incontinence by electronic

implant. Br J Urol 1968; 40(2):183–186.

18. Glen ES. Effective and safe control of incontinence

by the intra-anal plug electrode. Br J Surg 1971;

58(4):249–252.

19. Hopkinson BR. Electrical treatment of incontinence

using an external stimulator with intra-anal elec-

trodes. Ann R Coll Surg Engl 1972; 50(2):92–111.

20. Timm GW. Electromechanical restoration of void-

ing. Vet Clin North Am 1974; 4(3):525–533.

21. Timm GW, Bradley WE. Electronic micturic-

trion reflex stimulation. Proc 17th Spinal Cord

Injury Conference Veterans Administration 1969:

152–157.

22. Timm GW. An implantable incontinence device. J

Biomech 1971; 4(3):213–219.

23. Timm GW, Merrill DC, Bradley WE. Intermittent

occlusion system. IEEE Trans Biomed Eng 1970;

17(4):352.

24. Timm GW, Frohrib DA, Bradley WE. Genitourinary

prosthetics of the present and future. Mayo Clin

Proc 1976; 51(6):346–350.

25. Burton JH, Mikulich MA, Timm GW, et al.

Development of urethral occlusive techniques for

restoration of urinary incontinence. Med Instrum

1977; 11:217–220.

26. Scott FB, Bradley WE, Timm GW. Management of

erectile impotence: Use of implantable inflatable

prosthesis. Urol 1973; 2:80–82.

27. Montague DK. Evolution of implanted devices for

urinary incontinence. Cleve Clin Q 1984; 51(2):

405–409.

28. Montague DK. The Scott–Bradley–Timm artificial

urinary sphincters. J Urol 1981; 125(6):796–798.

29. Rosen M. A simple artificial implantable sphincter.

Br J Urol 1976; 48(7):675–680.

30. Rosen M. The Rosen inflatable incontinence pros-

thesis. Urol Clin North Am 1978; 5(2):405–414.

31. Small MP. The Rosen incontinence procedure: A

new artificial urinary sphincter for the manage-

ment of urinary incontinence. J Urol 1980; 123(4):

507–511.

32. Giesy JD, Barry JM, Fuchs EF, Griffith LD. Initial

experience with the Rosen incontinence device. J

Urol 1981; 125(6):794–795.

33. Augspurger RR. Pitfalls of the Rosen anti-inconti-

nence prosthesis. J Urol 1981; 125(2):201–203.

34. Vereecken RL, Van den Bussche L, Tailly G. The

Rosen prosthesis: A bad experience. Urol Int 1985;

40(1):30–32.

35. Griebling TL, Kreder KJ Jr, Williams RD.

Transurethral collagen injection for treatment of

postprostatectomy urinary incontinence in men.

Urol 1997; 49:907–912.

36. Martins FE, Bennett CJ, Dunn M, et al. Adverse

prognostic features of collagen injection therapy for

urinary incontinence following radical retropubic

prostatectomy. J Urol 1997; 158:1745–1749.

37. Sanchez-Ortiz RF, Broderick GA, Chaikin DC,

et al. Collagen injection therapy for post-radi-

cal retropubic prostatectomy incontinence: Role

of valsalva leak point pressure. J Urol 1997;

158:2132–2136.

38. Smith DN, Appell RA, Rackley RR, Winters JC.

Collagen injection therapy for post-prostatectomy

incontinence. J Urol 1998; 160(2):364–367.

39. Klutke JJ, Subir C, Andriole G, Klutke CG. Long-

term results after antegrade collagen injection for

stress urinary incontinence following radical retro-

pubic prostatectomy. Urol 1999; 53:974–977.

40. Montague DK, Angermeier KW. Postprostatectomy

urinary incontinence: The case for artificial uri-

nary sphincter implantation [editorial]. Urol 2000;

55(1):2–4.

41. Uhle CA. Use of anteropubic fascial sling for treat-

ment of surgical incontinence in the male. J Urol

1957; 77(3):478–484.

42. Uhle CA, Bradley RH Jr. The use of rectus fascia

and fascia lata in the sling operation for urinary

incontinence in the male. J Urol 1958; 80(2):

132–139.

43. Servadio C. The use of fascial sling for the correc-

tion of postprostatectomy incontinence. Isr J Med

Sci 1974; 10(6):612–616.

44. Pettersson S. Free fascial sling to correct urinary

incontinence after prostatic surgery. Results of

eight operated patients. Scand J Urol Nephrol 1975;

9(1):24–27.

45. Montague DK, Angermeier KW. Treatment of

postprostatectomy urinary incontinence: The case

against the male sling. Nat Clin Pract Urol 2006;

3(6):290–291.

30. Treatment for Male Incontinence 431

46. Castle EP, Andrews PE, Itano N, et al. The male sling

for post-prostatectomy incontinence: Mean follow-up

of 18 months. J Urol 2005; 173(5):1657–1660.

47. Rajpurkar AD, Onur R, Singla A. Patient sat-

isfaction and clinical efficacy of the new peri-

neal bone-anchored male sling. Eur Urol 2005;

47(2):237–242; discussion 242.

48. Ullrich NF, Comiter CV. The male sling for stress

urinary incontinence: 24-Month follow-up with

questionnaire based assessment. J Urol 2004;

172(1):207–209.

49. Stern JA, Clemens JQ, Tiplitsky SI, et al. Long-term

results of the bulbourethral sling procedure. J Urol

2005; 173(5):1654–1656.

50. Knight S, Susser J, Craggs M, et al. A new artificial

urinary sphincter with conditional occlusion for

stress urinary incontinence: Preliminary clinical

results. E Urol 2006; 50:574–580.

51. Montague DK. Reflections on a new artificial uri-

nary sphincter. Eur Urol 2006; 50:421–423.

461

The first reported case of a patient being cured with

radiation therapy was in 1899, shortly after the dis-

covery of X-rays and radium in the late 1800s [1] .

The intracavitary treatment of cervical cancer was

initiated in the early part of the twentieth century,

with a significant increase in use noted particularly

in the 1920s [1] .

The basic concept behind radiation therapy is

to minimize the damage to healthy, normal tissue

while maximizing destruction of malignant tis-

sue [2] . Radiation changes to tissues may appear

obvious soon after exposure, but in most cases the

changes are not apparent for long periods of time

and may be apparent only at a microscopic level

[2] . Long-term effects from radiation exposure,

such as urological complications, may not present

for several months to years after treatment.

Approximately one third of Americans will face

cancer during their lifetime [3] . With an aging popu-

lation, the gynecologist, as well as the urologist, are

going to see an increase in gynecological malignan-

cies and the complications resulting from the treat-

ment of these cancers [3] . Both the malignancy itself,

as well as the treatment, can result in urological side

effects [3] . Treatment of gynecological malignancies

involves chemotherapy, surgery, and irradiation, all

of which can lead to both temporary and permanent

urological complications [3] . This chapter will focus

on the postradiation effects on the female urogenital

tract, including primarily the bladder and urethra,

and the resulting effects on continence.

Radiation therapy plays a large role in the treat-

ment of pelvic cancers [3] . Cervical cancer is one

of the most common types of female cancers that

is treated with radiation therapy. The bladder, ure-

thra, and ureters are anatomically situated close to

the cervix, predisposing them to the damaging side

effects of radiation therapy [3] .

Other cancers that are treated with pelvic irra-

diation include prostate cancer, retroperitoneal or

pelvic sarcomas, and other gynecological malig-

nancies including uterine cancers. As one would

expect, bladder symptoms are not limited to those

patients being treated for cervical cancer with pel-

vic radiation. A questionnaire was distributed to

202 prostate cancer patients to assess bowel, blad-

der, and sexual function after pelvic radiotherapy

and 4% of patients reported significant bladder

symptoms (including urinary incontinence, hema-

turia, and severe dysuria); although 17% reported

daily incontinence, only 2% required usage of

pads [4] . A later study done by Nguyen et al. on

postradiation prostate cancer patients found an

even larger percentage of patients reporting incon-

tinence (30%) but again only 2% required the use

of pads [5] .

Biological Effects of Radiation

Therapeutic radiology is based on the ability to

selectively destroy tissues [2] . Neoplastic cells tend

to be more susceptible to the destructive effects of

radiation than do surrounding normal tissues, as

rapidly proliferating cells are highly radiosensitive

[2] . The biological effects seen in irradiated tissue

Chapter 33

Urologic Consequences of Pelvic

Irradiation in Women

Mary M.T. South and George D. Webster

462 M.M.T. South and G.D. Webster

are primarily the result of DNA damage [2] . DNA

damage can occur directly from absorption of the

radiation into the biological material or indirectly

via production of free radicals in the cell, ulti-

mately resulting in cell death [2] .

The key to successful destruction of neoplastic

cells is the ability to place the radiation in close

proximity to the malignancy while at the same

time using a dosage that is tolerable to surrounding

tissues (ie, for example, the use of brachytherapy

in the treatment of cervical cancer) [2] . The uterus

and normal tissues of the cervix are relatively

tolerant of high doses of radiation; however, other

organs, such as sigmoid, rectosigmoid, rectum, and

bladder, are less tolerant to exposure to radiation.

Pathological changes noted in tissues after radia-

tion reveal mainly fibrosis and some necrosis.

Autopsy in 22 patients who had undergone intra-

operative radiotherapy showed histological evi-

dence of fibrosis of the retroperitoneal soft tissues,

hypocellularity of the vertebral bone marrow, and

perineural fibrosis in the retroperitoneal and pelvic

nerve trunks [6] . These autopsies did not uncover a

significant amount of radiation-induced changes in

blood vessels, intestine, or ureters.

Complications of Pelvic Radiation

Complications from radiation therapy can occur

acutely or chronically over a long period of time

[3] . Acute complications usually occur during

the course of therapy or toward the completion of

treatment [3] . Patients may develop symptoms of

frequency and dysuria and, on occasion, hematuria

[3] . These patients also tend to have an increased

frequency of urinary tract infections [3] . Usually

these side effects can simply be treated with anti-

cholinergics or antibiotics [3] .

Chronic urological radiation complications

include vesicovaginal fistula, reduced bladder

capacity due to radiation fibrosis, neurogenic blad-

der, detrusor overactivity, and intrinsic sphincter

deficiency (ISD) [3] . Upon review of the literature,

severe urological complications can occur any-

where from 2 to 14% after pelvic irradiation [7,

8, 9, 10, 11] . Compared with complications of the

rectum or intestines, urological complications tend

to occur much later (6.4 vs 2.2 years respectively,

P < 0.0001) [11] . One study showed a dose-depend-

ent rate of rectal and bladder complications with

delay in symptoms of approximately 22 months

for the bladder [10] . A rare long-term complica-

tion after pelvic irradiation is bladder cancer.

Maier et al. found an increased risk of developing

urothelial bladder cancer in a population of 10,709

Austrian women treated with brachytherapy for

primary gynecological carcinomas (RR 4.66) [12] .

Physicians should have a high index of suspicion

for this condition even years after treatment [13] .

Another complication of pelvic irradiation, par-

ticularly with the use of high-dose-rate brachy-

therapy, is spontaneous rupture of the urinary

bladder, which may not be as rare as once thought

and urologists should be aware of this potentially

life-threatening event [14] .

Wilkinson et al. studied 366 women who received

brachytherapy for cervical cancer [9] . Of the 366

women, 60 women with bladder complications

were compared with 60 age- and stage-matched

controls without symptoms, specifically looking

at size of applicators, height of the applicators set

above the pubic symphysis, the degree of antever-

sion or retroversion of the applicator sets, and

radiation dosages. Unfortunately, based on their

findings, no reliable predictor of bladder compli-

cations following brachytherapy was identified.

However, it does appear that severe bladder injuries

(ie, fistulas) may be more common in patients with

stage IIIA and IIIB disease and those receiving

high external beam radiation (>5,000rads) [8] .

Vesicovaginal Fistula

Fewer than 5% of patients develop vesicovaginal

fistula following radiation therapy [3] . Presentation

may occur anytime from 6 months to 30 years after

completion of treatment [15, 16, 17] . Patients with

tumor that is close to the anterior vaginal wall

appear to be more predisposed to development of

a fistula [3] . In patients with a history of cervical

cancer who present with a vesicovaginal fistula, it

is important to biopsy the fistula because 50% if

these patients have evidence of recurrent disease

[18] .

Generally speaking vesicovaginal fistula will be

diagnosed by physical examination, cystoscopy,

and pyridium pad study. Other studies used have

included cystography, computed tomography (CT)

scan, and Doppler color ultrasound. CT findings

consistent with a diagnosis of vesicovaginal fistula

33. Urologic Consequences of Pelvic Irradiation in Women 463

include contrast, air, and/or fluid in the vagina.

Performing a CT scan also may be beneficial

for identifying associated findings such as radia-

tion changes, contiguous pelvic mass, or adherent

bowel. These findings may give an indication of

the etiology of the fistula, such as recurrent disease,

or aid in preparing for surgical repair [19] . Volkmer

et al. report on a method of vesicovaginal fistula

detection by filling the bladder with a diluted

contrast media and using ultrasound to detect a

jet phenomenon through the bladder wall into the

vagina, revealing the presence of a fistula in 11 of

12 patients studied [20] .

Many of the commonly employed methods

for repairing vesicovaginal fistula will not be

successful in the setting of radiation-damaged

tissue. The success rates reported after repair

in the irradiated patient range from 40 to 100%

compared with 70 to 100% in nonradiated patients

[21] . The reduced success rate seen with repair

of postirradiated vesicovaginal fistulas is likely

due to the poor vascularity of these tissues [22] .

In those circumstances where the fistula develops

in the early aftermath of radiation treatment, it is

recommended that repair be delayed for weeks or

months to allow for maturation of the fistulous

tract. Vaginal repair of vesicovaginal fistulas,

either with a modified Latzko procedure or a

layered closure, should be the preferred route in

general because the success rates are similar when

compared with abdominal repair with fewer com-

plications. Loran et al. report on a modification

of the Latzko procedure using a high colpocleisis

in 174 postradiated vesicovaginal fistulas that

resulted in spontaneous urination and a return to

preirradiated bladder capacities [16] .

Eilber et al. found excellent results with vaginal

repair of complex vesicovaginal fistulas by using

a tissue interposition after reviewing outcomes at

their institution over a 10-year period of time on

207 patients [23] . The most common etiology for

a fistula in their cohort was hysterectomy (91%),

while 4% of their patients had radiation-induced

fistulas. Their definition of a complex fistula was

any fistula that was either radiation-induced or

greater than 2cm in size. Of the 207 patients, tis-

sue interposition was used in 58% of the cases.

For proximal fistulas, they employed a peritoneal

flap and for distal fistulas they used a Martius flap.

In the event the patient had insufficient vaginal

epithelium, the authors used a full-thickness labial

flap. The cure rates for the Martius and peritoneal

flaps were 97 and 96%, respectively.

Most urologists would prefer an abdominal

approach to the repair of postradiation fistula with

the rationale that this gives the opportunity to

interpose omentum at the repair site and also offers

the opportunity to address small bladder capacity

by enterocystoplasty and to deal with associated

ureteral obstruction. Obviously there is a spectrum

of severities of presentation of such cases and the

approach must be individualized.

Some postradiation fistula are so complex and

severe that they are unable to be reconstructed and

urinary diversion may be necessary as the last resort

[24] . Mannel et al. reported the use of an ileocecal

continent urinary reservoir in patients with a history of

pelvic irradiation (6 of the 37 patients had radiation-

induced vesicovaginal fistulas while the rest had

pelvic exenterations) and found comparable results in

these patients compared to nonirradiated patients [25] .

A smaller report on four patients describes the use of

an interposition ileocystoplasty to repair large postra-

diation vesicovaginal fistulas. The benefits of this type

of repair in the postradiated patients, per the authors,

are as follows: (1) wide dissection of the bladder is not

necessary; (2) the defect in the bladder is repaired with

a well-vascularized (and undamaged) distal ileum; (3)

bladder capacity is enlarged; (4) improved quality of

life with high probability of spontaneous voiding; and

(5) the ability to adapt this procedure in the setting of

damaged distal ureters [26] .

Leissner et al. suggested that, should urinary

diversion be necessary to regain continence in

patients with postirradiated vesicovaginal cases,

some patients may desire reconstructive surgery to

create a neovagina [24] . The authors incorporated

the bladder into a neovagina in six patients who had

undergone urinary diversion, five of whom were

postirradiation. These patients had a mean follow-

up of 4.7 years with reported good functional and

cosmetic results. Vaginal reconstruction also may be

accomplished using enteric segments and by bilat-

eral pedicled rectus or grascilis flaps [22] .

Bladder Dysfunction after Pelvic

Radiation

In addition to direct damage resulting in fibrosis,

radiation may also damage the innervation to the

bladder and urthra. Although this was not believed

464 M.M.T. South and G.D. Webster

to be the case in the past, several studies have

shown that peripheral nerve damage can occur after

radiotherapy [27, 28, 29] . Olsen et al. evaluated

161 breast cancer patients for radiation-induced

brachial plexopathy [28] . Interestingly, they found

that larger fraction size and cytotoxic therapy

increased the damage done by radiotherapy and

that younger patients were more vulnerable to this

type of injury. Chemotherapy administered with

radiotherapy may result in further vulnerability of

the peripheral nervous system to damage depend-

ing on the dose and type of drugs used [30] . As

mentioned earlier, radiation therapy works by

damaging DNA, and if not repaired results in cell

death. Because glial and Schwann cells of the

peripheral nervous system have slow reproductive

cycles, damage may not become apparent for many

months if the original insult was not lethal to the

cell. Thus, the complication of neurogenic bladder

resulting in bladder dysfunction following radio-

therapy may not be immediately apparent [27] .

Damage to the peripheral nerves in the pelvis

may be difficult to avoid given their close proxim-

ity to the structures being irradiated, regardless of

the treatment method employed [27] . Tait et al.

performed a randomized trial comparing conformal

versus conventional pelvic radiotherapy to assess

acute toxicity, but they failed to show a difference

in urinary symptoms between the two arms [31] . In

one large animal model, an intraoperative radiation

dose of less than 20Gy was not associated with

significant peripheral nerve injury, but all animals

receiving 20Gy developed a paresis consistent

with nerve injury [32] . A long-term follow-up of

this study suggests that the intraoperative radiation

dose may be inversely related to time to develop

neuropathy (ie, the higher the dose, the sooner

neuropathy may present) [33] .

Although a large body of evidence supports the

concept that peripheral nerve damage results in the

neurogenic bladder seen after radiation exposure,

bladder hypertonicity also may be due to changes

at the neuromuscular junction. Michailov et al.

demonstrated that the detrusor muscle's response

to acetylcholine is diminished in the postirradi-

ated bladder in rats [34] . In a prior study, the same

authors also demonstrated an immediate tonic con-

traction in the detrusor muscle exposed to radiation

[35] . They conclude that both immediate exposure

of the detrusor muscle to radiation and long-term

changes in the muscles sensitivity to the neuro-

transmitter acetylcholine may help to explain the

hypertonicity seen in the postirradiated bladder.

Parkin et al. performed urodynamic studies

on 40 patients 5–11 years after radiation therapy

for cervical cancer [36] . The authors compared

these 40 patients to 27 patients prior to treatment.

Patients who had undergone radiation therapy had

mean volumes at first bladder sensation lower than

the mean volumes before treatment. The mean

maximum cystometric capacity also was lower

in the treatment group. The mean filling detrusor

pressure was higher and a significant reduction in

the maximal urethral closure pressure and func-

tional profile length was noted in the treatment

group. The authors also found detrusor instability

to be a common finding in the treatment group and

concluded that treatment of these symptoms should

be attempted before attributing symptoms to fibro-

sis. Similar findings were noted by Farquharson

et al., who studied 33 patients undergoing pelvic

irradiation for cervical cancer, noting reductions

in peak urinary flow, volume at first desire to

void, cystometric capacity, and bladder compliance

specifically in those patients receiving more than

3000rads to the entire bladder from external beam

irradiation [37] .

Little has been reported on the effects of radia-

tion therapy on bladder function compared with the

well-known effects following radical hysterectomy,

for example. Farquharson compared urodynamics

and symptoms in 30 patients who had undergone

radical hysterectomy alone (RH) to 30 patients

who had undergone both radical hysterectomy and

pelvic irradiation (RH+RT) and 30 patients who

had undergone pelvic irradiation alone (RT) [38] .

Altered bladder sensation and voiding problems

were more frequent after RH or RH+RT than RT

( P =0.002). Abdominal straining during voiding

was noted in 50% of RH patients compared to 10%

who had only RT. Fifteen percent of patients had

urinary incontinence prior to treatment. Following

treatment, the group with the largest percentage of

incontinence was the RH+RT group (63%), fol-

lowed by the RH patients (26%), and then the RT

group (23%). Bladder compliance was noted to be

reduced in the RT patients, and compared with RH

alone the RH+RT group was noted to have a signif-

icantly decreased bladder compliance ( P =0.0001).

No difference was found between any of the groups

33. Urologic Consequences of Pelvic Irradiation in Women 465

in reference to bladder neck and urethral function.

The authors noted that the urinary incontinence

seen in the RH+RT group, as well as the decrease

in bladder compliance, was related to the bladder

dose of external radiation.

Lin et al. assessed the urodynamic findings in

patients after radical hysterectomy or pelvic irra-

diation for cervical cancer and found abnormal

findings usually exist before treatment but worsen

or new abnormal findings are noted [39] . Detrusor

instability or low bladder compliance was seen

in 45% of patients treated with pelvic irradiation

alone and 80% of patients treated with both pelvic

irradiation and radical hysterectomy. Voiding with

abdominal strain was noted to be 100% in the

radical hysterectomy, pelvic irradiation, and radi-

cal hysterectomy plus pelvic irradiation groups,

but was noted to be 0% in the control group (stage

IB cervical cancer prior to treatment). Finally, the

frequency of a positive pad test was noted to be

46% in the pelvic irradiation group but 100% in the

group treated with both radical hysterectomy and

pelvic irradiation.

Behr et al. evaluated the urodynamics in 104

patients who had undergone primary irradiation

for cervical cancer [40] . All patients were found to

be incontinent of urine by 2 years after treatment.

Sixty percent of those patients appeared to have

urge urinary incontinence, which the authors felt

to be related to the radiation-induced fibrosis of the

bladder (decreased compliance and capacity). The

other 40% of the patients were found to have stress

incontinence that had already been present prior to

irradiation, with an increase in stress incontinence

seen only after 6 years or later, which the authors

conclude was presumably related to advancing age.

Parkin et al. mailed questionnaires to 66 patients

from 5 to 11 years after radiotherapy for cervical

carcinoma and found that 45% of these patients

had symptoms of urgency and urge incontinence

[41] . This study found that voiding dysfunction

was less common than bladder overactivity.

Management of Bladder

Dysfunction

There is no literature specific to the management

of bladder dysfunction following radiation therapy

and so the general principles of treatment of blad-

der overactivity, low bladder compliance, and poor

contractility must be followed. Unfortunately, it is

these authors' experience that treatments are much

less successful when radiation is the underly-

ing etiology. While anticholinergics may improve

symptoms in patients with detrusor overactivity,

those patients with reduced functional capacity

due to low bladder compliance are less likely

to be improved significantly. Botox and sacral

neuromodulation have been used with success in

intractable bladder overactivity of other causes, but

there currently is no literature supporting its use in

irradiated cases. These uses await further clinical

trial. Finally, augmentation enterocystoplasty also

has a long history of use to treat intractable bladder

overactivity and low compliance, but the literature

specific to bladder dysfunction following radiation

therapy is scant.

Intrinsic Sphincter Deficiency

and Stress Urinary Incontinence

after Radiation

A variety of factors determine whether or not a

urethra will remain continent in conditions of

stress (activity/increased abdominal pressure).

One factor is the ability of the urethra to form

a tight seal, which requires that it be suffi-

ciently pliable to easily coapt. The irradiated

rigid and fibrotic urethra loses this ability [42] .

Additionally, in the irradiated pelvis the urethra

may become fixed and immobile. The literature

provides very little insight into the management

of radiation-induced intrinsic sphincter deficiency

(ISD) resulting in stress urinary incontinence. No

studies have been done looking specifically at

the best way to manage these patients other than

urinary diversion.

The degree of urethral dysfunction following

radiation therapy occurs in a wide spectrum of

severities and may be accompanied by a spectrum

of associated bladder dysfunctions as discussed

above. In its least complex form a patient who

previously has undergone radiation therapy in the

pelvis develops stress urinary incontinence and

has no associated bladder dysfunction (bladder

overactivity or poor contractility) and has healthy

vaginal tissues and a mobile urethra. Such a patient

466 M.M.T. South and G.D. Webster

will likely be dealt with, as would any woman with

such symptoms, by a pubovaginal sling and similar

outcomes might be anticipated. At the other end of

the spectrum is the woman with a fibrotic, nonpli-

able, immobile, and incompetent urethra that also

is associated with a bladder of poor functional

capacity, overactivity, low compliance, and poor

contractility. Such patients are destined for urinary

diversion. Between these two extremes the entire

spectrum of combinations of urethral and bladder

dysfunction occur, and treatment must be individu-

alized and generally the prognosis for outcome is

guarded. The use of periurethral bulking agents is

an alternative to the pubovaginal sling, but once

again there are no data that comment on outcomes

[42 ]. It is probable that results will be less success-

ful than the already-mediocre results achieved in

nonradiated patients.

In these authors' experience the most frequent

dilemma is whether or not a pubovaginal sling is

appropriate for obvious stress incontinence, and if

so what technique and what sling product should

be chosen. Certainly when stress incontinence is

evident by history, a positive stress test is found

on examination, the pad weight is significant,

and urodynamics show a low leak point pressure,

then a sling is an appropriate treatment. These

authors prefer a minimally invasive (midurethral)

technique and the choice of synthetic versus bio-

logical material might be best based on how much

tension the sling requires. Our preference is for a

synthetic sling even when the sling is tensioned

to be coaptive, but this selection of material in

this situation remains controversial. Sling tension

is determined primarily by the degree of urethral

hypermobility and also by the “rigidity” of the

urethra. Most often the “rigid” urethra is not very

mobile, and in these circumstances the sling will

need to be tensioned to coapt the urethra to be

successful, but in doing so invites the problem of

urinary retention and increases the risk of urethral

erosion. On occasion, particularly when poor con-

tractility is also present, retention and an intermit-

tent self-catheterization program may be the only

way to achieve continence. Unfortunately, even

in this latter situation, the fact that these patients

also often have poor functional bladder capacity

because of bladder overactivity or low compli-

ance, their need for self-catheterization may be

too frequent to be acceptable.

References

1. Hoskins , ed. Principles and practice of gyneco-

logic oncology , 3rd ed. Phildadelphia : Lippincott

Williams & Wilkins ; 2000 .

2. DiSaia , ed. Clinical gynecologic oncology , 6th ed.

St Louis : Mosby ; 2002 .

3. Walters , ed. Urogynecology and reconstructive pel-

vic surgery , 2 nd ed. St Louis : Mosby ; 1999 .

4. Crook . Effect of pelvic radiotherapy for prostate

cancer on bowel, bladder, and sexual function: The

patient’s perspective . Urology 1996 ; 47 (3) :

387 – 394 .

5. Nguyen . Late effects after radiotherapy for prostate

cancer in a randomized dose–response study: Results

of a self-assessment questionnaire . Urology 1998 ;

51 (6) : 991 – 997 .

6. Sindelar WFHH , Restrepo C , Kinsella TJ . Pathological

tissue changes following intraoperative radiotherapy .

Am J Clin Oncol 1986 ; 9 (6) : 504 – 509 .

7. Wang CJ , Leung SW , Chen HC et-al. , High-dose-rate

intracavitary brachytherapy (HDR-IC) in treatment

of cervical carcinoma: 5-year results and implication

of increased low-grade rectal complication on initia-

tion of an HDR-IC fractionation scheme . Int J Rad

Oncol Biol Phys 1997 ; 38 (2) : 391 – 398 .

8. Stryker . Bladder and rectal complications following

radiotherapy for cervix cancer . Gynecol Oncol 1988 ;

29 (1) : 1 – 11 .

9. Wilkinson . A retrospective study of bladder morbid-

ity in patients receiving intracavitary brachytherapy

as all or part of their treatment for cervix cancer . Br

J Radiol 2003 ; 76 (912) : 897 – 903 .

10. Orton . Dose dependence of complication rates in

cervix cancer radiotherapy . Int J Rad Oncol Biol

Phys 1986 ; 12 (1) : 37 – 44 .

11. Fujikawa . High incidence of severe urologic compli-

cations following radiotherapy for cervical cancer in

Japanese women . Gynecol Oncol 2001 ; 80 (1) : 21 – 23 .

12. Maier . Late urological complications and malignan-

cies after curative radiotherapy for gynecological

carcinomas: A retrospective analysis of 10,709

patients . J Urol 1997 ; 158 (3) : 814 – 817 .

13. Kaplan . Bladder cancer after pelvic irradiation for

cervical cancer . South Med J 1985 ; 78 (9) : 1068 – 1070 .

14. Fujikawa . Spontaneous rupture of the urinary blad-

der is not a rare complication of radiotherapy

for cervical cancer: Report of six cases . Gynecol

Oncol 1999 ; 73 (3) : 439 – 442 .

15. Zoubek . The late occurrence of urinary tract damage

in patients successfully treated by radiotherapy for

cervical carcinoma . J Urol 1989 ; 141 (6) : 1347 – 1349 .

16. Loran OB-GL, Zaitsev AV, Lipskii VS. High col-

pocleisis in the treatment of postradiation vesicov-

aginal fistulas. Urologiia 2000; (4):41–42.

33. Urologic Consequences of Pelvic Irradiation in Women 467

17. Gellrich JHO , Oehischlager S , Wirth MP .

Manifestation, latency and management of late uro-

logical complications after curative radiotherapy for

cervical carcinoma . Onkologie 2003 ; 26 (4) : 334 – 340 .

18. Cushing . Major urologic complications following

radium and X-ray therapy for carcinoma of the cer-

vix . Am J Obstet Gynecol 1968 ; 101 (6) : 750 – 755 .

19. Kuhlman . CT evaluation of enterovaginal and vesi-

covaginal fistulas . J Comput Assist Tomogr 1990 ;

14 (3) : 390 – 394 .

20. Volkmer . Colour Doppler ultrasound in vesicovaginal

fistulas . Ultrasound MedBiol 2000 ; 26 (5) : 771 – 775 .

21. Angioli RPM , Muzii L , Mendez L et-al. , . Guidelines

of how to manage vesicovaginal fistula . Crit Rev

Oncol Hematol 2003 ; 48 (3) : 295 – 304 .

22 . Horch REGG , Schultze-Seemann W . Bilateral pedi-

cled myocutaneous vertical rectus abdominus muscle

flaps to close vesicovaginal and pouch-vaginal fistu-

las with simultaneous vaginal and perineal recon-

struction in irradiated pelvic wounds . Urology 2002 ;

60 (3) : 502 – 507 .

23 . Eilber KS , et al. Ten-year experience with transvagi-

nal vesicovaginal fistula repair using tissue interpo-

sition . J Urol 2003 ; 169 (3) : 1033 – 1036 .

24 . Leissner J , et al. Vaginal reconstruction using the

bladder and/or rectal walls in patients with radiation-

induced fistulas . Gynecol Oncol 2000 ; 78 (3) : 356 – 360 .

25 . Mannel RS , et al. Use of ileocecal continent urinary

reservoir in patients with previous pelvic irradiation .

Gynecol Oncol 1995 ; 59 (3) : 376 – 378 .

26 . Tabakov ID , Slavchev BN . Large post-hysterectomy

and post-radiation vesicovaginal fistulas: Repair by

ileocystoplasty . J Urol 2004 ; 171 (1) : 272 – 274 .

27. Corcos JSE , ed. Textbook of the neurogenic bladder:

Adults and children. London : Martin Dunitz ; 2004 .

28 . Olsen NK , et al. Radiation-induced brachial plex-

opathy: Neurological follow-up in 161 recurrence-

free breast cancer patients . International JRad Oncol

Biol Phys 1993 ; 26 (1) : 43 – 49 .

29 . Johnstone PASWE , O’Connell PG . Lumbosacral

plexopathy secondary to hyperfractionated radio-

therapy: A case presentation and literature review .

Radiat Oncol Invest Clin Basic Res 1993 ; 1 : 126 –

130 .

30 . Keime G . Neurological complications of radiotherapy

and chemotherapy . J Neurol 1998 ; 245 (11) : 695 – 708 .

31 . Tait DM , et al. Acute toxicity in pelvic radiotherapy;

A randomised trial of conformal versus conventional

treatment . Radiother Oncol 1997 ; 42 (2) : 121 – 136 .

32 . Kinsella TJ , et al. Threshold dose for peripheral

neuropathy following intraoperative radiotherapy

(IORT) in a large animal model . Int J Rad Oncol

Biol Phys 1991 ; 20 (4) : 697 – 701 .

33 . Johnstone PAS , et al. Clinical toxicity of peripheral

nerve to intraoperative radiotherapy in a canine model .

Int J Rad Oncol Biol Phys 1995 ; 32 (4) : 1031 – 1034 .

34 . Michailov MC , et al. . Influence of X-irradiation on

the motor activity of rat urinary bladder in vitro and

in vivo . Strahlenther Onkol 1991 ; 167 (5) : 311 – 318 .

35 . Michailov MC , et al. Immediate mechanical reac-

tions of isolated human detrusor muscle on x-irradi-

ation . Strahlentherapie 1979 ; 155 (4) : 284 – 286 .

36 . Parkin DE , et al. . Urodynamic findings following

radiotherapy for cervical carcinoma . Br JUrol 1988 ;

61 (3) : 213 – 217 .

37 . Farquharson DI , et al. The short-term effect of pelvic

irradiation for gynecologic malignancies on bladder

function . Obstet Gynecol 1987 ; 70 (1) : 81 – 84 .

38 . Farquharson DI , et al. The adverse effects of cervi-

cal cancer treatment on bladder function . Gynecol

Oncol 1987 ; 27 (1) : 15 – 23 .

39 . Lin HH , et al. Abnormal urodynamic findings after

radical hysterectomy or pelvic irradiation for cervical

cancer . Int J Gynecol Obstet 1998 ; 63 (2) : 169 – 174 .

40 . Behr J , et al. Funktionsveranderungen an den unteren

Harnwegen nach Bestrahlung des Kollumkarzinoms .

Strahlenther Onkol 1990 ; 166 (2) : 135 – 139 .

41 . Parkin DE , et al. Long-term bladder symptomatol-

ogy following radiotherapy for cervical carcinoma .

Radiother Oncol 1987 ; 9 (3) : 195 – 199 .

42. Nygaard . Stress urinary incontinence . Obstet

Gynecol 2004 ; 104 (3) : 607 – 620 .

433

Surgical Anatomy and Innervation

of the Sphincter

The last few decades have seen a refined definition

of the continence mechanism in the male, which

consists of two sphinteric mechanisms, with the

proximal continence mechanism provided by an

intact bladder neck with its smooth muscle, the

preprostatic sphincter. This definition has been

based primarily on numerous male autopsy and

radiological studies. The preprostatic sphincter is

a continuous structure that runs from the bladder

neck to the bulbar urethra with varying amounts

of tissue on the dorsal aspect [1] . This sphincter

is responsible for providing resting continence in

a normal male (Fig. 31.1 ). The second sphinteric

mechanism – the distal sphincteric mechanism –

described by Strasser et al. [2] , was about 1.5 cm

in a study of 14 male specimens, while Myers

et al. [3] found this to vary from 1.5 to 2.4 cm, with

a mean of 2.0 cm based on MRI imaging studies

[4] (Fig. 31.2 ) .

These findings have given rise to numerous con-

troversial issues. Myers suggests that this region,

also known as the rhabdosphincter, comprises both

striated and smooth muscle components extending

from the veru montanum to the bulbar urethra and

should be thought of as "sphincteric urethra" rather

than membranous urethra, since it encompasses

the various elements that provide continence at this

level [3] . The smooth muscle component lies inter-

nal to the striated muscle and is continuous with the

proximal smooth muscle sphincter [1, 3] . External

to this is the striated muscle layer that contains

predominantly type I slow-twitch fibers which are

adapted to maintain tone over long periods of time,

and thus provide resting continence [5] . These

muscle fibers apparent even in early fetal develop-

ment [6] do not surround the urethra and form a

horseshoe or omega configuration, are deficient

posteriorly, and are bulkiest anteriorly [1, 2] . The

fact that the native sphincteric mechanism does not

depend on a posterior support may be a reason for

relatively poor results of male sling procedures. It

is important to note that the levator ani muscles do

not form a part of this sphincteric mechanism and

are found to be separated from it by a clear layer

of connective tissue [1, 7] . The levator ani muscles

primarily consist of fast-twitch (type II) fibers that

are responsible for the “quick stop”

mechanism of urinary control [8] , provides the

voluntary control to voiding.

The innervation is complex, and debate persists

on whether the somatic innervation via the puden-

dal nerve reaches the sphincter or not. Karam et al.

[9] (Fig. 31.3 ) evaluated ten male human fetuses

in order to identify the innervation of the external

urethral sphincter. They found the presence of both

unmyelinated autonomic and myelinated somatic

nerves in the striated sphincter. The unmyelinated

nerves entered at the 5 o"clock and 7 o"clock

positions, while the myelinated nerves entered

the striated fibers of the prostatic capsule at the 9 and 3

o"clock positions. Both sets of nerves existed close

to the bladder neck and on the lateral and anterior

surfaces of the rectum. At the level of the bladder

Chapter 31

Treatment for Male Incontinence:

Surgical Procedures (Post-TURP/RRP)

Rajeev Kumar and Ajay Nehra

434 R. Kumar and A. Nehra

neck, the fibers were found to be below the pelvic

fascia. Studies by Narayan et al. [10] found that the

dorsal nerve of the penis also supplied the external

sphincter and were 0.3–1.3 cm away from the

prostatic apex. These nerves may be sensory and

damage to them could lead to abolition of a reflex

sphincteric mechanism that may be responsible for

continence, particularly during sleep [5] .

Prostatectomy, both radical and transurethral,

results in a destruction of the proximal smooth

muscle sphincteric mechanism. Continence in these

patients continues to be maintained through the

action of the distal urethral sphincter. Apposition

of the mucosal folds of the urethra and resting tone

maintained by the smooth muscle and the striated

muscle provide resting continence. During periods

of stress or during voluntary inhibition of stream,

the somatic fibers likely come into play, causing

contraction of the type II fibers of the levator ani

and also some of the fibers of the striated sphincter.

Damage to these fibers and their innervation prob-

ably is the prime cause for postprostatectomy stress

incontinence [11] .

Fig. 31.1. Functional anatomy of the male continence

mechanism. The proximal urethral sphincter extends

from the bladder neck through the prostatic urethra

above the verumontanum. The distal urethral sphincter

extends from the prostatic urethra below the verumon-

tanum through the membranous urethra. It includes the

rhabdosphincter (intrinsic skeletal and smooth muscle)

and extrinsic paraurethral skeletal muscle. Supf., super-

ficial (copywrite with permission)

Fig. 31.2. "Sphincteric urethra" might be more appropriate than "membranous urethra." Coronal view through blad-

der (bl), prostate (Pr), striated urethral sphincter (s), bulb, veins (V), obturator internus (o i), levator ani (l a), anterior

recess (AR) of ischioanal fossa, ischiopubic ramus (R), and corpus cavernosum (c). (Sagittal inset for orientation.)

(By permission of Mayo Foundation for Medical Education and Research) (copywrite with permission)

31. Treatment for Male Incontinence 435

Pathophysiology of Incontinence

Continence requires the storage of urine within the

bladder at low pressures with absence of involuntary

contractions, coupled with an outflow resistance that

voluntarily can be decreased. Postprostatectomy

incontinence (PPI) may be the result of a number of

mechanisms acting either alone or in combination.

These mechanisms are faulty sphincteric action,

bladder dysfunction, or anatomic abnormalities

of vesicourethral anastomosis. The most common

type of incontinence seen after radical prostatec-

tomy is stress incontinence. With sudden increases

in intra-abdominal pressure and subsequent rise in

vesical pressure, the sphincteric resistance would

prevent any urine leak during such rises. But a

compromised sphincteric function that results from

damage following the surgery would not be able

to resist this rise in pressure, resulting in a urine

leak. Detrusor instability with repeated involuntary

contractions may raise the bladder pressure above

the sphincteric resistance, resulting in a leak typi-

cally present as urgency or urge incontinence. Urge

incontinence is more common after transurethral

resection than after radical prostatectomy [12] . At

times, both mechanisms may be present simulta-

neously. Overflow incontinence due to an anasto-

motic stricture results in urinary retention followed

by overflow.

Intrinsic Sphincter Deficiency

Following radical prostatectomy, sphincteric defi-

ciency appears to be the most common cause of

incontinence [5] . Ficazzola and Nitti [12] evalu-

ated 60 patients with PPI in order to identify the

cause of incontinence and correlate symptoms

with urodynamic findings (Table 31.1 ). Stress

incontinence was the most commonly found com-

plaint, and intrinsic sphincter deficiency (ISD) was

demonstrated in 90% of the patients. Majoros et

al. [13] found ISD to be present in 90% of their

incontinent patients and the sole finding in 60%.

The finding of isolated sphincter deficiency as

the most common cause of incontinence has been

noted by other authors [14, 12] . However, Groutz

et al. [15] performed urodynamic examinations

in 83 men referred for PPI at a mean of 2.7 years

after surgery. They reported a combination of uro-

dynamic findings with 88% of the patients having

ISD (Table 31.2 ): 33.7% with bladder instabil-

ity and 20.5% with bladder outlet obstruction.

Maintenance of adequate urethral length has been

proposed in preventing postoperative incontinence.

Rudy et al. [16] found a significant decrease in the

mean functional sphincter length from 4.3 to 1.6

cm and believed this to be a significant contribu-

tion. Hammerer and Huland [17] found that the

mean functional urethral length decreased from

61 mm preoperatively to 25.9 mm postoperatively,

Fig. 31.3. Three-dimensional reconstruction of nervous

fibers from transverse sections of 36-week-old male

fetus (CRL 330 mm). ( a, b ) The unmyelinated nerves

(in yellow ) give branches, which penetrate into the pros-

tate (in magenta ) and emerge from the verumontanum

for innerved the prostate, the smooth muscles, and the

submucosa (in cyan ). ( c ) The striated muscular fibers (in

red ), situated at the anterolateral faces of the prostate,

are innerved by myelinated nervous fibers (in green )

(copywrite with permission)

436 R. Kumar and A. Nehra

and the maximal urethral pressure declined from

89.6 to 65.2 cm. However, other studies have noted

the length to be of no importance; rather, the maxi-

mal urethral closure pressure is of prime signifi-

cance [13, 18] . Following transurethral resection,

incontinence more often is urge rather than stress.

Sphincteric damage may occur in 3–47% of these

patients [19] .

Bladder Instability

Bladder instability is a common finding in patients

with PPI, both transurethral and radical. In transure-

thral resections, bladder instability is the most com-

mon finding in incontinent patients [19] . Patients

undergoing radical prostatectomy may have a

number of etiologies for their bladder instability.

Hellstrom et al. [20] noted a decreased bladder

compliance from 37 to 23 ml following surgery.

An incidence of 9–11% of poor compliance also

was found by Gomha and Boone [21] and Chao

and Mayo [22] . Groutz et al. [15] found detrusor

instability in 33.7% of their patients, and this was

the sole finding in 3.6%. Impaired contractility also

was present in 28.9% of their patients, and most of

these patients had a concomitant sphincteric weak-

ness, thus suggesting the lack of outflow resistance

is severe enough to allow incontinence even in the

presence of a hypocontractile detrusor. A number

of men undergoing this surgery may have had

Table 31.1. Summary of several contemporary series on post-radical prostatectomy incontinence with

regard to sphincter and bladder dysfunction a .

Sphincter dysfunction Bladder dysfunction

N Total (%) Alone (%) Total (%) Alone (%)

Leach et al. (1996) 162 82 40 36 14

Goluboff et al. (1995) 25 60 8 90 40

Chao and Mayo (1995) 74 96 57 43 4

Gudziak et al. (1996) 37 97 NA NA 3

Desautel et al. (1997) 35 95 59 39 3

Ficazzola and Nitti (1998) 60 90 53 45 3

Winters et al. (1998) 92 98.5 59 29 1 .5

Groutz at al. (2000) 83 88 33 a 34 4

NA, not applicable a This study considered urodynamic diagnoses of obstruction and impaired contractility so that

patients with sphincteric insuffiency and impaired contractility or obstruction without bladder dysfunction are not

included in this group

Table 31.2. Summary of several series on postprostatectomy incontinence for treatment of benign

disease with regard to sphincter and bladder dysfunction.

Sphincter dysfunction Bladder dysfunction

N Total (%) Alone (%) Total (%) Alone (%)

Andersen and Nordling (1978)

a 34 50 21 74 44

Fitzpatrick et al. (1979) b 68 79 28 66 16

Yalla et al. (1982)

c 21 62 52 38 29

Goluboff et al. (1995) 31 20 3 97 77

Leach et al. (1996)

d 51 78 39 59 20

Nitti et al. (1997) 20 20 20 75 75

Winters et al. (1998) 27 93 44 56 7

Patients underwent transurethral prostatic resection except when otherwise noted

a AII patients underwent open transvesical prostatectomy

b Contains 21 patients who underwent open prostatectomy

c Contains five patients who underwent radical prostatectomy, not stratified in data

d Contains 14 patients who underwent open prostatectomy

31. Treatment for Male Incontinence 437

preexisting bladder instability. This may have been

asymptomatic in the presurgery period and may

have arisen from advanced age or associated benign

prostatic hyperplasia (BPH) [11] . While evaluating

68 men scheduled for radical prostatectomy before

surgery, Majoros et al. [13] found detrusor overac-

tivity (DO) in 23.8% of the patients. In six of the

men, DO improved after surgery.

Giannantoni et al. [23] similarly evaluated 49

patients prior to radical prostatectomy and found

decreased bladder compliance in 20.4% of patients

at baseline. They also noted a de novo decrease in

compliance in 18.4% patients and 42.8% of patients

had impaired detrusor contractility at baseline.

There is evidence that this instability may be due

to the outflow obstruction and resolves after radical

surgery. Kleinhans et al. [24] reported an improve-

ment in detrusor instability in all but two of their

34.6% patients who had a preoperative unstable

bladder. It is important to realize that while bladder

instability often is present in these patients, it may

not be the primary cause of incontinence and may

actually be a coexisting feature with ISD. Patients

with severe ISD may have small bladder capacities,

which result in falsely decreased bladder compli-

ance values on cystometrograms [12] .

Nerve Damage

Denervation of the bladder base and proximal

urethra also may result in loss of posterior ure-

thral sensations. John et al. [25] used a catheter-

mounted stimulating ring electrode distal to the

bladder neck preoperatively and postoperatively

in 34 patients undergoing radical prostatectomy.

Incontinent patients had a higher sensory threshold

than the continent patients. The authors believe that

loss of afferent sensory stimuli may lead to a loss

of the reflex guarding and result in incontinence.

Bladder base denervation also may be responsible

for the development of bladder instability in previ-

ously stable bladders [20] . John et al. [26] noted a

decrease in the trigonal nerve fiber density in post-

prostatectomy bladder trigonal biopsies, and the

decrease was greater in incontinent patients than

in continent patients. They also noted an increase

in nerve fiber density in 19 incontinent patients

with a greater rise in the subset that regained

continence. Earlier studies on bladder biopsies of

patients undergoing pelvic surgery also revealed a

decrease in the density of nerve fibers in the trigone

with evidence of reinnervation on EMG studies of

the sphincter [27] . However, this denervation may

not solely be the result of surgery but also may be

the result of chronic outflow obstruction. In either

case, they provide evidence for bladder dysfunc-

tion due to neural damage.

Nerve preservation is considered a standard sur-

gical step in current radical prostatectomy. The pri-

mary reason for nerve preservation is maintenance

of postoperative erectile function. It is postulated

that continence primarily is mediated in the post-

surgical patients through the somatic fibers from

the pudendal nerve, which are always preserved in

radical prostatectomy, and thus cavernosal nerve

preservation may not contribute to continence.

Majoros et al. found the incontinence rate to be

similar in their cases irrespective of the surgical

technique [13] . Steiner et al. [28] reviewed 593 of

their patients and found the incontinence rate to

be similar in both the nerve-sparing and the non-

sparing group of patients. Catalona et al. [29] also

reported similar findings in their study of 1,870

men followed for a minimum period of 18 months.

It is possible that the failure to find a difference in

continence rates in these studies is due to the low

incidence of incontinence that generally existed in

these series. However, there is evidence to suggest

that nerve preservation also may help in improving

continence.

Burkhard et al. [30] evaluated 536 patients

who underwent open radical retropubic pros-

tatectomy and found the incidence of inconti-

nence to be 1.3, 3.4, and 13.7% among patients

who underwent bilateral or unilateral nonnerve-

sparing surgeries, respectively. The differences

were statistically significant. Eastham et al.

[31] reviewed their results in 581 patients and

found that nerve preservation had a significant

beneficial effect in preserving continence. This

was evident for even single-nerve preservation,

and preserving both bundles further added to

the continence. The role of these nerves in pre-

serving continence may be multifactorial. Apart

from preserving direct efferent innervation to the

sphincter as stated previously [6] , they also may

be important in providing afferent sensations and

mediating a reflex continence mechanism.

438 R. Kumar and A. Nehra

Bladder Neck Contracture and Fibrosis

Anastomotic strictures also contribute to the devel-

opment of incontinence. While Groutz’s

series [15] found the incidence to be about 20.5%,

Chao et al. [22] found this incidence to be 26%

among the incontinent patients. They also believed

that this scarring may extend down to the level of

the sphincter, causing impairment in its normal

closure. Ficazzola and Nitti [12] found a similar

incidence of anastomotic strictures, while Desautel

et al. [14] noted strictures in 67% of their patients.

The mechanism of incontinence in obstructed

patients is believed to be a combination of overflow

and urge incontinence. Continuous outflow obstruc-

tion can result in bladder instability, causing urge

incontinence, while chronic retention may result in

overflow. There also is a possibility of deranged

sphincteric function due to extensive postoperative

scarring and fibrosis which may prevent normal

coaptation of the urethral walls. Groutz et al. [15]

talk about this in terms of “decreased ure-

thral compliance.” They found urinary flow

with the 7 French catheter in situ to be lower by

greater than 10 ml s

– in 30% of patients compared

to catheter-free flow. Since a 7 French catheter

normally should not impede the flow of urine, they

believed this to be a manifestation of decreased

urethral compliance. They further stated that this

could be due to anastomotic strictures, fibrosis, or

bladder neck contractures and these are a contribu-

tory cause of incontinence.

Patient Evaluation

History and Examination

The history in a patient with PPI should focus on

determining the type and severity of incontinence

and its impact on the patient’s quality of

life. Stress urinary incontinence usually has a

typical presentation of leakage during periods of

mobility or increased abdominal pressure. Patients

with a history of stress incontinence usually have

a finding of ISD in cystometrograms. This symp-

tom has a positive predictive value of 95% and a

negative predictive value of 100% [12] . Urge, how-

ever, may not be an accurate predictor of bladder

instability. Ficazolla and Nitti [12] found unstable

bladders in only 8 of 18 men who complained of

urgency, while of 42 men who did not complain of

urgency 8 had bladder instability on urodynamics.

The severity of incontinence may be assessed by

the number of pads soaked per day or the use of a

penile clamp or such devices. The stream of urina-

tion and the need for straining may indicate the

presence of a stricture or bladder neck contracture.

It also is important to evaluate the presurgery con-

tinence status of the patient if this has not already

been documented in the surgical note. A detailed

history of associated comorbidities, particularly

stroke, spinal trauma, or other neurological condi-

tions, is important since it may impact the manage-

ment. The patient's physical dexterity to manage a

prosthetic implant also should be assessed. It also

is important to assess the erectile function dur-

ing this visit, since it may require simultaneous

management and may have been affected by the

incontinence. Finally, the impact on the patient's

quality of life and expectations after therapy are to

be evaluated in order to determine the therapeutic

options.

The goal of the examination is to rule out evident

causes for the incontinence. These include the pres-

ence of a distended bladder, which would suggest

outflow obstruction and overflow incontinence.

A brief neurological assessment is recommended

to evaluate the perineal innervation and the deep

tendon reflexes. A demonstration of urinary leak-

age using the Valsalva maneuver in patients with

stress incontinence may be performed; however,

this is not essential in case urodynamic testing is

being ordered.

Urodynamics

A complete urodynamic examination is manda-

tory when evaluating any patient with PPI (Figs.

31.4 and 31.5 ). The relative frequency of bladder

instability among these patients, particularly those

who have undergone a transurethral resection,

already has been discussed. The history, per se, is

an inadequate guide to the presence or severity of

bladder instability, and concurrent management of

both sphincter deficiency and instability is required

in order to achieve optimal results.

A urodynamic assessment may begin with a void-

ing uroflowmetry and postvoid urine assessment.

The patient should be asked to void at the time of a

normal desire. An obstructed uroflow pattern will

31. Treatment for Male Incontinence 439

suggest the presence of an anastomotic stricture

and the need for a videourodynamic study. The

postvoid residual urine assessment should be per-

formed using either an ultrasonogram or bladder

catheterization. An ideal urodynamic evaluation

includes a videourodynamic study that visualizes

the bladder neck and urine leak along with pressure

measurements. This allows a clear separation of

the relative contributions of bladder instability and

sphincteric deficiency to the pathology.

The study is performed using a 7–8 French

double-lumen catheter placed in the bladder. One

lumen is used to record the vesical pressure, while

the other is used to infuse saline or radiographic

contrast material. A 7 French diameter catheter

normally should not impede the outflow in a

patient with a compliant urethra. A second cath-

eter, connected to a pressure transducer, is placed

in the rectum to measure the intra-abdominal

pressure. The detrusor pressure is calculated after

deducting the abdominal pressure from the vesi-

cal pressure. A fill rate of 25–50 ml/min

– is used.

Slower rates may be preferred in patients with

severe urgency or documented low bladder capaci-

ties, since a faster fill rate can induce uninhibited

contractions of the detrusor. The patient’s

symptoms are recorded during the filling process.

Any uninhibited contraction of greater than 15 cm

H

2 O pressure is considered to be detrusor instabil-

ity [32] . It also is recommended that incontinence

should be documented during the procedure. An

unstable contraction, along with a sensation of

urgency and associated with urinary leak, is indica-

tive of urge incontinence. In patients with pure

stress incontinence, a Valsalva leak point pressure

(VLPP) assessment is required. The patient is

asked to perform a Valsalva maneuver at various

bladder volumes, beginning with about 150 ml.

The abdominal pressure at which the urine leaks

is designated the VLPP. Failure to demonstrate a

leak at 150 ml necessitates a repeat assessment

at progressively higher volumes. Some patients

with a clear history of stress incontinence may not

leak during the study. Such patients may have an

anastomotic stricture or the presence of a 7 French

catheter which prevents leakage. Such patients

should be tested for the VLPP at the end of the

study after removal of the urethral catheter; the

pressure reading from the rectal catheter is used

for pressure recording. At the end of the study,

Fig. 31.4. Urodynamic evaluation of a 75-year-old man,

2 years after transurethral prostatic resection, with severe

urge incontinence, increased with standing up. Note

episodes of detrusor instability ( straight arrows ) on two

separate fills. Also, incontinence is noted on flowmeter

( curved arrows ) and volume lost on the volume graft

maximum bladder capacity was 88 ml. Patient was tested

for stress incontinence on three occasions (simultaneous

spikes in abdominal and detrusor pressure), and none

was demonstrated. Diagnosis – severe detrusor instabil-

ity with urge incontinence (copywrite with permission)

50

0

Flow

600

100

Volume

Pves

Pabd

Pdet

ml/s

ml

cmH2O

Fig. 31.5. Urodynamic tracing of a 67-year-old man 1 year

after radical retropubic prostatectomy with incontinence,

which by history is related to increases in abdominal

pressure. Patient wears three pads per day. Urodynamics

showed loss of urine only during increases in abdominal

pressure, with an abdominal leak point pressure of 145 cm

H2O ( arrows ). Patient otherwise had a stable and compli-

ant bladder with a capacity of 500 mg. Voiding phase is

normal (copy write with permission)

50

0

Flow

150

100

Pves

Pabd

Pdet

ml/s

cmH2O

0cmH2O

440 R. Kumar and A. Nehra

a pressure flow graph is obtained by asking the

patient to void of his own volition. The detrusor

pressure generated in order to void is compared

against standardized nomograms to determine the

presence or absence of outflow obstruction. A low

pressure voiding is suggestive of a hypocontractile

bladder with concomitant sphincteric damage. The

video study demonstrates the leak at the time of the

recorded event and also may demonstrate the pres-

ence or absence of an anastomotic site stricture.

A simultaneous urethrogram may be obtained if a

stricture is suspected.

While a VLPP routinely is obtained during an

urodynamic study for incontinence, its importance

in management of the patient or in determining the

type of treatment is unclear. Twiss et al. [33] evalu-

ated 29 men 9 months following prostatectomy for

stress incontinence. They found the mean VLPP to

be 92.8 cm H

2 O, and it had an insignificant, weak

association with the amount of leakage per day. In

contrast to female patients where VLPP is used

to grade the degree of incontinence and to deter-

mine the type of therapeutic intervention necessary

for their management, the authors concluded that

VLPP had little bearing on the degree of leakage or

determining treatment outcomes in the postprosta-

tectomy-incontinent man. They did agree, however,

that a urodynamic study was useful in confirming

the presence of stress incontinence and evaluating

the presence and severity of bladder instability.

Cystoscopy

We recommend a cystourethroscopic examination

in all patients prior to any surgical intervention.

Patients with pure bladder instability who are to

be managed with oral medications may not need a

cystoscopy. However, in all other patients, particu-

larly those scheduled for an artificial genitourinary

sphincter, a visual examination confirms the absence

of a urethral, anastomotic stricture, or foreign body,

which, if present, would need to be treated before

the implantation of a sphincter (Fig. 31.6 ).

Management Strategies

It is widely accepted that PPI is significantly

affected by surgical technique of radical prostatec-

tomy, particularly the handling of the dorsal venous

complex, distal urethra, and the bladder neck apart

from direct damage to the sphincter. Modifications

in the surgical technique to minimize this compli-

cation are discussed elsewhere in this text. We will

limit ourselves to the management of the problem

once it is established.

Conservative/Medical

While the incidence of PPI may be up to 56% in

the early postoperative period, continence tends to

increase over time. In the early postsurgical period,

a trial of conservative therapy is recommended

both to improve continence and to help the patient

adjust to the problem and achieve social accept-

ance. Patients need reassurance and support, with

regular reviews to assess the degree of improve-

ment. Basic measures to help improve continence

are a decrease in fluid intake, minimization of

caffeine-based products, and medical management

with imipramine [34] . Pelvic floor exercises (PFE)

were promoted by Kegel in 1951 in an attempt to

enhance urinary control through increase in ure-

thral resistance [35] . PFE along with biofeedback

also may be useful in the management of PPI.

Various exercises aimed at strengthening the pelvic

Fig. 31.6. Cystoscopic evaluation of patient following

radical retropubic prostatectomy and external beam radi-

ation therapy which reveals bladder neck contracture and

multiple surgical clips at the level of the bladder neck

31. Treatment for Male Incontinence 441

floor muscles have been devised. These include

pelvic musculature contraction while in the supine,

standing, and squatting positions; during increased

abdominal stress; and with the use of varying

groups of muscles. A physical therapist generally

is involved in the training during these exercises,

and a home-based program then is developed for

the patient to continue without supervision. This is

supplemented with regular visits with the physical

therapist to reinforce the benefit and confirm the

adequacy of the technique. A number of studies

attest to the beneficial effects of PFE and bio-

feedback. Filocamo et al. [36] randomized 300

postprostatectomy patients to receive either PFE

training or no intervention beginning immediately

following catheter removal. The intervention group

performed PFE regularly for at least 6 months. All

patients underwent an objective and subjective

evaluation for continence at regular intervals up

to 12 months. At 12 months, the incontinence rate

in the nontreated group was 12.1% compared with

1.3% in the treated group. This difference in conti-

nence was visible as early as 1 month postsurgery.

Biofeedback and PFE may be started even before

the surgery. Burgio et al. [37] performed a prospec-

tive randomized study to evaluate the benefits of

preoperative PFE in 125 men and found training

reduced the time to continence and the proportion

of patients with severe incontinence at 6 months of

follow-up. However, Parekh et al. [38] did not con-

cur in their report wherein, while the return to con-

tinence was quicker in the treated group, patients

with severe incontinence did not benefit, and there

were no significant improvements in the long-term

outcomes. A recent Cochrane database review

confirms the current doubts about the efficacy of

PFE in the management of PPI [39] . Since these

exercises do no harm and potentially may benefit

the patient, a trial during the phase of conservative

management is justifiable.

Surgical Options

Most patients with persistent urinary incontinence

after 1 year of prostatectomy will require some

form of surgical intervention in order to become

dry. Currently used surgical procedures to augment

continence are based on devices that often date

back to the eighteenth century [40] . The function-

ing of these devices is based on one of two principles.

The first aims at providing a fixed resistance

to urine outflow. This fixed resistance prevents

urine leakage during periods of stress but is not

enough to occlude the normal micturition proc-

ess completely. Dynamic resistance devices allow

the patient to modulate the resistance manually,

lowering it during micturition and raising it during

periods of continence.

Penile Clamps

The penile clamp is one of the most rudimentary

and earliest devices available for the management

of male incontinence. The availability of a penile

shaft surrounding the urethra allows the placement

of a clamp during periods of activity to prevent

incontinence. This clamp can be removed during

micturition. Various modifications of the penile

clamps are available and continue to serve an

important function. However, they are associated

with the possibility of local trauma, erosion, and

discomfort, and do not have significant patient

acceptance. Modifications of this device in order

to minimize complications include the Baumrucker

clamp that provides an “S” curve to

the urethra rather than compressing it at opposing

points [41] .

Artificial Genitourinary Sphincters

The first artificial urinary sphincter and surgery for

its placement was described by Foley in 1947 [42] .

This procedure required the isolation of a segment

of the urethra with the surrounding corpora spongi-

osa from the remaining components of the penile

shaft. These were then encircled with an inflatable

cuff that was connected to an external pump car-

ried in the patient’s pocket. The first model

of the currently available artificial genitourinary

sphincter (AGUS) was described by Scott in 1973

[43] . This device, called the AS-721, was devel-

oped by American Medical Systems, Minnetonka,

Minnesota. It had four components: an inflatable

cuff that was placed around the urethra, a reservoir

that contained fluid, and two pumps – one placed

in each hemiscrotum to activate or deactivate the

pump. Activation of one pump pushed fluid out of

the reservoir into the cuff to occlude the urethra.

Activating the opposite pump resulted in a flow of

fluid in the opposite direction out of the cuff into

442 R. Kumar and A. Nehra

the reservoir and resulted in subsequent opening

of the urethra. Mechanical valves controlled the

one-way action of the pumps while the device itself

was made of a polyethylene terephthalate polymer.

This device and its modifications continued to be in

use until the development of the currently available

AMS 800 sphincter (Fig. 31.7a, b).

Design

The AMS 800™ AGUS device is the most

commonly used prosthesis for the management of

PPI. It is a refined version of the original AS-721

device. Unlike the original device, the AMS 800

consists of only three components: the urethral

cuff, a pressure-regulating balloon (PRB), and the

pump control which has both the activating and

deactivating mechanisms in one assembly. The

pressure on the urethra is controlled by balloons

rather than valves, and the cuff is made of a dip-

coated silicone rubber. The cuff is usually 2 cm

wide after deflation and is available in a variety of

lengths ranging from 4 to 11 cm depending on the

size of the urethra and the site of placement. The

cuff has clear tubing that is connected to similar

clear tubing on the pump. The pump also is made

of a silicone elastomer and is placed in the scrotal

soft-tissue to allow patient and physician access

for activation and deactivation. It consists of a soft

lower part and a hard upper part. The hard upper

part contains the valves that regulate the direction

and flow of fluid while the lower part is mechani-

cally pumped by the patient to drive the fluid. The

hard upper part also contains a deactivation but-

ton that freezes the function of the pump so that

fluid cannot flow in either direction. The pump

has two exit tubes, a clear tube that connects to

the cuff and a black tube for connection to the PRB.

Fig. 31.7. ( a ) Plain abdominal X-rays 6 weeks following placement of an AGUS revealing the reservoir, the deacti-

vated tandem cuff, and the scrotal activating/deactivating mechanism ( b ) Plain abdominal X-rays of the same patient

revealing the tandem cuff in the inflated state

31. Treatment for Male Incontinence 443

The PRBsusually are implanted in the prevesical

space. They are available in a variety of pressure

ranges, and the device is chosen depending on the

amount of pressure required at the patient’s

cuff. The balloons are connected to the pump using

a black connecting tube.

The standard device packaging also includes

an accessory kit of materials necessary for an

implant. These include a disposable cuff sizer used

to estimate the length of the cuff required, special

needles for preparing the device components, tub-

ing connection tools, and documentation. Most of

the components are disposable and presterilized.

However, some components such as the insertion

needles or tubing connectors are made of steel and

need to be sterilized before each procedure. The

implantable components are not resterilizable and

must not be reused.

Preparation for Surgical Implant

Since the device is made out of a synthetic polymer,

a possibility of allergic reactions to the implanted

materials exists, and this needs to be highlighted

during patient consent. Prevention of infection is

the single-most important precaution during the

preparation of the patient and device. Certain steps

taken in order to minimize this are prophylactic

antibiotics, part preparation only in the operating

room, laminar flow, minimal traffic, and strict

aseptic surgical scrub and component handling.

Silicone attracts dust and lint. Therefore it is

essential to use nonpowdered surgical gloves and

totally avoid the use of paper or cloth drapes. These

may result in device malfunction and also serve

as a nidus for device infection. The device-filling

solution usually is a diluted radiopaque contrast

material. This must be completely sterile and

isotonic. During preparation of the various com-

ponents before implant, it is important to ensure

the egress of all air bubbles, since these can cause

an air lock in the pumping mechanism resulting in

device malfunction.

Control pump preparation: Both the tubings

exiting the pump are dipped in a basin containing

the filling solution. The bulb is repeatedly squeezed

until all the air inside is expelled through the tub-

ing. While the tubings are kept submerged in the

solution, they are clamped with a rubber-shod fine

artery clamp.

Pressure-regulating balloon preparation: The

PRB is actively filled with the filling solution using

a blunt-tipped needle and syringe. The balloon then

is squeezed to expel all the air inside and finally

aspirated with the syringe and needle to withdraw

any remaining air bubbles. This process may be

repeated to ensure removal of all air bubbles before

the hemostat is applied to the tubing with the bal-

loon in a collapsed state. The balloon is kept in a

basin of filling solution until implantation.

Cuff preparation: The cuff is filled with the fill-

ing solution using a blunt-tipped needle. It then

is squeezed to deflate into the syringe, and any

remaining air is aspirated. The cuff is then refilled

with 1–5 cc of solution depending on the cuff size

so that the cuff is just filled and not over distended.

The tubing is then clamped.

Surgical Procedure

The AMS 800 AGUS can be implanted either

around the bladder neck or the bulbar urethra. The

bulbar urethral implant is the most common pro-

cedure and will be described here. There are two

basic surgical approaches for implantation of the

AGUS. These are the scrotal incision and perineal

incision. The choice of procedure depends prima-

rily on the familiarity of the surgeon with each

approach. The perineal approach requires two inci-

sions while the transverse scrotal approach requires

only one. However, the perineal approach provides

a more direct access to the bulbar urethra.

Perineal approach : The patient is placed in a

lithotomy position and prepped and draped for both

the perineal and suprapubic incisions.

Cuff placement : A Foley catheter is inserted into

the urethra to aid in identification. A midline peri-

neal incision is made to expose the bulbocaverno-

sus muscle surrounding the urethral bulb. The space

around the muscle is carefully dissected so that the

urethral bulb is not denuded of this muscle coat.

Anteriorly, the bulb is mobilized bluntly to allow

a circumferential placement of a Penrose drain

of about 2–3 cm width. A cuff sizer may be used

at this time to measure the circumference of the

urethra and the length of cuff required. Most such

placements require a 4- or 4.5-cm cuff. It should

be remembered that the cuff length reflects the outer

circumference of the cuff, whereas the direct measure-

ment is closer to the inner circumference of the

444 R. Kumar and A. Nehra

cuff. Once the cuff has been prepared, it is brought

into the operating field and gently placed around

the urethra and secured. The “tab”

end of the cuff is passed under the urethra and held

gently with a mosquito clamp while the cuff is

manipulated. The tubing is passed through the des-

ignated hole after serial unclamping and clamping

of the two hemostats on it so as to avoid entry of

any air bubble. The cuff is locked using the tab, and

the tubing is positioned to exit lateral to the urethral

midline (Fig. 31.8 ).

PRB placement: A transverse suprapubic inci-

sion is made and the rectus fascia is divided. The

linea alba is gently spread, and the prevesical space

is exposed. Space for the balloon is created using

blunt dissection ensuring complete hemostasis. The

balloon is placed in this space. A separate incision

is made in the rectus fascia below the original inci-

sion, and the exit tubing of the PRB is guided out

through this hole using sequential clamping of two

hemostats on the tubing to prevent entry of air bub-

bles. The balloon is filled with appropriate filling

solution, and gentle suprapubic pressure is applied

on the balloon region to allow excess fluid to enter

the syringe. The tubing is then clamped until its

connection with the pump is completed.

Pump placement: Using blunt dissection through

the perineal incision, a subdartos pouch is created in

the scrotum anterolaterally. The pump placement is

on the same side as the PRB placement. The pump

is placed into the scrotal pouch with the deactiva-

tion button facing outward so that it is palpable.

The special introducer needle is passed through the

Scarpa’s fascia from near the PRB tubing

into the perineal incision. It is important to stay lat-

eral to the spermatic cord, which is protected from

injury by one of the surgeon’s fingers. The

black tubing from the pump is attached to the spe-

cial end of this needle and its hemostats removed.

The needle is withdrawn into the suprapubic inci-

sion, bringing the tubing from the pump close to

the tubing exiting the PRB. The tubing is then

connected to the PRB using the supplied connect-

ing device. The white tubing exiting the pump is

trimmed and connected to the white tubing exiting

the cuff in the perineal incision.

Transverse scrotal approach: Unlike the peri-

neal approach, the patient stays in the supine

position with legs gently abducted. An upper

transverse scrotal incision is made and kept open

using a Scott retractor. The bulb of the urethra is

freed from its posterior attachment to the perineal

septum and anteriorly from the corpora cavernosa

in order to allow circumferential mobilization

for placement of the cuff. Cuff measurement and

placement is similar to the perineal approach. For

placement of the PRB, the surgeon performs a fin-

ger dissection of the superficial inguinal ring and

then uses a sharp hemostat to pierce the posterior

wall of the ring and enter the perivesical space. It

is important to ensure that the bladder is empty

and the cord is protected by the surgeon’s

finger. The perivesical space is developed, and the

PRB is placed within it. The tubing exits through

the external ring, which may be tightened using

an absorbable suture. Placement of the pump is

identical to that in the perineal approach, and all

connections are similarly completed.

Fig. 31.8. Intraoperative photograph revealing placement

of the tandem cuff

31. Treatment for Male Incontinence 445

Deactivation at completion: Once the compo-

nents have been connected, the device is tested.

The pump is squeezed and released repeatedly to

empty the cuff. The pump is allowed to fill partially

by waiting for about 15 s before the deactivation

button of the pump is pressed, thus leaving it in a

deactivated status for 6 weeks.

Results

The quantification of success of therapy is dif-

ficult because of the subjective influence of the

patient’s attitude and behavior. While a

strict definition would mean total absence of any

leakage at any time and under any condition,

individual perception varies, and some patients

may be content with the occasional leak of a few

drops while others may be happy wearing one pad

a day. Since the aim of therapy is improvement

in patient quality of life, various researchers have

used different definitions of success. A rationale

evaluation would combine both these parameters:

an objective evaluation of the amount of leakage

or number of pads changed and an assessment of

the quality of life.

The number of pads used to define success has

varied from none to two pads per day [44, 45] .

Litwiller et al. [44] evaluated the results of AGUS

implant in 65 patients, 51 postradical prostatectomy,

13 after TURP, and one after open prostatectomy.

All patients had severe preoperative incontinence.

They defined continence strictly as no leakage and

found an initial continent rate of 44%. This declined

to 20% over 28 months. However, the majority

of patients (90%) reported satisfaction with the

surgery, since it helped improve their continence

from the preoperative status. Ninety-six percent

believed they would recommend the procedure to

their friends, and 92% agreed that, in retrospect,

they would undergo the procedure again. Gousse

et al. [46] reviewed their data on 71 men who had

undergone an artificial sphincter implant following

radical prostatectomy. At a mean follow-up of 7.7

years, 27% patients used no pads, 32% used one,

and 15% used up to three pads per day. Fifty-eight

percent of the patients were very satisfied, while

another 19% were satisfied with the outcome of

their surgery. Hussain et al. [47] recently reviewed

the data on AGUS use in postprostatectomy

patients. Their own experience with 10 years of

follow up had a continence rate of 91%. One of

the largest experiences in the use of AGUS for

PPI has been reported by Elliot and Barrett [48]

from the Mayo Clinic. In a mixed population of

patients, they noted a continence rate of 88% at a

mean of 6.5 years following surgery. Long-term

results of AGUS implant for PPI are not widely

available. Fulford et al. [49] reported a 10-year

follow-up with implants including a majority for

neurogenic bladder dysfunction. The continence

rate was over 60%.

Complications

Complications frequently are seen with the use of

an AGUS. Most would result in a device replace-

ment. In a study of 36 children operated on over

10 years, Levesque et al. [50] found only 33%

required no second surgery and Kryger [51] et al.

found only 56% of original devices to be func-

tional. Similarly, high revision and explantation

rates have been described in other studies [46] .

The common complications necessitating these

revisions are infection, erosion, and mechanical

failure. All these may present with progressive

incontinence.

Infection: As with all prosthetic devices, AGUS

are prone to infection. The source of pathogens

may be hematogenous, intraoperative introduction

through the skin, unsterile instruments, environ-

ment, or unrecognized urethral breach. This may

manifest early in the form of local signs of inflam-

mation or with an erosion of the device through

the urethra. Erosion also may occur later where

the etiology may be either infection or pressure

necrosis. The use of a strict aseptic operative room

procedure is the only preventive measure to avoid

this significant problem apart from ensuring ster-

ile urine before surgery. The infection rate may

be as high as 14.5% in some series [52] , but the

average rates are around 4–5% [47] . Infected or

eroded devices need removal and the placement of

a urethral catheter to allow healing of the urethra.

The urethra usually heals well with rare stricture

formation.

Urethral atrophy: Atrophy of the urethra

may occur either due simply to pressure or as a

consequence of infection. It may occur in up to 9%

of cases [48] and is manifest as progressive loss

of continence, erosion, or the need for increased

446 R. Kumar and A. Nehra

pumping to void and deflate the cuff. One of the

device modifications that have helped decrease the

incidence of pressure necrosis is the narrow cuff

design. Gousse et al. [46] reported a revision rate of

7 of 42 in the patients with a narrow cuff compared

with 18 of 23 with the older design. Similarly,

Elliott and Barrett [48] reported a lower failure and

revision rate with the narrow cuff design compared

with the original sphincter design. Downsizing the

cuff also may be an option for the management of

urethral atrophy. Saffarian et al. [53] reviewed 17

patients with urethral erosion following a standard

AGUS placement. All patients underwent cuff

downsizing to a 4-cm cuff within the capsule of

the original cuff, and the patient satisfaction rate

improved from 15 to 80%.

If the urethral atrophy cannot be managed by a

simple downsizing, a tandem-cuff placement may

be used. The second or tandem cuff usually is

placed distal to the first cuff, but on occasion it may

need to be placed more proximally if it is detected

that the primary cuff was placed too distally on the

urethra. It is advisable to include the bulk of the bul-

bospongiosus muscle within the cuff to lend it more

tissue. Some authors also may prefer to replace the

original cuff while placing a tandem cuff, especially

if the duration of cuff placement has been greater

than 5 years [54] . The two cuffs are joined with a

Y connector and connected to the already existing

pump and PRB. Dimarco and Elliott [54] found the

tandem cuff to be effective in most patients, with

89% of the 19 patients requiring less than three pads

per day with an 88% satisfaction rate.

Another option for the management of erosion

is the transcorporal cuff placement. Erosion of the

urethra often necessitates a more distal placement

of the cuff, either the primary cuff or a second tan-

dem cuff. Guralnick et al. [55] describe a procedure

whereby the urethra is dissected dorsally through

the two corpora cavernosum, maintaining a layer

of the tunica albuginea on the urethra. This adds

bulk to the urethra and minimizes the risk of dorsal

perforation. In their series of 31 patients at a mean

of 17 months follow-up, 26 patients had mild or

no stress incontinence. None of the cuffs had an

erosion or infection. However, there is a risk of

inducing erectile dysfunction in a preoperatively

potent patient. In this series, only one patient was

fully potent preoperatively, and he continued to

have normal erections postsurgery.

Mechanical failure: This usually results from an

incorrect choice of cuff or balloon or an incorrect

surgical procedure. There may be an obstruction to

the flow of fluid due to kinks in the tubes. A large

cuff may require a greater pressure balloon or cuff

downsizing. Most of these complications were seen

in the earlier devices and have decreased since the

introduction of the narrow cuff design. However,

the incidence is still about 3–5% [47] . Improvement

in surgeon experience may significantly decrease

the incidence of such complications.

Male Sling Procedures

Following the principles of incontinence sur-

gery in females, increasing the urethral outflow

resistance by urethral compression was attempted

surgically by Kaufman. He described three differ-

ent procedures including crural crossover, crural

approximation, and subsequently the addition of

an implantable gel prosthesis [56– 58] . These pro-

cedures showed early promise and have now been

used to devise the male urethral sling procedures.

These use synthetic, dermal, or porcine tissue to

provide a similar posterior support to the urethra

and bladder neck. Jorion et al. [59] described their

experience of using the rectus fascia sling in 30

patients where the sling was constructed prophy-

lactically during the radical prostatectomy proce-

dure itself. They reported a 90% continence rate

compared with 70% in the group without the sling

at 3 months. The results improved to 100 and 93%,

respectively, at 12 months.

Schaeffer et al. [60] described a procedure

using synthetic material in which three bolsters of

Cooley soft vascular graft material or polyethylene

terephthalate covered by a polytetrafluoroethylene

sleeve were used in 64 men with PPI. A Stamey

needle was used to guide a nylon thread from each

bolster into the suprapubic area from either side of

the bladder neck. With a mean follow up of 22.4

months following a single-sling procedure, 64% of

patients were either dry or improved. Twenty-three

retightening procedures were performed. They

found previous irradiation to be the only significant

poor risk factor for success.

Castle et al. [61] reported their results with the

use of a synthetic device, the InVance Male Sling

System (AMS, Minnetonka, Minnesota). This

device consists of a silicone-coated knitted mesh

31. Treatment for Male Incontinence 447

of polyester. The authors used the mesh in combi-

nation with a porcine dermis sheet that was placed

between the mesh and the bulbar urethra. The mesh

is placed through a perineal incision and anchored

on either side of the urethra to the undersurface of

the pubic bone using three bone anchors on either

side. The mesh was tightened by imbricating in the

midline. Defining success as wearing one pad or

less per day, the authors reported a 39.5% conti-

nence rate at 18 months. Only 15.6% patients were

completely dry.

The AdVance Male Sling (AMS, Minnetonka,

Minnesota) consists of a synthetic mesh (Fig. 31.8 )

that recently has been introduced. While single-

and multicenter trials are ongoing, modifications

by the individual surgical group(s) have apparently

enhanced the effectiveness of the sling in predomi-

nantly mild and moderate incontinence-associated

surgical candidates (personal communication). The

mesh here is introduced at the level of the bulbar

urethra following a perineal incision and brought

out at the skin level via proprietary trocars with-

out anchoring the sling (Figs. 31.9 and 31.10 ) .

Continence rates of 50% have been reported ini-

tially; however, as selection criteria and long-term

results are published, we may see an improvement.

Another device based on these principles is

the adjustable continence therapy – ProACT

(Uromedical, Plymouth, Minnesota). This device

consists of two balloons that are inserted parau-

rethrally to lie on either side of the urethra under

the bladder neck to increase its resistance. The

balloons contain a titanium port that can be used

to increase or decrease the balloon inflation and

control the amount of resistance. The balloon

insertion is performed through a perineal incision

under fluoroscopic guidance with a cystoscopic

confirmation of the safety of the urethra and blad-

der from perforation and correct placement of the

balloons. The balloon ports are placed into the

scrotum below the dartos fascia to allow percu-

taneous needle access for inflation and deflation.

Trigo-Rocha [62] reported their results following

the use of this device in 23 patients with a mean

follow up of 22.4 months. Of these patients, 65%

were continent at up to one pad soakage level.

Patients not satisfied with the results were 35%,

and two opted for an AGUS placement. Four

patients required revision surgery. There were no

major complications.

All these procedures and devices are relatively

new with limited results. Most reported results are

of short-term duration and are no better than the

AGUS. The main reason for their development

seems to be the relatively cheaper cost. Efficacy

data and direct comparison with AGUS are still

lacking.

Bulking Agents

While the AGUS has proven efficacy in the manage-

ment of PPI, complications such as infection, ero-

sion, and cost deter some patients from accepting

this treatment. The use of an AGUS requires man-

ual dexterity, and its placement requires regional

or general anesthesia. These may not be feasible

in a subgroup of patients with incontinence who

would then require alternative therapy. One of the

initially used bulking agents, polytetrafluoroethyl-

ene, had good results but was difficult to inject and

had reports of migration/granuloma formation at

distant sites, which prompted its discontinuation.

Glutaraldehyde cross-linked collagen is FDA

approved for treatment of ISD. It has no propensity

for migration, induces only a mild local inflam-

matory reaction, is safe, and does not compromise

subsequent therapies if needed. Collagen injec-

tions may be deployed through either a retrograde

Fig. 31.9. Advance male urethral sling

Fig. 31.10. Positioning of the sling following a perineal

incision, localization of the sling at the bulbar urethra

448 R. Kumar and A. Nehra

or antegrade route. The retrograde approach is

performed using transurethral cystoscopy. For the

antegrade approach, a suprapubic cystostomy is

performed, and the tract may be dilated to accom-

modate an Amplatz sheath through which either a

nephroscope or cystoscope is introduced to reach

the bladder neck. Loughlin et al. [63] described

a modified antegrade approach that required a

smaller 15.5 French cystoscope instead of a larger

dilatation.

In 1998, Smith et al. [64] reported their experi-

ence with the use of transurethral collagen injection

in 62 men with PPI, 54 after radical prostatectomy,

and eight after TURP. At a median follow-up of 29

months, 38.7% were using one pad or less per day

while 8.1% became totally dry. The success rate was

higher in post-TURP patients than the postradical

prostatectomy cases. Percentage of patients who

were continent at 1 year was 65%, and they continued

to remain so with no further treatment. At 2 years,

42% maintained social continence. A median of four

injection procedures were required to achieve social

continence. Westney et al. [65] recently reported the

long-term outcomes of transurethral collagen injec-

tion in 307 men with ISD after therapy for prostate

carcinoma and in 15 for BPH. Their mean follow-up

was 40 months. Only 17% achieved complete con-

tinence with a mean duration of response being 11

months. The overall mean duration of response was

6.3 months. The authors concluded that collagen

injections are a good option for short-term therapy

in men with PPI.

Rahman et al. [66] reported the combined use

of bulking agents with AGUS implantation. Five

patients with recurrent incontinence following an

AGUS or sling placement underwent a bulking

agent injection (Surgisis ES: Cook Urological,

Spencer, Indiana) followed by an AGUS placement.

The original eroded cuff or sling was removed in

all cases. At a mean 11 months of follow-up, all

patients reported an improvement in their conti-

nence while two were completely dry.

Conclusions

Incontinence following prostatectomy is a significant

problem. It is multifactorial with intrinsic sphincter

deficiency being the most common cause in radical

prostatectomy patients. Complete evaluation is nec-

essary to confirm the contribution of various factors

to the etiology, and thus tailor the management. A

number of patients may improve spontaneously,

and definitive therapy should be deferred for about

a year postsurgically. AGUS implant provides the

best long-term cure rates for the condition. Other

modalities of treatment include male slings and

bulking agents. Neither has proven long-term results

or efficacy superior to the AGUS.

References

1. Yucel S, Baskin LS. An anatomical description of

the male and female urethral sphincter complex. J

Urol 2004; 171(5):1890–1897.

2. Strasser H, Ninkovic M, Hess M, et al. Anatomic

and functional studies of the male and female ure-

thral sphincter. World J Urol. 2000; 18(5):324–329.

3. Myers RP. Practical surgical anatomy for radi-

cal prostatectomy. Urol Clin North Am 2001; 28:

473–490.

4. Myers RP, Cahill D, Devine RM, et al. Anatomy of

radical prostatectomy as defined by magnetic reso-

nance imaging. J Urol 1998; 159:2148.

5. Heinzer H, Hammerer PG, Huland H. Anatomy and

physiology of the male urethral sphincter and its

preservation in prostatic surgery. Urol Res. 1999;

27(6):404–408.

6. Ludwikowski B, Oesch Hayward I, et al. The devel-

opment of the external urethral sphincter in humans.

BJU Int 2001; 87(6):565–568.

7. Dorschner W, Biesold M, Schmidt F, Stolzenburg

JU. The dispute about the external sphincter and

the urogenital diaphragm. J Urol 1999; 162(6):

1942–1945.

8. Gosling JA, Dixon JS, Critchley HO, et al. A com-

parative study of the human external sphincter and

periurethral levator ani muscles. Br J Urol 1981;

53:35.

9. Karam I, Droupy S, Abd-Alsamad I, et al. The pre-

cise location and nature of the nerves to the male

human urethra: Histological and immunohistochem-

ical studies with three dimensional reconstruction.

Eur Urol 2005; 48:858–864.

10. Narayan P, Konety B, Aslam K, et al. Neuroanatomy

of the external urethral sphincter: Implications for

urinary continence preservation during radical pros-

tate surgery. J Urol 1995; 153:337.

11. Carlson KV, Nitti VW. Prevention and management

of incontinence following radical prostatectomy.

Urol Clin North Am 2001; 28:595–612.

12. Ficazzola MA, Nitti VW. The etiology of post-rad-

ical prostatectomy incontinence and correlation of

31. Treatment for Male Incontinence 449

symptoms with urodynamic findings. J Urol 1998;

160:1317.

13. Majoros A, Bach D, Keszthelyi A, et al. Urinary

incontinence and voiding dysfunction after radical

retropubic prostatectomy (prospective urodynamic

study). Neurourol Urodyn 2006; 25(1):2–7.

14. Desautel MG, Kapoor R, Badlani GH. Sphincteric

incontinence: The primary cause of post-prostatec-

tomy incontinence in patients with prostate cancer.

Neurourol Urodynam 1997; 16:153.

15. Groutz A, Blaivas JG, Chaikin DC, et al. The patho-

physiology of post-radical prostatectomy inconti-

nence: A clinical and video urodynamic study. J

Urol 2000; 163(6):1767–1770.

16. Rudy DC, Woodside JR, Crawford ED. Urodynamic

evaluation of incontinence in patients undergoing

modified Campbell radical retropubic prostatec-

tomy. A prospective study. J Urol 1984; 132:708.

17. Hammerer P, Huland H. Urodynamic evaluation of

changes in urinary control after radical retropubic

prostatectomy. J Urol 1997; 157:233–236.

18. Kleinhans B, Gerharz E, Melekos M, et al. Changes

of urodynamic findings after radical prostatectomy.

Eur Urol 1999; 35:217.

19. Nitti VW, Kim Y, Combs AJ. Voiding dysfunction

following transurethral resection of the prostate:

Symptoms and urodynamic findings. J Urol. 1997;

157(2):600–603.

20. Hellstrom P, Lukkarinen O, Kontturi M. Urodynamics

in radical retropubic prostatectomy. Scand J Urol

Nephrol 1989; 23:21.

21. Gomha MA, Boone TB. Voiding patterns in patients

with post-prostatectomy incontinence: Urodynamic

and demographic analysis. J Urol 2003; 169(5):

1766–1769.

22. Chao R, Mayo ME. Incontinence after radical

prostatectomy: Detrusor or sphincter causes. J Urol

1995; 154:16.

23. Giannantoni A, Mearini E, Di Stasi SM, et al.

Assessment of bladder and urethral sphincter func-

tion before and after radical retropubic prostatec-

tomy. J Urol 2004; 171:1563–1566.

24. Kleinhans B, Gerharz E, Melekos M, et al. Changes

of urodynamic findings after radical retropubic pros-

tatectomy. Eur Urol 1999; 35:217–221.

25. John H, Sullivan MP, Bangerter U, et al. Effect of

radical prostatectomy on sensory threshold and pres-

sure transmission. J Urol 2000; 163(6):1761–1766.

26. John H, Hauri D, Leuener M, et al. Evidence of

trigonal denervation and reinnervation after radi-

cal retropubic prostatectomy. J Urol 2001; 165(1):

111–113.

27. Kirby RS, Fowler CJ, Gilpin SA, et al. Bladder mus-

cle biopsy and urethral sphincter EMG in patients

with bladder dysfunction after pelvic surgery. J R

Soc Med 1986; 79:270–273.

28. Steiner MS, Morton RA, Walsh PC. Impact of

anatomical radical prostatectomy on urinary conti-

nence. J Urol 1991; 145:512–514.

29. Catalona WJ, Carvalhal GF, Mager DE, Smith DS.

Potency, continence and complication rates in 1,870

consecutive radical retropubic prostatectomies. J

Urol 1999; 162:433–438.

30. Burkhard FC, Kessler TM, Fleischmann A, et al.

Nerve sparing open radical retropubic prostatectomy

— does it have an impact on urinary continence? J

Urol 2006; 176:189–195.

31. Eastham JA, Kattan MW, Rogers E, et al. Risk fac-

tors for urinary incontinence after radical prostatec-

tomy. J Urol 1996; 156:1707–1713.

32. Abrams P, Blaivas JG, Stanton S, et al. The stand-

ardization of terminology of lower urinary tract

function. Scand J Urol Nephrol 1988; 114(Supp):5.

33. Twiss C, Fleischmann N, Nitti VW. Correlation of

abdominal leak point pressure with objective incon-

tinence severity in men with post-radical prostatec-

tomy stress incontinence. Neurourol Urodyn 2005;

24(3):207–210.

34. Walsh PC. Anatomic radical retropubic prostatec-

tomy. Campbell's 8th edn, 2002; vol. 4:3107–3129.

35. Kegel AH. Physiologic therapy for urinary stress

incontinence. JAMA 1951; 146:915.

36. Filocamo MT, Marzi VL, Popolo GD, et al.

Effectiveness of early pelvic floor rehabilitation

treatment for post prostatectomy incontinence. Eur

Urol 2005; 48:734–738.

37. Burgio KL, Goode PS, Urban DA, et al. Preoperative

biofeedback assisted behavioral training to decrease

post-prostatectomy incontinence: a randomized,

controlled trial. J Urol 2006; 175:196–201.

38. Parekh AR, Feng MI, Kirages D, et al. The role of

pelvic floor exercises on post prostatectomy incon-

tinence. J Urol 2003; 170:130–133.

39. Moore KN, Cody DJ, Glazener CMA. Conservative man-

agement for post prostatectomy urinary incontinence.

Cochrane Database Syst Rev 2001; 2:CD001843.

40. Madjar S, Raz S, Gousse AE. Fixed and dynamic

urethral compression for the treatment of post-pros-

tatectomy urinary incontinence: Is history repeating

itself? J Urol 2001; 166:411–415.

41. Baumrucker GO. A new male incontinence clamp. J

Urol 1979; 121:201.

42. Foley FEB. An artificial sphincter: A new device

and operation for control of enuresis and urinary

incontinence. J Urol 1947; 58:250.

43. Scott FB, Bradley We, Timm GW. Treatment of uri-

nary incontinence by implantable prosthetic sphinc-

ter. Urology 1973; 1:252.

450 R. Kumar and A. Nehra

44. Litwiller SE, Kim KB, Fone PD, et al. Post prostate-

ctomy incontinence and the artificial urinary sphinc-

ter: A long-term study of patient satisfaction and

criteria for success. J Urol 1996; 156:1975–1980.

45. Wang Y, Hadley HR. Experiences with the artificial

urinary sphincter in the irradiated patient. J Urol.

1992; 147(3):612–613.

46. Gousse AE, Madjar S, Lambert MM, Fishman IJ.

Artificial urinary sphincter for post-radical prosta-

tectomy urinary incontinence: Long-term subjective

results. J Urol 2001; 166(5):1755–1.

47. Hussain M, Greenwell TJ, Venn SN, Mundy AR.

The current role of the artificial urinary sphincter for

the treatment of urinary incontinence. J Urol 2005;

174(2):418–424.

48. Elliott DS, Barrett DM. Mayo Clinic long-term

analysis of the functional durability of the AMS 800

artificial urinary sphincter: A review of 323 cases. J

Urol 1998; 159(4):1206–1208.

49. Fulford SC, Sutton C, Bales G, et al. The fate of the

“modern” artificial urinary sphincter with a follow-up

of more than 10 years. Br J Urol 1997; 79(5):713–716.

50. Levesque PE, Bauer SB, Atala A, et al. Ten-year

experience with the artificial urinary sphincter in

children. J Urol 1996; 156(2 Pt 2):625–628.

51. Kryger JV, Spencer Barthold J, Fleming P, Gonzalez

R. The outcome of artificial urinary sphincter place-

ment after a mean 15-year follow-up in a pediatric

population. BJU Int 1999; 83(9):1026–10231.

52. Scott FB. The artificial urinary sphincter. Experience

in adults. Urol Clin North Am 1989; 16:105.

53. Saffarian A, Walsh K, Walsh IK, Stone AR. Urethral

atrophy after artificial urinary sphincter placement: Is

cuff downsizing effective? J Urol 2003; 169:567–569.

54. DiMarco DS, Elliott DS. Tandem cuff artificial

urinary sphincter as a salvage procedure following

failed primary sphincter placement for the treatment

of post-prostatectomy incontinence. J Urol 2003;

170(4 Pt 1):1252–1254.

55. Guralnick ML, Miller E, Toh KL, Webster GD.

Trans-corporal artificial urinary sphincter cuff

placement in cases requiring revision for erosion and

urethral atrophy. J Urol 2002; 167(5):2075–2078.

56. Kaufman JJ. Surgical treatment of post prostatec-

tomy incontinence: Use of the penile crura to com-

press the bulbous urethra. J Urol 1972; 107:293.

57. Kaufman JJ. Urethral compression operations for

the treatment of post prostatectomy incontinence. J

Urol 1973; 110:93.

58. Kaufman JJ. Treatment of post prostatectomy incon-

tinence using a silicone gel prosthesis.Br J Urol

1973; 45:646.

59. Jorion JL. Rectus fascial sling suspension of the

vesicourethral anastomosis after radical prostatec-

tomy. J Urol. 1997; 157(3):926–928.

60. Schaeffer AJ, Clemens JQ, Ferrari M, Stamey TA.

The male bulbourethral sling procedure for post-

radical prostatectomy incontinence. J Urol 1998;

159(5):1510–1515.

61. Castle EP, Andrews PE, Itano N, et al. The male sling

for post-prostatectomy incontinence; mean follow up

of 18 months. J Urol 2005; 173(5):1657–1660.

62. Trigo-Rocha F, Gomes CM, Pompeo AC, et al.

Prospective study evaluating efficacy and safety of

adjustable continence therapy (ProACT) for post

radical prostatectomy urinary incontinence. Urology

2006; 67(5):965–969.

63. Loughlin KR, Comiter CV. New technique for

antegrade collagen injection for post-radical prosta-

tectomy stress urinary incontinence. Urology 1999;

53(2):410–411.

64. Smith DN, Appell RA, Rackley RR, Winters JC.

Collagen injection therapy for post-prostatectomy

incontinence. J Urol 1998; 160(2):364–367.

65. Westney OL, Bevan-Thomas R, Palmer JL, et al.

Transurethral collagen injections for male intrinsic

sphincter deficiency: University of Texas-Houston

experience. J Urol 2005; 174(3):994–997.

66. Rahman NU, Minor TX, Deng D, Lue TF. Combined

external urethral bulking and artificial urinary

sphincter for urethral atrophy and stress urinary

incontinence. BJU Int 2005; 95(6):824–826.

451

Part VII

Special Situations

453

History of Vesicovaginal Fistula

Vesicovaginal fistula (VVF) is a debilitating con-

dition that has plagued women for thousands of

years. The first recorded references of VVF were

made in 1550 BC in ancient Egypt. Avincenna, a

renowned Arabic physician, was the first person

to document the relationship between VVF and

obstructed labor, or traumatic delivery, in 1037

[1] . In 1923, Derry examined the earliest case of

VVF (2050 BC) in the mummified body of Queen

Henherit [2] .

James Marion Sims established the foundations

of VVF repair in 1852, after a series of experimen-

tal surgeries on slaves in Montgomery, Alabama, in

1845. These fundamentals included:

1. Proper exposure with the knee–chest position

2. Use of a weighted vaginal retractor

3. The use of silver wire sutures

4. Tension-free closure of the defect

5. Proper postoperative bladder drainage

Definition and Incidence

Vesicovaginal fistulae are epithelialized or fibrous

communications between the bladder and vagina.

VVF are relatively uncommon and yet are some of

the most socially devastating conditions a patient

may experience. Third World countries have a

drastically higher prevalence compared to that

of developed nations [2] . The true incidence of

VVF is unknown but is estimated at 0.3–2% in

countries such as the United States (Table 32.1 )

[3] . Iatrogenic postsurgical VVF are estimated at

81–91% from iatrogenic surgical injury in these

patients [1] . In countries such as Nigeria, it has

been estimated by the World Health Organization

(2001) to occur in 800,000 to 1 million women.

Obstetric trauma is by far the most common cause

in most Third World countries.

Etiology of Adult VVF

Latrogenic

Postsurgical VVF accounts for 81–91% of VVF

occurrence in developed countries. Hysterectomy

is the most common surgery leading to VVF in

developed countries with an 80% incidence [4] . The

incidence varies with the approach: 1:1000 transab-

dominal, 0.2:1000 transvaginal, and 2.2:1000 with

laparoscopic procedures. The most common sites

are superior to the trigone, corresponding to the

vaginal cuff [5] . Other gynecological procedures

account for up to 11%, including cesarean sec-

tion and dilation and curettage. Incontinence sur-

gery, formalin injections, and laparoscopy are less

reported causes of VVF [6] .

Pelvic radiation for malignancy has a 5% inci-

dence of VVF formation, even after many years.

The resulting fibrosis with arthritis nodosa and

decreased blood supply leads to tissue necrosis,

sloughing, and fistula formation.

Chapter 32

Current Concepts and Treatment Strategies

for Genitourinary Fistulas

Gamal M. Ghoniem and Carolyn F. Langford

454 G.M. Ghoniem and C.F. Langford

Noniatrogenic

Obstetric trauma, including obstructed and pro-

longed second stage labor is the leading cause of

VVF in underdeveloped countries, especially the

South Sahara of Africa. In Western countries, this

encompasses only 5% of all VVF. Pelvic tumor,

pelvic trauma, congenital anomalies, foreign body,

and abscess account for 5% or less of VVF [6, 7] .

Presentation

Generally, time to onset is 7–10 days after sur-

gery, but it can range from immediate to 6 weeks.

Postradiation VVF takes months to years to

develop. Usually the patient presents with continu-

ous leakage of urine. This can be mistaken for early

postoperative discharge, leading to more frustra-

tion for the patient and delayed diagnosis. If there

is intra-abdominal urine extravasation, the patient

may present with abdominal pain and ileus.

Diagnosis

The most critical factor in diagnosing a VVF is a

high suspicion. Many times the history and physi-

cal will reveal the pathology and sometimes even

the etiology. Review of operative reports indicat-

ing technical difficulties encountered, such as

excessive bleeding, tumor endometriosis, previous

surgery, pessary use, elevated creatinine, and obes-

ity will suggest the etiology. A critical part of the

diagnosis is confirmation of urine leakage. This

can be done in a number of ways. At the Cleveland

Clinic Florida, we use the double-dye technique to

help differentiate between vesicovaginal and ure-

terovaginal fistula (UVF). The patient is brought

to the clinic after taking phenazopyridine. The

nurse instills 100 ml of diluted methylene blue

solution into the bladder, and the catheter is then

removed. A tampon is inserted vaginally and the

patient is asked to come back in 2 h. The tampon is

inspected. If it is stained blue, it is VVF. If stained

orange, it is UFV, and further workup is needed.

Further evaluation includes oral Indigo Carmine

IV or phenazopyridine to detect ureterovaginal

fistula. An intravenous pyelography (IVP) also can

help define anatomical defects. In 25% of VVFs

there will be a hydronephrosis, with 10% having a

concomitant UVF [8] .

An antegrade pyelogram also can help define

anatomy using the nephrotomy tube, which may

show filling of the vagina with contrast. Cystoscopy

and vaginoscopy may help determine the site, size,

and number, as well as the location in relation to

ureteral orifices [9, 10] . There may be multiple,

small fistulae in a supratrigonal transverse position

found, especially after aggressive closure of the

vaginal cuff. Biopsy is recommended if there is

a history of malignancy. Flourourodynamic stud-

ies can be used to determine bladder compliance,

capacity, and outlet competence. It also allows bet-

ter identification of fistulae that may otherwise be

missed (Fig. 32.1 ).

Management

Conservative Treatment

Only in small, clean, nonmalignant VVF may

conservative treatment be attempted. Prolonged

catheter drainage for 3–5 weeks is suggested.

Additionally, anticholinergic medication relaxes

the detrusor muscle and prevents spasm. Topical

estrogens are used routinely in postmenopausal

women to promote healing. Raz et al. as well as

our group, have utilized conservative therapy for

fistulae less than 5 mm, including therapy such as

catheter drainage alone or with electrocautery [1,

3] (Fig. 32.2 ) .

Fig. 32.1. Flouroscopy of vesicovaginal fistula

32. Current Concepts and Treatment Strategies for Genitourinary Fistulas 455

In the last few years, we have been successful in

managing small VVF with catheterization and cys-

toscopic fulguration with/without fibrin glue injec-

tion. In a case report from Osaka, Japan, fibrin glue

was used for a 1-mm VVF at the site of recurrent

endometrial tumor at the “vaginal stump.” They

used 1 cc of fibrin glue (Beriplast-P™, Aventis

Pharma, LTD) after curetting a small area of tissue

around the fistula. They reported maintenance of

continence for 26 months. This same patient then

developed a second separate fistula, 1.2 mm in

size, which was treated in a similar fashion, with

continence lasting 33 months [11] . Conservative

treatments, including the use of glue products,

report varying degrees of success and are depend-

ent on the cause, size, and location of the fistula.

The literature in this area is very limited.

Surgical Repair Considerations

Each case of VVF should be individualized and,

as in most surgeries, the first attempt at surgical

repair is the best and most likely to succeed. The

choice of surgical approach also should be deter-

mined by the surgeon’s familiarity and skill with

the technique.

Fig. 32.2. Cystoscopy of a small VVF. ( a ) Supratrigonal lateral VVF. ( b ) F5 ureteric catheter inserted into fistula.

( c ) Vaginoscopy confirming the connection. ( d ) Fulgeration of fistulous tract, followed by 3 weeks bladder drainage

and anticholinergics

456 G.M. Ghoniem and C.F. Langford

Surgical Timing

VVF is most likely to heal well when properly

diagnosed and repaired close to the time of forma-

tion. For example, an uncomplicated posthyster-

ectomy VVF will still have many of the planes

evident and is easier to surgically repair than an

obstetric fistula. Zimmern observed no increased

rate in morbidity or failure in patients with early

repair performed only 2 to 3 weeks after injury

[12] . Fistulae such as those caused by radiation or

obstetrics need time for tissue regeneration prior to

repair. In the latter situations, a delayed repair at

3–6 months is more appropriate.

Surgical Approach

Clearly, location of the fistula will dictate the best

approach to a VVF repair. The most common site

for VVF in the Western world is at the vaginal cuff

status postabdominal hysterectomy. The current

trend toward a transvaginal approach, even for

deep and large fistulae, has been shown to have

lower morbidity rates than transabdominal repairs.

In addition, the approach to the type of vascular-

ized interposition flap also is determined by how

proximal (peritoneal) or distal (Martius) the geni-

tourinary fistula is in the vagina.

Raz et al. evaluated their 10-year data on 207

women with interposition grafts and found that

peritoneal tissue is an excellent source for inter-

position in complex proximal VVF and is at least

as successful as Martius grafts in VVF [3] . Evans

et al. evaluated the need for interposition grafts in

both benign and malignant VVF, which showed

a clearly higher success rate with interposition

grafts regardless of type or etiology of fistula in

the transabdominal approach. The key to success

appeared to be related to a quality vascular pedicle

in the interposition graft [7] .

The approach usually is determined by the

surgeon’s preference, experience, and also the

position of the fistula. The transvaginal approach,

which is our personal preference at the Cleveland

Clinic Florida, causes less morbidity and can be

used for most VVF. The transabdominal approach

is best when ureteric reimplantation or augmenta-

tion is necessary or if the woman has a deep and/or

narrow vagina. The transvesical approach is a less

commonly used approach, with higher morbidity.

A transvaginal approach for distal fistula

requires wide dissection for mobilization. Closure

is nonoverlapping layers under no tension. There

also must be a method for checking for leaks. We

like to use Foley instillation with diluted methylene

blue and a clean white laparotomy sponge allowing

for precise leakage site identification. If radia-

tion or poor tissue quality is an issue, a Martius

graft (in distal) or other biological graft materials

have been used to assist in fistula reconstruction.

Success rates are reported at 92–96% [1, 3, 13] . A

minimum of a three-layer closure is one of the keys

to success in treatment of VVF. Layer one is com-

posed of revised bladder mucosa or epithelialized

edges of the fistula tract, layer two is imbricated

perivesical fascia, and level three is undermined

vaginal epithelium or an advancement flap.

We prefer a Latzko procedure, or minicolpoclei-

sis, as our method of choice for high vaginal cuff

VVF (Fig. 32.3 ). In this repair there is no need

to excise the fistula, as its margins provide good

anchoring for the first-layer of sutures. The dam-

aged vaginal wall is closed in layers over the

fistula. The resulting vaginal shortening is nearly

negligible and has no sequelae.

The transabdominal approach is intraperito-

neal with wide mobilization of the bladder. If this

technique is chosen, the O’Conor technique is our

preferred technique. This allows excellent mobili-

zation of different layers and omental interposition.

Success rates are 85–100% [7] . The technique

includes:

• Bivalving the bladder in the midline passing the

fistula and excising it (O’Conor technique)

• Isolate the bladder in two layers

• Close bladder in two to three layers

• Close vagina in two layers

• Routine use of omental interposition (Fig. 32.4 )

The transvesical approach is best utilized when

the fistula is loculated and the ureteric orifices are

cannulated. The fistulous tract must be incised using a

scalpel, leaving the vaginal wall intact. The dissection

would be carried out circumferentially for 1–2 cm.

During closure it is key not to overlap the suture lines

and to use both transverse and perpendicular suture

lines if possible.

Complications include frequency, urgency, urge

incontinence, recurrence, stress urinary incontinence

(10–12%), ureteral obstruction, and bowel obstruc-

32. Current Concepts and Treatment Strategies for Genitourinary Fistulas 457

tion. The only alternative with end-stage bladder and

multiple failed surgeries is urinary diversion.

Laparoscopic repair using the O’Conor tech-

nique has been reported by Chibber et al. They

report the main advantages of a laparoscopic

approach are decreased morbidity and recovery

time. Maintaining pneumoperitoneum once the fis-

tula is excised is a challenge, and a Foley catheter

is used for this purpose. They were successful in

7 of 8 patients. Mean operative time was 220 min

[7] . Success rates are reported to be as high as 93%

at 26 months [14] . Omental J-flaps also were suc-

cessfully utilized by other groups, such as Miklos

et al. even after transvaginal failures with Latzko

procedures [12, 15] .

Laparoscopic VVF repair with robotic recon-

struction has been reported twice in the Journal of

Urology since 2004. Melamud et al. reported a case

using the DaVinci™ robot with a total operative time

of 280 min [16] . There was an estimated blood loss

of 50 cc with 16-week follow-up revealing cure for

a proximal VVF at the cuff posthysterectomy [17] .

A second article reporting five cases by Sundaram

et al. showed a 100% cure rate at 6 months [14] .

Clearly, the robotic repairs will require further

evaluation and randomized controlled studies in

the future, allowing for better options for VVF

patients. The disadvantages to robotic VVF repair

are obvious, including increased learning curve,

time, expense, and availability as well as surgeon

experience.

Large posthysterectomy and postradiation VVFs

also can be managed by ileocystoplasty. This

technique carries a high rate of morbidity but has

proven effective in small groups of women with

large VVF. The key to its success is using a well-

vascularized portion of ileum, which has not been

radiated [18] .

Fig. 32.3. Latzko technique. ( a ) VVF catheterized with small Foley’s catheter. ( b ) The vaginal epithelium around the

fistula is denuded, leaving the fistula margins. ( c ) Water-tight closure of the fistula. ( d ) Multiple mattress sutures in

2–3 layers. ( e ) Insignificant shortening of the vaginal cuff after complete closure

458 G.M. Ghoniem and C.F. Langford

Postoperative Care

Postoperative care is as crucial to the procedure

as is the procedure itself. A vaginal pack is placed

after surgery until the following morning. Usually,

antibiotics are administered for 1–2 weeks post-

surgery depending on the length of need for Foley.

We recommend anticholinergics until catheters are

removed. We will traditionally do a cystogram in 3

weeks, if the suprapubic tube or Foley is out.

References

1. Ghoniem GM, Khater UM. Vesicovaginal fistula, pel-

vic floor dysfunction. Springer, London, 2006.

2. Riley VJ. Vesicovaginal fistula. EMedicine for

WebMD, June 25, 2006.

3. Schlunt Eilber K, Kavalier,E, Rodriguez L, et al.

Ten-year experience with transvaginal vesicovaginal

fistula repair using tissue interposition. J Urol 2003;

169:1033–1036.

4. Tancer, M.L. Observations on prevention and man-

agement of vesicovaginal fistula. J Urol 1980;

123:839–840.

5. Harkki-Siren P, Sjoberg J, Tiitinen A. Urinary tract

injuries after hysterectomy. Obstet Gynecol 1998;

92 (1):113–118.

6. McKay HA, Hanlon K. Vesicovaginal fistula after

cervical carclage: Repair by transurethral suture

cystorrhaphy. J Urol 2003; 169:1086–1087.

7. Chibber PJ, Navinchandra Shah H, Jain P.

Laparoscopic O'Conor's repair for vesico—vaginal

and vesico-uterine fistulae. BJU Int 2005; 96:

183–186.

8. Goodwin WE, Scardino PT. Vesicovaginal and ure-

terovaginal fistulas: A summary of 25 years experi-

ence. J Urol 1980; 123:370–374.

9. Andreoni C, Bruschini H, Truzzi JC, et al. Combined

vaginoscopy—cystoscopy: A novel simultaneous

approach improving vesicovaginal fistula evalua-

tion. J Urol 2003; 170:2330–2332.

10. Cassio A, Bruschini 1H, Truzzi JC, et al. Combined

vaginoscopy—cystoscopy: A novel simultaneous

approach improving vesicovaginal fistula evalution.

J Urol 2003; 170:2330–2332.

11. Kanaoka Y, Hurai., Ishiko O, et al. Vesicovaginal

fistula treated with fibrin glue. Int J Gynecol Obstet

2001; 73:147–149.

12. Zimmern PE, Hadley HR, Staskin DR, Raz S.

Genitourinary fistulae. Vaginal approach for repair

of vesico-vaginal fistulae. Urol Clin North Am

1985; 12:361.

13. Ghoniem GM. Transvaginal repair of recurrent vesi-

covaginal fistula utilizing suburethral sling and mar-

tius grafts. Video-Urology Times, Vol. 5, Program 4,

1992.

14. Sundaram BM, Kalidasan G, Hemal A. Robotic

repair of vesicovaginal fistula: Case series of five

patients. Urology 2006; 67:970–973.

15. Miklos JR, Sobolewski C, Lucente V. Laparoscopic

management of recurrent vesicovaginal fistula. Int

Urogynecol J 1999; 10:116–117.

16. Melamud O, Eicheel B, Turbow B, Shanberg A.

Laparoscopic vesicovaginal fistula repair with

robotic reconstruction. Urology 2005; 65.(1)

17. Melamud O, Eichel B, Turbow B, et al. Laparoscopic

vesicovaginal fistula repair with robotic reconstruc-

tion. J Urol 2005; 65:163–166.

18. Tabakov ID, Slavchev BN. Large post-hysterectomy

and post-radiation vesicovaginal fistulas: Repair by

ileocystoplasty. J Urol 2004; 171:272–274.

Fig. 32.4. Omental interposition

32. Current Concepts and Treatment Strategies for Genitourinary Fistulas 459

19. Eilber KS, Rosenblum N, Rodriguez LV.

Vesicovaginal fistula: Complex fistulae, female urol-

ogy, urogynecology, and voiding dysfunction. New

York: Marcel Dekker, 2005.

20. Richman MB, Goldman HB. Vesicovaginal fistula:

Complex fistulae, female urology, urogynecol-

ogy, and voiding dysfunction. New York: Marcel

Dekker, 2005.

21. Latzko W. Postoperative vesicovaginal fistulas;

Genesis and therapy. Anat J Surg 1942; LVIII(2).

22. Sotelo R, Marandolino B M, Garcia-Segui A, et al.

Laparoscopic vesicovaginal fistula. J Urol 2005;

173:1615–1618.

23. Dolan LM, Easwaran SP, Hilton P. Congenital

vesicovaginal fistula in association with hypoplastic

kidney and uterus didelphys. J Urol 2004; 63(1).

469

Surgical treatment of urinary incontinence has been

excellently described in the previous chapters, includ-

ing inclusive failure rates and complications. Recurrent

incontinence may be seen in as many as 10–40% [1] ,

and although it has decreased considerably during the

last years, it still involves a relatively high number

of patients and deserves special attention. Recurrent

incontinence involves patients with an initially suc-

cessful operation suffering from reoccurrence of

their urinary incontinence but patients with persisting

incontinence due to failure of the surgical procedure

to correct the initial malfunction sufficiently often

are included. All should be handled in the same way

since they present with the same basic problem of

urinary incontinence and anatomical consequences of

previous surgery for urinary stress incontinence.

Recurrent urinary incontinence does not

necessarily mean recurrence of the initial type of

incontinence, but may be due to a wrong diagnosis

up-front or due to the development of a new type of

incontinence, which might be but not necessarily is

caused by the previous surgery. It is therefore man-

datory to do a meticulous evaluation of the patient

before embarking on a new treatment.

Evaluation and Treatment of the

Female Patient with Recurrent

Urinary Incontinence

The evaluation should include [2] :

● General assessment

● Urinary symptom assessment including frequency

volume chart and an assessment of quality of life

and desire for treatment

● Physical examination, abdominal and pelvic

● Cough test to demonstrate stress incontinence if

appropriate

● Urinanalysis ± urine culture

● Assessment of voluntary pelvic floor muscle con-

traction

● Postvoid residual urine assessment

But in the complicated case of the patient with

recurrent incontinence, full urodynamic investiga-

tion, urethrocystoscopy, voiding cystourethrogra-

phy, ultrasound, and in the future possibly even

MRI should be considered.

Different risk factors have been identified for

failure after operations for genuine stress urinary

incontinence: (1) incorrect diagnosis, (2) improper

selection of surgical therapy or faulty surgical tech-

nique, (3) previous bladder neck procedures, which

resulted in urethral and anterior vaginal wall scar-

ring and shortening, (4) preoperative low resting

urethral closure pressure, (5) preexisting detrusor

overactivity, (6) age in association with hypoestro-

genism, and (7) denervation attributed to childbirth

[3] . Patient evaluation therefore should be able to

identify such risk factors in order to allow appro-

priate decision making.

De novo urgency is a feared complication of sur-

gery for stress urinary incontinence. It is not a rare

complication and has been reported in 8% after a

modified Burch colposuspension [4] and in 14.5%

after a tension-free vaginal tape (TVT) procedure

Chapter 34

Recurrent Incontinence

Jørgen Nordling

470 J. Nordling

[5] . In the latter material 11% had both de novo

urgency with urinary incontinence and patients

were as troubled by this as they had been by their

stress incontinence. It is evident that in such cases

it is important to direct the treatment against the

overactive bladder and not the previous malfunc-

tioning closure mechanism.

Before the introduction of the TVT treatment,

it was generally agreed that previous incontinence

surgery impaired the chance of a good outcome

after repeated surgery. The cure rate declined

almost proportionally with the number of pre-

vious surgical procedures for incontinence [3,

6] . Different risk factors for failure of repeated

surgery like detrusor overactivity on preopera-

tive cystometry, low-pressure urethra, fibrotic

urethra, rigid urethra with significant periurethral

scarring, negative Q-tip test, and neurogenic

incontinence were described by Holschneider et

al. [7] . Cure rate in patients without risk factors

was 81.6%, while patients with one or more risk

factors had a cure rate of only 43.8% ( P = 0.005).

In a retrospective study of Amaya-Obu et al. it

was found that cure rates of 77, 73, and 38% were

obtained with a two-team sling procedure after

one, two, and three, respectively, previous incon-

tinence procedures. The corresponding numbers

after a Burch procedure was 81, 25, and 0%. It

was concluded that a Burch procedure should

be avoided after more than one previous inconti-

nence operation. Also Bidmead et al. reported an

81% cure rate after colposuspension for recurrent

incontinence [4] .

This picture has changed completely after the

introduction of the TVT procedure. The first indica-

tion of this change was published by Rardin et al. [8]

in a multicenter study, where cure rate was 87% in

primary surgery in 157 patients and 85% in the recur-

rent stress incontinence population of 88 patients.

Rezapour and Ulmsten reported a similar success rate

of 82% in 34 patients with recurrent incontinence,

where actually a further 9% had significant improve-

ment [9] . Others have not the same high cure rate.

Liapis reported a cure rate 70% in 33 patients with a

better cure rate if patients had sufficient preoperative

urethral mobility (90% cure rate) [10] .

The TVT procedure also has demonstrated good

results after recurrence of incontinence after the TVT

procedure itself. In two cases (with persistent incon-

tinence in one and recurrence in one) a repeated TVT

cured the patients [11] . A shortening procedure for

recurrent or persistent incontinence after TVT was

reported by Lo et al. [4] in five patients with persistent

incontinence and nine patients with recurrent inconti-

nence. Cure rate was 71.4% after 1 year.

Other treatment modalities such as bulking

agents or another type of sling might be tried in the

difficult patient with recurrent stress incontinence.

Evaluation and Treatment

of the Male Patient with Recurrent

Urinary Incontinence

Stress urinary incontinence in the male is almost

always due to previous surgery and especially pros-

tatic surgery. The aetiology is however often multifac-

torial [12] and evaluation must therefore be extensive

before at least surgical treatment is attempted. Primary

treatment involves conservative treatments like pelvic

floor exercise [13] while surgical treatment includes

bulking agents [14, 15, 16] , slings [17, 18] and the

artificial urinary sphincter [19, 20] .

In the case of recurrent incontinence the same

applies as in females, a proper assessment is necessary

to evaluate if the cause of incontinence is due to

another type of incontinence or failure of a previous

operation. The evaluation therefore involves the

following to diagnose a possible detrusor overac-

tivity and/or bladder outlet obstruction:

● Focused history and physical examination

● Urine analysis and culture

● Voiding diary

● Pad test

● Urodynamics

In the case of implanted material filled with

contrast medium a plain film of the abdomen will

demonstrate whether the system has lost fluid.

Cystourethrography might be indicated to demon-

strate fistulas, strictures, or urethral diverticula.

Persistent incontinence after bulking agents or

slings often will lead to a more invasive procedure and

an artificial sphincter will be implanted. Treatment

of recurrent urinary incontinence therefore is

mainly a matter of handling the failed artificial

urinary sphincter [21] .

In the case of the failed artificial urinary sphincter,

the patient presents with persistent or recurrent

incontinence. As in female incontinence the etiol-

ogy for failures varies but an accurate diagnosis is

necessary to handle the problem.

34. Recurrent Incontinence 471

Causes of Persistent or Recurrent

Incontinence After Implantation

of an Artificial Urinary Sphincter

● Urinary tract infection

● Detrusor overactivity

● Initial selection of incorrect cuff size or balloon

pressure

● Urethral atrophy resulting in a too large cuff

● Leakage of fluid from the system

● Cuff erosion

● Device malfunction most often due to valve prob-

lems

● Silicone aging

● Urinary tract infection

A simple cystitis is in many cases the cause of

recurrent incontinence and treatment of the infec-

tion restores normal function. A urine analysis and a

culture therefore always is performed before moving

on to more sophisticated diagnostic procedures.

Detrusor Overactivity

The male population receiving an artificial sphinc-

ter often is elderly because the main indication is

postprostatectomy incontinence. Detrusor overac-

tivity is common in this age group and it is often

difficult to separate the detrusor and sphincter com-

ponent of the urinary incontinence. The restoration

of continence might reveal an overactive bladder

problem in the case with severe stress incontinence

previously hidden by the bladder never getting

filled. The incidence of overactive bladder also

increases with age and de novo urgency inconti-

nence therefore also is a possibility.

Initial Selection of Incorrect Cuff

Size or Balloon Pressure

or Urethral Atrophy Resulting

in a Too Large Cuff

The circumference of the posterior bulbous ure-

thra is difficult to measure because of the sur-

rounding spongious tissue. The best cuff size is

4.0 or 4.5 cm. Larger cuffs will not be able to

compress the urethra sufficiently and will result

in incomplete closure. With time, the tissue inside

the cuff undergoes a considerable atrophy, which

also might cause improper urethral closure. If the

cuff is too large, it is unable to close completely,

and consequently emptying demands more pumps.

Normally one to three pumps is sufficient, but if

that number increases, it is an indication of a too

large cuff. It is possible during urethroscopy to

visualize the incomplete cuff closure and at the

same time rule out cuff erosion. If possible the

cuff should be downsized, but the smallest cuff

size is 4 cm, so something else has to be done.

Relocation of the cuff either proximally or distally

is a possibility in the case of urethral atrophy.

Distal positioning may require a transcorporal

approach [22] . Another possibility is the implan-

tation of a second cuff [23, 24] . Recently, pre-

liminary good results of using an external urethral

bulking agent have been reported [25]

Leakage of Fluid from the System

Leakage might occur at any time and might be

caused by trauma or material fatigue. It is most

often seen from the cuff, but it might happen any

place in the system. If the system has been filled

with contrast medium, a plain X-ray will dem-

onstrate a downsizing of the balloon or an empty

system. Ultrasound also might be used. The leak-

ing part of the system must be changed and it might

be difficult to determine which part is actually

leaking. Intraoperative electrical testing might be

useful [26] , but if in doubt the whole system should

be changed.

Cuff Erosion

Infection or pressure often is the cause of cuff

erosion. Cuff erosion often presents as recurrent

incontinence or pain. It is diagnosed by urethros-

copy and demands explantation of the cuff. A 16-Ch

urethral catheter is left in place for 3–4 weeks and

a new cuff implanted in another location after 3–6

months. In case of severe erosion with circumferen-

tial loss of urethra, a urethroplasty at the time of cuff

explantation might be necessary [21] . Results after

reimplantation is almost as good as after primary

implantation, with a success rate of 82% compared

to 90% after primary implantation [27] .

472 J. Nordling

Device Malfunction Most Often

due to Valve Problems or Aging

If by accident blood has come into the system, clots

will develop. They might circulate in the system

for a while, but when they reach the control unit,

valves or connections will become dysfunctional

and retention or recurrent incontinence will occur.

Inability to pump might be caused by the patient

accidentally inactivating the system. The problem

is easily solved by reactivation.

The artificial sphincter is made of silicone,

a material in many ways similar to glass. It

changes with time, loses elasticity, and eventually

degrades. This means that the implanted sphincter

has a limited lifetime and has to be changed after

10–15 years. Malfunction might appear as recur-

rent incontinence, pump problems, or leakage.

As with females, bulking agents or slings might

be tried if implantation of a urinary sphincter is no

longer possible.

Conclusion

Recurrent incontinence in the male and the female

demands thorough evaluation in order to make an

accurate diagnosis. In the female the introduction

of the TVT and related procedures have made han-

dling of recurrent stress incontinence easier, with a

high cure rate similar to the primary procedure. In

the difficult case, bulking agents or another type of

sling might be indicated.

In the male persistent or recurrent incontinence

after treatment with less invasive procedures such

as bulking agents or slings might be handled by

the implantation of an artificial urinary sphincter.

If this fails, reimplantation almost always is pos-

sible and almost always as successful as primary

implantation.

References

1. Bent AE. Management of recurrent genuine stress

incontinence . Clin Obstet Gynecol 1990 ; 33 (2) :

358 – 366 .

2. Abrams P , Andersson K-E , Brubaker L , et al.

Recommendations of the international scientific

committee in incontinence. In: Abrams P , Cardozo

L , Khoury S , Wein A , eds. Incontinence. Plymouth :

Health Publicatons , 2005 : 1589 – 1630 .

3. Amaye-Obu FA , Drutz HP . Surgical manage-

ment of recurrent stress urinary incontinence: A

12-year experience. Am J Obstet Gynecol 1999 ;

181 (6) : 1296 – 1307 .

4 . Bidmead J , Cardozo L , McLellan A , et al. A com-

parison of the objective and subjective outcomes of

colposuspension for stress incontinence in women .

BJOG 2001 ; 108 (4) : 408 – 413 .

5 . Holmgren C , Nilsson S , Lanner L , Hellberg D .

Frequency of de novo urgency in 463 women who

had undergone the tension-free vaginal tape (TVT)

procedure for genuine stress urinary incontinence

– A long-term follow-up. Eur J Obstet Gynecol

Reprod Biol 2007 ; 132 (1) : 121 – 125 .

6 . Petrou SP , Frank I . Complications and initial conti-

nence rates after a repeat pubovaginal sling proce-

dure for recurrent stress urinary incontinence. J Urol

2001 ; 165 (6 Pt 1) : 1979 – 1981 .

7 . Holschneider CH , Solh S , Lebherz TB , Montz FJ .

The modified Pereyra procedure in recurrent stress

urinary incontinence: A 15-year review. Obstet

Gynecol 1994 ; 83 (4) : 573 – 578 .

8 . Rardin CR , Kohli N , Rosenblatt PL , et-al. Tension-

free vaginal tape: Outcomes among women with

primary versus recurrent stress urinary incontinence.

Obstet Gynecol 2002 ; 100 (5 Pt 1) : 893 – 897 .

9. Rezapour M , Ulmsten U . Tension-free vaginal tape

(TVT) in women with recurrent stress urinary incon-

tinence – A long-term follow up. Int Urogynecol J

Pelvic Floor Dysfunct 2001 ; 12 (Suppl 2) : S9 – S11 .

10 . Liapis A , Bakas P , Salamalekis E , et-al. Tension-

free vaginal tape (TVT) in women with low urethral

closure pressure. Eur J Obstet Gynecol Reprod Biol

2004 ; 116 (1) : 67 – 70 .

11. Riachi L , Kohli N , Miklos J . Repeat tension-free

transvaginal tape (TVT) sling for the treatment of

recurrent stress urinary incontinence. Int Urogynecol

J Pelvic Floor Dysfunct 2002 ; 13 (2) : 133 – 135 .

12 . Andersen JT , Nordling J . Urinary incontinence after

transvesical prostatectomy. Urol Int 1978 ; 33 : 191 –

198 .

13. Hunter KF, Moore KN, Cody DJ, Glazener CM.

Conservative management for postprostatectomy

urinary incontinence. Cochrane Database Syst Rev

2004; (2):CD001843.

14 . Cespedes RD , Leng WW , McGuire EJ . Collagen

injection therapy for postprostatectomy inconti-

nence. Urology 1999 ; 54 (4) : 597 – 602 .

15 . Bugel H , Pfister C , Sibert L , et-al. [Intraurethral

macroplastic injections in the treatment of urinary

incontinence after prostatic surgery.] Prog Urol

1999 ; 9 (6) : 1068 – 1076 .

34. Recurrent Incontinence 473

16 . Hubner WA , Schlarp OM . Treatment of inconti-

nence after prostatectomy using a new minimally

invasive device: Adjustable continence therapy. BJU

Int 2005 ; 96 (4) : 587 – 594 .

17 . Ullrich NF , Comiter CV . The male sling for stress uri-

nary incontinence: 24-month follow-up with question-

naire based assessment. J Urol 2004 ; 172 (1) : 207 – 209 .

18 . Ullrich NF , Comiter CV . The male sling for stress

urinary incontinence: Urodynamic and subjective

assessment. J Urol 2004 ; 172 (1) : 204 – 206 .

19. Montague DK . The artificial urinary sphincter (AS

800): Experience in 166 consecutive patients. J Urol

1992 ; 147 (2) : 380 – 382 .

20 . Klijn AJ , Hop WC , Mickisch G , et-al. The artificial

urinary sphincter in men incontinent after radical

prostatectomy: 5 year actuarial adequate function

rates. Br J Urol 1998 ; 82 (4) : 530 – 533 .

21 . Webster GD , Sherman ND . Management of male

incontinence following artificial urinary sphincter

failure. Curr Opin Urol 2005 ; 15 (6) : 386 – 390 .

22 . Guralnick ML , Miller E , Toh KL , Webster GD .

Transcorporal artificial urinary sphincter cuff place-

ment in cases requiring revision for erosion and ure-

thral atrophy. J Urol 2002 ; 167 (5) : 2075 – 2078 .

23 . Brito CG , Mulcahy JJ , Mitchell ME , Adams MC . Use

of a double cuff AMS800 urinary sphincter for severe

stress incontinence. J Urol 1993 ; 149 (2) : 283 – 285 .

24 . DiMarco DS , Elliott DS . Tandem cuff artificial

urinary sphincter as a salvage procedure following

failed primary sphincter placement for the treatment

of post-prostatectomy incontinence. J Urol 2003 ;

170 (4 Pt 1) : 1252 – 1254 .

25 . Rahman NU , Minor TX , Deng D , Lue TF . Combined

external urethral bulking and artificial urinary

sphincter for urethral atrophy and stress urinary

incontinence. BJU Int 2005 ; 95 (6) : 824 – 826 .

26 . Kreder KJ , Webster GD . Evaluation and manage-

ment of incontinence after implantation of the arti-

ficial urinary sphincter. Urol Clin North Am 1991 ;

18 (2) : 375 – 381 .

27 . Raj GV , Peterson AC , Toh KL , Webster GD .

Outcomes following revisions and secondary

implantation of the artificial urinary sphincter. J

Urol 2005 ; 173 (4) : 1242 – 1245 .

475

Introduction

Pelvic organ prolapse (POP) is a major health care

problem. It was reported to be present in 50% of parous

women [1] , with aggregated rates of prolapse surgery

estimated to be between 15 and 49 per 10,000 women/

years [2] . Olsen et al., reporting data from the Kaiser

Permanent Group, a large health maintenance organi-

zation with nearly 393,000 members which draws

epidemiological data from a service area of more than

2 million people from North America, showed that

the lifetime risk of surgery for POP or stress urinary

incontinence (SUI) was 11.1% for a woman with an

average life expectancy of 79 years [3] .

In the United States, each year approximately

300,000 women require inpatient surgery for POP

or SUI [4, 5] and about 100,000 more procedures

are performed on an outpatient basis [6] . Moreover,

Olsen's study highlighted that 29% of the patients

experienced surgical failure and required repeated

surgical procedures and that the time interval

between reoperation decreased with each suc-

cessive repair [3] . Consequently, each year about

116,000 operations are repeated surgical proce-

dures, showing that the current available treatments

for pelvic floor dysfunction are suboptimal [6] .

The pathophysiology of recurrent POP and SUI

is not clearly understood. Obviously, many risk fac-

tors for pelvic floor dysfunction, such as age, parity,

obstetrical factors, cognitive impairment, or genetic

factors, are unmodifiable and other relevant ones,

such as obesity, smoking habits, or lower urinary

tract dysfunction, can persist after the primary sur-

gery and can be regarded as possible causes of recur-

rence [7] . On the other hand, the effect of multiple

surgeries and dissections on sphincter function, as

well as the chance of neural injuries, can contribute

to the occurrence of further pelvic floor dysfunc-

tion. Specifically, Kenton et al. showed by the use of

urethral electromyography that women with previ-

ous continence surgery had more neural injury to

their striated urethral sphincter than women without

previous surgery after controlling for age and parity

[8] . Other studies hypothesized that pudendal neu-

ropathy or lesions to the somatic urethral innervation

can be caused during vaginal dissection in case of

anterior colporrhaphy, needle suspension, and par-

avaginal repair [9, 10, 11, 12] .

In the treatment of recurrent pelvic floor dys-

function, the available evidence is largely insuf-

ficient due to the lack of long-term results from

randomized controlled trials. Moreover, most of

the low-quality pieces of evidence provide data

only at short- or intermediate-term follow-up.

The present review focuses on the currently

available data and recommendations on diagnostic

workup and treatment of recurrent POP and SUI.

Materials and Methods

We performed a nonsystematic review of the litera-

ture. Data were identified by searching MEDLINE

database, using both MeSH and free text searches.

With regard to recurrent POP, the MeSH search

was conducted using the terms “Prolapse/surgery,”

Chapter 35

Multioperated Recurrent

Incontinence/Prolapse

Giacomo Novara and Walter Artibani

476 G. Novara and W. Artibani

“Prolapse/therapy,” “Uterine Prolapse/surgery,”

“Uterine Prolapse/therapy,” “Rectal Prolapse/sur-

gery,” “Rectal Prolapse/therapy,” “Visceral Prolapse/

surgery,” “Visceral Prolapse/therapy” retrieved from

the MeSH browser provided by MEDLINE. The free

text search employed the following terms through

the field “title and abstract” of the records: “pelvic

organ prolapse,” “rectocele,” “cystocele,” “ante-

rior vaginal wall prolapse,” “posterior vaginal wall

prolapse,” “vaginal vault prolapse,” “colpocele,”

“hysterocele,” “recurr*.” The MEDLINE searches

were pooled and the following search limits were

used: languages (“English”), gender (“Female”),

“humans,” and publication type (“Clinical Trial,

Meta-Analysis, Practice Guideline, Randomized

Controlled Trial, Review, “Clinical Trial, Phase III,”

“Clinical Trial, Phase IV,” Consensus Development

Conference, “Consensus Development Conference,

NIH,” Controlled Clinical Trial, Guideline”).

Regarding recurrent SUI, the MeSH search was

conducted using the terms “Urinary Incontinence,

Stress/surgery,” “Urinary Incontinence, Stress/ther-

apy.” The free text search employed the following

terms through the field “title and abstract” of the

records: “stress urinary incontinence,” “recurr*.”

Once the searches pooled, the following search

limits were used: languages (“English”), gen-

der (“Female”), “humans,” and publication type

(“Clinical Trial, Meta-Analysis, Practice Guideline,

Randomized Controlled Trial, Review, “Clinical

Trial, Phase III,” “Clinical Trial, Phase IV,”

Consensus Development Conference, “Consensus

Development Conference, NIH,” Controlled

Clinical Trial, Guideline”).

One hundred and two records were identified in

the first search and 135 in the second. The full texts

of the papers were reviewed by the authors to select

the studies for the present purposes. In addition,

other significant texts cited in the reference lists of

the selected papers as well as the volumes of the

Third International Consultation on Incontinence

were considered.

Multioperated Recurrent Stress

Urinary Incontinence

The available surgical options for recurrent SUI

include Burch colposuspension, pubovaginal sling,

tension-free vaginal tape (TVT), urethral bulking

agents, placement of an artificial urinary sphincter

(AUS), and as last resort bladder neck closure with

continent catheterizable augmentation.

Burch Colposuspension

Burch colposuspension was the most popular sur-

gical treatment for SUI for decades. However, the

development of the integral theory of continence

as well as the widespread use of the tension-free

slòings, which are less invasive and are followed

by a more favorable profile of complications,

substantially have limited the current indications

for colposuspension. A few papers specifically

addressed the use of Burch colposuspension in the

setting of recurrent SUI. Table 35.1 summarizes

the main clinical data from the available studies on

Burch colposuspension in recurrent SUI. In one of

Table 35. 1. Surgical series using Burch colposuspension in patients with recurrent stress urinary incontinence .

Reference Cases

Nr. previous anti-

SUI procedures

Follow-up

(months) Cure rate (%) Complication rate (%)

Enzelsberger [13] 36 NR 32–48 86 Postoperative LUTS 11

Postoperative POP 16

Cardozo [14]

52

1.2

9

80

Intraoperative (overall) 5.7

Postoperative LUTS 2

Maher [15] 53 2.1 9 89 Postoperative LUTS 10

Amaye-Obu [16] 26 1.5 NR Subj. 88

Obj. 69

Postoperative LUTS 8

Bidmead [17] 32 NR 6–12 Obj. 81 Postoperative LUTS 6

Thakar [18] 56 1.2 48 Subj. 80

Obj. 71

Perioperative (overall) 49

Postoperative POP 20

NR, not reported LUTS, lower urinary tract symptoms POP, pelvic organ prolapse Subj, . subjective cure rate Obj, objective cure rate

35. Multioperated Recurrent Incontinence/Prolapse 477

the largest series, Takar et al. analyzed the efficacy

of the procedure in 56 patients who previously had

undergone a mean of 1.2 surgical procedures for

incontinence, mainly Burch colposuspension or

anterior colporrhaphy. At a mean follow-up of 48

months, 80% of the patients were subjectively and

71% objectively cured. Stratifying the outcome by

the available variables, there was no relationship

between failure rate and maximum urethral clo-

sure pressure, maximum urethral closure pressure

(MUCP) being higher than 20 cm H

2 O in all the

failed patients. Similarly, age, hysterectomy, par-

ity, body mass index, number, and kind of previous

incontinence procedures did not correlate with

patients’ outcomes. Twelve percent of the patients

developed de novo detrusor overactivity but 20%

needed further surgery for POP [18] . Similar suc-

cess rates were provided by Cardozo et al. [14] ,

Maher et al. [15] , and Amaye-Obu et al. [16] .

Further data come from a comparative study

assessing the efficacy of Burch colposuspension

and the dura mater pubovaginal sling [13] . Although

the study was not randomized, the authors analyzed

two small series of patients with similar preopera-

tive characteristics, demonstrating similar success

rates (86% for Burch colposuspension vs. 92%

for sling) and similar perioperative complications.

However, patients undergoing sling procedure had

a significantly higher risk of storage (16% vs. 8%)

and voiding (13% vs. 3%) symptoms but lower

incidence of POP (3% vs. 13%) [13] .

However, the limited follow-up of those studies

did not allow us to draw a definitive conclusion on

the long-term efficacy of Burch procedure, as well

as on the related complications. The available lit-

erature on Burch colposuspension as primary treat-

ment of SUI indeed clearly showed that cure rates

decreased with time and that a percentage of patients

as high as 75% can experience lower urinary tract

symptoms [19] . Moreover, the patients analyzed in

such old reports are quite different from those cur-

rently treated for recurrent SUI, due to the declining

number of colposuspension performed as primary

treatment since the widespread use of TVT.

Pubovaginal Sling

In 1995, De Lancey proposed the hammock hypoth-

esis, suggesting that in the continent patient, the

intra-abdominal pressure compresses the urethra

against a stable, supporting layer and surgical tech-

niques that reconstruct this supportive layer would

effectively cure SUI [20] . Those concepts prompted

many urogynecologists to recommend sling proce-

dures to reestablish the hammock mechanism in

all cases of SUI. These observations, together with

the poor clinical results for patients with internal

sphincter deficiency, led to the use of the sling as

the most appropriate surgical technique for SUI.

Its effectiveness is based on the correction of the

hypermobility of the urethra or the coaptation of

the mucosa near the bladder neck, promoting a

sealing effect with no obstruction of the urethra in

situations of increased abdominal pressure [21] .

The traditional suburethral sling operation

requires a combined abdominal and vaginal

approach. Strips of material are tunneled under

the urethra. They are attached either to the rectus

muscle or the ileopectineal ligaments resulting in a

tightening of the sling and increased bladder sup-

port every time the woman strains [22] .

The materials that have been used for slings may

be biological or synthetic. Autologous biological

materials include rectus fascia, fascia lata, pubo-

coccygeal muscle, vaginal wall, aponeurosis, and

pyramidalis fascia. Exogenous biological materials

include fascia and porcine dermis. Synthetic mate-

rials include Teflon, Mersilene, Lyodura, poly-

tetrauoroethylene (Gore-Tex), Marlex, Silastic, and

polypropylene [22] . Autologous rectus fascia and

fascia lata were the most common materials in use

until recently and were reported to be associated

with high cure rate and low complications [23] .

On the other hand, there are several advantages in

the use of synthetic slings, such as the reduction in

the morbidity of harvesting from a second surgical

site, shortened operative time, early postoperative

patient recovery, and an unlimited supply of arti-

ficial materials [23] . These issues have led to an

increase in the number of sling procedures and the

use of synthetic material. Although polypropylene

meshes had been shown to have low incidence

of complications, the use of prosthetic materials

raises concerns about the potential occurrence of

both sling erosions and infections.

Several papers addressed the use of both autolo-

gous and synthetic sling in patients with recurrent

SUI. Tables 35.2 and 35.3 summarize the most

important studies analyzing the use of autologous

(Table 35.2 ) and synthetic (Table 35.3 ) sling in

478 G. Novara and W. Artibani

Table 35. 2. Surgical series using autologous sling in patients with recurrent stress urinary incontinence .

Reference Material Cases

procedures

Follow-up

(months)

Cure rate

(%) Complication rate (%)

Enzelsberger [13]

Dura mater

36

NR

32–48

92

Postoperative LUTS 29

Postoperative POP 3

Beck [24] Fascia lata 170 NR NR 98.2 NR

Breen [25]

Fascia lata

72

2.1

6–38

Subj. 90

UTI 17

CIC 30

Abscess 3

Kaplan [26]

Rectus sheath

43

1.6

23.4

95

Infection 14

CIC 12

LUTS 14

Kane [27]

Rectus sheath anchor sling

13

1.4

26

Subj. 100

Obj. 92

Postoperative LUTS 15

Petrou [28]

Rectus or fascia lata

14

NR

17

Subj. 86

Obj. 50

Abscess 7

Osteitis pubis 7

Juma [29] Vaginal wall 65 NR 23.9 94 CIC 5.5

LUTS 14.8

Pidutti [30] Vaginal wall 12 NR 17.3 92 a NR

Couillard [31] Vaginal wall 18 NR 18 100 CIC 6

Kaplan [26]

Vaginal wall

36

1.3

23.4

97

CIC 3

Infection 3

LUTS 8

Raz [32] Vaginal wall

160

2.8

17

93

Infections 3

Postoperative POP 1

LUTS 5

Litwiller [33]

Vaginal wall

33

1.1

31

74 a

Hematoma 2

Postoperative POP 3

CIC 12

Dyspareunia 4

Chronic pelvic pain 2

Su [34] Vaginal wall 23 1 15 Subj. 61 Epithelial inclusion

cysts 13

Obj. 35

NR, not reported LUTS, lower urinary tract symptoms POP, pelvic organ prolapse Subj,. subjective cure rate Obj,. objective cure

rate CIC, clean intermittent catheterization UTI, urinary tract infection

aCured or improved

Table 35. 3. Surgical series using prosthetic sling in patients with recurrent stress urinary incontinence .

Reference Material Cases

Previous anti-

SUI procedures

Follow-up

(months) Cure rate (%) Complication rate (%)

Morgan [35] Marlex 281 NR 60 77.4 NR

Amaye-Obu [16] Marlex 45 1.3 NR Subj. 89 CIC 2

Obj. 69 Postoperative POP 4

Erosion 2

Morgan [36] Polypropylene 88 1.6 49.7 85.2 UTI 5.7

CIC 3

Dyspareunia 3

Hematoma 3

Rutman [37] Polypropylene 69 a 1.4 60 Subj. 88 Postoperative LUTS 7

Rutman [38]

Polypropylene

(spiral sling)

47

2.6

12

68 b Postoperative (overall) 1.9

Postoperative LUTS 7

NR, not reported, LUTS , lower urinary tract symptoms, POP , pelvic organ prolapse, Subj . subjective cure rate, Obj . objective cure

rate, CIC clean intermittent catheterization, UTI urinary tract infection

aOnly 52% with recurrent SUI

bCured or improved

35. Multioperated Recurrent Incontinence/Prolapse 479

patients with recurrent SUI.There is a considerable

volume of literature on autologous slings, mainly

in the setting of primary anti-incontinence proce-

dure, demonstrating high objective and subjective

cure rates (about 85%) at long-term follow-up.

However, although more recent studies reported

lower figures, long-term voiding dysfunctions can

occur in 30% of the patients. On the other hand,

both rectus fascia and fascia lata were proved to

be safe materials, with only a few cases of erosion

being reported [39] . Pubovaginal slings are associ-

ated with higher morbidity and longer convales-

cence compared to other vaginal procedures.

Only a few papers were retrieved that assessed

the role of rectus fascia and fascia lata in the set-

ting of recurrent incontinence. Although previous

surgery leads to significant scarring around the ure-

thra, rendering tissue planes less recognizable and

reoperation somewhat more difficult, those studies

reconfirmed the high efficacy of pubovaginal sling

procedures, with objective and subjective success

rates ranging between 50 and 100%. Similarly,

even complication rates, including long-term void-

ing dysfunction and need for clean intermittent

self-catheterization (CISC) (15–30%) were within

acceptable ranges (Table 35.3 ).

Interestingly, even patients who had failed a

previous pubovaginal sling can be considered

candidates for further similar procedures. Failure

of a previous sling can be due to several reasons,

including sling material failure, sling suture break-

age, poor sling position, and inadequate urethral

coaptation due to the sling [28] . However, in the

words of Petrou and Frank, it might be difficult to

“resist to the temptation to overtighten the sling

secondary to the concern that the original sling was

tight enough” [28] .

Several published papers addressed the efficacy

of vaginal wall slings in the setting of recurrent

SUI. Compared to the traditional sling procedures,

the advantages of the vaginal wall sling procedure

were reported to be less tissue dissection, and con-

sequently less neurovascular damage, and simpler

surgical procedure with at least the same success

rate. In addition, indigenous material is superior

to allogenic material, with less infection, rejection,

and urethral erosion. Success rates of this tech-

nique were reported to range from 74 to 100%.

In the attempt to reduce the morbidity of harvest-

ing fascia, improving effectiveness, and decreas-

ing complications, newer techniques have been

described which use different materials. Among

these the most popular currently is polypropylene,

which has been proven to have long-term efficacy

and safety.

Morgan et al., analyzing a series of 88 patients

who had previously undergone 1.4 continence pro-

cedures, reported success rates as high as 85% at

a follow-up of about 50 months [36] . Similar data

were provided by Rutman et al. [37] . Interestingly,

these studies reported favorable complication rates,

with rates of postoperative lower urinary tract

symptoms, needs for CISC, and urinary tract infec-

tions below 10% [36, 37] .

An innovative approach to the surgery for recur-

rent SUI recently was reported by Rutman et al.

[38] . The authors used a spiral polypropylene pub-

ovaginal sling, placed at the level of the proximal

urethra. A complete circle of mesh was created

around the urethra, folding the sling spirally. The

technique was employed as salvage therapy in

those patients with multiple failed surgeries and

an incompetent “lead pipe” urethra. The authors

reported preliminary results on 47 patients who had

previously undergone a mean of 2.6 incontinence

procedures. At a mean follow-up of 12 months,

65% reported never having symptoms of SUI and

87% reported symptoms of SUI never or less than

once weekly. On the UDI-6 questionnaire, 95%

reported never or rarely being bothered by SUI.

Moreover, the mean number of pads decreased

from 6.0 before surgery to 0.9 postoperatively

( P < 0.005). Those figures were paralleled by a

quality of life score related to urinary symptoms,

which was as low as 1.4, indicating that patients

were between “pleased” and “mostly satisfied.”

These results, which are encouraging considering

the baseline patient characteristics, were associ-

ated with low rates of postoperative complication

(1.9%) and de novo urge incontinence (7.4%).

Moreover, no patients needed CISC or experienced

urethral or vaginal erosion [38] .

Tension-Free Vaginal Tape

The advent of TVT was a major revolution in the

management of SUI, because it offered patients a

surgical procedure with reduced morbidity, a low

complication rate, and high intermediate-term effi-

cacy [40] . Following the initial encouraging reports

of the use of the TVT as a primary treatment of

SUI, a few groups attempted its use in patients

480 G. Novara and W. Artibani

who had failed previous anti-incontinence surgery.

Table 35.4 summarizes the data from the main

reports concerning the use of TVT in patients with

recurrent SUI.The series with the largest follow-up

was reported by Rezapour et al., who pioneered the

development of the procedure [41] . The authors

assessed 34 patients with recurrent SUI at a mean

follow-up of 48 months, showing that 82% of the

patients were cured (urinary leakage <10 g/24 h

pad test; negative stress test; patients satisfaction

>90% at the quality of life evaluation) and a further

9% significantly improved after surgery. Moreover,

the authors reported a low complication rate (a sin-

gle case of bladder perforation in a patient who had

been operated on three times with the Marshal–

Marchetti–Krantz procedure) and emphasized that

there was no significant decline in the results along

the follow-up [41] .

Similar results were reproduced by other series

with shorter follow-up duration [42– 47] ; the

study by Abdel-Hady et al. was the largest one

and included 118 cases [47] . The data clearly

showed that TVT procedure can be safely and

efficaciously performed in patients with recurrent

SUI, even outside reference centers. Interestingly,

even patients with urethral hypermobility and low

Valsalva leak point pressure (VLLP) (<60 cm

H

2 O) had very high cure rate (86%) [47] , while

those with reduced urethra mobility (Q-tip test

<30°) had unfavorable outcome (failure rate 50%)

[46] . Consequently, these findings suggested that

patients with recurrent SUI and concomitant ure-

thral hypermobility can be best treated by TVT, in

spite of concomitant intrinsic sphincter deficiency.

No data are currently available on tension-free

trans-obturator tapes in the setting of patients with

recurrent SUI.

Bulking Agent Injection

Urethral mucosal coaptation, due to properties of

the mucosa as well as to the presence of submu-

cosal vascular cushions and the activity of smooth

muscle cells, is considered an important compo-

nent of the mechanism of urinary continence in

women. Failure of this component can play a role

in the development of stress incontinence [48] .

The injection of bulking agents into the urethral

submucosa is designed to create artificial urethral

cushions that can improve urethral coaptation, and

hence restore continence.

Due to the short length of the female urethra,

the technique for administering periurethral bulk-

ing agents by injection for treatment of stress

incontinence is simple, minimally invasive, and

can be performed under local anesthesia, even on

an outpatient basis. The agent is injected into the

submucosa at two or more sites at the level of the

proximal urethra under endoscopic control, which

is considered mandatory to allow accurate place-

ment of the substance into the submucosa layer and

demonstrate adequate expansion.

Currently no ideal material to inject exists. A

urethral bulking agent should be nonimmunogenic

and biocompatible, leading to minimal inflamma-

tory and fibrotic response. The particles that make

Table 35. 4. Surgical series using TVT in patients with recurrent stress urinary incontinence.

Reference Cases

Previous anti-SUI

procedures

Follow-up

(months)

Cure rate

(%)

Improvement

rate (%) Complication rate (%)

Rezapour [41] 34 1.2 48 82 9 Perioperative (overall) 2.9

Riachi [42] 2 1.5 9.5 100 – 0

Lo [43] 41 1.3 16 82.9 4.8 Perioperative (overall) 9.8

Postoperative LUTS 4.9

Rardin [44] 88 1.3 9.5 85 4.5 Perioperative (overall) 4.5

Postoperative LUTS 5.5

Kuuva [45] 51 1.2 25.3 89.6 6.2 Bladder perforation 5.9

Postoperative LUTS 5.9

Urinary tract infection 5.9

Liapis [46] 33 1.2 20.5 70 6 Urinary retention 9

Urinary tract infection 6

Abdel-Hady [47] 118 NR 6 89 11 NR

NR not reported, LUTS , lower urinary tract symptoms

35. Multioperated Recurrent Incontinence/Prolapse 481

Table 35.5. Surgical series of injectable bulking agents in patients with stress urinary incontinence .

Reference Cases

Follow-up

(months) Cured (%)

Cured or

improved (%) Injection sessions

Glutaraldehyde cross-linked collagen

Eckford [49] 25 3 64 80 1.7

Herschorn [50] 31 8.4 48 90 2

O’Connell [51] 44 NA 45 63 1.5

Monga [52] 29 24 48 68 1.6

Richardson [53] 42 46 40 83 2

Herschorn [54] 187 22 23 75 2.5

Faerber [55] 12 10 83 100 1.25

Kreder [56] 22 NA 40 NA NA

Smith [57] 94 14 38 67 2.1

Haab [58] 22 7 24 86 1.9

Khullar [59] 21 7 48 57 NA

Cross [60] 139 18 NA 74 NA

Corcos [61] 40 48 30 70 NA

Groutz [62] 63 6.4 13 40 2.1

Winters [63] 58 2 48 79 1.9

Lightner [64] 68 12 NA 69 1.5

Bent [65] 58 12 33 66 NA

Autologous fat

Santarosa [66] 12 18 NA 57 2.4

Trockman [67] 32 NA NA 56 1.6

Su [68] 26 12 NA 65.4 1

Haab [58] 45 7 14 43 1.7

Lee [69] 27 3 NA 22 3

Teflon

Politano [70] 51 6 NA 71 1.8

Lim [71] 28 12 21 75 1

Schulman [72] 56 3 NA 86 1–3

Deane [73] 28 3 NA 61 NA

Osther [74] 26 NA NA 50 NA

Lockhart [75] 20 NA NA 90 1.8

Vesey [76] 36 NA NA 67 1–2

Kiikholma [77] 22 60 NA 18

Lopez [78] 128 31 54 73 1.5

Herschorn [79] 46 17.9 30.4 71.7 2

Silicone

Koelbl [80] 32 12 60 NA 1

Barranger [81] 21 31 19 48 NA

Peeker [82] 15 24 68 87 1.3

Tamanini [83] 21 12 57 76 1.4

NA, n ot available

up the agent should be sufficiently large to prevent

migration from the site of injection and suffi-

ciently durable to maintain the clinical efficacy over

time. The list of currently available agents includes

autologous fat, polytetrauroethylene (Polytef™),

glutaraldehyde cross-linked bovine collagen

(Contigen™), Silicon particles (Macroplastique™),

carbon beads (Durasphere™), calcium hydroxylapa-

tite (Coaptite™), ethylene vinyl alcohol copolymer

(Uryx™), and several other agents under investiga-

tion in phase II and III trials. The main limitation of

the available bulking agents concerns the long-term

efficacy, which in almost all the series is suboptimal,

due to absorption or migration of the particles from

the implant site, leading to the need for repetitions

of the procedure.

Several papers have been published assessing

the role of bulking agents in SUI (Table 35.5 ).

The largest series, reported by Herschorn et al. in

1996, included 187 patients treated by the injection

482 G. Novara and W. Artibani

of glutaraldehyde cross-linked bovine collagen

(Contigen™). At a median follow-up of 22 months,

only 23% turned out to be cured, although about 50%

of them had subjectively improved [54] . Although

several series reported significantly higher success

rates, the overall methodological quality of the availa-

ble pieces of evidence was weak, due to study design,

short follow-up, inaccurate outcome definitions, and

so on [39] . In this context, injection of a bulking agent

can be considered a possible option for patients with

recurrent SUI mainly because of the limited morbid-

ity, but patients should be informed of the limited

long-term efficacy.

Artificial Urinary Sphincter

The last chance to achieve urinary continence

maintaining physiological voiding habits is the

placement of an AUS, the AMS-800 being the most

widespread device. The standard approach to the

insertion of the AUS in a female patient requires

a suprapubic incision into the preperitoneal space.

Once the space of Retzius is developed, the blad-

der neck is dissected and measured. A fitted cuff

is placed around the bladder neck and the pump

placed into a pocket created in the labia majora.

The reservoir is placed in the standard preperi-

toneal space behind the rectus abdominis (see

Fig. 35.1 ). Another approach uses a transvaginal

incision. The bladder neck can be dissected from

the anterior vaginal vault and the urethra is cir-

cumferentially freed and appropriately sized. Strict

antisepsis with copious antibacterial irrigation also

should be used during the procedure. By dissecting

into the labia through the same vaginal incision

the cuff and pump are easily placed but a small

infraumbilical incision may be required to place

the reservoir [84] .Although the overall experience

with AUS is far greater in male patients, several

series of implanted female patients have been pub-

lished (Table 35.6 ). However, in most cases, the

patients had incontinence due to different causes,

often including neurogenic dysfunction, without

any stratification of the data.

As shown in Table 35.6 , the reported continence

rates were quite high, ranging from 52 to 100%.

Although in some series complications were virtu-

ally absent, revision rates due to erosions, infec-

tions, or mechanical failure were shown to be quite

high in most of the experiences. Even in the most

recent publications, revision rates ranged from 25

to 50%. In one of the series with a longer follow-

up, Petero et al. reported data on 55 patients where

80 AMS-800 had been implanted. Satisfactory

continence was achieved in 84% of the patients,

with 64% wearing no pad and 7% a single one.

Revisions were needed, in fact, in 35% of the

patients and 9% required sphincter explantation.

The overall median duration of the device was

11.2 ± 1.19 years [98] .

When other kinds of incontinence surgery have

failed, placement of AUS can be regarded as a very

effective procedure in selected cases. The overall cure

rates are acceptable, although the risk of complica-

tions and need for reoperation increases with follow-

up durations and patients should be clearly informed.

Recommendations for Assessment and

Treatment of Recurrent Stress Urinary

Incontinence

Assessment of the patients with recurrent incon-

tinence has to be as accurate as possible, always

including evaluation of quality of life impairment,

comprehensive urodynamics, with pressure-flow

studies, urethral profilometry, and whenever feasible,

videourodynamics to visualize the bladder cycle

under fluoroscopy. Although not extensively studied,

translabial or introital ultrasound scans are emerging

Fig. 35.1. Implanted artificial urinary sphincter in female

patients

35. Multioperated Recurrent Incontinence/Prolapse 483

as reliable techniques to evaluate bladder neck posi-

tion and mobility, as well as the morphology of rhab-

dosphincter and pelvic floor muscle activity.

Due to the lack of well-performed, randomized,

controlled studies the recommendations for treat-

ments of the patients with recurrent SUI have to

be based on low-quality evidence only, often an

expert's opinion only. The choice among the avail-

able surgical options has to be founded on the

expectations, wishes, comorbidity and life expect-

ancy of the patients, severity of the stress inconti-

nence, quality of life impairment, kind and number

of the previously failed anti-incontinence proce-

dures, and, whenever possible, pathophysiology of

the stress recurrent incontinence.In case of patients

with mild incontinence, low impact on quality of

life, and/or limited life expectancy or significant

comorbidity, the most suitable surgical option is

likely the injection of a bulking agent, which pro-

vides acceptable short-term efficacy but very low

perioperative and long-term complication rates.

When urethral hypermobility is thought to play a

major role in recurrent incontinence, tension-free

midurethral slings, such as TVT, can allow quite

high success rates with an acceptable risk of inter-

mediate-term complications, even in patients with

clues of sphincter deficiency. However, data of the

literature do not allow drawing definitive conclu-

sions on the efficacy of a further TVT procedure

after failure of previous tension-free midurethral

slings and prospective studies are strongly recom-

mended in the field.

Pubovaginal slings are very effective anti-incon-

tinence procedures in the setting of recurrent

incontinence, also in patients with intrinsic sphinc-

ter deficiency. However, the risk of postoperative

lower urinary tract symptoms needing clean inter-

mittent self-catheterization is high and the patients

should be clearly aware of such potentially frustrat-

ing conditions before surgery.

For the patients who had failed all the above-

mentioned surgical solution, AUS is the only chance

to preserve micturition and regaining urinary con-

tinence. Indeed, the long-term risk of complica-

tions needing reoperation can be as high as 50%.

Consequently, the patient candidates for placement

of an AUS have to be highly motivated, with suffi-

cient mental and manual skill to allow adequate use

of the device, ideally with limited comorbidity and,

due to the costs, good life expectancy.

Table 35. 6. Surgical series of artificial urinary sphincter in female patients .

Reference Cases Cure rate (%) Complication rate (%) Revision rate (%)

Scott [85] 139 Socially continent 91 Infection 3 NR

Dry 66 Erosion 4

Light et al. [86] 39 92 Infection 2.5 54

Erosion 7

Donovan [87] 31 68 Erosion 29 32

Diokno [88] 32 91 Dehiscence 3 21.8

Pelvic abscess 3

Abbassian [89] 4 100 0 NR

Appell [90] 34 100 0 8.9

Duncan [91] 29 52 Infection 3.5 3.5

Erosion 28

Webster [92] 25 92 Postoperative death 4 16

Infection/erosion 0

Costa [93] 54 93 Infection 2 NR

Erosion 6

Hadley [94] 18 89 Erosion 11 NR

Stone [95] 54 84 Erosion 6 20

Thomas [96] 18 82 Erosion/infection 28 50

Ngninkeu [97] 4 Socially continent 100 Erosion 0 25

Dry 75

Petero [98] 55 84 Erosion 12 44

NR, not reported

484 G. Novara and W. Artibani

Bladder neck closure with continent catheter-

izable augmentation has to be considered as the

last resort for the patients who have failed all the

options allowing preservation of the micturition,

including artificial sphincter or unwilling or unfit

for sphincter implantation.

Multioperated Recurrent Prolapse

In case of POP recurrence, repeated prolapse repair,

with or without mesh graft can be performed. In

selected cases, however, colpectomy and colpoclei-

sis can provide a definitive solution to prolapse. As

stated, the available evidence is largely insufficient,

due to the lack of randomized, controlled trials in

patients with recurrent POPs.

Mesh Graft

The ideal prosthetic material should be biocompat-

ible, inert, have minimal allergic or inflammatory

reaction, be sterile, noncarcinogenic, resistant to

infection, and should avoid shrinkage and mechan-

ical stress while being easy to handle and readily

available at a reasonable cost [99] . As to the physi-

cal properties of the prosthesis, Amid suggested

a classification based mainly on the porosity and

filament type. Type 1 meshes (Atrium, Marlex,

Prolene and Trelex) have pore size >75 nm, which

allows the infiltration by macrophages, fibroblasts,

collagen fibers, and angiogenesis, reducing the risk

of infection, extrusion, or erosion of the prosthetic

material. Moreover, materials with large pores

have lower stiffness, reducing tissue trauma and

erosive risk. Type II meshes (Gore-Tex), indeed,

are microporous, with pore size is <10 nm, which

presents a barrier to new tissue formation. Type III

meshes (Teflon, Mersilene, SurgiPro) are macro-

porous materials with multifilamentous or micro-

porous components, while type IV grafts (Silastic,

Cellgard) had submicronic pores [100] .

With regard to the mesh in anterior vaginal wall

prolapse repair, Julian and colleagues published an

interesting randomized, controlled trial (RCT) in

which the use of Marlex mesh was assessed in a

cohort of 24 patients with recurrent anterior vaginal

wall prolapse [101] . The authors demonstrated sig-

nificantly better outcomes in patients where mesh

grafts were used (recurrence rate 0% vs. 34%),

but mesh erosion occurred in 25% of the patients,

requiring surgical excision [101] . Further trials were

subsequently published, mainly in the setting of pri-

mary prolapse repair. In 2001, Sand et al. reported

significantly higher objective success rates in the

anterior vaginal wall repair with the use of Vicryl

mesh (75% vs. 57%), without any mesh-related

complication [102] . A nice RCT recently was

published by Gandhi et al., assessing the efficacy

of a patch of cadaveric fascia lata in an adequately

powered cohort of patients with recurrent anterior

vaginal wall prolapse [103] . At a median follow-

up of 13 months, the authors showed similar rates

of prolapse recurrence (21% in the patch group

and 29% in the control group), failing to show any

statistically significant benefit for biological graft

in anterior vaginal repair [103] . However, the short

follow-up time and the lack of reliable data regard-

ing reoperation and complication rates limited the

quality of the evidence. A few large retrospective

surgical series, in fact, reported very high cure rates

(75–100%) associated with acceptable low inci-

dence of infections, erosion, fistula formation, and

other mesh-related complications (0–16%) [104] ,

supporting the use of synthetic type I mesh graft in

the setting of recurrent cystocele repair.

As with anterior vaginal wall defects, the use

of mesh in the treatment of vaginal vault prolapse

is not adequately established. A landmark RCT

recently was published by Culligan et al., who

compared cadaveric fascia lata and polypropyl-

ene mesh in a cohort of 100 patients undergoing

abdominal colposacropexy for posthysterectomy

vaginal vault prolapse. At a median follow-up of 12

months, the authors demonstrated higher success

rates in the mesh arm (91% vs. 68%) [105] . Data

on mesh-related complications were not provided

in the report, but a large review on abdominal col-

posacropexy reported only 70 cases of mesh ero-

sion out of 2178 procedures (3.4%). In that review,

specifically, cadaveric fascia and Prolene mesh

were followed by very low rates of erosion (0 and

0.5%, respectively) [106] . Those figures, as well

as the failure rates in the surgical series employing

fascia in sacrocolpopexy, might support the use of

polypropylene mesh graft in this setting.

In the context of recurrent posterior vaginal wall

prolapse, the available evidence, based on two

RCT [102, 107] , discourages the use of homologous,

autologous, or synthetic meshes in posterior repair.

35. Multioperated Recurrent Incontinence/Prolapse 485

Obliterative Procedures

This kind of operation is indicated in the case of

recurrent or high-stage POP, when operating time

has to be kept to the minimum and patients no

longer wish to preserve coital function. A total

colpocleisis usually refers to the removal of the

majority of the vaginal epithelium from within

the hymenal ring posteriorly and to within 0.5–

2.0 cm of the external urethral meatus anteriorly

(Fig. 35.2 ). In partial colpocleisis, some portion of

the vaginal epithelium is left in place, providing

drainage tracts for cervical or other upper genital

discharge using the technique of LeFort or modifi-

cations of LeFort (Fig. 35.3 ) [108] .Several surgical

series have been published. Table 35.7 summarizes

the data from the contemporary series of partial

and total colpocleisis. As shown in Table 35.7,

prolapse recurrence rates after colpocleisis are very

low, below 10%, and complication rates are quite

favorable. However, in some series certain major

complications, such as vesical injury, ureteral

occlusion, and sepsis, have been reported.

Conclusions

Recurrent SUI and POP are clinical conditions

that represent a considerable challenge for both

patients and physicians. The patients require a

complete preoperative assessment. Urinary tract

imaging always should be performed, including

ultrasonography, voiding cystourethrography, or,

ideally, MRI, which was proven to have significant

accuracy in the assessment of both pelvic organs

and the pelvic floor structures. In the meantime,

urodynamics or, better, videourodynamics should

be performed in each case, aimed at assessing

Fig. 35.2. Schematic representation of total colpectomy. ( a , b ) The vagina is circumscribed by an incision at the site

of the hymen and marked into quadrants, which is removed by sharp dissection. ( c ) Purse string sutures are placed.

( d ) The sutures are tied. ( e ) A perineorrhaphy may complete the operation

486 G. Novara and W. Artibani

Fig. 35.2. (continued)

the presence of detrusor overactivity, intrinsic

sphincter deficiency, and all the characteristics of

the voiding pattern, as well as the impact of pro-

lapse on the lower urinary tract function.Several

surgical options are currently available for the

treatment of recurrent stress incontinence, pub-

ovaginal sling, TVTs, and bulking agents being

the most frequently used approaches. Despite the

limited availability of randomized controlled tri-

als and even nonrandomized controlled studies to

provide an evidence-based approach for this type

of patient, the published data clearly suggest that

those procedures can be safely and efficaciously

used, although TVTs and bulking agents are by far

less invasive than the other procedures. The roles

of AUS and, as a last resort, bladder neck closure

35. Multioperated Recurrent Incontinence/Prolapse 487

Fig. 35.3. Schematic representation of partial colpocleisis. ( a ) Anterior vaginal wall is removed and plication stitches

are placed at the bladder neck. ( b ) Posterior vaginal wall is removed. ( c , d ) Edges of anterior and posterior vaginal

walls are sewn to invert uterus and vagina

488 G. Novara and W. Artibani

Table 35.7. Contemporary series of colpocleisis .

Reference Cases

Follow-up

(months) Cure rate (%) Complication rates (%)

Langmade [109] 102 12–144 100 Sepsis 1

Denehy [110] 20 4–40 95 UTI 15

DeLancey [111] 33 35 97 UTI 6

Cespedes [112] 38 24 100 0

Harmanli [113] 41 28.7 100 Vesical injury 2

Late rectal bleeding 10

Von Pechmann [114] 62 12 97 Transfusion 22

Ureteral occlusion 4

Moore [115] 30 19 90 0

Fitzgerald [116] 64 2–56 97 Vaginal hematomata 3

One postoperative death due to

multisystem organ failure (1.5)

Glavind [117] 42 46 90 0

NA, not available, UTI, urinary tract infections

and continent catheterizable augmentation are lim-

ited to those patients who have failed all the other

options and who have significant quality of life

impairment due to urinary problems.

The data available on recurrent POP are even

more limited. Further repair with mesh augmenta-

tion is the most common option, with partial or

total colpocleisis limited to frail patients not wish-

ing to preserve coital function.

References

1. Beck RP, McCormick S, Nordstrom L. A 25-year

experience with 519 anterior colporrhaphy proce-

dures. Obstet Gynecol 1991; 78(6):1011–1018.

2. Hunskaar S, Burgio K, Ckark A, et al. Epidemiology

of urinary (UI) and faecal incontinence. In: Abrams

P, Cardozo L, Khoury S, Wein A, eds. Incontinence,

3rd International Consultation on Incontinence.

Plymouth: Health Publication 2005:255–312.

3. Olsen AL, Smith VJ, Bergstrom JO, et al.

Epidemiology of surgically managed pelvic organ

prolapse and urinary incontinence. Obstet Gynecol

1997; 89:501–506.

4. Boyles SH, Weber AM, Meyn L. Procedures for

pelvic organ prolapse in the United States, 1979–

1997. Am J Obstet Gynecol 2003; 188:108–115.

5. Boyles SH, Weber AM, Meyn L. Procedures for

urinary incontinence in the United States, 1979–

1997. Am J Obstet Gynecol 2003; 189:70–75.

6. DeLancey JOL. The hidden epidemic of pelvic

floor dysfunction: Achievable goals for improved

prevention and treatment. Am J Obstet Gynecol

2005; 192:1488–1495.

7. Hunskaar S, Bugio K, Clark A, et al. Epidemiology

of urinary and faecal incontinence and pelvic organ

prolapse. In: Abrams P, Cardozo L, Khoury S, Wein

A, eds. Incontinence. Plymouth: Health Publication

2005:255–312.

8. Kenton K, Mahajan S, FitzGerald MP, et al. Recurrent

stress incontinence is associated with decreased neu-

romuscular function in the striated urethral sphincter.

Am J Obstet Gynecol 2006; 194:1434–1437.

9. Ball J, Teichman J, Sharkey F, et al. Terminal

distribution to the urethra and bladder neck:

Considerations in the management of stress urinary

incontinence. J Urol 1997; 158:827–829.

10. Borirakchanyavat S, Aboseif S, Carroll P, et al.

Continence mechanisms of the isolated female

urethra: An anatomical study of the intrapelvic

somatic nerves. J Urol 1997; 158:822–826.

11. Benson J, McClellan E. The effect of vaginal dis-

section on the pudendal nerve. Obstet Gynecol

1993; 82:387–389.

12. Zivkovic F, Tamussino K, Ralph G, et al. Long-

term effects of vaginal dissection on the inner-

vation of the striated urethral sphincter. Obstet

Gynecol 1996; 87:257–260.

13. Enzelsberger H, Helmer H, Schatten C. Comparison

of Burch and Lyodura sling procedures for repair of

unsuccessful incontinence surgery. Obstet Gynecol

1996; 88:251–256.

14. Cardozo L, Hextall A, Bailey J, et al. Colposuspension

after previous failed incontinence surgery: A prospec-

tive observational study. BJOG 1999; 106:340–344.

15. Maher C, Dwyer P, Carey P, et al. The Burch

colposuspension for recurrent urinary stress incon-

tinence following retropubic continence surgery.

BJOG 1999; 106:719–724.

35. Multioperated Recurrent Incontinence/Prolapse 489

16. Amaye-Obu FA, Drutz HP. Surgical management

of recurrent stress urinary incontinence: A 12-year

experience. Am J Obstet Gynecol 1999; 181:

1296–1309.

17. Bidmead J, Cardozo L, McLellan A, et al. A com-

parison of the objective and subjective outcomes of

colposuspension for stress incontinence in women.

BJOG 2001; 108:408–413.

18. Thakar R, Stanton S, Prodigalidad L, et al.

Secondary colposuspension: Results of a prospec-

tive study from a tertiary referral centre. BJOG

2002; 109:1115–1120.

19. Kjølhede P. Long-term efficacy of Burch colposus-

pension: A 14-year follow-up study. Acta Obstet

Gynecol Scand 2005; 84:767–772.

20. De Lancey JOL. Structural support of the urethra

as it relates to stress urinary incontinence: The

hummock hypothesis. Am J Obstet Gynecol 1994;

170:1713–1714.

21. Rodrigues P, Hering F, Meler A, et al. Pubo-fascial

versusvaginal sling operation for the treatment of

stress urinary incontinence: A prospective study.

Neurourol Urod 2004; 23:627–631.

22. Bezerra CA, Bruschini H, Cody DJ. Traditional

suburethral sling operations for urinary inconti-

nence in women. Cochrane Database Syst Rev

2005, Issue 3:CD001754.

23. Bhargava S, Chapple CR. Rising awareness of the

complications of synthetic slings. Curr Opin Urol

2004; 14:317–321.

24. Beck RP, McCormick S, Nordstrom L. The fascia

lata sling procedure for treating recurrent genuine

stress incontinence of urine. Obstet Gynecol 1988;

72(5):699–703.

25. Breen JM, Geer BE, May GE. The fascia lata subu-

rethral sling urinary stress incontinence for treating

recurrent urinary stress incontinence. Am J Obstet

Gynecol 1997; 177:1363–1366.

26. Kaplan SA, Santarosa RP, Te AE. Comparison of

fascial and vaginal wall slings in the management

of intrinsic sphincter deficiency. Urology 1996;

47:885–889.

27. Kane L, Chung T, Latrie H, et al. The pubofascial

anchor sling procedure for recurrent genuine uri-

nary stress incontinence. BJU Int 1999; 83:1010–

1014.

28. Petrou SP, Frank I. Complications and initial

continence rates after a repeat pubovaginal sling

procedure for recurrent stress urinary incontinence.

J Urol 2001; 165:1979–1981.

29. Juma S, Little NA, Raz S. Vaginal wall sling: Four

years later. Urology 1992; 39(5):424–428.

30. Pidutti RW, Gorge SW, Morales A. Correction of

recurrent stress urinary incontinence by needle

urethropexy with a vaginal wall sling. BJU 1994;

73(4):418–422.

31. Couillard DR, Deckard-Janatpour KA, Stone AR.

The vaginal wall sling: A compressive suspension

procedure for recurrent incontinence in elderly

patients. Urology 1994; 43(2):203–208.

32. Traz S, Stothers L, Young GP, et al. Vaginal wall

sling for anatomical incontinence and intrinsic

sphincter dysfunction: Efficacy and outcome anal-

ysis. J Urol 1996; 156(1):166–170.

33. Litwiller SE, Nelson RE, Fone PD, et al. Vaginal

wall sling: Long-term outcome analysis of factors

contributing to patient satisfaction and surgical

success. J Urol 1997; 157(4):1279–1282.

34. Su TH, Huang JP, Wang YL, et al. Is modified in

situ vaginal wall sling operation the treatment of

choice for recurrent genuine stress incontinence? J

Urol 1999; 162:2073–2077.

35. Morgan JE, Farrow GA, Stewart FE. The Marlex

sling operation for the treatment of recurrent stress

urinary incontinence: A 16-year review. Am J

Obstet Gynecol 1985; 151(2):224–226.

36. Morgan JE, Heritz DM, Stewart FE, et al. The

polypropylene pubovaginal sling for the treatment

of recurrent stress urinary incontinence. J Urol

1995; 154(3):1013–1014.

37. Rutman MP, Itano N, Deng D, et al. Long-term

durability of the distal urethral polypropylene

sling procedure for stress urinary incontinence:

Minimum 5-year follow-up of surgical outcome

and satisfaction determined by patient reported

questionnaires. J Urol 2006; 175:610–613.

38. Rutman MP, Deng DY, Shah SM, et al. Spiral

sling salvage anti-incontinence surgery in female

patients with a nonfunctional urethra: technique

and initial results. J Urol 2006; 175:1794–1799.

39. Smith ARB, Daneshgari F, Dmochowski R, et

al. Surgery for urinary incontinence in women.

In: Abrams P, Cardozo L, Khoury S, Wein A,

eds. Incontinence. Plymouth: Health Publication

2005:1297–1370.

40. Cody J, Wyness L, Wallace S, et al. Systematic

review of the clinical effectiveness and cost-effec-

tiveness of tension-free vaginal tape for treatment

of urinary stress incontinence. Health Tech Assess

2003; 7(21).

41. Rezapour M, Ulmsten U. Tension-free vaginal

tape (TVT) in women with recurrent stress uri-

nary incontinence – a long-term follow up. Int

Urogynecol J 2001; (Suppl 2):S9–11.

42. Riachi L, Kohli N, Miklos J. Repeat tension-

free transvaginal tape (TVT) sling for the treat-

ment of recurrent stress urinary incontinence. Int

Urogynecol J (2002); 13:133–135.

490 G. Novara and W. Artibani

43. Lo TS, Horng SG, Chang CL, et al. Tension-free

vaginal tape procedure after previous failure in

incontinence surgery. Urology 2002; 60:57–61.

44. Rardin CR, Kohli N, Rosenblatt PL, et al. Tension-

free vaginal tape: outcomes among women with

primary versus recurrent stress urinary inconti-

nence. Obstet Gynecol 2002; 100:893–897.

45. Kuuva N, Nilsson CG. Tension-free vaginal tape

procedure: an effective minimally invasive operation

for the treatment of recurrent stress urinary inconti-

nence? Gynecol Obstet Invest 2003; 56:93–98.

46. Liapis A, Bakas P, Lazaris D, et al. Tension-

free vaginal tape in the management of recurrent

stress incontinence. Arch Gynecol Obstet 2004;

269:205–207.

47. Abdel-Hady E, Constantine G. Outcome of the use

of tension-free vaginal tape in women with mixed

urinary incontinence, previous failed surgery, or

low Valsala pressure. J Obstet Gynecol Res 2005;

31(1):38–42.

48. Pickard R, Reaper J, Wyness L, et al. Periurethral

injection therapy for urinary incontinence in

women. Cochrane Database Syst Rev 2003; Issue

2:CD003881.

49. Eckford SD, Abrams P. Para-urethral collagen

implantation for female stress incontinence. Br J

Urol 1991; 68(6):586–589.

50. Herschorn S, Radomski SB, Steele DJ. Early expe-

rience with intraurethral collagen injections for uri-

nary incontinence. J Urol 1992; 148(6):17971800.

51. O’Connell HE, McGuire EJ, Aboseif S, et al.

Transurethral collagen therapy in women. J Urol

1995; 154(4):1463–1465.

52. Monga AK, Robinson D, Stanton SL. Periurethral

collagen injections for genuine stress incontinence:

A 2-year follow-up. Br J Urol 1995; 76(2):156–160.

53. Richardson TD, Kennelly MJ, Faerber GJ.

Endoscopic injection of glutaraldehyde cross-

linked collagen for the treatment of intrinsic

sphincter deficiency in women. Urology 1995;

46(3):378–381.

54. Herschorn S, Steele DJ, Radomski SB. Follow-up

of intraurethral collagen for female stress urinary

incontinence. J Urol 1996; 156(4):1305–1309.

55. Faerber GJ. Endoscopic collagen injection therapy

in elderly women with type I stress urinary incon-

tinence. J Urol 1996; 155(2):512–514.

56. Kreder KJ, Austin JC. Treatment of stress urinary

incontinence in women with urethral hypermobil-

ity and intrinsic sphincter deficiency. J Urol 1996;

156(6):1995–1998.

57. Smith DN, Appell RA, Winters JC, et al. Collagen

injection therapy for female intrinsic sphincteric

deficiency. J Urol 1997; 157(4):1275–1278.

58. Haab F, Zimmern PE, Leach GE. Urinary stress

incontinence due to intrinsic sphincteric defi-

ciency: Experience with fat and collagen periure-

thral injections. J Urol 1997; 157(4):1283–1286.

59. Khullar V, Cardozo LD, Abbott D, et al. GAX col-

lagen in the treatment of urinary incontinence in

elderly women: A two year follow up. Br J Obstet

Gynaecol 1997; 104(1):96–99.

60. Cross CA, English SF, Cespedes RD, et al. A fol-

lowup on transurethral collagen injection therapy for

urinary incontinence. J Urol 1998; 159(1):106–108.

61. Corcos J, Fournier C. Periurethral collagen injec-

tion for the treatment of female stress urinary

incontinence: 4-year follow-up results. Urology

1999; 54(5):815–818.

62. Groutz A, Blaivas JG, Kesler SS, et al. Outcome

results of transurethral collagen injection for female

stress incontinence: Assessment by urinary incon-

tinence score. J Urol 2000; 164(6):2006–2009.

63. Winters JC, Chiverton A, Scarpero HM, et al.

Collagen injection therapy in elderly women:

Long-term results and patient satisfaction. Urology

2000; 55(6):856–861.

64. Lightner D, Calvosa C, Andersen R, et al. A new

injectable bulking agent for treatment of stress

urinary incontinence: Results of a multicenter,

randomized, controlled, double-blind study of

Durasphere. Urology 2001; 58(1):12–15.

65. Bent AE, Tutrone RT, McLennan MT, et al.

Treatment of intrinsic sphincter deficiency using

autologous ear chondrocytes as a bulking agent.

Neurourol Urodyn 2001; 20(2):157–165.

66. Santarosa RP, Blaivas JG. Periurethral injection

of autologous fat for the treatment of sphincteric

incontinence. J Urol 1994; 151(3):607–611.

67. Trockman BA, Leach GE. Surgical treatment of

intrinsic urethral dysfunction: Injectables (fat).

Urol Clin North Am 1995; 22(3):665–671.

68. Su TH, Wang KG, Hsu CY, et al. Periurethral fat

injection in the treatment of recurrent genuine

stress incontinence. J Urol 1998; 159(2):411–414.

69. Lee PE, Kung RC, Drutz HP. Periurethral autolo-

gous fat injection as treatment for female stress

urinary incontinence: A randomized double-blind

controlled trial. J Urol 2001; 165(1):153–158.

70. Politano VA. Periurethral polytetrafluoroethylene

injection for urinary incontinence. J Urol 1982;

127(3):439–442.

71. Lim KB, Ball AJ, Feneley RC. Periurethral Teflon

injection: A simple treatment for urinary inconti-

nence. Br J Urol 1983; 55(2):208–210.

72. Schulman CC, Simon J, Wespes E, et al. Endoscopic

injection of Teflon for female urinary incontinence.

Eur Urol 1983; 9(4):246–247.

35. Multioperated Recurrent Incontinence/Prolapse 491

73. Deane AM, English P, Hehir M, et al. Teflon

injection in stress incontinence. Br J Urol 1985;

57(1):78–80.

74. Osther PJ, Rohl H. Female urinary stress inconti-

nence treated with Teflon injections. Acta Obstet

Gynecol Scand 1987; 66(4):333–335.

75. Lockhart JL, Walker RD, Vorstman B, et al.

Periurethral polytetrafluoroethylene injection follow-

ing urethral reconstruction in female patients with

urinary incontinence. J Urol 1988; 140(1):51–52.

76. Vesey SG, Rivett A, O’Boyle PJ. Teflon injection

in female stress incontinence. Effect on urethral

pressure profile and flow rate. Br J Urol 1988;

62(1):39–41.

77. Kiilholma P, Makinen J. Disappointing effect

of endoscopic Teflon injection for female stress

incontinence. Eur Urol 1991; 20(3):197–199.

78. Lopez AE, Padron OF, Patsias G, et al. Transurethral

polytetrafluoroethylene injection in female patients

with urinary continence. J Urol 1993; 150(3):

856–858.

79. Herschorn S, Glazer AA. Early experience with

small volume periurethral polytetrafluoroethylene

for female stress urinary incontinence. J Urol

2000; 163(6):1838–1842.

80. Koelbl H, Saz V, Doerfler D, et al. Transurethral

injection of silicone microimplants for intrin-

sic urethral sphincter deficiency. Obstet Gynecol

1998; 92(3):332–336.

81. Barranger E, Fritel X, Kadoch O, et al. Results of

transurethral injection of silicone micro-implants

for females with intrinsic sphincter deficiency. J

Urol 2000; 164(5):1619–1622.

82. Peeker R, Edlund C, Wennberg AL, et al. The

treatment of sphincter incontinence with periure-

thral silicone implants (macroplastique). Scand J

Urol Nephrol 2002; 36(3):194–198.

83. Tamanini JT, D’Ancona CA, Tadini V, et al.

Macroplastique implantation system for the treat-

ment of female stress urinary incontinence. J Urol

2003; 169(6):2229–2233.

84. Kowalczyk JJ, Mulcahy JJ. Use of the artificial uri-

nary sphincter in women. Int Urogynecol J 2000;

11:176–179.

85. Scott FB. The use of the artificial sphincter in the

treatment of urinary incontinence in the female

patient. Urol Clin N Am 1985; 12:305–315.

86. Light JK, Scott FB. Management of urinary incon-

tinence in women with the artificial urinary sphinc-

ter. J Urol 1985; 134:476–478.

87. Donovan MG, Barrett DM, Furlow WL. Use of

the artificial urinary sphincter in the management

of severe incontinence in females. Surg Gynecol

Obstet 1985; 161:17–20.

88. Diokno AC, Hollander JB, Alderson TP. Artificial

urinary sphincter for recurrent female urinary

incontinence: Indications and results. J Urol 1987;

138:778–780.

89. Abbassian A. A new operation for insertion of

the artificial urinary sphincter. J Urol 1988; 140:

512–513.

90. Appell RA. Techniques and results in the implanta-

tion of the artificial urinary sphincter in women with

type III stress urinary incontinence by a vaginal

approach. Neurourol Urodyn 1988; 7:613–618.

91. Duncan HJ, Nurse DE, Mundy AR. Role of the artifi-

cial urinary sphincter in the treatment of stress incon-

tinence in women. Br J Urol 1992; 69:141–143.

92. Webster GD, Perez LM, Khoury JM, et al.

Management of type III stress urinary incontinence

using artificial urinary sphincter. Urology 1992;

39:499–503.

93. Costa P, Mottet N, Le Pellec L, et al. Artificial

urinary sphincter AMS 800 in operated and unop-

erated women with type III incontinence. J Urol

1994; 151 (part 2):477A, abstract 1000.

94. Hadley R, Loisides P, Dickinson M. Long-term

follow-up (2–5 years) of transvaginally placed arti-

ficial urinary sphincters by an experienced surgeon.

J Urol 1995; 153(part 2):432A, abstract 816.

95. Stone KT, Diokno AC, Mitchell BA. Just how

effective is the AMS 800 artificial urinary sphinc-

ter? Results of long-term follow-up in females.

J Urol 1995; 153(part 2):433A, abstract 817.

96. Thomas K, Venn SN, Mundy AR. Outcome of the

artificial urinary sphincter in female patients.

J Urol 2002; 167:1720–1722.

97. Ngninkeu BN, van Heugen G, di Gregorio M, et al.

Laparoscopic artificial urinary sphincter in women

for type III incontinence: Preliminary results. Eur

Urol 2005; 47:793–797.

98. Petero VG, Diokno AC. Comparison of the long-

term outcomes between incontinent men and

women treated with artificial urinary sphincter.

J Urol 2006; 175:605–609.

99. Birch C. The use of prosthetics in pelvic recon-

structive Surgery. Best Pract Res Clin Obstet

Gynaecol 2005; 19(6):979–991.

100. Amid PK. Classification of biomaterials and their

related complication in abdominal wall surgery.

Hernia 1997; 1:15–21.

101. Julian TM. The efficacy of Marlex mesh in the

repair of severe, recurrent vaginal prolapse of the

anterior midvaginal wall. Am J Obstet Gynecol

1996; 175:1472–1475.

102. Sand PK, Koduri S, Lobel RW, et al. Prospective

randomized trial of polyglactin 910 mesh to pre-

vent recurrence of cystoceles and rectoceles. Am J

Obstet Gynecol 2001; 184(7):1357–1364.

492 G. Novara and W. Artibani

103. Gandhi S, Goldberg RP, Kwon C, et al. A prospec-

tive randomized trial using solvent dehydrated

fascia lata for the prevention of recurrent anterior

vaginal wall prolapse. Am J Obstet Gynecol 2005;

192(5):1649–1654.

104. Brubaker L, Bump R, Fynes M, et al. Surgery

for pelvic organ prolapse. In: Abrams P, Cardozo

L, Khoury S, Wein A, eds. Incontinence, 3rd

International Consultation on Incontinence.

Plymouth: Health Publication, 2005:1371–1402.

105. Culligan PJ, Blackwell L, Goldsmith LJ, et al. A

randomized controlled trial comparing fascia lata

and synthetic mesh for sacral colpopexy. Obstet

Gynecol 2005; 106(1):29–37.

106. Nygaard IE, McCreery R, Brubaker L, et al.

Abdominal sacrocolpopexy: A comprehensive

review. Obstet Gynecol 2004; 104:805–823.

107. Gandhi S, Kwon C, Goldberg R, et al. Does fascia

lata graft decrease recurrent posterior vaginal wall

prolapse (abstract 86). Int Urogynecol J Pelvic

Floor Dysfunct 2003; 14 (Suppl 1):S26.

108. FitzGerald MP, Richter HE, Siddique S, et al.

Colpocleisis: A review. Int Urogynecol J Pelvic

Floor Dysfunct. 2006; 17(3):261–271.

109. Langmade CF, Oliver JA. Partial colpocleisis. Am

J Obstet Gynecol 1986; 154:1200–1205.

110. Denehy TR, Choe JY, Gregori CA, et al. Modified

LeFort partial colpocleisis with Kelly urethral

plication and posterior colpoperineoplasty in the

medically compromised elderly: A comparison

with vaginal hysterectomy, anterior colporrhaphy,

and posterior colpoperineoplasty. Am J Obstet

Gynecol 1995; 173:1697–1701.

111. DeLancey JO, Morley GW. Total colpocleisis for

vaginal eversion. Am J Obstet Gynecol 1997;

176:1228–1232.

112. Cespedes RD, Winters JC, Ferguson KH.

Colpocleisis for the treatment of vaginal vault

prolapse. Tech Urol 2001; 7(2):152–160.

113. Harmanli OH, Dandolu V, Chatwani AJ, et al.

Total colpocleisis for severe pelvic organ prolapse.

J Reprod Med 2003; 48(9):703–706.

114. von Pechmann WS, Mutone M, Fyffe J, et al. Total

colpocleisis with high levator plication for the

treatment of advanced pelvic organ prolapse. Am J

Obstet Gynecol 2003; 189(1):121–126.

115. Moore RD, Miklos JR. Colpocleisis and tension-

free vaginal tape sling for severe uterine and vagi-

nal prolapse and stress urinary incontinence under

local anesthesia. J Am Assoc Gynecol Laparosc

2003; 10(2):276–280.

116. FitzGerald MP, Brubaker L. Colpocleisis and

urinary incontinence. Am J Obstet Gynecol 2003;

189(5):1241–1244.

117. Glavind K, Kempf L. Colpectomy or Le Fort

colpocleisis – a good option in selected elderly

patients. Int Urogynecol J Pelvic Floor Dysfunct

2005; 16(1):48–51.

493

Introduction

Stress urinary incontinence (SUI) affects a large

population of adult women. Not surprisingly, over

200 surgical procedures have been described for

its treatment. Procedures to treat SUI have evolved

which probably cause less voiding dysfunction. An

increase in the number of procedures preformed

probably has made up for this possible reduction

in incidence. When lower urinary tract symptoms

(LUTS) replace stress incontinence, patients may

be more distressed than at initial presentation.

This leaves the clinician with a challenging task

of deciding on the timing and type of anti-incon-

tinence procedure to use in the treatment of a

patient’s troublesome LUTS. The most important

factor in preventing obstruction is the understand-

ing that surgical treatment of SUI works by restor-

ing support to the urethrovesical junction and/or

improving coaptation of the urethra in intrinsic

sphincter dysfunction (ISD), not by changing the

position of the urethra. Obstruction often goes

undiagnosed. With the recent widespread use of

synthetic midurethral slings such as the tension-

free vaginal tape (TVT) and transobturator tape

(TOT), expedient diagnosis and treatment of blad-

der outlet obstruction (BOO) is advantageous.

This chapter covers the incidence and etiology of

postsurgical obstruction, the diagnostic evaluation,

management options, and outcomes of surgical

interventions.

Incidence of Obstruction after SUI

Surgery

The true incidence of iatrogenic obstruction and

voiding dysfunction after incontinence surgery is

unknown. Variability in reported rates may be due

to a variety of factors, such as underdiagnosis and

loss to follow-up. Obstruction may go undiagnosed

if it is not severe enough to cause urinary retention.

For example, an obstructed patient may experience

detrusor overactivity with normal emptying. Also,

some patients will seek second opinions regarding

their surgical outcome. This leaves most series on

obstruction after incontinence surgery lacking in

the total number of patients undergoing surgery

from which the obstructed patients were derived

[1] . In 1997, the American Urological Association

SUI Clinical Guideline Panel conducted a meta-

analysis of surgical procedures for the treatment

of SUI. They showed that the reported incidence

of urinary retention for more than 4 weeks postop-

eratively was 3–7% (median CI 5%) for retropubic

suspension, 4–8% (median CI 5%) for transvaginal

suspensions, and 6–11% (CI 8%) for sling proce-

dures. The incidence of permanent retention was

not known, but the panel’s opinion was that it was

less than 5% for all procedures [2] . Morgan et al.

reported on a large pubovaginal sling series with

a de novo urgency rate of 23% and de novo urge

urinary incontinence (UUI) rate of 5%. There was

a 74% resolution of UUI (concomitant anterior

Chapter 36

Voiding Dysfunction after Female

Anti-Incontinence Surgery

Priya Padmanabhan and Victor W. Nitti

494 P. Padmanabhan and V.W. Nitti

colporrhaphy may have contributed, P = 0.07) and

92% returned to normal voiding one month post-

operatively [3] .

Dunn et al. performed an extensive literature

review to determine the incidence of “voiding

dysfunction” after incontinence procedures per-

formed from 1966 to 2001. All available informa-

tion were retrospective collections, case reports,

or case cohort series. Rates of voiding dysfunction

varied from 4 to 22% following Burch colposus-

pension, 5–20% following Marshall–Marchetti–

Krantz (MMK) urethropexy, 4–10% following

pubovaginal sling, 5–7% after needle suspension,

and 2–4% following TVT. It is inferred that a

large number of patients with voiding dysfunction

in these series were obstructed [4] .

The introduction of new techniques such as

the midurethral synthetic slings (done by a ret-

ropubic or transobturator approach) has reduced

the incidence of postoperative obstruction, but it

still remains an issue. Reported rates of urinary

retention after TVT have ranged from 1.4 to 9%

[5 5, 6, 7, 8, 9, 10, 11] and 2–4% in other studies

[12] . Delorme et al. created the TOT to avoid

known vascular, bowel, and bladder complica-

tion. They reported on 1-year results, noting that

3% of patients developed obstructive voiding

disorders. Only one patient in this group had

persistent obstructive symptoms [13] . Two series

evaluated the results after treatment with a TOT

for SUI. Costa et al. reported 4% of their patients

to have postoperative voiding disorders, with five

of seven patients recovering normal micturition

by 1-year follow-up . De novo UUI was observed

in only 5% of their patients with the symptoms

of urgency and UUI disappearing in 56.3 and

48.3% of patients, respectively [14] . Deval et al.

performed a longitudinal study on 129 consecu-

tive women and assessed voiding function at 1,

6, and 12 months postoperatively. Only 1.5% of

women developed urinary retention, but 5.4%

had voiding difficulties (residual volume >150

ml) requiring clean intermittent catheterization

(CIC) for 4.2 ± 2 days. Postoperative urinary

tract infections and de novo urgency were diag-

nosed in 5.4 and 9.3% of patients, respectively,

and 34.2% of the 70 women with preoperative

urge symptoms had persistent urgency postop-

eratively [15] .

Etiology

Surgical procedures for the correction of SUI are

designed to provide urethrovesical junction support

and/or improve urethral coaptation in the cases of

ISD. Retropubic cystourethropexy and colposus-

pension, transvaginal bladder neck suspension, and

sling procedures all have been utilized to achieve

this. Midurethral synthetic slings by both the ret-

ropubic and transobturator approaches appear to

work by causing a dynamic kinking of the urethra

with stress, and thus can be effective without stop-

ping hypermobility [16, 17, 18, 19] . The voiding

dysfunction that develops from iatrogenic outlet

obstruction is related to obstruction, detrusor over-

activity, or impaired detrusor contractility. The risk

of iatrogenic obstruction usually relates to techni-

cal factors, ie, placement and tension of sutures or

sling material. In a retropubic urethropexy, sutures

placed too medially (close to the urethra) can cause

urethral deviation or periurethral scarring. Sutures

placed too distally may cause kinking with obstruc-

tion and an inadequately supported bladder neck/

proximal urethra with potentially continued SUI.

If retropubic sutures are tied too tightly, exces-

sively elevating the bladder neck toward the pubic

bone, “hypersuspension” or overcorrection of the

urethrovesical angle may occur. However, in most

cases, hypersuspension is not evident on physi-

cal examination. In placement of a bladder neck,

suburethral, or midurethral sling, it is excessive

tension on the sling under or around the bladder

neck or urethra that is responsible for obstruction.

Excessive tension on a midurethral synthetic sling

can result in rolling of the sling into a tight band.

Additional factors affecting a patient’s ability

to empty after anti-incontinence surgery include

preoperative voiding dysfunction and prolapse

that was either uncorrected at time of surgery or

occurred postoperatively. Prolapse of sufficient

size may kink or angulate and externally compress

the urethra. It is very important to examine and rule

out apical, anterior, and posterior prolapse as an

etiology of urethral obstruction. Impaired detrusor

contractility, a condition that is present preopera-

tively, may manifest symptomatically with even a

“relative obstruction” when urethral resistance is

increased by an anti-incontinence surgery. These

should be warned of the possibility of postoperative

36. Voiding Dysfunction after Female Anti-Incontinence Surgery 495

voiding dysfunction. Learned voiding dysfunction

(dysfunctional voiding) or failure of relaxation of

the striated urethral sphincter may affect emptying

after surgery [20] . A patient who habitually voids

by abdominal straining may have difficulty empty-

ing after incontinence surgery. Patient education and

biofeedback can be helpful, but when the problem

persists, botulinum A toxin injection into the urethral

sphincter has been successful [21] .

Presentation

The most obvious symptom of obstruction is

complete/partial urinary retention or inability to

void continuously or slow stream with or without

intermittency. Instead, some women will present

with predominate storage symptoms, ie, frequency,

urgency, and urge incontinence, with or without

voiding symptoms. The prevalence of various

symptoms varies tremendously among authors.

Some report on cohorts with only obstructive

symptoms or retention, while others have shown

the true variability of voiding dysfunction second-

ary to obstruction. Carr and Webster reviewed the

presenting symptoms of 51 women who under-

went urethrolysis [22] . They observed the follow-

ing symptoms/signs: storage (irritative) symptoms

(75%), voiding (obstructive) symptoms (61%),

de novo urgency (55%), need for CIC (40%),

persistent retention (24%), recurrent urinary

tract infections (UTIs) (8%), and painful voiding

(8%). Obviously storage and voiding symptoms

and retention can coexist in any combination.

Therefore, in evaluating a patient who presents

with de novo voiding and/or storage symptoms and

recurrent UTIs, obstruction must be entertained. In

our experience, early presentations of obstruction,

ie, within the first 3 months after surgery, tends be

more weighted toward retention and obstructive

voiding symptoms.

Risk Factors for Postoperative

Voiding Dysfunction

In counseling patients preoperatively, it would

be useful to know which patients are at risk for

postoperative voiding dysfunction. As expected,

this question does not have a definite answer.

Urodynamic studies have investigated multiple

factors to determine which may be predictive.

Miller et al. noted that women undergoing an

allograft pubovaginal sling who voided with no or

minimal detrusor pressure (19%) had a significantly

increased risk of postoperative retention. In con-

trast, no patient with a detrusor contraction devel-

oped retention postoperatively. Valsalva voiding did

not affect the incidence of postoperative retention

[23] . Weinberger and Ostergard studied 108 women

undergoing synthetic suburethral slings and found

that the absence of detrusor contractions predicted

delayed returns to normal voiding. Valsalva voiding

had no association with voiding dysfunction [24] .

Bhatia and Bergman noted that women who void

with Valsalva maneuver (intra-abdominal pres-

sure greater than 10 cm H

2 O during voiding and

a detrusor pressure less than 15 cm) were at a 12

times greater risk of needing prolonged catheteriza-

tion in a series of Burch cystourethropexies [25] .

Others showed that patients reporting preoperative

Valsalva voiding or detrusor hypocontractility are

more likely to report de novo urgency [26] . Wang

and Chen found that patients with preoperative dys-

functional voiding [maximum free flow (NIQmax)

less than 12 ml s

−1 and detrusor pressure at maxi-

mum flow (Pdet@Qmax) of greater than or equal to

20 cm H

2 O] were more likely to have a lower objec-

tive cure rate and lower quality of life scores after

TVT than those with normal pressure–flow voiding

dynamics [27] . More recently, Kawashima et al.

evaluated the preoperative urodynamic findings

predicting postoperative voiding difficulties in 14

women after a TVT [28] . Although there was a pau-

city of data, they noted that a peak detrusor pressure

(Pdetmax) × average flow rate (Qavg) was a good

marker for potential detrusor contractility, and a low

Pdetmax × Qavg predicted significantly increased

postvoid residual after the TVT. No patients voided

without a detrusor contraction preoperatively [28] .

The association of low voiding detrusor pressures

and Valsalva voiding with subsequent voiding dys-

function has not been seen in several other studies

[29, 30] . While urodynamic studies are useful in

evaluating voiding dynamics of incontinent women,

low detrusor pressures or Valsalva voiding preop-

eratively should not per se exclude patients from

anti-incontinence procedures.

496 P. Padmanabhan and V.W. Nitti

To date, data are lacking on risk factors for void-

ing dysfunction when an anti-incontinence proce-

dure is performed with surgery for pelvic organ

prolapse. Sokol et al. noted that among 267 women

(66% having concurrent prolapse repair), there was

no significant difference in median days to void-

ing and rate of urinary retention based on prolapse

repair status. Yet, increasing age, decreasing body

mass index (BMI), and postoperative UTI were

independent predictors of time to adequate voiding.

Only previous history of incontinence surgery was

an independent predictor of urinary retention [31] .

Diagnostic Evaluation

Transient voiding dysfunction and urinary reten-

tion are frequent and expected after any type of

anti-incontinence surgery. This is the rationale

behind concomitant placement of suprapubic tubes

or teaching CIC preoperatively. After traditional

pubovaginal sling (and variants) or colposuspen-

sion, most women will begin voiding sufficiently

within a few days to weeks, while others may

take longer to resume normal voiding. Storage

symptoms, such as urgency, frequency, and urge

incontinence often are more refractory than reten-

tion because they can be related to bladder changes

and may take months to resolve. Traditionally,

evaluation of urinary retention or severe storage

symptoms after pubovaginal sling, colposuspen-

sion, and needle suspension has been delayed for

up to 3 months depending on symptoms and their

degree of bother. This time frame is arbitrary, and

has been predicated on the fact that most data in the

literature are based on a waiting period of 3 months

to ensure adequate time for obstruction to resolve.

After 3 months, there is a low probability that per-

sistent retention will resolve without intervention.

Recently, some surgeons, including ourselves, have

advocated earlier intervention in cases of complete

retention and severe symptoms; however, few data

on outcomes and recurrence of stress incontinence

are available. Few studies have focused on out-

comes with respect to waiting a longer period of

time before intervention. While it seems intuitive

that longer-standing symptoms (especially detrusor

overactivity) will be less likely to respond to relief

of obstruction, this has not been proven conclu-

sively. Leng et al. conducted a retrospective review

of 15 women who underwent urethrolysis and

found that patients with persistent symptoms post-

operatively (53%) had a significantly longer time

for surgery to intervention than those who had no

symptoms (47%) [32] . Mean time to urethrolysis

was 31.25 ± 21.94 months versus 9 ± 10.1 months,

respectively. However, the large overlap, small

sample size, and the fact that more patients in the

successful group had urinary retention (5/7 vs. 3/8)

makes it difficult to make definitive conclusions. In

our practice, we do not exclude obstructed patients

from intervention based on the duration of their

obstruction.

The waiting period advocated for obstruction

and retention for more traditional anti-incontinence

procedures has been largely abandoned for TVT

and other midurethral synthetic slings. In these

cases, quicker intervention is suggested when

obstruction is suspected [5, 7, 33, 34] . Due to the

immobility of the polypropylene mesh and the

tremendous ingrowth of fibroelastic tissue at 1–2

weeks, patients with severe symptoms or urinary

retention are less likely to improve after this time

period.

History and Physical Examination

A focused history and physical exam is the first

step in diagnostic evaluation of a patient with void-

ing dysfunction after incontinence surgery. Key

points in the history include patient’s preoperative

voiding status and symptoms and the temporal

relationship of the LUTS to the surgery. The type

of anti-incontinence procedure performed and the

number and type of other procedures done also

are important. Urodynamic data, such as uroflow

and pressure flow studies from before incontinence

surgery, are useful if available. If patients are

straining to void (perhaps by habit), they should

be instructed to discontinue this behavior, since

incontinence procedures are designed to prevent

the flow of urine with abdominal straining. Finally,

it is important to determine whether the symptoms

of SUI persist.

The most obvious presenting symptom of

obstruction after incontinence surgery is inability

to void or intermittent/partial urinary retention.

Patients also may experience voiding (obstructive)

symptoms including slow or interrupted stream and

straining to void. Storage (irritative) symptoms of

36. Voiding Dysfunction after Female Anti-Incontinence Surgery 497

urinary frequency, urgency, and urge incontinence

which persist after surgery also may be a sign of

obstruction even if emptying is complete.

Physical examination may show overcorrec-

tion or hypersuspension where the urethra and

urethral meatus appear to be pulled up toward the

pubic bone and “fixed,” making the angle of the

urethra more vertical than normal. When severe,

this usually is quite obvious, but can be confirmed

by a Q-tip test. Not all obstructed patients appear

to be overcorrected. It is important to assess for

cystocele and other forms of prolapse, which may

cause obstruction (due to a kinking of the urethra).

The patient also should be examined for persistent

urethral hypermobility and SUI.

Urodynamics

Recent interest in female BOO has resulted in

publication of several unique proposals of urody-

namic criteria for the diagnosis of female BOO.

Chassagne et al. used the cutoff values of Pdet@

Qmax of more than 20 cm H

2 O and maximum

flow rate (Qmax) of less than 15 ml s

−1 to define

obstruction [35] . In 2000, Lemack and Zimmern

revised these values to a cutoff of Qmax of 11 ml

s

−1 or less and Pdet@Qmax of 21 cm H

2 O or more

[36] . The same group made another update with

criteria published in 2004, using a small group of

controls, elevating the Pdet@Qmax cutoff to 25 cm

H

2 O [37] . We have used videourodynamic criteria

to diagnose BOO. Obstruction is defined as radio-

graphic evidence of an obstruction between the

bladder neck and distal urethra in the presence of

a sustained detrusor contraction of any magnitude

during voiding, with less emphasis on strict pres-

sure–flow criteria [38] . Blaivas and Groutz realized

the possibility of test-induced catheter obstruction

and designed a nomogram based on the Qmax and

the Pdet@Qmax [39] . Although each urodynamic

definition has merit, further investigation should

provide clarity of when to use which criteria [40] .

The diagnosis of obstruction in women after

incontinence surgery can be particularly diffi-

cult to make urodynamically. In cases of urinary

retention and incomplete emptying, urodynamic

studies may not be necessary before interven-

tion, particularly if preoperative contractility and

emptying are known to be normal. However, in

cases of de novo or worsened storage symptoms,

including urge incontinence without a significantly

elevated postvoid residual urine volume (PVR), a

formal urodynamic evaluation is preferred. Many

women with suspected obstruction after inconti-

nence surgery do not generate a significant contrac-

tion on UDS but are still obstructed. Outcomes of

surgical intervention in such cases are identical to

those women with classic high-pressure, low-flow

dynamics.

There are no consistent preoperative or urody-

namic parameters that predict success or failure

of urethrolysis. Foster and McGuire found that

patients with detrusor overactivity had a higher rate

of failure, but later studies found this not to be the

case [41] . Nitti and Raz found that as the postvoid

residual increased, so did the failure; but others

have not confirmed this correlation [42] . Carr and

Webster found that the only parameter predictive

of success was no prior urethrolysis [22] . In the

study by Nitti and Raz, four women who failed

to generate a contraction during UDS testing had

a successful urethrolysis. They also reported that

UDS findings in patients considered failures after

transvaginal urethrolysis failed to elucidate the rea-

son for their continued voiding dysfunction [42] .

Due to the limitation of UDS in evaluation of these

patients, the temporal relationship of surgery to the

onset of symptoms is relied on as an indicator of

obstruction. If a patient fails to resume voiding or

improve significantly, then continued obstruction

is suspected.

Classic high-pressure, low-flow voiding dynam-

ics do confirm the diagnosis of obstruction, but

are far from a consistent finding. Urodynamics

do yield important information regarding instabil-

ity, impaired compliance, bladder capacity, and

voiding characteristics. Based on our experience,

videourodynamics offer an advantage over simple

urodynamics in this patient population, because

of the ability to simultaneously image the blad-

der outlet. It must be emphasized that the best

selection criteria for intervention for suspected

postincontinence surgery obstruction is a temporal

relationship between surgery and onset of void-

ing symptoms. The utility of urodynamics in the

postincontinence surgery female patient may be

considered as follows: (1) For the patient in reten-

tion, UDS can provide valuable information (eg,

detrusor overactivity or significantly impaired

compliance, the latter being an absolute indication

498 P. Padmanabhan and V.W. Nitti

for intervention) and can confirm diagnosis of

obstruction but should not exclude the patient from

urethrolysis, even with impaired contractility or

lack of a detrusor contraction. (2) For the patient

with storage symptoms with normal emptying,

urodynamics can diagnose obstruction and equally

as importantly rule out obstruction. It can help to

provide a specific diagnosis that is useful in direct-

ing therapy, especially if obstruction cannot be

ruled out.

Cystourethroscopy and Imaging

Cystoscopic evaluation of the urethra may show

scarring, narrowing, occlusion, kinking, or devia-

tion of the urethra. These findings are especially

helpful when UDS are equivocal. The urethra and

bladder should be carefully inspected for eroded

sutures or sling material and the presence of a

fistula. This is facilitated by a rigid scope with

a 0–30° lens and little or no beak to allow for

complete distention of the urethra. In case inter-

vention is anticipated, cystoscopy should be per-

formed either before surgery or prior to incision.

Radiographic imaging may be done independently

of UDS. A standing cystogram in the anterior–

posterior, oblique, and lateral positions, with and

without straining, can assess the degree of bladder

and urethral prolapse and displacement or distor-

tion of the bladder. A voiding cystourethrogram

can assess the bladder, bladder neck, and urethra

during voiding to determine narrowing, kinking,

or deviation. While not mandatory, imaging can be

extremely useful in equivocal cases.

Management of Iatrogenic

Obstruction

Conservative Treatment

Treatment of obstruction and its timing usually

are dictated by the degree of bother of symptoms.

In some cases an obstructed patient opts for con-

servative management, including CIC. This is

a reasonable option for women not bothered by

catheterization or who prefer this option to repeat

surgery and risk of recurrent SUI. Most women

eventually choose definitive treatment, but chronic

CIC is an option in select cases. Patients who are

emptying well but have significant storage symp-

toms from iatrogenic obstruction may be initially

treated with pharmacotherapy, ie, anticholinergics,

or pelvic floor physiotherapy. In our experience,

these measures are not usually successful when

obstruction exists, but can be considered before

surgery. The role of urethral dilation in iatrogenic

obstruction secondary to pubovaginal sling and

colposuspension is unclear. Karram et al. did

report an 82% cure or improved rate with urethral

dilation using a Walther sound performed within

2–6 weeks of TVT insertion for 28 patients with

varying amounts of postoperative voiding dys-

function [33] . Two additional groups highlighted

the role of urethral dilation in management anti-

incontinence obstruction. Paick et al. studied 247

women with a minimum of 6 months follow-up

after TVT placement [43] . They performed ure-

thral dilation (once or twice) with downward push

in the immediate postoperative period and noted

resolution of voiding dysfunction in 85% (23 of 27

patients; 14 with retention, 12 with poor urinary

flow, and 2 with dysuria). Mishra et al. performed

urethral dilation on 3 of 52 cases who had reten-

tion 3 months following TVT. Two of the three

patients voided effectively after urethral dilation

[44] . In this series, the postoperative retention rate

is significantly higher (23%) than published data.

In all three studies, the use of urethral dilation

was uncontrolled and ideally a randomized trial is

necessary to prove its efficacy. While many prac-

titioners report anecdotal success, no randomized

trials exist in peer-reviewed literature. It is our

opinion that urethral dilation is of limited utility

and if used too aggressively, it may be detrimental.

There are concerns about the potentially traumatic

nature of dilation, which could induce scarring of

the urethra.

When conservative measures in a symptomatic

patient fail, definitive surgical therapy by either

formal urethrolysis (transvaginal or retropubic)

or sling incision may be required. In addition,

there is growing experience with manipulation of

midurethral synthetic slings in the early postopera-

tive period.

Surgical Intervention

When voiding dysfunction secondary to obstruc-

tion exists beyond a proper waiting period (refer to

36. Voiding Dysfunction after Female Anti-Incontinence Surgery 499

Diagnostic Evaluation section), surgical intervention

is indicated. The success rate for various proce-

dures ranges from 67 to 100% (see Table 36.1 )

and is independent of the particular procedure

chosen. One procedure is not superior to another,

excluding independent factors, ie, surgeon experi-

ence; however, some procedures are potentially

less morbid with quicker recovery. There have not

been any consistent predictors for success identi-

fied. Individual series have cited certain factors

that are associated with success or failure, but dif-

ferent series have not identified the same factors.

For example, Carr and Webster found that the only

predictors of success were no prior urethrolysis and

omental interposition [22] . Nitti and Raz found that

the postvoid residual increased as did the risk of

failure [42] . Foster and McGuire noted that patients

with detrusor overactivity had a higher rate of fail-

ure [41] . This was not confirmed in a later study

[45] . Several studies failed to show correlation

between urodynamic findings and the likelihood of

successful voiding after urethrolysis [41, 42, 46] .

Furthermore, outcomes of urethrolysis of women

with demonstrable detrusor contraction on UDS

(with normal void prior to incontinence surgery)

are equivalent to women with classic findings of

obstruction.

With all surgical interventions for obstruction,

there is an inherent risk of recurrent stress incon-

tinence. In general, the risk is approximately

15%, but reported rates vary from 0 to 39% (see

Table 36.1 ). Segal et al. compared the efficacy of

retropubic urethrolysis (10/44 with retropubic ure-

thropexy, laparoscopic bone anchor urethropexy,

bladder neck needle suspension, pubovaginal

sling), vaginal urethrolysis (20/44 with retropubic

urethropexy, bone anchor sling, protegen sling,

pubovaginal sling, and Stamey needle suspension),

and sling incision (14/44 with TVT) in treating

postoperative voiding dysfunction of 44 women

after anti-incontinence surgery and reported the

SUI recurrence rates of each [47] . All patients

were at least 6 weeks post anti-incontinence sur-

gery. Of all the risk factors evaluated for recurrent

SUI after urethrolysis, only postmenopausal status

and previous hysterectomy were significant. They

showed a trend based on type of surgical procedure

chosen. SUI was 4.3 times more likely after a TVT

takedown, while it was almost 75% less likely

after a retropubic urethrolysis. Either the sign of

SUI on simple cystometry or UDS diagnosis was

found postoperatively in 63.6% of sling incision,

46.7% of vaginal urethrolysis patients, and 25% of

retropubic urethrolysis patients [47] . Starkman et

al. conducted a retrospective review of 19 patients

to evaluate persistent voiding dysfunction and

recurrent SUI after surgical excision of an eroded

synthetic midurethral sling at mean of 10.1 months

postoperative [48] . This represents a special popu-

lation with the added complication of erosion or

extrusion. Sling excision was accomplished by a

vaginal, retropubic, or combined surgical approach.

They reported complete cure in only 21 and 42%

with recurrent SUI. Five of the patients underwent

simultaneous pubovaginal sling, none of whom

had recurrent SUI. The worst outcomes noted in

this study are most likely due to the intense inflam-

matory reaction associated with mesh erosion.

Residual irritative symptoms (frequency, urgency,

UUI) may be an issue for many patients following

surgical intervention for obstruction. Goldman et

al. suggested that postincision residual irritative

symptoms are related to a longer interval between

initial surgery and takedown [49] .

While some have recommended concomitant

anti-incontinence procedures at the same time as

the procedure to relieve obstruction [42] , others

have argued that this is not necessary. Currently we

do not routinely perform a repeat anti-incontinence

procedure. We believe that in the majority of cases,

patients are so disturbed by the symptoms caused

by obstruction that relieving them must be the

primary goal. If SUI does recur, it can be treated

separately with a urethral bulking agent or even a

repeat surgical procedure in the future.

Surgical techniques usually are tailored toward

individual scenarios and previous surgeries. For

example, in certain cases where the incontinence

procedure causing obstruction was a retropubic

suspension, a retropubic urethrolysis approach

may be used to cut sutures and free retropubic

adhesions. For transvaginal sling procedures,

transvaginal sling lysis alone or formal urethroly-

sis usually can be performed successfully with

less patient morbidity and quicker convalescence.

A transvaginal suprameatal approach also may

be done; however, we rarely use this. With more

common use of the TVT or synthetic midurethral

slings, sling-loosening techniques and incision

alone may be performed in the clinic setting with

500 P. Padmanabhan and V.W. Nitti

local anesthesia in the early postoperative period,

prior to the occurrence of significant scarring. The

decision of which procedure to perform is based

on multiple factors, including the incontinence

procedure performed, associated complications,

surgeon comfort, and patient preferences.

Midurethral Sling Loosening or Incision

In women with postoperative urinary retention after

midurethral synthetic sling, some surgeons, includ-

ing ourselves, advocate early intervention, within

7–14 days. With midurethral synthetic slings, the

vast majority of patients are able to empty fairly

normally within 72 h. Early intervention allows one

to perform a minimally invasive procedure under

local anesthesia in the office or outpatient setting if

appropriate. The anterior vaginal wall is infiltrated

with local anesthetic and the suture used to close the

vaginal wall is opened. The synthetic sling is eas-

ily visualized and hooked with a right-angle clamp

(or Metzenbaum scissors dilator). Spreading of the

right-angle clamp or downward traction on the tape

usually will loosen it 1–2 cm [5] . This usually is pos-

sible if intervention is done within 10 days of sling

placement. Thereafter, tissue ingrowth may prevent

loosening of the sling, in which case, we recommend

cutting it in the midline. The incision then is closed

and the patient then may attempt to void.

Loosening or cutting of TVT has had excellent

results [5, 7, 33, 34, 50] . In the two largest series

of 17 and 23 patients [5, 7] , there was restoration

of normal voiding and emptying in all patients

postincision, while storage symptoms were par-

tially relieved in 70% and completely relieved in

30%. Klutke et al. reported resolution of obstruc-

tion in all 17 patients, while recurrent SUI occurred

in one patient [5] . Rardin and associates found that

Table 36. 1. Summary of series on urethrolysis and sling incision/loosening for the treatment of obstruction after

incontinence surgery .

Reference No Type of urethrolysis Success a Recurrent SUI b (%)

Zimmern et al. [61] 13 Transvaginal 92% N/A

Foster and McGuire [41] 48 Transvaginal 53% 0

Nitti and Raz [42] 42 Transvaginal 71% 0

Cross et al. [45] 39 Transvaginal 72% 3

Goldman et al. [59] 32 Transvaginal 84% 19

Carey et al. [58] 23 Transvaginal with Martius flap 87% 16

Petrou et al. [53] 32 Suprameatal 67% 3

Webster and Kreder [41] 15 Retropubic 93% 13

Petrou and Young [60] 12 Retropubic 83% 25

Carr and Webster [22] 54 Mixed 78% 14

Amundsen et al. [53] 32 Transvaginal and sling incision 94% retention 9

67% urge sx

Nitti et al. [54] 19 Sling incision 84% 17

Goldman [49] 14 Sling incision 93% 21

Klutke et al. [5] 17 TVT incision or loosening 100% 6

Rardin et al. [7] 23 TVT incision 100% retention 39 (2/3 less SUI than

pre-TVT)

30% urge sx cured

70% urge sx improved

Segal et al. [47] 44 Retropubic (10) and vaginal

urethrolysis (20), sling incision (14)

32% urge sx cured 25–63.6

73% obstructive

sxcured

Long et al. [50] 7 Lateral TVT incision 86% 14

Thiel et al. [55] 13 Sling incision 92% 8

a Success is usually defined as cure or significant improvement in presenting symptoms (resumption of normal bladder emptying

for patients in retention, and resolution symptoms for patients with obstructive symptoms or frequency, urgency or urge inconti-

nence). In some series success for specific sx (symptoms) is noted

b Recurrent SUI is defined as percentage of patients without SUI before urethrolysis who experienced SUI after urethrolysis

36. Voiding Dysfunction after Female Anti-Incontinence Surgery 501

impaired bladder emptying resolved in 100% of 23

patients with 61% remaining continent, 26% with

partial recurrence, and 13% with complete recur-

rence of SUI [7] .

In cases of voiding difficulty or dysfunction

beyond 4–6 weeks, the lysis of the TVT sling is

better performed in the operating room because of

tissue ingrowth. Scarring and patient discomfort

are factors to consider, as more extensive dissec-

tion may be needed to identify and cut the sling.

The technique described below for sling incision is

applicable to midurethral slings.

Transvaginal Sling Incision

The transvaginal incision of the pubovaginal sling

(autologous, allograft, xenograft, or synthetic)

rather than formal urethrolysis may limit morbid-

ity, potential soft tissue and nerve injury, and fibro-

sis from surgical dissection. Notably, sling incision

alone may effectively eliminate obstruction with

similar results to formal urethrolysis. In 1995,

Ghoniem described a technique of incising the

sling in the midline using a free vaginal epithelial

interposition graft sutured to each cut end of the

pubovaginal sling, theoretically keeping it intact to

theoretically reduce the risk of postoperative stress

incontinence [51] . Over time, this technique has

evolved and interposition no longer is routinely

used [49, 52, 53, 54] .

Our technique starts with cystoscopy to assess

the urethra and rule out erosion or urethral injury.

An inverted U or midline incision is made to expose

the area of the bladder neck and proximal urethra

[54] . As the vaginal flap is dissected off, the sling

should be identified above the periurethral fascia.

The sling may be encased in scar tissue, and thus

require careful dissection of the scar to identify the

sling. If the sling has significant tension on it, it

may be especially difficult to identify. Insertion of

a cystoscope or sound into the urethra with upward

deflection may help to expose the bladder neck

and isolate the sling. Once the sling is isolated,

it should be separated from the underlying periu-

rethral fascia with sharp or blunt dissection. This

dissection is facilitated by grasping the sling with

an Allis clamp on either side of the midline and

exerting downward pressure. Care should be taken

to avoid injury to the bladder and urethra by begin-

ning dissection distally, identifying normal urethra,

then proceeding more proximally until the plane

between the sling and urethra is identified. A right-

angle clamp can be placed between the urethra,

periurethral fascia, and the sling, enabling lifting of

the sling. The sling then is cut in the midline (Fig.

36.1a ). Alternatively, if scarring is dense and the

plane between the sling and periurethral fascia can-

not be developed, the sling can be isolated laterally

to the midline, off of the urethra. The edges of the

sling are mobilized off of the periurethral fascia to

(not through) the endopelvic fascia (Fig. 36.1b ). In

cases of extreme tension, the ends of the sling may

retract back into the retropubic space after incision,

but more often the sling stays secure to allow this

mobilization. Lateral support is preserved because

the retropubic space is not entered and the urethra

is not freed from the under surface of the pubic

bone. The ends of the sling can be left in situ or

excised. We typically excise synthetic material and

leave autograph and allograft in place. If there is

any concern about urethral injury, cystourethros-

copy should be done. In cases of autologous or bio-

logical materials, when the sling cannot be clearly

identified, formal transvaginal urethrolysis should

be done (see below).

TVT and other midurethral slings can be isolated

and incised in a similar manner. Unlike autologous

and biological slings, it is imperative to identify the

sling and cut it. Conversion to urethrolysis without

specifically cutting the sling may fail to relieve

obstruction. Usually the sling is easily found, but

identification can be aided by palpation of the sling

or using a sound or cystoscope in the urethra with

upward deflection as described above. Sometimes,

identification can be difficult especially in cases

where the sling rolls onto itself and creates a

tight narrow band. In such cases, patience and

careful dissection to isolate the sling is required.

Sometimes it is necessary to retract the portion of

the urethra distal to the sling distally and the por-

tion of the urethra proximal to the sling proximally

to find the tight narrow band. In many cases, after

the midurethral sling is cut, it retracts away from

the urethra. At the surgeon’s discretion, segmental

resection of the suburethral portion of the sling

may be done. Our experience with sling incision

has shown results equivalent to formal urethrolysis.

The success of the procedure has been reported,

ranging from 84 to 93.5% with 8–21% recurrent

SUI rate [49, 53, 54, 55] . If the sling incision is

502 P. Padmanabhan and V.W. Nitti

not successful in relieving obstruction, formal

urethrolysis may be done.

Transvaginal Urethrolysis

Formal urethrolysis may be accomplished through

a retropubic or a transvaginal approach. Both

methods have shown equivalent success rates and

rates of recurrent SUI, although most series include

patients who are obstructed from a number of

different anti-incontinence surgeries. The type of

urethrolysis chosen will depend on several factors

including patient presentation, type of incontinence

procedure performed, failed prior urethrolysis,

and surgeon preference. It has been our practice

to perform transvaginal urethrolysis as a primary

operation and a retropubic urethrolysis as a second-

ary operation. We prefer the transvaginal technique

because of its ease and the reduced morbidity and

recovery time afforded by avoiding an abdominal

procedure. However, there are times when a retro-

pubic approach may be the best primary procedure:

for example, when vaginal anatomy precludes a

transvaginal approach; in cases where the origi-

nal anti-incontinence surgery was associated with

bladder perforation, fistula, or other operative com-

plication; when there is a synthetic sling thatmust

be removed; or in cases where the patient wishes to

avoid a vaginal incision.

All urethrolysis procedures begin with a thorough

endoscopic examination of the urethra, bladder

neck, and bladder. Urethroscopy may show scarring,

narrowing, occlusion, kinking, or deviation of the

urethra. Eroded sutures or sling material or evidence

of a fistula should be excluded. A rigid cystoscope

with a 0 to 30° lens and little or no beak to allow for

complete distention of the urethra is ideal for female

urethroscopy. Also, it is common to find that the

Fig. 36.1. Transvaginal sling incision. ( a ) After an inverted U or midline incision, the sling is isolated in the midline

and incised. A right angle clamp may be placed between the sling and the periurethral fascia to avoid injury to the

urethra. ( b ) The sling is freed from the undersurface of the urethra toward the endopelvic fascia. Ends may be excised

or left in situ (from [54] )

36. Voiding Dysfunction after Female Anti-Incontinence Surgery 503

urethra and/or urethrovesical junction are fixed and

there is a lack of mobility when moving the cys-

toscope up and down. After urethrolysis, mobility

should be restored.

The most commonly used transvaginal technique

originally was described by Leach and Raz [56] . A

midline or inverted U incision approximately 3 cm

long is made in the anterior vaginal wall. A mid-

line incision should extend from the midurethra to

1–2 cm proximal to the bladder neck. In the case

of an inverted U, the apex should be located half

way between the bladder neck and urethral meatus

and the lateral wing should extend proximal to

the bladder neck. With either incision, lateral dis-

section is performed along the glistening surface

of the periurethral fascia to the pubic bone. The

retropubic space is entered sharply by perforating

the attachment of the endopelvic fascia to the obtu-

rator fascia (Fig. 36.2a ). The urethra is dissected

bluntly and sharply off of the undersurface of the

pubic bone and completely freed proximally

to the bladder neck. Sharp dissection usually is

required here (Fig. 36.2b ). The urethra should be

completely freed proximally to the bladder neck

so that the index finger can be placed between

the urethra and the symphysis pubis. Attachments

to the undersurface of the pubic bone are sharply

incised or swept down with the index finger retro-

pubically. We recently have found that placement

of a Penrose drain around the urethra (after initial

mobilization, a right-angle clamp is placed between

the pubic bone and the urethra, which allows for its

placement) aids in visualization and sharp dissec-

tion of all retropubic attachments (Fig. 36.3 ) [57] .

The index finger then may be placed completely

around the urethra between the pubic bone. When

urethrolysis is finished, there should be complete

mobility of the urethra which can be tested with up

and down movement of an intraurethral sound or

cystoscope. Once this is achieved, the vaginal wall

is closed with absorbable sutures. Prior to closure,

endoscopic examination is preformed to rule out

urethral or bladder injury. In cases of extensive

urethrolysis, it is a good idea to assess ureteral

integrity by giving intravenous Indigo Carmine

prior to endoscopy and assessing ureteral efflux.

Success rates with transvaginal urethrolysis vary

from 53 to 93% (see Table 36.1 ).

Carey et al. reported the use of a Martius labial

fat pad flap with transvaginal urethrolysis with

Fig. 36.2. Transvaginal urethrolysis. ( a ) An inverted U

incision in the anterior vaginal wall and entrance into the

retropubic space. ( b ) The urethra is sharply dissected off

of the undersurface of the pubic bone. The endopelvic

fascia, periurethral fascia, and vaginal wall are retracted

medially to expose the urethra in the retropubic space

(from [42] )

504 P. Padmanabhan and V.W. Nitti

success in 87% of patients [58] . The Martius

flap may decrease the risk of recurrent fibrosis,

provide some urethral support, and a future sling

may be placed outside the fat pad, decreasing the

risk of urethral injury. We reserve it for select

cases (eg, repeat urethrolysis, extensive fibro-

sis). We usually divide the robust fat pad flap

midway along its longitudinal axis and wrap the

flap around the urethra effectually supporting

the undersurface and retropubic surface of the

urethra.

In select cases (eg, extensive mobilization or

stress incontinence coexisting with obstruction)

it may be desirable to resupport the urethra at the

time of urethrolysis. Resuspension or pubovagi-

nal sling may be done. Currently our practice is

to consider a resuspension or sling only if the

patient has stress incontinence prior to urethroly-

sis or if support structures are severely compro-

mised during urethrolysis. Resuspension does

increase the risk of persistent obstruction, and

since most patients are distraught about obstruc-

tion, we feel it is best to take care of that problem

and deal with recurrent SUI at a later time should

it occur. Rates of recurrent SUI after resuspen-

sion vary between 0 and 19% when resuspension

is not performed [22, 41, 45, 58, 59] . Many of

these patients may be salvaged with transurethral

bulking agents should stress incontinence recur.

Goldman et al. reported a 66% response rate to

collagen in women with recurrent stress incon-

tinence after transvaginal urethrolysis [59] . In

addition, the option for repeat surgery for SUI at

a later date exists. It is important to discuss the

pros and cons of resuspension and the treatment

of recurrent stress incontinence with patients

preoperatively, as this could affect the decision

to resuspend or not.

A variant of transvaginal urethrolysis is the

suprameatal approach described by Petrou and

colleagues [60] . We have found this to have quite

limited applicability. A theoretical advantage of

this technique is that lateral perforation of the

urethropelvic ligament is not needed, minimiz-

ing the chance of recurrent urethral hypermobil-

ity and subsequent incontinence. An inverted U

incision is made around the top of the urethral

meatus (approximately 1 cm away) between the

3 and 9 o’clock positions. Using sharp dissection,

a plane is developed above the urethra. Then with

a combination of sharp and blunt dissection the

urethra, vesical neck, and bladder are freed from

the pubic and pelvic attachments anteriorly and

laterally. The index finger then may be passed

into the retropubic space, and with a sweeping

motion from medial to lateral, further freeing

may be performed. If obstruction is caused by a

pubovaginal sling, the lateral wings of the sling

may be cut. Likewise, if the obstruction is caused

by suspension sutures, these may be cut. As with

transvaginal urethrolysis, a Martius flap may be

placed. The authors reported a 65% success rate

for retention, 67% success for urgency symp-

toms, and a 3% recurrent SUI rate [60] . This

approach may be beneficial if dissection between

the urethra and pubic bone is excessively dif-

ficult. It may be particularly applicable for cases

of repeat transvaginal urethrolysis (after a failed

prior urethrolysis) or when scarring is particu-

larly dense.

Fig. 36.3. Intraoperative photo after completed urethrol-

ysis. A Penrose drain has been placed around the urethra,

isolating it from the pubic bone (from [57] )

36. Voiding Dysfunction after Female Anti-Incontinence Surgery 505

Retropubic Urethrolysis

Retropubic approaches to urethrolysis may be

the preferred method under circumstances which

include surgeon experience/familiarity with vaginal

anatomy, inadequate vaginal access, original incon-

tinence surgery, or urethrolysis associated with blad-

der perforation, fistula, or synthetic sling removal,

and when the patient desires to avoid another

vaginal incision. Complicated cases that have failed

prior extensive transvaginal urethrolysis also may

be performed retropubically. Previous retropubic

surgery such as the MMK still may be managed

transvaginally, as shown by Zimmern [61] .

The technique of retropubic urethrolysis has been

described by Webster and Kreder (Fig. 36.4 ) [46] .

It may be accomplished through a Pfannensteil or

low midline incision. The rectus fascia and muscle

are opened in midline to the level of the pubic

symphysis. After exposing the retropubic space,

all prevesical and retropubic adhesions are sharply

incised. Complications can be avoided by keeping

the tips of the scissors against the pubic symphysis

during sharp dissection. The object is to restore

complete mobility to the anterior vaginal wall,

allowing free movement of the vesicourethral unit.

The urethra and urethrovesical junction are dis-

sected off of the pubic bone, without separating

them from the anterior vaginal wall. The boundaries

of the vagina in relation to the urethrovesical junc-

tion are identified by placement of the surgeon’s

nondominant hand in the vagina. Alternatively, a

sponge stick or similar instrument may be used.

Some degree of sharp dissection lateral to the ure-

thra usually is required. In cases of severe scarring,

it may be necessary to mobilize laterally as far as

the ischial tuberosities. As a result, one is often

left with a paravaginal defect. In cases where a

paravaginal defect is created as a result of urethral

mobilization, the defects should be repaired by

reapproximating the paravaginal fascia to the fascia

of the obturator internus along the arcus tendine-

ous. The paravaginal repair sutures are left untied.

Finally, the peritoneum is opened with a small

incision and an omental flap is mobilized. The

flap then is placed between the pubic bone and the

urethra and secured to the underside of the pubic

bone with a 2–0 polyglycolic acid (PGA) suture.

The omentum fills the dead space and helps to

prevent recurrent adhesion. The paravaginal repair

sutures then are tied and the abdomen is closed.

Cystoscopy is performed to rule out urethral injury

and confirm efflux of Indigo Carmine from the

ureteral orifices.

Webster and Kreder reported successful out-

comes in 93% of 15 women undergoing retropubic

urethrolysis and obturator shelf repair [46] . In

another series of 12 women, Petrou and Young

reported resolution of obstruction in ten patients

with new-onset stress incontinence in 18% of the

women [62] . Carr and Webster reported complete

or significant resolution of symptoms in 86% of

patients with retropubic urethrolysis [22] .

Fig. 36.4. Retropubic urethrolysis. The urethra and urethrovesical junction are dissected off of the pubic bone,

without separating them from the anterior vaginal wall with sharp dissection. A paravaginal defect repair is then

performed (from [46] )

506 P. Padmanabhan and V.W. Nitti

Failed Urethrolysis

Failure of urethrolysis may be due to persist-

ent or recurrent obstruction, detrusor overactivity,

impaired detrusor contractility, or learned void-

ing dysfunction. Recurrent obstruction may result

from periurethral fibrosis and scarring or intrinsic

damage to the urethra that has occurred as a result

of the urethrolysis surgery. We believe that inad-

equate dissection and lysis of the urethra probably

represents the most common reason for failure of

initial urethrolysis. When obstruction persists, it

is reasonable to attempt a repeat urethrolysis. We

have found this to be effective in relieving urinary

retention, but not as effective in treating persist-

ent storage symptoms. We have reported on the

efficacy of repeat urethrolysis in 24 women who

failed initial urethrolysis and remained in urinary

retention [63] . Both transvaginal and retropubic

approaches were chosen depending on the clini-

cal situation. Obstruction was cured in 92%, but

storage symptoms completely resolved in only

12% and were improved and required medication

in 69%. SUI recurred in 18%. These data clearly

support aggressive repeat urethrolysis in the face of

initial failure, at least for retention and incomplete

emptying. In general, if an aggressive transvaginal

urethrolysis fails, then a retropubic approach may

be considered. In cases where it is unknown how

aggressive the initial transvaginal procedure was

or whether only a sling incision was done, then a

repeat transvaginal approach may be appropriate.

Conclusions

Even with the introduction of newer, less invasive

anti-incontinence procedures (TVT, TOT), urethral

obstruction after incontinence surgery remains a

bothersome problem for the patient and a challeng-

ing dilemma for the surgeon. The diagnosis usually

is based on signs and symptoms, but urodynamic

definitions of BOO, cystourethroscopy, and imag-

ing are helpful. The decision to intervene is based

on the degree of bother and the clinician’s sus-

picion of obstruction. In this discussion, patients

must be informed of the possibility of recurrent

SUI and residual or de novo irritative symptoms

with surgical treatment of obstruction. Fortunately,

the various surgical options are highly successful

at restoring efficient voiding. Continued effort will

be directed at identifying improved methods of

diagnosis and treatment of anti-incontinence pro-

cedure obstruction and associated irritative voiding

symptoms.

References

1. Rosenblum N , Nitti VW. Post-urethral suspension

obstruction . Curr Opin Urol 2001 ; 11 : 411 – 416 .

2. Leach GE , Dmochowski RR , Appell RA , et-al.

Female stress urinary incontinence clinical guidelines

panel summary report on surgical management of

female stress urinary incontinence. The American

Urological Association . J Urol 1997 ; 158 : 875 – 880 .

3. Morgan TO , Westney OL , McGuire EJ . Pubovaginal

sling: 4-year outcome analysis and quality of life

assessment . J Urol 2000 ; 163 : 1845 – 1848 .

4 . Dunn JS , Bent AE , Ellerkman RM , et-al. . Voiding

dysfunction after stress incontinence: Literature and

survey results . Int Urogynecol J 2004 ; 15 : 25 – 31 .

5 . Klutke C , Siegel S , Carlin B , et-al. . Urinary retention

after tension-free vaginal tape procedure: Incidence

and treatment . Urology 2001 ; 58 : 697 – 701 .

6. Niemczyk , Klutke JJ , Carlin BI , et-al. United States

experience with tension-free vaginal tape procedure

for urinary stress incontinence: Assessment of safety

and tolerability . Tech Urol 2001 ; 7 : 261 – 265 .

7 . Rardin CR , Rosenblatt PL , Kohli N , et-al. . Release

of tension-free vaginal tape for the treatment of

refractory postoperative voiding dysfunction . Obstet

Gynecol 2002 ; 100 : 898 – 902 .

8 . Sander P , Moller LM , Rudnicki PM , et-al. . Does the

tension-free vaginal tape procedure affect the void-

ing phase? Pressre-flow studies before and 1 year

after surgery . BJU Int 2002 ; 89 : 694 – 698 .

9 . Tamussino K , Hanzal E , Kolle D , et-al. . The Austrian

tension-free vaginal tape registry . Int Urogynecol J

2001 ; 12 (Suppl 2) : S28 – S29 .

10 . Kuuva N , Nilsson CG . A nationwide analysis

of complications associated with the tension-free

vaginal tape (TVT) procedure . Acta Obstet Gynecol

Scand 2002 ; 81 : 72 – 77 .

11 . Moran PA , Ward KL , Johnson D , et-al. . Tension-free

vaginal tape for primary genuine stress inconti-

nence: A two centre follow-up study . BJU Int 2000 ;

86 : 39 – 42 .

12 . Rackley RR , Abdelmalak JB , Tchetgen MB ,

et-al. . Tension-free vaginal tape and percutaneous

vaginal tape sling procedures . Tech Urol 2001 ; 7 (2) :

90 – 100 .

13 . Delorme E , Droupe S , Tayrac R , et-al. . Transobturator

tape (Uratape): A new minimally invasive procedure

36. Voiding Dysfunction after Female Anti-Incontinence Surgery 507

to treat female urinary incontinence . Eur Urol 2004 ;

45 : 203 – 207 .

14 . Costa P , Grise P , Droupy S , et-al. . Surgical treatment

of female stress urinary incontinence with a trans-

obturator-tape (TOT) Uratape: Short term results

of a prospective multicentric study . Eur Urol 2004 ;

46 : 102 – 107 .

15 . Deval B , Ferchaux J , Berry R , et-al. . Objective

and subjective cure rates after trans-obturator tape

(OBTAPE) treatment of female urinary inconti-

nence . Eur Urol 2006 ; 49 : 373 – 377 .

16 . Atherton MJ , Stanton SL . A comparison of blad-

der neck movement and elevation after tension-free

vaginal tape and colposuspension . BJOG 2000 ;

107 : 1366 – 1370 .

17 . Sarlos D , Kuronen M , Schaer GN . How does ten-

sion-free vaginal tape correct stress incontinence?

Investigation by perineal ultrasound . Int Urogynecol

J 2003 ; 14 : 395 – 398 .

18 . Lo TS , Horng SG , Liang CC , et-al. . Ultrasound

assessment of mid-urethra tape at three-year fol-

low-up after tension-free vaginal tape procedure .

Urology 2004 ; 63 : 671 – 675 .

19 . Minaglia S , Ozel B , Hurtado E , et-al. . Effect of

transobturator tape procedure on proximal urethral

mobility . Urology 2005 ; 65 (1) : 55 – 59 .

20 . FitzGerald MP , Brubaker L . The etiology of urinary

retention after surgery for genuine stress inconti-

nence . Neurourol Urodyn 2001 ; 20 : 13 – 21 .

21 . Smith CP , O’Leary M , Erickson J , et-al. . Botulinum

toxin urethral sphincter injection resolves urinary

retention after pubovaginal sling operation . Int

Urogynecol J 2002 ; 13 : 185 – 186 .

22 . Carr LK , Webster GD . Voiding dysfunction follow-

ing incontinence surgery; diagnosis and treatment

with retropubic or vaginal urethrolysis . J Urol 1997 ;

157 : 821 – 823 .

23 . Miller EA , Amundsen CL , Toh KL , et-al. .

Preoperative urodynamic evaluation may predict

voiding dysfunction in women undergoing pub-

ovaginal sling . J Urol 2003 ; 169 : 2234 – 2237 .

24 . Weinberger MW , Ostergard DR . Postoperative cath-

eterization, urinary retention and permanent void-

ing dysfunction in women undergoing pubovaginal

sling . Obstetand Gynecol 1996 ; 87 : 50 – 54 .

25 . Bhatia NN , Bergman A . Urodynamic predictability

of voiding following incontinence surgery . Obstet

Gynecol 1984 ; 63 : 85 – 91 .

26 . Gateau T , Faramarzi-Roques R , Le Norman L , et-al. .

Clinical and urodynamic repercussions after TVT

procedure and how to diminish patient complaints .

Eur Urol 2003 ; 44 : 372 – 376 .

27 . Wang AC , Chen MC . The correlation between preop-

erative voiding mechanism and surgical outcome of

the tension-free vaginal tape procedure, with refer-

ence to quality of life . BJU Int 2003 ; 91 : 502 – 506 .

28 . Kawashima H , Kouzo H , Okada N , et-al. . The

importance of studying pressure-flow for predicting

postoperative voiding difficulties in women with

stress urinary incontinence: A preliminary study

that correlates low Pdet × Qave with postoperative

residual urine . Urol Res 2004 ; 32 : 84 – 88 .

29 . Kobak WH , Walters MD , Piedmonte MR .

Determinants of voiding after three types of incon-

tinence surgery: A multivariable analysis . Obstet

Gynecol 2001 ; 97 : 86 – 91 .

30 . McLennan MT , Melick CF , Bent AE . Clinical and

urodynamic predictors of delayed voiding after

fascia lata suburethral sling . Obstet Gynecol 1998 ;

92 : 608 – 612 .

31 . Sokol AI , Jelovsek JE , Walters MD , et-al. . Incidence

and predictors of prolonged urinary retention after

TVT with and without concurrent prolapse surgery .

Am J Obstet Gynecol 2005 ; 192 : 1537 – 1543 .

32 . Leng WW , Davies BJ , Tarin T , et-al. . Delayed

treatment of bladder outlet obstruction after sling

surgery: Association with irreversible bladder dys-

function . J Urol 2004 ; 172 : 1379 – 1381 .

33 . Karram MM , Segal JL , Vassallo BJ , Kleeman SD .

Complications and untoward effects of the tension-

free vaginal tape procedure . Obstet Gynecol 2003 ;

101 : 929 – 932 .

34 . Croak AJ , Schulte V , Peron S , et-al. . Transvaginal

tape lysis for urinary obstruction after tension-

free vaginal tape placement . J Urol 2003 ; 169

: 2238 – 2241 .

35 . Chassagne S , Bernier PA , Haab F , et-al. . Proposed

cutoff values to define bladder outlet obstruction in

women . Urology 1998 ; 51 : 408 – 411 .

36 . Lemack GE , Zimmern PE . Pressure flow analysis

may aid in identifying women with outflow obstruc-

tion . J Urol 2000 ; 163 : 1823 – 1828 .

37 . Defreitas GA , Zimmern PE , Lemack GE , Shariat

SF . Refining diagnosis of anatomic female bladder

outlet obstruction: Comparison of pressure-flow

study parameters in clinically obstructed women

with those of normal controls . Urology 2004 ; 64

: 675 – 681 .

38 . Nitti VW , Tu LM , Gitlin J . Diagnosing bladder

outlet obstruction in women . J Urol 1999 ; 161

: 1535 – 1540 .

39 . Blaivas JG , Groutz A . Bladder outlet obstruc-

tion nomogram for women with lower urinary

tract symptomatology . Neurourol Urodyn 2000 ; 19 :

553 – 556 .

40 . Akikwala TV , Fleischman N , Nitti VW . Comparison

of diagnostic criteria for female bladder outlet

obstruction . J Urol 2006 ; 176 : 2093 – 2097 .

508 P. Padmanabhan and V.W. Nitti

41 . Foster HE , McGuire EJ . Management of urethral

obstruction with transvaginal urethrolysis . J Urol

1993 ; 150 : 1448 – 1451 .

42 . Nitti VW , Raz S . Obstruction following anti-

incontinence procedures: Diagnosis and treat-

ment with transvaginal urethrolysis . J Urol 1994 ;

152 : 93 – 98 .

43 . Paick J , Hyeon JK , Shin JW , et-al. . Complications

associated with the tension-free vaginal tape pro-

cedure: The Korean experience . Int Urogynecol J

2005 ; 16 : 215 – 219 .

44 . Mishra VC , Mishra N , Karim OM , et-al. . Voiding

dysfunction after tension-free vaginal tape: A

conservative approach is often successful . Int

Urogynecol J 2005 ; 16 : 210 – 214 .

45 . Cross CA , Cespedes RD , English SF , McGuire

EJ . Transvaginal urethrolysis for urethral obstruc-

tion after anti-incontinence surgery . J Urol 1998 ;

159 : 1199 – 1121 .

46 . Webster GD , Kreder KJ . Voiding dysfunction fol-

lowing cystourethropexy: Its evaluation and man-

agement . J Urol 1990 ; 144 : 670 – 673 .

47 . Segal J , Steele AC , Vassallo BJ , et-al. . Various

surgical approaches to treat voiding dysfunction fol-

lowing anti-incontinence surgery . Int Urogynecol J

2006 ; 17 : 372 – 377 .

48 . Starkman JS , Wolter C , Gomelsky A , et-al. . Voiding

dysfunction following removal of eroded synthetic

mid urethral slings . J Urol 2006 ; 176 : 1040 – 1044 .

49 . Goldman HB . Simple sling incision for the treat-

ment of iatrogenic urethral obstruction . Urology

2003 ; 62 : 714 – 718 .

50 . Long C , Lo T , Liu C , et-al. . Lateral excision of

tension-free vaginal tape for the treatment of iatro-

genic urethral obstruction . Obstet Gynecol 2004 ;

104 : 1270 – 1274 .

51 . Ghoniem GM , Elgamasy AN . Simplified surgical

approach to bladder outlet obstruction following

pubovaginal sling . J Urol 1995 ; 154 : 181 – 183 .

52 . Kusuda L . Simple release of pubovaginal sling .

Urology 2001 ; 57 : 358 – 359 .

53 . Amundsen CL , Guralnick ML , Webster GD .

Variations in strategy for the treatment of urethral

obstruction after a pubovaginal sling procedure . J

Urol 2000 ; 164 : 434 – 437 .

54 . Nitti VW, Carlson KV, Blaivas JG, Dmochowski RR .

Early results of pubovaginal sling lysis by midline

sling incision Urology 2002 ; 59 : 47 – 52 .

55 . Thiel DD , Pettit PDM , McCllelan WT , et-al. . Long-

term urinary continence rates after simple sling

incision for relief of urinary retention following

fasca lata pubovaginal slings . J Urol 2005 ; 174 (5) :

1878 – 1881 .

56. Leach GE , Raz S. Modified Pereyra bladder neck

suspension after previously failed anti-incontinence

surgery. Surgical technique and results with long-

term follow-up . Urology 1984 ; 23 : 359 – 362 .

57. Huckabay C , Nitti VW. Diagnosis and treat-

ment of obstruction following incontinence surgery:

Urethrolysis and other techniques . In: Cardoza L ,

Stastkin D , eds. Textbook of female urology and

urogynecology , 2nd edn . Oxford, UK , Isis Medical

Media , 2006 : 981 – 995 .

58 . Carey JM , Chon JK , Leach GE . Urethrolysis with

Martius labial fat pad graft for iatrogenic bladder

outlet obstruction . Urology 2003 ; 61 : 21 – 25 .

59 . Goldman HB , Rackley RR , Appell RA . The efficacy

of urethrolysis without re-suspension for iatrogenic

urethral obstruction . J Urol 1999 ; 161 : 196 – 199 .

60 . Petrou SP , Brown JA , Blaivas G . Suprameatal

transvaginal urethrolysis . J Urol 1999 ; 161 :

1268 – 1271 .

61 . Zimmern PE , Hadley HR , Leach GE , Raz S . Female

urethral obstruction after Marshall–Marchetti–

Krantz operation . J Urol 1987 ; 138 : 517 – 520 .

62 . Petrou SP , Young PR . Rate of recurrent stress uri-

nary incontinence after retropubic urethrolysis . J

Urol 2002 ; 167 : 513 – 615 .

63 . Scarpero HM , Dmochowski RR , Nitti VW . Repeat

urethrolysis after failed urethrolysis for iatrogenic

obstruction . J Urol 2003 ; 169 : 1013 – 1016 .

509

Part VIII

Social Aspects of Incontinence

511

Introduction

Much of the literature on stress urinary incon-

tinence (SUI) and pelvic organ prolapse briefly

mentions costs or cost effectiveness, but few actu-

ally involve formal cost analysis [1, 2, 3, 4] . There

are several relevant types of cost analysis, from the

simple to the very sophisticated:

• Cost of illness analysis (COI) typically quantifies

the burden of medical expenses (direct costs) and

the resulting value of lost productivity (indirect

costs) attributable to a specific condition such as

an illness or injury [5] .

• Cost effectiveness analysis (CEA) measures the

costs and consequences of two or more diag-

nostic or treatment pathways related to a single

common effect or health outcome. It then sum-

marizes the results in ratios that demonstrate the

cost of achieving a unit of health effect for dif-

ferent types of patients and for variations of the

intervention [6] .

• Cost utility analysis (CUA) is a form of CEA in

which particular attention is paid to the quality

of health outcome related to treatment. In CUA,

health effects are expressed in terms of quality-

adjusted life years (QALYs) [7] . A QALY is a

measure of health outcome that assigns to a given

period of time a weighting that corresponds to the

health-related quality of life during that period,

and then aggregates these weights across time

periods. The QALY is important because it con-

siders both quantity and quality of life.

• Cost benefit analysis estimates the net social ben-

efit of an intervention by comparing the benefit

of the intervention with the cost, with all benefits

and costs measured in dollars [7] . Health out-

comes are converted into monetary values using

“willingness to pay” (the value an individual

would pay for reduction in illness severity) or

“risk of death” or “human capital” methods (an

individual’s value to society based on productiv-

ity or future wages) [4, 8] .

SUI and Costs

Research into SUI usually is limited to women,

because they are the most commonly affected. Very

little has been done to study the economic burden

of SUI in men, although postprostatectomy stress

incontinence occurs in up to 20% of patients. This

makes it difficult to determine the actual combined

costs of male and female SUI to society.

Comparison of costs for conservative, medical,

and surgical treatment of SUI also is hampered by a

lack of harmonization in defining SUI, standardiza-

tion of survey methods and validation criteria, and

outcome measures [9, 10] . In addition, studies on

incontinence often combine SUI with overactive

bladder and urge incontinence, making it difficult

to isolate costs specifically related to SUI.

Direct costs of SUI are those borne by both the

health sector and by individual patients and their fam-

ilies. Direct health sector costs ideally should include

supplies, equipment, and health professionals for

Chapter 37

Economic Impact of Stress Urinary

Incontinence and Prolapse: Conservative,

Medical, and Surgical Treatments

Lynn Stothers

512 L. Stothers

both inpatient and outpatient services. Direct costs

carried by the patient range from medications and

protective devices such as pads and diapers to treat-

ments ranging from pelvic floor muscle training

(PFMT), bladder training, electrical stimulation,

vaginal or urethral devices, to drugs and surgery.

The costs of pads and protective undergarments

are the most commonly compared direct cost in the

SUI literature, but the costs of these products vary

widely, and information about the actual product

and cost often is not provided in the description

of the study. For example, in chart reviews, if the

patient reports using three pads per day, it is not

known whether they use three small liners which

typically cost a few cents each or a sophisticated

undergarment which may cost as much as a few

dollars per garment.

Indirect costs include lost earnings for both the

patient and family or friends who provide care

for the affected person. Age and working status

are particularly important with respect to indirect

costs. For example, since the prevalence of urinary

incontinence increases dramatically with age, the

working status of the 60+ age group is of particular

importance.

Intangible costs include the monetary value of

pain, suffering, and anxiety from the disease in

question. Intangible costs are difficult to determine

in most cases, and are generally the least well

measured in the literature.

Costs vary to some extent by year, region, prac-

tice patterns in the area, and country. For the sake

of simplicity, all costs from the literature discussed

subsequently have been converted to US$ 2006.

The Economic Burden of SUI

There are few recent European or North American

studies on the economic burden of SUI, which

includes both direct costs such as surgical proce-

dures and hospital stay and indirect costs, such as

lost productivity. Even when studies are published,

it is difficult to generalize costs from one jurisdic-

tion to another due to the different health care

system models. Payne estimates the overall cost

of urinary incontinence to the American economy

to be $16 billion dollars annually, but does not

differentiate the costs of SUI from other forms of

incontinence [11] .

In 2002, Birnbaum, Leong, and Kabra estimated

the lifetime medical costs of cardiovascular disease,

diabetes, and SUI in women under and over 65 in

the United States. For women under 65, annual

medical costs were extrapolated from claims from

a large employer ( n > 100,000) with locations

throughout the United States and a wide range

of job positions. For women 65 years of age and

older, calculations were based on the estimate for

those <65 years of age, combined with published

government statistics. The incremental lifetime

medical cost (the difference between the total med-

ical costs of patients with SUI compared to those

of controls without the condition) was $58,000

for SUI, compared to $233,000 for diabetes and

$423,000 for cardiovascular disease. Incremental

medical costs for women treated for SUI increase

significantly as women age, from $3,300 annually

to $15,000 annually. A woman with SUI has total

lifetime medical costs 1.8 times greater than the

costs of a similar woman without SUI [12] .

The Birnbaum team continued their research in

this area with a 2004 claims data analysis (using

the same employer database) of the cost of SUI.

Using an incremental cost-of-illness model (which

controls for comorbid conditions and patient demo-

graphics) patients with SUI had direct costs that

were 134% more than those for their controls and

indirect costs that were 163% more than those

for controls. Surgical treatment widened the gap

substantially between patients and controls – for

patients who received surgical treatment for their

SUI, annual direct medical costs (in the year of

treatment) were 206% higher than for controls. The

authors estimated that the annual average direct

medical costs of SUI for 1 year (1998) were $5,642

and the indirect workplace costs were $4,208 per

patient [13] .

Turner et al. estimated the prevalence and costs

of clinically significant urine storage conditions

including leakage, urgency, frequency, and noctu-

ria in community-dwelling men and women ≥ 40

years of age. Prevalence estimates were based on

responses from 23,000 questionnaires mailed to a

randomly selected sample, and costs were based on

home interviews of 613 individuals with urine stor-

age conditions and 523 controls. Total annual cost

to the United Kingdom’s National Health Service

was estimated to be just over $1 billion (1999/2000

prices) ($568 million and $437 million, for men

37. Economic Impact of Stress Urinary Incontinence and Prolapse 513

and women, respectively). This was approximately

1.1% of National Health Service spending for the

1999/2000 fiscal year. Individuals reported bear-

ing a substantial cost as well – $55 million and

$334 million, for men and women, respectively.

In addition, intangible costs, based on willingness

to pay as an indicator of the value of alleviating

symptoms were estimated to be an additional

$1.25 billion ($564 million and $690 million, for

men and women, respectively). Costs associated

specifically with SUI were not separated out in this

study. Interestingly, cost of treatment was greater

for males, while individual and indirect costs

were greater for females [14] . O’Sullivan et al.

found that it was more costly and often more time

consuming to treat women with mild compared to

moderate SUI [15] (see Table 37.1 ).

Diagnostic Testing

Two preoperative testing strategies for women

with pelvic organ prolapse and SUI symptoms

were compared using predicted success rate (cure

of urinary incontinence) and cost-effectiveness of

treatment as outcomes. According to Weber et al.,

“the outcome of importance for a test is not merely

diagnostic accuracy. For testing to be worthwhile,

it must be accompanied by a clinically important

improvement in outcome (effectiveness of treat-

ment)” [16] . A decision–analytic approach was

used to compare basic office evaluation and urody-

namic testing for accuracy in assignment of diag-

noses of urinary incontinence for women with SUI

symptoms. Based on published data used to predict

the probability of outcomes (cure rate of SUI and

need for retreatment), the success of treatment and

costs were calculated to assess cost-effectiveness.

Basic office evaluation and urodynamic testing had

the same cure rate (96%) after initial and secondary

treatment. The average cost of treatment was lower

for basic office evaluation than urodynamic test-

ing ($4,959 vs. $5,302, respectively). The cost of

achieving a single additional cure was achieved by

urodynamic testing at a cost of $328,601 relative to

basic office evaluation. The only scenario in which

basic office evaluation was more cost-effective

than urodynamic testing was unlikely because it

required that detrusor instability occur in less than

8% or the cost of urodynamic testing was less than

$103 [16] . For example, Lemack and Zimmern

reported the 2000 Medicare reimbursement for

urodynamic studies to be $214.82 [17] .

To minimize diagnostic costs, Lemack and

Zimmern conducted a retrospective study to deter-

mine whether previous surgical history for inconti-

nence and a validated lower urinary tract symptom

questionnaire would have identified those who

needed urodynamic testing before surgery for SUI.

No single test, including physical examination, his-

tory, voiding diaries, and validated questionnaires,

proved adequate for diagnosing incontinence and

in particular in differentiating SUI from detru-

sor instability. However, the authors reported a

response of “2” or “3” to question 3 on the UDI-6

(ie, leakage related to physical activity or straining

was moderately or greatly bothersome) combined

with a history of previous surgery correctly identi-

fied 91% of critical diagnoses while reducing costs

substantially. Using this approach in their popula-

tion of 172 consecutive women who completed

the UDI-6 and underwent urodynamic testing, the

costs of testing would have been $7,089.06 with a

total cost savings of $29,859.98 [17] .

Table 37.1. Cost of treating and achieving objective versus subjective cure of stress urinary incontinence in

mildly and moderately incontinent women .

Median cost of treatment Cost to achieve an objective

pad test cure Cost to achieve a subjective

cure

Mildly incontinent $99.52 $98.15 $91.04

Moderately incontinent $84.65 $74.49 $72.98

Wilcoxon P value P = 0.21 P = 0.13 P = 0.11

From [15]

514 L. Stothers

Conservative Management

The annual cost of protective devices and related

costs such as laundry often are borne as out-of-

pocket expenses by those suffering from SUI,

although some jurisdictions, such as Germany,

reimburse some of these expenses [18] . The cost of

diagnosis and treatment with drugs and diapers for

SUI for women over 40 in Italy was estimated to be

$221.87 [19] . A 1998 study in the United Kingdom

showed the preoperative cost of protective pads and

towels before surgery to be $7.11/month (mean

$15.89), although 15% of women spent over $37/

month while others used self-made pads or towels

and had zero cost appointed to them for the pur-

pose of the study. After surgery for SUI, median

costs dropped sharply to $2.49 (mean $5.48) per

month [20] .

Pharmaceutical Management

The pharmaceuticals used in the treatment of SUI

historically have been available over the counter

in many countries as treatment for colds and flu.

They include the α -adrenoceptor agonists, some

of which have now been removed from the market

in certain countries due to serious side effects.

Because they are not prescription drugs, informa-

tion on costs related to these medications often is

not captured in studies.

Brunenberg et al. used a Markov model to exam-

ine the cost-effectiveness of duloxetine alone and

duloxetine (Eli Lily and Company, brand names

Cymbalta/Yentreve, Xeristar, or Ariclaim) after

inadequate response to PFMT in women aged

≥ 50 years with SUI. Duloxetine, a serotonin and

norepinephrine reuptake inhibitor used primarily

for major depressive disorders, has been shown in

a small number of studies to improve the quality

of life of women with SUI. It is approved for use

in Europe but is not FDA approved for this use

in the United States. According to their model,

PFMT would cost $0.04 per incontinence episode

avoided compared to no treatment. Duloxetine

taken when PFMT has failed would cost $4.85 per

incontinence episode avoided. PFMT had a high

probability of being more cost-effective up to $4.64

per incontinence episode avoided. Beyond that

point, duloxetine after failed PFMT had the highest

cost-effectiveness probability, but would require

society to pay an additional $4.88 to avoid a single

incontinence episode [21] .

Surgical Management

It was estimated that, in 1991, the direct cost of

surgical and other procedures for the treatment of

SUI in the United States was $0.5 billion. Although

this number has likely grown substantially, the

growing population and trend toward more surgi-

cal management of SUI is likely offset by more

cost-effective procedures [22] . Where possible this

section is organized from least to most invasive.

Cost of Illness Analysis

COI has been performed for a variety of individual

and comparative surgical approaches. Cost analysis

does not allow a comparison of cost-effectiveness

among procedures because it does not compare

success rates and the costs associated with reop-

eration.

Bulking Agents

Berman and Kreder compared the cost of endo-

scopic transurethral collagen injection and fascia

lata sling cystourethropexy for the treatment of

intrinsic sphincter deficiency, type III genuine SUI

(Table 37.2 ). Immediate costs for fascia lata pro-

cedures were an average of $10,381 ± 1,440 com-

pared to $4,996 ± 885 for collagen. However, this

does not take into consideration cost-effectiveness.

At follow-up (mean 14.9 months for cystoure-

thropexy and 21.3 months for collagen injection),

cystourethropexy had better outcome in terms of

continence rate (71.4 and 26.7%, respectively) and

a lower reoperation rate (one secondary operation

for the entire cystourethropexy group versus an

average of 1.6 collagen injections per patient in the

collagen group). Morbidity was higher in the cys-

tourethropexy group. CEA was not performed, but

the authors concluded that the sling procedure was

likely more cost-effective due to the higher success

rate with fewer reoperations [23] .

Maher et al. compared pubovaginal sling ver-

sus transurethral Macroplastique™ (Uroplasty,

Minnestota, USA) in terms of hospital stay, oper-

ating room costs, and the cost of the disposable

37. Economic Impact of Stress Urinary Incontinence and Prolapse 515

Macroplastique. The average cost per patient for

Macroplastique (including reoperations) ($3,378.55)

was significantly greater than the cost for the sling

($2,680.24) ( P ≤ 0.0001) [24] . A detailed cost

breakdown was not provided.

The authors of a Cochrane review on periure-

thral injection of bulking agents for treatment of

SUI identified the need for cost-effectiveness stud-

ies before any specific recommendation could be

made [25] .

Laparascopic Procedures

Walter et al. retrospectively analyzed chart data

on patients undergoing laparoscopic ( n = 76) or

open ( n = 143) Burch retropubic urethropexy for

SUI. Mean hospital charges were $9,900 (SD ±

$2,400) for laparoscopic procedures compared to

$9,400 (SD ± $2,100) for open procedures. Given

the sample size, the 5% difference in costs was not

considered statistically significant [26] . In contrast

to studies that show stand-alone laparoscopic pro-

cedures to be more cost-effective than open proce-

dures [16, 23, 24, 27, 28, 29, 30, 31, 32, 33, 34] , the

authors concluded that there is no cost advantage to

the laparoscopic approach when concurrent trans-

vaginal repairs are required to correct a coexisting

pelvic organ prolapse.

In a Cochrane review of laparoscopic colposus-

pension, the laparoscopic approach was found to

be more costly than the open procedure [35] . Kohli

et al. found that the higher surgical costs were

not offset by shorter length of stay in a retrospec-

tive chart review of 21 women undergoing open

Burch colposuspension versus 17 undergoing the

same procedure laparoscopically. The laparoscopic

group had significantly longer operative time (110

vs 66 min, P < 0.01), resulting in increased operat-

ing room charges ($3,479 vs $2,138 respectively, P

< 0.001). Mean length of stay was 1.3 days in the

laparoscopic group versus 2.1 days for the open

group ( P < 0.005), incurring accommodation costs

of $4,960 versus $4,079, respectively ( P < 0.01).

Some of the higher operating rooms costs for the

laparoscopic group could be attributed to the use

of disposable rather than reusable equipment. In

contrast, Loveridge et al. reported no significant

difference in overall costs in a retrospective COI of

laparoscopic ( n = 26) versus open colposuspension

( n = 23). The authors concluded that higher surgi-

cal costs were offset by shorter length of stay ( P =

0.533). However, not all surgical costs (eg, nursing

time in the operating room) were considered, and

the mean difference in costs (the only cost data

presented) does not support this conclusion. In

addition, the length of stay reported for these pro-

cedures is not representative of current practice in

North America [36] .

Slings and Burch Procedures

Quievy et al. compared the tension-free vaginal

tape (TVT) ( n = 21) to Burch open colposuspen-

sion ( n = 17). Costs included medical devices,

drugs, laboratory procedures, operating time,

hospital stay, and duration of postoperative fol-

low-up. The Burch cost $5,125.47 compared to

$2,133.71 for TVT. The difference in cost was

attributed to shorter operating room times and

hospital stay [34] .

Cost-Effectiveness

Subak et al. critiqued research on new gynecologic

procedures and found that many studies do not

adhere to basic recommended analytic guidelines

for CEA [4] . According to the authors, “many of

these studies described their research methodol-

ogy as ‘cost-effectiveness analysis’ but either

failed to include an evaluation of effectiveness or

failed to combine cost and effectiveness into a

single summary measure (ie, cost per life-year

Table 37.2. Average costs for individual procedures

and percentages of total costs for fascia lata sling

cystourethropexy versus collagen injection.

Economic

parameters

Fascia lata

(n = 14)

Collagen

(n = 14)

Hospital room $1,132 ± 306 (11) $0 (0)

Supply $398 ± 122 (4) $63 ± 44 (1.3)

Pharmacy $492 ± 267 (5) $112 ± 82 (2.2)

Radiology $2.8 ± 10.4 (< 1) $85 ± 163 (1.7)

Collagen $0 (0) $1,974 ± 412 (40)

Operating room $3,706 ± 694 (36) $643 ± 245 (13)

Postoperative care $1,233 ± 441 (12) $627 ± 215 (13)

Laboratory $63 ± 121 (< 1) $107 ± 91(2)

Total hospital cost $7,004 ± 1,185 (68) $3,883 ± 822 (78)

Physician fee $3,378 ± 807 (33) $1,112 ± 130 (22)

Total costs $10,381 ± 1,440 $4,996 ± 885

Mean US dollars ± standard deviation (percent). From [23]

516 L. Stothers

gained). In addition, many articles stated in their

conclusions that one intervention was more ‘cost-

effective’ than an alternative intervention without

performing a CEA.” In addition, they found stud-

ies that compared effectiveness and costs of two or

more procedures without combining the measures

to perform a formal CEA. The authors encouraged

investigators to be more precise in their use of the

term “cost-effective.”

Persson et al. conducted a cost-effectiveness

study comparing laparoscopic colposuspension

with TVT in 79 women presenting for evaluation

of SUI symptoms in terms of direct costs to the

hospital owner (the county) and included perioper-

ative and postoperative hospital care and outpatient

medical care (Table 37.3 ). TVT was significantly

more expensive to perform than laparoscopic

colposuspension. Sensitivity analysis showed that

surgical time and anesthesia were the areas of

greatest difference. The high investment costs of

the TVT kit outweighed the longer surgical time

for laparoscopic colposuspension. The authors

suggest that differences might have been less if

performed by other researchers with more exper-

tise in the TVT procedure, as the surgical time was

44.9 min compared to 29 min reported by Ulmsten

et al. [32] and a median time of 22 min reported by

Nilsson and Kuuva [31, 33].

Kung et al. evaluated cost-effectiveness of open

versus laparoscopic Burch procedure. Costs included

professional fees, diagnostic tests, capital and dis-

posable equipment, hospital stay, and indirect costs.

Costs of laparoscopic Burch repair were signifi-

cantly less than for the open procedure ($2,398 vs

$5,692), primarily due to the shorter length of hos-

pital stay associated with the laparoscopic procedure

(3.6 days vs 11.2 days, considerably longer than

routinely seen in North America) [37] . Buller and

Cundiff converted the length of stay costs to stand-

ard North American practice (1 day vs 2–3 days) and

concluded that the laparoscopic procedure was still

less expensive than the open procedure ($666.11 vs

$1,016.42–$1,524.64, respectively) [38] . According

to Subak et al., the original study met eight of the ten

principles for performing CEA, but would have been

more informative if follow-up had been longer than

1–2 years, since life expectancy following surgery is

far greater [4] .

Cost Utility

In a large, multicenter, randomized controlled

trial, Manca et al. employed a cost-utility analy-

sis with health outcomes expressed as QALYs.

Costs for operating room, hospital, follow-up,

complications, reoperations, and further treatments

to 6 months following surgery were considered.

TVT resulted in a mean cost saving per patient

of US$451 (95% CI $373–$633) compared with

colposuspension while generating a mean improve-

ment in health outcomes of 0.01 (95% CI –0.01 to

0.03). The probability of TVT being, on average,

less costly than colposuspension was 100%. The

probability of TVT being more cost-effective than

colposuspension was 94.6% if the decision maker

was willing to pay $55,700 per additional QALY.

The higher operating room costs associated with

TVT were offset by a shorter hospital stay [30] .

Cody et al. performed a systematic review of

82 published studies on the effectiveness and

Table 37.3. Total costs to the county in US$ for lapar-

oscopic colposuspension versus TVT procedure .

Economic parameters

Laparoscopic

colposuspension

( n = 32) TVT

(n = 38)

Basic costs a ($0.73 min −1 ) $92.97 $69.86

Anesthesia costs a

($4.19 min −1 )

$491.65 $325.18

Surgical costs a

($0.75 min −1 )

$45.56 $32.93

Surgical materials b $130.18 $544.59

Hospital care c $797.94 $726.34

Depreciation of video

equipment

$22.97 $0.00

Depreciation of laparo-

scopic instruments

$22.21 $0.00

Outpatient visits to a physi-

cian ($74.41 per visit) or

a nurse ($29.61 per visit)

$21.83 $14.94

Average total cost per

procedure

d

$1,625.71 $1,714.24

Total costs including

reoperations

$1,678.11 $1,867.28

From [31]. Note: Original costs presented in 2001 Euros,

converted to 2006 US dollars

a Mean times are multiplied with the specific costs per minute

b Includes drapes, gloves, gowns, packing, and sterilization of

instruments

c Includes costs for postoperative analgesics

d P < 0.01

37. Economic Impact of Stress Urinary Incontinence and Prolapse 517

cost-effectiveness of TVT for the treatment of SUI.

Their findings are summarized in Table 37.4 .

In terms of cost utility, compared to open col-

posuspension, TVT had a lower mean cost ($503)

and the same or more QALYs (+0.00048). The

likelihood of TVT being considered cost-effective

was 100% if decision makers were unwilling to

pay for an additional QALY, and 95% if they were

prepared to pay up to $37,745 for an additional

QALY. TVT was more likely to be considered cost-

effective than other surgical procedures if one can

assume the following: traditional slings have the

same effectiveness as open colposuspension and

also are more costly, laparoscopic colposuspension

has the same or lower effectiveness as open colpo-

suspension and similar costs, and injectable agents

are less effective than TVT but cost more [10] .

Conservative versus Surgical

Management of SUI in Women

Ramsey et al. used a Markov cohort simulation

to calculate expected costs for behavioral therapy,

medications, and surgery for the treatment of SUI

in elderly women. Decision trees were created for

each treatment, incorporating treatment efficacy

rates stated in the Agency for Health Policy and

Research guideline for urinary incontinence. Two

representative, plausible scenarios were used: (1)

initial treatment with behavioral therapy and (2)

treatment of behavioral therapy failures with

medication (phenylpropanolamine plus estrogen)

and initial treatment with medication and treatment

of medication failures with surgery (needle suspen-

sion) (see Fig. 37.1 for the decision tree) [39] .

Ten-year expected costs per patient, in 1994

dollars, from lowest to highest, were $25,388

for needle suspension surgery, $52,021 for phe-

nylpropanolamine (no longer available in some

countries due to serious side effects) and estrogen,

$68,924 for behavioral therapy, and $86,726 for

untreated incontinence. Behavioral and pharma-

cological therapies were less costly only if life

expectancy was less than 3.5 years. Significant

factors were the likelihood of a patient entering

a nursing home, the cost of nursing home care,

and the long-term relapse rate after surgery. On

the basis of data from the urinary incontinence

guideline, the authors concluded that early surgi-

cal intervention was the least costly treatment for

chronic stress incontinence in elderly women.

Unfortunately, the study was performed in 1996

and predates many of the more recent and cost-

effective advances in surgical treatment of SUI.

However, the lower cost and higher success rates

of some of the newer surgical procedures would

likely strengthen this conclusion [39] .

A retrospective analysis of the direct cost of

SUI among women in a Medicaid population was

performed using data derived from a four-state

Medicaid claims database (MarketScan, Medicaid,

Medstat, Inc.). The database included inpatient,

outpatient, outpatient prescription drugs, and

long-term care claims of approximately 8 million

Medicaid recipients from 1999 to 2002. During

the study period, 13,672 women were newly diag-

nosed with SUI. Of these, only 13% were treated

surgically, usually with a sling procedure. Mean

direct costs for SUI-related care were $795, with

a significant difference between surgically and

nonsurgically managed patients ($3,258 vs $424,

respectively, P < 0.001) [40] .

Conservative versus Surgical

Management of SUI in Men

Brown et al. compared the cost of pads and drip

collectors with outpatient transurethral collagen

injection or placement of an artificial genitouri-

nary sphincter (AGUS) over a 10-year period (see

Table 37.5 ). Conservative management with pads

or drip collectors was significantly less expensive

than collagen or AGUS, while treatment with

Table 37.4. Costs of TVT compared to other treatment

modalities for SUI .

Costs a Costs after 5-year

follow-up

a

TVT $2,101 $2,818–$2,940

Colposuspension $2,484 $3,120–$3,652

Traditional slings $2,528 $3,071–$3,600

Laparoscopic

colposuspension

$2,484 Not available

Injectable agents $2,461 Not available

From [10]

a Operating room, inpatient, and outpatient costs

518 L. Stothers

AGUS was comparable to three or more collagen

injections or the continued use of pads after col-

lagen injection. However, the authors suggest that

“when the benefit of urinary continence is consid-

ered, however, transurethral injection of collagen

or AGUS placement often becomes the preferred

treatment” [41] .

Conclusion

In this era of rising health care costs, procedures

need to be justified not only for their clinical

effectiveness, but for their cost impact. In order to

understand the cost implications of any new proce-

dure, modeling under various clinical scenarios can

Table 37.5. Cost comparison of maintenance and surgical treatment of postprostatectomy incontinence in 1998

US dollars .

Therapy Cost/item Pads/day Items/10 years Cost/10 years

Depends undergarments $0.52 5 18,263 $9,497

Active style pads $0.52 5 18,263 $9,497

Entrust undergarments $0.99 5 18,263 $18,080

Conveen drip collectors $1.05 5 18,263 $19,176

Collagen + 0 pads/day $4,300 0 4 $17,200

Collagen + 2 pads/day $4,300 2 4 $20,999

AGUS × 1 + 0 pads/day $15,400 0 1 $15,400

AGUS × 1 + 2 pads/day $15,400 2 1 $19,199

AGUS × 2 + 0 pads/day $15,400 0 2 $30,800

AGUS × 2 + 2 pads/day $15,400 2 2 $34,599

Collagen = transurethral collagen injection, AGUS = artificial genitourinary sphincter. From [41]

Start

Behavioral

therapy

Pharmacologic

therapy

Surgery

Comply

Not comply

Cure

Partial cure

No change

Cure

Partial cure

No change

Cure

Partial cure

No change

Continue

therapy

Change

therapy

Continue

therapy

Change

therapy

Change

therapy

Continue

therapy

0-6 months 6-12 months

Fig. 37.1. Decision tree representing the Agency for Health Care Policy and Research urinary incontinence treatment

options and outcomes. From [39]

37. Economic Impact of Stress Urinary Incontinence and Prolapse 519

be helpful to determine the place of each procedure

in the clinical decision tree. Access to certain

financial information from individuals, institutions,

and insurance companies is necessary to produce

realistic cost analyses.

References

1. Cammu H , Van Nylen M . Pelvic floor exercises

versus vaginal weigh cones in genuine stress

incontinence . Eur J Obstet Gynecol Reprod Biol

1998 ; 77 (1) : 89 – 93 .

2. Diokno AC , Dimaculangan RR , Lim EU , Steinert

BW . Office based criteria for predicting type II

stress incontinence without further evaluation stud-

ies . J Urol 1999 ; 161 : 1263 – 1267 .

3. Schall CH , Costa RP , Sala FC , Vanni AP , Cortez

JP . Longitudinal urethral sling with prepubic and

retropubic fixation for male urinary incontinence .

Int Braz J Urol 2004 ; 30 : 307 – 312 .

4. Subak LL , Caughey AB . Measuring cost-effective-

ness of surgical procedures . Clin Obstet Gynecol

2000 ; 43 (3) : 551 – 560 .

5. Finkelstein E , Corso P . Cost-of-illness analyses for

policy making: A cautionary tale of use and misuse .

Expert Rev Pharmacoeconomics Outcomes Res

2003 ; 3 (4) : 367 – 369 .

6. Russell LB , Gold MR , Siegel JE , Daniels N , Weinstein

MC . The role of cost-effectiveness analysis in health

and medicine . JAMA 1996 ; 276 (14) : 1172 – 1177 .

7. Gallin JI. Principles and practices of clinical research .

Academic Press , New York , 2002 .

8. Chang RW , Pellisier JM , Hazen GB . A cost-effec-

tiveness analysis of total hip arthroplasty for oste-

oarthritis of the hip . JAMA 1996 ; 275 (11) : 858 – 865 .

9. Hampel C , Artibani W , Espuna Pons M , Haab F ,

Jackson S , Romero J , Gavart S , Papanicolaou S .

Understanding the burden of stress urinary inconti-

nence in Europe: A qualitative review of the litera-

ture . Eur Urol 2004 ; 46 (1) : 15 – 27 .

10. Cody J , Wyness L , Wallace S , Glazener C , Kilonzo

M , Stearns S , McCormack K , Vale L , Grant A .

Systematic review of the clinical effectiveness and

cost-effectiveness of tension-free vaginal tape for

treatment of urinary stress incontinence . Health Tech

Assess 2003 ; 7 (21) : 182 – 189 .

11. Payne CK . Epidemiology, pathophysiology, and

evaluation of urinary incontinence and overactive

bladder . Urology 1998 ; 51 (2A Suppl) : 3 – 10 .

12. Birnbaum H , Leong S , Kabra A . Lifetime medical

costs for women: Cardiovascular disease, diabetes,

and stress urinary incontinence . Women’s Health

Issues 2003 ; 13 : 204 – 213 .

13. Birnbaum HG , Leong SA , Oster EF , Kinchen K ,

Sun P. Cost of stress urinary incontinence. A claims

analysis . Pharmacoeconomics 2004 ; 22 ( 2 ): 95 – 105 .

14. Turner DA , Shaw C , McGrother CW , Dallosso HM ,

Cooper NJ . The cost of clinically significant urinary

storage symptoms for community dwelling adults in

the UK . BJU Int 2004 ; 93 (9) : 1246 – 1252 .

15. O’Sullivan R , Simons A , Prashar S , Anderson P ,

Louey M , Moore KH . Is objective cure of mild

undifferentiated incontinence more readily achieved

than that of moderate incontinence: Costs and 2-year

outcome . Int Urogynecol J Pelvic Floor Dysfunct

2003 ; 14 (3) : 193 – 198 .

16. Weber AM , Walters MD . Cost-effectiveness of uro-

dynamic testing before surgery for women with pel-

vic organ prolapse and stress urinary incontinence .

Am J Obstet Gynecol 2000 ; 183 : 1338 – 1347 .

17. Lemack GE , Zimmern PE . Identifying patients who

require urodynamic testing before surgery for stress

incontinence based on questionnaire information

and surgical history . Urology 2000 ; 55 : 506 – 511 .

18. Jung U . Hilfsmittelversorgung von Patienten mit

Harninkontinenz . Kontinenz 1993 ; 2 : 210 – 213 .

19. Tediosi F , Parazzini F , Bortolotti A , Garattini L.

The cost of urinary incontinence in Italian women.

A cross-sectional study . Pharmacoeconomics 2000 ;

17 ( 1 ): 71 – 76 .

20. Black NA , Bowling A . Impact of surgery for stress

incontinence on the social lives of women . Br J

Obstet Gynaecol 1998 ; 105 (6) : 605 – 612 .

21. Brunenberg DEM , Joore MA , Veraart CPWM ,

Berghmans BCM , van der Vaart CH , Severens

JL . Economic evaluation of duloxetine for the

treatment of women with stress urinary inconti-

nence: A Markov model comparing pharmaco-

therapy with pelvic floor muscle training . Clin Ther

2006 ; 28 (4) : 604 – 618 .

22. Korn AP , Learman LA . Operations for stress uri-

nary incontinence in the United States, 1988–1992 .

Urology 1996 ; 48 (4) : 609 – 612 .

23. Berman CJ , Kreder KJ . Comparative cost analysis

of collagen injection and fascia lata sling cystoure-

thropexy for the treatment of type III incontinence in

women . J Urol 1997 ; 157 : 122 – 124 .

24. Maher CF , O’Reilly BA , Dwyer PL , Carey MP ,

Cornish A , Schluter P . Pubovaginal sling versus

transurethral Macroplastique for stress urinary

incontinence and intrinsic sphincter deficiency: A

prospective randomised controlled trial . Br J Obstet

Gynaecol 2005 ; 112 (6) : 797 – 801 .

25. Pickard R, Reaper J, Wyness L, Cody DJ, McClinton

S, N’Dow, J. Periurethral injection therapy for uri-

nary incontinenc in women. Cochrane Database Syst

Rev 2003;(2):CD003881.

520 L. Stothers

26. Walter AJ , Morse AN , Hammer RA , Hentz

JG , Magrina JF , Cornelia JL , Magtibay PM .

Laparoscopic versus open Burch retropubic ure-

thropexy: Comparison of morbidity and costs when

performed with concurrent vaginal prolapse repairs .

Am J Obstet Gynecol 2002 ; 186 : 723 – 728 .

27. Saidi MH , Gallagher MS , Skop IP , Saidi JA , Sadler

RR , Diaz KC . Extraperitoneal laparoscopic colpo-

suspension: Short-term cure rate, complications,

and duration of hospital stay in comparison with

Burch colposuspension . Obstet Gynecol 1998 ; 92 :

619 – 621 .

28. Kohli N , Jacobs PA , Sze FH , Roat TW , Karram

MM . Open compared with laparoscopic approach

to Burch colposuspension: A cost analysis . Obstet

Gynecol 1997 ; 90 : 411 – 415 .

29. Das S . Comparative outcome analysis of laparo-

scopic colposuspension, abdominal colposuspension

and vaginal needle suspension for female urinary

incontinence . J Urol 1998 ; 160 : 368 – 371 .

30. Manca A , Sculpher MJ , Ward K , Hilton P . A cost-

utility analysis of tension-free vaginal tape versus

colposuspension for primary urodynamic stress incon-

tinence . Br J Obstet Gynaecol 2003 ; 11 : 255 – 262 .

31. Persson J , Teleman P , Eten-Bergquist C , Wolner-

Hanssen P . Cost-analyses based on a prospective,

randomized study comparing laparoscopic colposus-

pension with a tension-free vaginal tape procedure .

Acta Obstet Gynecol Scand 2002 ; 81 : 1066 – 1073 .

32. Ulmsten U , Henriksson L , Johnsson P , Vahos G . An

ambulatory surgical procedure under local anesthe-

sia for treatment of female urinary incontinence . Int

Urogynecol J 1996 ; 7 : 81 – 86 .

33. Nillson CG , Kuuva N . The tension-free vaginal tape

procedure is successful in the majority of women with

indications for surgical treatment of urinary stress incon-

tinence . Br J Obstet Gynaecol 2001 ; 108 : 414 – 419 .

34. Quievy A , Couturier F , Prudhon C , Abram F , Al

Salti R , Ansieau JP . Economic comparison of 2 sur-

gical techniques for the treatment of stress urinary

incontinence in women: Burch’s technique versus

the TVT technique . Prog Urol 2001 ; 11 (2) : 347 – 353 .

35. Dean N, Ellis G, Wilson P, Herbison G.

Laparoscopic colposuspension for urinary incon-

tinence in women. Cochrane Database Syst Rev

2006;3:CD002239.

36. Loveridge K , Malouf A , Kennedy C , Edgington A ,

Lam A . Laparoscopic colposuspension . Is it cost-

effective? Surg Endosc 1997 ; 11 (7) : 762 – 765 .

37. Kung RC , Lie K , Lee P , Drutz HP . The cost-

effectiveness of laparoscopic versus abdominal

Burch procedures in women with urinary stress

incontinence . J Am Assoc Gynecol Laparosc

1996 ; 3 (4) : 537 – 544 .

38. Buller JL , Cundiff GW. Laparoscopic surgeries

for urinary incontinence. A critique of new gynae-

cologic surgical procedures . Clin Obstet Gynecol

2000 ; 43 ( 3 ): 604 – 618 .

39. Ramsey SWT , Bavendam T . Estimated costs of treat-

ing stress urinary incontinence in elderly women

according to the AHCPR clinical practice guide-

lines . Am J Manag Care 1996 ; 2 : 147 – 154 .

40. Kinchen KS , Long S , Chang S , Girts TK , Pantos B .

The direct cost of stress urinary incontinence among

women in a Medicaid population . Am J Obstet

Gynecol 2005 ; 193 : 1936 – 1944 .

41. Brown JA , Elliott DS , Barrett DM . Postprostatectomy

urinary incontinence: A comparison of the cost of

conservative versus surgical management . Urology

1998 ; 51 (5) : 715 – 720 .

521

Urinary incontinence (UI) is a significant health

issue affecting children, women, and men of all

ages, resulting in physical, social, quality of life,

and economic implications for the individual, their

caregivers, and the community. Despite the high

prevalence of UI, it is consistently underdiagnosed

and undertreated, since only one of four women

with symptoms of UI and the related overac-

tive bladder (OAB) seeks clinical help [1– 3] . A

contributing factor is the “stigma” surrounding

bladder control problems and the fact that patients

have many misconceptions about these conditions

and they lack knowledge and understanding about

causes and treatments, thus preventing them from

seeking care [4] . It is believed that raising aware-

ness in the community can improve help-seeking

behavior for men and women with UI. This chapter

will explore the barriers to seeking solutions to UI

and what has been accomplished worldwide in the

area of community awareness.

Barriers to Help-Seeking Behavior

UI usually comes to a health care provider’s (HCP)

attention only when the patient complains of spe-

cific symptoms and in most cases not often [5] .

Recent research has reported that only from 13 to

54% of women and 29 to 48% of men with symp-

toms initiated conversation with a physician about

incontinence or OAB symptoms [2, 6, 7] . It is not

uncommon for women of all ages to wait from

1 to 3 years before seeking help [8] . According

to Mason [9] , following childbirth, only 16% of

women with stress UI sought help for their symp-

toms at 8 weeks and only 25% sought help at 1 year

postpartum. Those who seek treatment tend to have

more significant symptoms that are increasing and

causing more personal distress or impact on physi-

cal activities [2, 10] .

Most are unaware of available treatment while

others have low expectations from treatment. A

national survey [11] of women with symptoms

of OAB indicated that over 50% wait longer than

a year (mean = 3.1 years) before seeking treat-

ment. Reasons cited included not feeling that the

problem was important enough to bother with, not

being asked about symptoms by a HCP, not want-

ing to take medications or undergo surgery, and

feeling that symptoms were something to just live

with. This survey also identified the problem with

current treatment, in this case, drug therapy for

OAB. Women revealed dissatisfaction with current

therapies for OAB because of bothersome adverse

effects, inconvenient dosing schedules, and lack of

efficacy. Many women in this study felt that the

ratio of benefits to undesirable aspects of current

OAB therapies was unacceptable. They expressed

the desire for new treatments that are more effec-

tive and convenient and that offer reduced potential

for adverse effects such as dryness.

To many, urine leakage, urgency, and frequency

are minor problems that can be self-managed and do

not require medical intervention. HCPs may dismiss

bladder control problems as not worthy of investiga-

tion and treatment [12] . Unless specifically addressed

Chapter 38

Community Awareness and Education

Diane K. Newman

522 D.K. Newman

by providers, most patients are too embarrassed by

their symptom of urine leakage to seek medical

help [13] . Even patients reporting with associated

symptoms such as urgency and frequency may still

be too embarrassed to mention urinary leakage.

Consequently, while patients with severe symp-

tomatology inevitably seek treatment, the majority

of patients with mild or moderate symptoms of UI

often are overlooked [14] . Patients often are una-

ware that there are effective behavioral and phar-

macological therapies that can significantly reduce

and even eliminate their symptoms.

What does appear to be major components of

help-seeking behavior are the person’s beliefs,

perceptions, and emotions. Common myths or

“urban legends” prevail. Older people may think

UI is part of the normal aging process, something

to be accepted and managed independently [6, 7] .

In a study by Hannestad [15] , women reported

misconceptions about UI including beliefs that it

is inevitable with aging, is too embarrassing to dis-

cuss, and that they should just learn to cope.

This lack of help-seeking behavior has been

seen in many countries. Great Britain has a gov-

ernment-supported health care system allowing

the elderly access to a primary care provider on

a routine basis. However, Horrocks [7] found that

in a survey of older persons who had UI (39%),

only 15% has accessed services specifically for UI.

This study found that participant’s attitudes about

incontinence correlated with attitudes about aging

and beliefs about the cause of incontinence: they

“normalized” the incontinence as a consequence of

aging and as being inevitable. When UI is viewed

as normal aging, it negates its cause as a medi-

cal condition, thus one that does not need medi-

cal intervention [16] . HCPs may be contributing

unconsciously to this by their own attitudes and

reduced expectations of improvement.

Women are more concerned with the hygienic

effects of urine leakage, which may cause embar-

rassment and shame, so they conceal the problem

from family members and friends. Therefore,

instead of seeking medical advice, people turn

to self-care practices such as restricting fluid

intake, carrying containers for voiding whenever

the “urge” occurs, crossing legs, avoiding travel

outside the home, and practicing daily routines

such as “toilet mapping.” The use of absorbent

pads and products (eg, disposable underwear, adult

briefs) are common and often are reported as the

initial self-management strategy for over 75% of

women with UI [17] . Men, though, avoid use of

pads, which they consider for women’s use only

[7] . The gender of the provider also may be a bar-

rier to seeking treatment, as women may not be

comfortable speaking with a male physician.

Overcoming the “Stigmatization”

of Incontinence

Triggers for help-seeking behavior are complex

and multifactorial and are beyond the scope of this

chapter to review here. With a chronic problem like

UI, it is important to understand what triggers the

patient to consult with a HCP. Incontinence and

bodily functions remain taboo in many cultures.

Many people also do not consider themselves

“incontinent,” as this has a negative connotation or

is not well understood. In a series of in-depth inter-

views with 28 young and middle-aged women with

UI, it was found that incontinence was considered a

taboo, making it difficult to seek professional help

or even to focus on and think clearly about [18] .

Some reacted with apathy; others were always on

the brink of taking action. Many worked hard to

maintain “normalcy” and hide the problem. For

some there was defensive denial or they subordi-

nated the problem to other priorities.

Bladder continence is an adjustment to the

social norm, especially in Western cultures, which

have developed acceptable rules and behavior for

bladder emptying [19] . Bladder control is a skill

that is socially acquired during childhood by toilet

training and compliance often is achieved through

shame and embarrassment. Children quickly learn

that “wetting” themselves is unacceptable and

“bad.” If incontinence occurs in adulthood, persons

revive those childhood beliefs and begin to inter-

nalize their condition, causing a decrease in self-

esteem and feelings of not being “normal” [4] .

The National Association For Continence

(NAFC), a public advocacy organization in the

United States, has conducted several public surveys

over the past two decades [20] . A 2000 survey

examined bathroom-related attitudes and behaviors

and their relationship to bladder control problems.

38. Community Awareness and Education 523

Some respondents found the bathroom to be a

personal place; a haven to seek refuge. Bathroom

activities reported by respondents included reading

in the bathroom (53%), contemplation of serious

things (47%,) talking on the telephone (33%), and

among the 30- to 39-year-old respondents, 27%

reported making love in the bathroom. Others

felt it symbolized incarceration because of the

preoccupation with the need to be near one at all

times because of bladder control problems. Older

respondents felt that the bathroom is a “private”

place and only 25% were comfortable using bath-

rooms outside their home, which may impact the

use of public facilities and the ability to participate

in social interaction.

One of the barriers to help-seeking behavior may

be misunderstanding of terminology. It has been

suggested that when promoting awareness of blad-

der control disorders, simple language and termi-

nology (eg, bladder health, bladder control, OAB)

should be used [21] . The word “incontinence”

itself carries stigma, and most individuals with this

symptom resist being labeled with this term or even

with a problem, such as the loss of bladder control.

Mass marketing for OAB medications has demon-

strated the effectiveness of terminology in helping

to destigmatize incontinence or bladder control

problems to the public.

Newman [22] conducted a mail survey that noted

that respondents were comfortable (51%) using the

terms overactive bladder and incontinence when

discussing this condition. When provided with

additional terms, 39% said they were very comfort-

able with loss of bladder control , 33% with leaks ,

26% with accident, and 23% with incident . Only

one fourth (23%) of respondents said they were not

“very comfortable” using any of the terms listed

above when discussing their condition/situation.

However, this survey was conducted on custom-

ers of a mail order medical supply company who

were over the age of 65 and probably were more

educated about managing incontinence.

Increasing Continence Awareness

Because UI affects millions of men and women of

all ages, public health services and private sectors

should be encouraged to conduct mass public edu-

cation regarding the basic physiology of bladder

control, especially to dispel the many myths that

are prevalent in the community regarding the diag-

nosis and treatment of UI and OAB [6] . Currently,

there is little evidence-based research about public

education to promote continence awareness in the

community. Building awareness among the general

public has been difficult and fragmented and it is

difficult to assess the impact of any one health-

promotion initiative, as there are many interacting

variables and individuals obtain information from

many sources. A promotion program for raising

awareness must consider several aspects:

• Target population : The prevalence of UI and

the lack of knowledge about incontinence are

sufficient to justify a health-promotion program

without segmentation by age or gender [21] .

• Target issues : A promotion program should iden-

tify the issues that warrant promotion effort as

well as barriers to promotion. Issues such as lack

of willingness or readiness to seek treatment pre-

vent people from seeking help [23] .

• Content of promotional material : Any type of

advertisement that deals with incontinence, even

advertising campaigns for incontinence absorb-

ent products, can have a positive impact on less-

ening taboos about talking about incontinence.

This increased willingness to discuss urinary

incontinence can be followed by advice on effec-

tive methods of coping with incontinence [24] .

A media campaign should use multiple channels

(eg, print media and radio) to ensure the broad-

est coverage [25] . A second channel would be

specialized age and health publications. A third

channel is the use of posters and brochures

placed in physician’s offices, hospitals, senior

center, pharmacies, and churches. A final chan-

nel is direct presentations to the public, such as

at senior centers. Another source of information

is provided on the internet through websites that

provide useful information on incontinence, what

it is, and how it can be managed, treated, and

cured [26– 28] . Table 38.1 lists the top inconti-

nence-related websites on Google.

• Channels of communication : Self-interest may

be a motivator for public education. HCPs may

launch campaigns to increase practice revenues.

In Australia, medical entrepreneurs advertised

widely in the press to promote urodynamic cent-

ers and in so doing stimulated the inception of

524 D.K. Newman

the Australian Urodynamic Society. Such profit-

motivated initiatives also may have the effect of

raising the profile of incontinence as a health

issue, to the benefit of all. Manufacturers often

fund public campaigns in order to sell their prod-

ucts. Direct advertising raises public awareness to

advance sales and to serve a commercial advan-

tage. Continence-based public advocacy organi-

zations may consider partnering with industry to

reach a wider, general public audience. Increased

exposure in the media, especially print and televi-

sion media, has positively influenced attitudes,

beliefs, and knowledge about incontinence [7] .

Regardless of motivation, care should be taken

to avoid raising public expectations beyond what

the services or products can deliver.

• Outcome assessment : Prior to implementing

a UI awareness campaign, it is important to

identify outcome variables that will evaluate its

effectiveness.

In many cultures, one of the best vehicles to reach-

ing the public is through an informed journalist

who uses a “media hook,” an interesting story that

will take priority over other news on the television,

radio, or newspaper. A study of Chinese women

by Yu et al. [29] reported that 16% of women who

sought help did so because of advice from public

media. Having a spokesperson with the problem or

finding a celebrity who is willing to speak for the

cause can help. This has been used repeatedly in

the United States by drug and product manufactur-

ers who have used Hollywood actresses (Debbie

Reynolds, June Allyson) and Olympic sports fig-

ures (Mary Lou Retton) to get out the message

to the public about UI or OAB. These individuals

can act as “influence leaders.” Using the media

to disseminate information in the form of public

service announcements has been used extensively

in the United States to promote AIDS aware-

ness and in antismoking campaigns. In 2001, the

NAFC produced and disseminated public service

announcements to 380 media markets in the United

States for the purpose of promoting continence

awareness.

Television and print advertisements for OAB

drugs have helped to destigmatize the condition by

showing that it happens to normal individuals and

by giving it a culturally accepted name in a society

that places a high value on being active. Being

“over” active does not conjure the same negative

attribute as being “incontinent.” HCP have noticed

an increase in patients seeking treatment for their

“overactive bladder symptoms” as a result of the

drug advertising campaigns.

Telephone help-lines provide an opportunity

for individuals suffering from UI to obtain infor-

mation and advice without having to go through

embarrassment of a face-to face meeting with a

HCP.

Gartley [30] notes that one of the best ways to

promote awareness and encourage people to seek

help is through education about the bladder and

incontinence. Through education, people become

empowered and realize they are not alone and

help is available. The United States-based Simon

Foundation for Continence, of which Cheryle

Gartley is the founder, has proposed a “bladder

health mobile” to promote continence. It is hoped

that this traveling exhibit would elevate the stature

of bladder-related conditions, remove the stigma

surrounding incontinence, and provide public

awareness and education at the community level. It

is not known whether this project will be successful

in increasing awareness and driving more sufferers

to seek treatment.

Table 38.1. Websites: Top five websites on urinary incontinence (Google search) .

Website Sponsor

http://www.incontinence.org/ American Urology Association Foundation for Urologic Disease, USA

http://www.nafc.org/ National Association for Continence, USA

http://www.incontinet.com/ Dr John Perry, USA – focused on pelvic floor disorders and biofeedback

http://www.uib.no/isf/people/inkter.htm Dr Hogne Sonvik, Department of Public Health and Primary Health Care,

University of Bergen, Norway

http://www.seekwellness.com/incontinence Ms Diane Newman, Nurse Continence Specialist, Division of Urology,

University of Pennsylvania, USA

38. Community Awareness and Education 525

Also, a greater effort in the medical and nursing

community must be made to educate physicians and

nurses of the need to be proactive in identifying and

treating these conditions. In 2007, the US National

Institutes of Health (NIH) hosted a state-of-the-sci-

ence conference on fecal and urinary incontinence

and explore strategies to improve the identification

and screening of persons at risk for developing fecal

and urinary incontinence [38].

The Role of Patient Advocacy

Continence Organizations

Professionals (eg, urologists, urogynecologists,

gynecologists, primary care physicians, nurses)

and professional organizations have been instru-

mental in promoting awareness of continence in

all care settings. The International Continence

Society established the Continence Promotion

Committee (CPC) to promote education, serv-

ices, and public awareness about incontinence

throughout the world and to facilitate communi-

cation, exchange of information, and partnerships

between continence organizations, health care

professionals, governments, and industry [31] . The

CPC’s multinational and multidisciplinary rep-

resentation aims to identify broad issues through

an international forum that can facilitate transla-

tion at the local and national level. In the past 15

years, national organizations (50 organizations

in 36 countries) have been formed under various

auspices to tackle issues pertaining to incontinence

awareness, education, and promotion [24] . Table

38.2 is a list of countries that have national organi-

zations, the organization names, and websites.

While each organization is unique in its mandate,

what they have in common is their commitment to

improve the status for persons with incontinence.

Each year at the International Continence

Society’s annual meeting, the CPC has held work-

shops pertaining to various themes that have a

broad national focus such as prevention, general

practitioner education, and promotional strategies.

Its relevance, as is the case with each of the national

organizations, is to recognize the interface between

continence management and continence awareness

and promotion. The role of national organization

is even more relevant because of the underreport-

ing of the problem [31] . The CPC is planning to

increase community awareness through the hosting

of “public forums” at the time of the International

Continence Society annual meeting.

Table 38.2. National continence organizations

Australia

Continence Foundation of Australia Ltd: http://www.continence.org.au/

Austria

Medizinische Geseelschaft fur Inkontinenhlife Osterreich: http://www.inkontinenz.at

Belgium

U-Control vzw (Belgian Association for Incontinence): http://www.sosincontinence.org/

Brazil

Brazilian Foundation for Continence Promotion: seabrarios@uol.com.br

Canada

The Canadian Continence Foundation: http://www.continence-fdn.ca

China

Hong Kong Continence Society: emfleung@ha.org.hk

Colombia

Colombian Continence Society, http://www.urologiacali.com Czechoslovakia

Czech Republic Inco Forum http://www.inco-forum.cz

Denmark

Kontinensoreningen (The Danish Association of Incontinent People), www.kontinens.dk/

Danish Continence Association

Email: info@kontinens.dk

France

Feemes pour Toujourns

Email: francoise.kremer@femsante.com

Web: www.femsante.com

(continued)

526 D.K. Newman

Germany

Gsellschaft fur Inkontinenzhilfe e.V. (GIH), http://www.gih.de

Hungary

Inko Forum: http://www.inkoforum.hu

India

Indian Continence Foundation:

http://www.indiancontinencefoundation.org

Indonesia

Indonesian Continence Society: urogyn@centrin.net.id

Ireland

Continence Foundation of Ireland http://www.continence.ie/

Israel

National Center for Continence: ig054@hotmail.com

Italy

Fondazione Italiana Continenza (The Italian Continence Foundation), http://www.continenza-italia.org

Associazione Italiana Donne Medico (AIDM): http://www.donnemedico.org

The Federazione Italiana Incontinenti (FINCO): finco@finco.org

Japan

Japan Continence Action Society: http://www.jcas.org

Korea

Korea Continence Foundation: http://www.kocon.or.kr

Malaysia

Continence Foundation: lohcs@medicine.med.um.edu.my

Netherlands

Pelvic Floor Netherlands: http://www.pelvicfloor.nl

Pelvic Floor Patients Foundation (SBP): http://www.bekkenbodem.net

Vereniging Nederlandse Incontinentie, Verpleegkundigen (VNIV): http://www.vnic.nl

New Zealand

New Zealand Continence Association: http://www.continence.org.nz

Norway

NORFUS (Norwegian Society for Patients with Urologic Diseases, www.siralf@sensewave.com

Philippines

Continence Foundation of the Philippines: ( http://www.mela@info.com.ph )

Poland

NTM (INCO) Forum (The Polish Continence Organisation): http://www.ntm.pl

Singapore

Society for Continence: http://www.sfcs.org.sg

Spain

Associacion Nacional de Ostomizados e Incontinentes (ANOI): http://www.coalicion.org

Sweden

Swedish Urotherapists: birgtha.lindehall@vgregion.se

Sinoba: http://www.sinoba.se

Taiwan

Taiwan Continence Society: http://www.tcs.org.tw

Thailand

Thai Continence Society

Email: ravkc@mahidol.ac.th

United Kingdom

Association For Continence (ACA): http://www.aca.uk.com/

The Continence Foundation, UK: http://www.continence-foundation.org.uk

Incontact, http://www.incontact.org

Enuresis Resource and Information Centre (ERIC): http://www.eric.org.uk

United States

American Urologic Association Foundation: http://www.afud.org

International Foundation for Functional Gastrointestinal Disorders, http://www.aboutincontinence.org/

Interstitial Cystitis Association, Web: http://www.ica.org

National Association For Continence: http://www.nafc.org

Simon Foundation for Continence: http://www.simonfoundation.org

Table 38.2. (continued)

38. Community Awareness and Education 527

Examples of Community

Awareness Programs

There are very few published reports of commu-

nity awareness for continence. The Continence

Promotion, Prevention, Education, and Organization

committee of the International Consultation on

Incontinence published the results of a 2003 sur-

vey from 24 organizations in 19 countries (67.7%

response rate) [24] . Organizations have identified

education about incontinence as the most important

method to decrease the perceived stigma associated

with the disorder. A successful method to educate

persons has been through public awareness cam-

paigns, health promotion projects, or health fairs.

Examples of the programs are found in Table 38.3

and some are detailed here.

In the United States, the Oklahoma State Health

Department developed “Dry Anticipations,” which

was a community demonstration prowject that

included a curriculum on UI for small groups of

elderly women [25] . This project had three com-

ponents: an educational intervention with physi-

cians, an educational campaign for the general

public, and a test of behavioral treatments for older

women. It was implemented by contracting with

six sites in Oklahoma using a train-the-trainer

model. A train-the-trainer approach, in which a

project prepares a group of instructors to deliver

an educational intervention to members of a target

population, is a useful method when one wishes to

introduce an intervention into existing agencies or

ongoing social settings [32, 33] .

The New Zealand Continence Foundation (NZCA)

undertakes annual public awareness campaigns by

supporting an annual “continence awareness” week,

held the first week of September. The NZCA felt

that terminology was important to public initiatives

and initially branded “Dry Pants Day,” an unpopu-

lar title so the name was changed to “Life without

Limits – Continence Awareness.” The NZCA has

experience with public meetings organized by con-

tinence professional staff in their area and through

small interest groups such as community groups (eg,

Parkinson’s, aging concerns, Alzheimer’s, arthritis,

etc.), and national awareness campaign events. The

NZCA also conducts “public expos and shows” with

HCPs to counteract embarrassment and to encour-

age people to seek professional help.

Western Australian municipal governments have

provided funding through development grants that

allow for the planning, implementation, and evalu-

ation of continence health promotion seminars

targeted at citizens in these areas. The most recent

health promotion, called “Simply Busting,” was

community continence health promotion and edu-

cation sessions. Participants also are provided with

information on further support and management

options. Local HCPs including medical centers,

pharmacies, and physiotherapy practices, commu-

nity service organizations, seniors groups, disabil-

ity and aged care providers, and local sporting and

recreation centers are asked to display flyers and

posters. Evaluations are conducted immediately

afterward and outcome evaluations are conducted

at 3 and 12 months after the session. The major-

ity of participants indicate they intend to make

changes to their lifestyle as a result of attending

the session. These changes include increasing fluid

intake, decreasing caffeine consumption, doing

pelvic floor muscle exercises, and seeking help

from a health care professional.

The NAFC has hosted public forums in certain

communities. At an event in 2006, NAFC part-

nered with a nationally recognized health care

center (Duke University Medical Center) to multiply

resources. This was especially helpful in reducing

costs of advertisement of the forum. They also

used government experts and celebrities to increase

exposure and credibility of the forum.

Table 38.3. Examples of national continence organiza-

tions initiatives .

Australia – Helpline promotion

Belgium – GP and incontinence

Canada – Incontinence awareness month

Hong Kong – Continence promotion

Indonesia – GP seminars

India – Public awareness exhibition

Japan – Let’s talk and think about continence

Korea – Incontinence awareness campaign

New Zealand – National bladder awareness week

Poland – National billboard campaign

Singapore – Women’s health issues & healthy aging

Taiwan – A dry and comfortable spring

UK, Continence Foundation – Continence awareness week

UK, ERIC – Bed-wetting awareness in schools

UK, Incontact – Healthy bladder campaign

USA, IFFGD – Irritable bowel syndrome (IBS) awareness

month

USA, SFC – Stigma in healthcare

USA, NAFC – Women’s forum on lifelong bladder health

528 D.K. Newman

In Great Britain, 2003 saw the launch of the

“healthy bladder campaign” by the patient advo-

cacy group INCONTACT. The purpose of the

healthy bladder campaign was to raise awareness

through the media and provide information through

booklets and its website ( http://www.incontact.

org ). Since 2003, ten regional and national news-

papers, lifestyle and consumer magazines, and

health care publications have been targeted, along

with 14 regional radio stations. This coverage has

resulted in extensive dissemination of the healthy

bladder booklet and generated 46,000 hits on the

INCONTACT website.

The interventions that best reach the public and

trigger the desired behavior seem to vary between

countries and cultures. The Japan Continence

Action Society held a “toll-free telephone clinic”

and callers were asked how they heard about the

line. Sixty-five percent replied from a newspaper,

26% from television, and 8% from a poster. A

Great Britain campaign found that newspapers

were by far the most common source of informa-

tion, followed by radio [34] .

The Singapore Continence Foundation has held

an “Incontinence Awareness Day” in the city’s

biggest shopping mall, which highlighted differ-

ent types of incontinence, symptoms, and avail-

able treatment options. A disc jockey was trained

on UI and was the host of the show. This was

a very successful program that attracted 2,500

persons. Participants were asked to complete a

quiz to determine if learning occurred and prizes

were awarded. From the answers on the quiz,

participants felt that aging causes incontinence

and nobody can avoid this problem, so it was an

opportunity to change/correct the common myth

that aging causes incontinence.

Evaluating the Effectiveness

of Public Awareness Campaigns

It is important to assess whether efforts to educate

the public have the desired effect and to define the

criteria by which to judge “success.” Measures

of success could include the number of media

“impressions” through newspaper, television, or

radio; the number of people who sought help; or

the numbers who were actually helped. The mes-

sage should be crafted to encourage and motivate

the desired action. A questionnaire survey of

callers 3 months after phoning the Continence

Foundation of the United Kingdom help line dur-

ing National Continence Week in 1994, found that

callers appreciated the information but did not

necessarily act on it [34] .

In France, the effect of health education was

evaluated in a randomized study in sheltered

accommodations for the elderly [35] . Twenty cent-

ers were randomized to a single 1-h health infor-

mation meeting or control group. During a 30-min

talk, a nurse encouraged people to visit a doctor

if they had urinary problems. A questionnaire 3

months later found that the experimental group

was much more likely to have had treatment if they

were incontinent (41% vs 13% controls) and 82%

said that they had received some information about

incontinence in the previous 3 months (compared

to 22% controls).

A health promotion project called “Dry

Expectations” was developed and implemented in

six ethnically diverse, predominantly minority, and

inner-city senior centers in the United States [36] .

The program was designed to address an older

population. The project consisted of three phases:

orientation and training of key staff members/peer

educators at the centers (train-the-trainer model);

educating seniors through four 1-h weekly sessions

involving visual aids and completion of bladder

records and quizzes; and follow-up sessions with

senior staff/peer educators to reinforce the previ-

ous training. The program was very well received

by the participants, and roughly 80% felt they had

more control over their bladder by the end of the

last session.

This project recently was expanded to determine

the health promotion needs of senior citizens con-

cerning bladder control issues [21] . Focus groups

of older adults attending health seminars in an

urban, community setting were conducted. The

primary objective of the project was to determine

the understanding of older adults in the areas of

general health and their beliefs surrounding the

problem of UI. The 81 participants were predomi-

nantly African-American women representing all

socioeconomic levels. Seniors expressed confusion

when asked if “overactive bladder, bladder control

issues, and urinary incontinence” were the same

condition. Most seniors said they felt comfortable

38. Community Awareness and Education 529

about discussing bladder control issues, but most

admitted that their doctor had never asked them

nor had they raised the issue. However, they did

discuss UI with family members and friends and

they were aware that many persons with whom

they socialized might have a problem with UI. The

majority of seniors answered “no cure” when asked

if treatments were successful.

Australian “Continence Awareness”

Success

The most successful country in promoting commu-

nity awareness for continence has been Australia,

which has promoted communitywide programs

while evaluating their effectiveness [37] . The

Australian National Continence National Continence

Management Strategy was established in 1998 by

the Australian Government Department of Health

and Ageing to provide funding (initial funding of

$15.4 million over 4 years) to research and service

development initiatives aimed at prevention and

treatment of this significant problem. Four major

priorities were identified: public awareness, edu-

cation, and information; prevention and health

promotion; quality of service; and research. An

additional $16 million were approved in 2003 to

focus on the implementation of projects on preven-

tion, community education, and improved man-

agement of incontinence by primary HCPs, and

within community care and residential care facili-

ties. Each funded project is independently evalu-

ated or has built-in outcome measures. The goals

of the National Continence National Continence

Management Strategy are as follows:

1. Incorporate evidence-based research to pro-

mote awareness and encourage prevention,

early intervention, and help-seeking behavior

with a focus on meeting the needs and access

issues of all population groups.

2. Formulate strategies for effective management

of awareness-raising activities, ensuring that

the roles of both state and federal governments

are included.

3. Increase the capacity of all service provid-

ers (including consumers and carers as “first-

line” service providers) to provide continence

promotion and advice. Plan awareness-raising

campaigns in conjunction with service provid-

ers in order to anticipate and provide appropri-

ate resources to meet increase demand.

4. Ensure mechanisms are in place to measure

the impact and cost effectiveness of awareness-

raising activities. Establish standard measure-

ments and reporting processes that will identify

the changing level of awareness of continence

issues within the community.

5. Promote initiatives such as the National

Continence Helpline and National Public Toilet

Map and ensure that community-focused access

points are readily available. Identify opportuni-

ties to promote cross-fertilization of all initia-

tives and evaluate outcomes.

6. Focus national awareness and promotion cam-

paigns on encouraging target groups to access

continence-related information; take up pre-

vention and early intervention messages; be

prompted to seek help and access links to con-

tinence services.

7. Consider the diversity of cultural, linguistic,

and ability levels in Australian communities

in the development of current and future conti-

nence information materials.

Among the various consumer projects is the

“public toilet map” – a national mapping of toilets

to assist travel for persons with incontinence that

will show information about opening hours and

disability access, http://www.toiletmap.gov.au.

The National Continence Helpline was estab-

lished to provide prompt, confidential, and profes-

sional advice for people with incontinence, their

care givers, and organizations with an interest in

continence management. It also provides printed

information and educational material to Helpline

clients about continence management and to sup-

port appropriate referral. As of December 2005,

the number of calls to the Helpline had risen to

an annual rate of almost 18,000 calls per annum

or an average of 1.487 calls per month. A patient

satisfaction survey undertaken in September 2005

found a 93% ( n = 51) response rate for overall

satisfaction with the service provided. Eighty-

eight percent ( n = 35) of applicable respondents

indicated that the call to the Helpline had provided

them with encouragement and empowerment to

seek further help by responding to the referral

information provided to them. Changes to the

530 D.K. Newman

survey processes are being implemented with

greater emphasis placed on assessing outcomes

for callers to the Helpline. Initial funding for the

Helpline also included specific funding for print-

ing and promotions to raise community awareness

and promote the Helpline.

An early intervention project specifically tar-

geted mothers of young children under 2 years and

encouraged a call to action through a continence

awareness narrowcast program using convenience

advertising with posters and “take away” informa-

tion. Over 1,000 display points, either a poster

or a poster and cardholder, were placed in baby

change rooms of selected community health cent-

ers, shopping centers, cinemas, and hospitals with

maternal health facilities throughout Australia. The

results indicated that in excess of 12,000 brochures

were taken from these display points during the

project period. An evaluation of the project was

undertaken using intercept interviews in shopping

centers and Maternal Health Care clinics. The

results indicated that the respondents recognized

the materials used and viewed them positively.

Unprompted recall was low but on prompting the

recognition rate rose to over 85%. The findings

also indicated that respondents saw the initiative as

an awareness-raising communication rather than a

call for action.

Conclusion

Continence promotion involves informing and edu-

cating the public and health care professionals that

incontinence is not inevitable or shameful, but is

treatable or at least manageable. Taboos about men-

tioning disorders of the bladder gradually are lifting

in most cultures. Two decades ago it was almost

impossible to have a discussion about urinary

incontinence in the media. Today, in most countries,

national “continence” organizations are promoting

awareness in communities. Many countries have

run national or local public awareness campaigns.

Many also have confidential help lines, which can

be accessed anonymously. The world wide web

provides a convenient source of health information

for a growing number of consumers. Continence

awareness is growing but there is more needed to

increase the numbers of persons seeking treatment.

References

1 . Herzog AR , Fultz NH , Normolle DP , Brock BM ,

Diokno AC . Methods used to manage urinary

incontinence by older adults in the community . J Am

Geriatr Soc 1998 ; 37 (4) : 339 – 347 .

2 . Kinchen KS , Burgio K , Diokno AC , Fultz NH , Bump

R , Obenchain R . Factors associated with women’s

decisions to seek treatment for urinary incontinence .

J Womens Health 2003 ; 12 (7) : 687 – 698 .

3 . Roberts RO , Jacobsen SJ , Rhodes T , et-al. Urinary

incontinence in a community based cohort:

Prevalence and healthcare-seeking behavior. J Am

Geriatr Soc 1998 ; 46 : 467 – 472 .

4 . Garcia JA , Crocker J , Wyman JF . Breaking the cycle

of stigmatization . J Wound Ostomy Continence

Nurs 2005 ; 32 (1) : 38 – 52 .

5 . Hagglund D , Walker-Engstrom M , Larsson G , Leppert

J . Reasons why women with long-term urinary incon-

tinence do not seek professional help: A cross-sec-

tional population-based cohort study . Int Urogynecol

J Pelvic Floor Dysfunct 2003 ; 14 : 296 – 304 .

6 . Diokno AC , Sand PK , Macdiarmid S , Shah R ,

Armstrong RB . Perceptions and behaviours of

women with bladder control problems . Fam Pract

2006 ; 23 : 568 – 577 .

7 . Horrocks S , Somerset M , Stoddart H , Peters TJ .

What prevents older people from seeking treatment

for urinary incontinence? A qualitative exploration

of barriers to the use of community continence serv-

ices . Fam Pract 2004 ; 21 : 689 – 696 .

8 . Koch LH . Help-seeking behaviors of women with

urinary incontinence: An integrative literature review.

J Midwifery Womens Health 2006 ; 51 (6) : e39 – e44 .

9 . Mason L , Glen S , Walton I , Hughes C . Women’s

reluctance to seek help for stress incontinence dur-

ing pregnancy and following childbirth . Midwifery

2001 ; 17 : 212 – 221 .

10 . Teunissen D , van Weel C , Lagro-Janssen T . Urinary

incontinence in older people living in the com-

munity: Examining help-seeking behaviour . Br J

General Pract 2005 ; 55 : 776 – 782 .

11 . Dmochowski R , Newman DK . Impact of over-

active bladder on women in the United States:

results of a national survey . Curr Med Res Opin

2007 ; 23 (1) : 65 – 76 .

12 . Newman DK . Managing and treating urinary incon-

tinence , 2nd ed. Edition . Health Professions Press ,

Baltimore, MD , 2008 : 19 – 28 .

13. Fantl JA, Newman DK, Colling J, et al. Urinary

incontinence in adults: Acute and chronic manage-

ment clinical practice guideline, No. 2, Update.

Rockville, MD: US Department of Health and

Human Services. Public Health Service, Agency

38. Community Awareness and Education 531

for Health Care Policy and Research, AHCPR

Publication No. 96–0682. March 1996.

14 . Brittain KR , Perry S , Williams K . Triggers that

prompt people with urinary symptoms to seek help .

Br J Nurs 2001 ; 19 (2) : 74 – 85 .

15 . H annestead YS , Rortveit G , Hunskaar S . Help-

seeking and associated factors in female urinary

incontinence (The Norweigan EPINCONT study:

Epidemiology of Incontinence in the County

of Nord-Trondelag) . Scan J Prim Health Care

2002 ; 51 : 801 – 804 .

16 . Bush TA , Castellucci DT , Phillips C . Exploring

women’s beliefs regarding urinary incontinence .

Urol Nurs 2001 ; 21 (3) : 211 – 218 .

17 . Subak LL , Brown JS , Kraus SR , Brubaker L , Lin

F , Richter HE , Bradley CS , Grady D . The “costs”

of urinary incontinence for women . Obstet Gynecol

2006 ; 107 (4) : 908 – 916 .

18 . Ashworth PD , Hagan MT . The meaning of incontinence:

A qualitative study of non-geriatric urinary incontinence

sufferers . J Adv Nurs 1993 ; 18 : 1415 – 1423 .

19 . N orton C . Nurses, bowel continence, stigma

and taboos . J Wound Ostomy Continence Nurs

2004 ; 31 (2) : 85 – 94 .

20 . Muller N . What Americans know and how they are

affected by bladder control problems: Highlights

of a recent national consumer survey . Urol Nurs

2005 ; 25 (2) : 109 – 115 .

21 . P almer MH , Newman DK . Bladder control edu-

cational needs of older adults . J Gerontol Nurs

2006 ; 32 (1) : 28 – 32 .

22 . N ewman DK . Report of a mail survey of women

with bladder control disorders . Urol Nurs

2004 ; 24 (6) : 499 – 507 .

23 . McFall SL , Yerkes AM . Targets, messages, and

channels for educational intervention on urinary

incontinence . J Appl Gerontol 1998 ; 17 : 403 – 418 .

24 . N ewman DK , Denis L , Gruenwald I , Ee CH , Millard

R , Roberts R , Sampselle C , Williams K . Promotion,

education and organization for continence care. In:

Abrams P , Cardozo L , Khoury S , Wein A , eds..

Incontinence, proceedings from the 3rd international

consultation on incontinence. Plymouth UK : Health

Publication 2005 ; 35 – 72 .

25 . McFall SL , Yerkes AM , Belzer JA , et al . Urinary

incontinence and quality of life in older women:

A community demonstration in Oklahoma . Fam

Commun Health 1994 ; 17 : 64 – 75 .

26. Boyington AR , Dougherty MC , Yuan-Mei Liao .

Analysis of interactive continence health informa-

tion on the web. J Wound Ostomy Continence Nurs

2003 ; 30 (5) : 280 – 286.

27 . D iering C , Palmer MH . Professional information

about urinary incontinence on the world wide

web: Is it timely? Is it accurate? J Wound Ostomy

Continence Nurs 2001 ; 27 (6) : 1 – 9 .

28 . Sandvik H . Health information and interaction on

the internet: A survey of female urinary inconti-

nence . Br Med J 1999 ; 319 : 29 – 32 .

29 . Yu H , Wong W , Chen J , Chic W . Quality of life and

treatment seeking in Chinese women with urinary

incontinence . Qual Life Res 2003 ; 12 : 327 – 333 .

30. Gartley , C . Bringing Mohammed to the mountain;

educating the community for continence. Urol Nurs

2006 ; 26 (5) : 387 – 393 .

31 . Fonda D , Newman DK . Tackling the stigma of

incontinence – Promoting continence worldwide. In:

Cardozo L , Staskin D , eds. Textbook of female urol-

ogy and urogynecology. 2nd edn . United Kingdom

Isis Medical Media , 2006 : 75 – 80 .

32 . McFall SL , Yerkes AM , Cowan LD . Overcomes of

a small group educational intervention for urinary

incontinence, Health-related quality of life . J Aging

Health 2000a ; 12 (3) : 301 – 317 .

33 . McFall SL , Yerkes AM , Cowan LD . Overcomes of a

small group educational intervention for urinary incon-

tinence, episodes of incontinence and other urinary

symptoms . J Aging Health 2000b ; 12 (3) 250 – 267 .

34 . Norton C , Brown J , Thomas E . Continence: A phone

call away . Nurs Stand 1995 ; 9 : 22 – 23 .

35 . Beguin AM , Combes T , Lutzler P , et-al. . Health edu-

cation improves older subjects’ attitudes toward uri-

nary incontinence and access to care: A randomised

study in sheltered accommodation centers for the

aged (letter) . JAGS 1997 ; 45 : 391 – 392 .

36 . Newman DK , Wallace J , Blackwood N . Promoting

healthy bladder habits for seniors . Ostomy Wound

Manage 1996 ; 42 : 18 – 28 .

37 . Byles JE , Chiarelli P , Hacker AH , et-al. . An evalua-

tion of three community-based projects to improve

care for incontinence . Int Urogynecol J Pelvic Floor

Dysfunct 2005 ; 16 (1) : 29 – 38 .

38 . Shamliyan T , Wyman J , Bliss DZ , Kane RL , Wilt

TJ . Prevention of urinary and fecal incontinence in

adults . Evid Rep Technol Assess (Full Rep) . 2007

Dec; (161) : 1 – 379 .

533

A

Abdominal sacrocolpopexy (ASC), 335, 341

complications, 346

concomitant procedures, 345–346

cul-de-sac closure, 345

efﬁ cacy of, 346

pelvic anatomy, 342

sacral dissection, 344

surgical technique, 342–343

vaginal apex prolapse, 341

Acupuncture

b-endorphins, 204

evidence reviewing, 204–205

peripheral circulation, 204

Adenosine triphosphate, 23, 25, 260

α-adrenoceptor agonists, 100–101

β-adrenoceptor agonists, 101

Agency for Health Care Policy and Research, 517

urinary incontinence treatments, 518

AGUS. See Artiﬁ cial genitourinary sphincter

Allografts

donor cadaveric grafts, 317–318

in prolapse surgery, 318

Amreich-Richter procedure, 309

AMS-800. See Artiﬁ cial urinary sphincter

Anorectal manometry, 374–375

Anterior colporrhaphy, 333–334

Anticholinergics, iatrogenic obstruction, 498

Arcus tendineus fasciae pelvis (ATFP), 334

Artiﬁ cial genitourinary sphincter (AGUS), 517

components, 441

long-term cure rates for, 448

postprostatectomy patients in, 445

surgical implant and procedures

control pump and cuff preparation, 443

device replacements in, 445

infection and urethral atrophy, 445–446

mechanical failure in, 446

perineal approach and cuff placement, 443

PRB and pump placement, 444

tandem cuff, 444

Artiﬁ cial urinary sphincter (AUS), 127, 476, 482, 486

AMS-800 and continence rates, 482

endopelvic fascia, 143

recurrent incontinence and treatments, 471

surgical series of, 483

ASC. See Abdominal sacrocolpopexy

AT P. See Adenosine triphosphate

Augmentation cystoplasty, 233–234

“Clam” ileocystoplasty, 236–237

complications

bowel-related complications, 238

malignant transformation, 239–240

metabolic disturbance, 238–239

mucus formation, 239

perforation, 241

stone formation, 241–242

surveillance and follow-up tactics, 240–241

urinary tract infections, 239

voiding dysfunction, 242

contraindication, 235–236

enterocystoplasty results, 242–243

lifelong follow-up, 237

nonpharmacological options, 243–244

patient selection and evaluation, 234–235

AUS. See Artiﬁ cial urinary sphincter

Australian National Continence Management Strategy

goals of, 529

helpline and, 529–530

mothers, young children, 530

public toilet map, 529

Autologous grafts

rectus abdominis fascia, 316–317

tensor fascia lata, 317

Index

534 Index

B

Behavioral therapies, 517

Benign prostatic hyperplasia (BPH), 395, 437

Benign prostatic obstruction (BPO), 395

Biofeedback

functional electrical stimulation

biofeedback therapy, 295

contraindications, 297

pelvic ﬂ oor exercises, 296

vaginal and rectal sensors, 296–297

home training programs, 295

training technique, 294

Bioglass, 160

Biological grafts

allografts, 317–318

autologous grafts, 316–317

xenografts, 319–321

Biomaterial

clinical translation, 315

collagen metabolism, 313–314

deﬁ nition, 313

host remodeling, 315–316

pelvic prolapse and incontinence

genetic predisposition, 315

with hernias, 314

type I and type III collagens, 314

Bioplastique, 156–157

Bladder autoaugmentation

autoaugmentation results, 246–247

complications, 247

demucosalized gastrointestinal segments, 245

detrusor myectomy–myotomy, 244–245

surgical technique, 245–246

Bladder cancer, 462

Bladder erosion, 325

Bladder function, 68

Bladder outlet obstruction (BOO), 394, 493

Bladder–sphincter–bladder reﬂ ex pathway, 19

Bladderwort, 206–207

Bladderwrack, 207–209

Botulinum toxin (BTX), 404

Botulinum toxin-A

idiopathic detrusor overactivity (IDO), 264–266

neurogenic detrusor overactivity (NDO),

261–262

pediatric use, 266–267

vs. resiniferatoxin (RTX), 262–264

Botulinum toxin-B, 267

Botulinum toxins, urge incontinence

Clostridium botulinum, 257

intradetrusor administration techniques

Dasgupta technique, 268

NDO treatment, 267–268

rigid vs. ﬂ exible cystoscopic techniques, 269

suburothelial injection, 268–269

medicine and urinary tract applications, 261

overactive bladder (OAB) treatment, 257–258

side effects, 269–270

therapeutic use

acetylcholine (ACh) release, 259–260

action mechanism, 258–259

afferent mechanism of action, 261

ATP and CGRP release, 260

neuromuscular junction, 258

SNARE proteins, 258–259

synaptosomal-associated protein-25, 258

BTX-A. See Botulinum toxin-A

BTX-B. See Botulinum toxin-B

Bulking agent injection, 483, 486

limitation of, 481

surgical series of, 481–482

Burch colposuspension, 476–477, 515

arcus tendineus fascia pelvis, 135

Burch suture, 136

cure rate, 137

lateral vaginal fornix elevation, 136

postoperative complications, 137

C

Cadaveric fascia lata (CFL), 123, 124

Cadaveric grafts, 317–318

Calcitonin gene-related peptide, 22–23, 260

Calcium hydroxyapatite, 158–159

Camellia sinensis, 209

Capsaicin, 20

Carbon-coated zirconium beads, 157–158

Cervical cancer

brachytherapy, 462

intracavitary treatment, 461

CFL. See Cadaveric fascia lata

CGRP. See Calcitonin gene-related peptide

Chronic obstructive pulmonary disease, 57

CISC. See Clean intermittent self-catheterization

CJD. See Creutzfeldt-Jakob disease

”Clam” ileocystoplasty, 236–237

Clean intermittent catheterization (CIC)

in augmentation cystoplasty

patient selection and evaluation, 236

urinary tract infections, 239

voiding dysfunction, 242

neurogenic bladder dysfunction, 231

urinary diversion, 248

Clean intermittent self-catheterization

(CISC), 479

Clostridium botulinum

botulinum toxin, 257

photomicrograph, 260

Coaptite. See Calcium hydroxyapatite

Collagen, 68

Colpocystopexy, 306

Index 535

Connective tissue

anatomic symptoms, 58–59

predisposing events, 55

Constipation

cinedefecography, 378

defecation, 371–372

outlet type constipation surgical treatment

enterokinetic agents, 383

osmotic and stimulant laxatives, 383

pelvic ﬂ oor biofeedback, 383

rectocele repair, 384

stapled transanal rectal resection (STARR), 384

Continence

bladder neck

hammock system, 36–37

urethral hypermobility and intrinsic sphincter

deﬁ ciency, 36

estrogen receptors and hormonal factors, 65–66

hormonal inﬂ uences

urinary tract function, 67–68

urinary tract infection, 67

urinary tract symptoms, 67

midurethra, 37–38

stress urinary incontinence, 35

surgical therapy efﬁ cacy, 38

urethral closure insufﬁ ciency, 35

urinary dysfunction management

incontinence, 70–71

recurrent urinary tract infection, 74

stress incontinence, 73

systemic HRT and urinary incontinence, 71–72

urge incontinence, 73–74

urogenital atrophy, 74

vaginal estrogens, 76–78

urinary tract and continence mechanisms, 35–36

Continence Promotion Committee (CPC), 525

Continence surgery

midurethral approach, 166

patient selection, 167

COPD. See Chronic obstructive pulmonary disease

Cost beneﬁ t analysis, 511

Cost effectiveness analysis (CEA), 511

Cost of illness analysis (COI), 511

Creutzfeldt–Jakob disease (CJD), 124

Cube pessary, 288

Cystoceles, 313

Cystoscopy

cystourethroscopic examination for, 440

radiation therapy in, 440

Cystourethrography, 470

D

Defecatory dysfunction, 60

Detrusor hyperactivity with impaired contractility

(DHIC), 394

Detrusor overactivity (DO), 231, 437

botulinum toxin-A (BTX-A)

idiopathic detrusor overactivity (IDO), 264–266

neurogenic detrusor overactivity (NDO), 261–262

pediatric use, 266–267

vs. resiniferatoxin (RTX), 262–264

botulinum toxin-B (BTX-B), 267

sphincter component and urinary incontinence, 471

Diabetes mellitus, 9–10

Dimethylsulfoxide (DMSO), 211–212

Division of Reproductive Urologic Drug Products

(DRUDP), 105

Donut pessary, 286–287

Duloxetine. See Serotonin and norepinephrine reuptake

inhibitors

Durasphere. See Carbon-coated zirconium beads

E

Electrical stimulation. See Functional electrical

stimulation

Electromyography, 375–376

Endopelvic fascia

collagen-rich, 110

intrapelvic aspect, 112

pelvic ﬂ oor

anterior and posterior pelvic triangles, 48–49

DeLancey’s functional level description, 46

Denonvilliers’ fascia, 48

external urethra sphincter, 47

ligaments, 44–46

proximal and distal urethra, 47

vagina and supportive structures, 46, 47

viscerofascial layer, 43

proximal urethra resuspension, 111

Estrogen

randomized controlled clinical trials, 70, 71

recurrent urinary tract infection, 74

squamous epithelium, 65

stress incontinence, 73

urge incontinence, 73–74

urogenital atrophy, 74

vaginal therapy

efﬁ cacy, 76

Estring, 77

FSH suppression, 77

meta-analysis, 77

shorter latency period, 76

Ethylene vinyl alcohol copolymer, 158

Euphorbia resinifera, 262

F

Fecal incontinence, 60

anal sphincter muscles/anal canal, 371

imaging studies

anal canal musculature, 376–377

536 Index

Fecal incontinence (Continued)

anal endosonography, 376

endoanal ultrasound, 378

ultrasound measurements, 377–378

medical intake, 372–373

outlet type constipation surgical treatment

enterokinetic agents, 383

osmotic and stimulant laxatives, 383

pelvic ﬂ oor biofeedback, 383

rectocele repair, 384

stapled transanal rectal resection (STARR), 384

perineal body, 370–371

physical examination

anorectal examination, 374

components of, 373

internal vaginal examination, 374

neurological examination, 373

palpation, 373–374

rectal and combined pelvic organ prolapse surgical

treatment, 384–385

rectum, 371

sacrum

and coccyx, 368–369

posterior vaginal wall, 369–370

posterior compartment dysfunction

deﬁ nitions and challenges, 367–369

diagnostic studies, 374–375

electromyography/pudendal nerve latency,

375–376

treatment options

anal sphincteroplasty, 382

biofeedback, 381–382

neosphincter procedures, 383

patient management, 381

posterior levatorplasty, 382

sacral nerve stimulation (SNS), 382

Female sexual dysfunction, 60

FES. See Functional electrical stimulation

FMS. See Functional magnetic stimulation

Follicle-stimulating hormone (FSH), 77

Fucus vesiculosus. See Bladderwrack

Functional electrical stimulation (FES), 184–185

biofeedback therapy, 295

contraindications, 297

pelvic ﬂ oor exercises, 296

vaginal and rectal sensors, 296–297

Functional magnetic stimulation (FMS), 185–186

G

Gehrung pessary

for cystocele, 288

insertion and removal, 289–290

Glutaraldehyde cross-linked bovine collagen

(GAX-collagen), 154–155

H

Hemostasis, 111

Herbology

bladderwort, 206–207

bladderwrack, 207–209

dimethylsulfoxide, 211–212

goldenrod, 210–211

lower urinary tract symptoms, 206

pumpkin seed oil, 207

sweet sumach, 210

teas, 209–210

Hormone replacement therapy (HRT), 58, 99–100

Hyaluronic acid, 159

Hysterectomy, 453

I

Iatrogenic obstruction

conservative treatment, 498

surgical intervention, 500

Idiopathic detrusor overactivity (IDO), 21–22

botulinum toxin-A, 264–266

therapeutic use, BTX, 260–261

Ileocystoplasty technique, 457

Impaired detrusor contractility and urethral obstruction,

494–450

Implantable pulse generator (IPG), 222

Ingelman–Sundberg bladder denervation,

232–233

International Continence Society (ICS), 309, 525

InteXen™, 320

InteXen LP™, 320

Intravenous pyelography (IVP), 454

Intrinsic sphincter deﬁ ciency (ISD), 36, 462

in cystometrograms, 438

incontinence and correlate symptoms, 435

treatments, 447

Intrinsic sphincter dysfunction, 493

L

Laparoscopic retropubic suspensions

artiﬁ cial urinary sphincter

endopelvic fascia, 143

Pfannensteil incision, 142, 143

pubovaginal sling

allograft/synthetic material, 140

autologous slings, 140

cadaveric transvaginal sling (CaTS) technique, 139

complications, 140–141

Crawford clamp, 139

pyramidalis muscle, 138

rectus fascial strip, 138

Laparoscopic retropubic urethropexy, 120–121

Laparoscopic sacrocolpopexy

diagnostic work-up, 356–357

Index 537

indication

genital prolapse, 356

pelvic organ prolapse (POP), 355–356

types of laparoscopic techniques, 356–357

results

advantages of laparoscopic prolapse repair, 363

complications, 362

laparoscopic technique problems, 363

perspectives, 363

success deﬁ nition and technical issues, 362

vaginal apex, 360–361

technique

anterior dissection, 358–359

incontinence procedure, 359

posterior dissection, 358

presacral dissection and sacropexy, 359–361

surgical principle, 358

trocar placement, 357–358

LeFort technique and modiﬁ cations, 485

Lever pessaries, 290

Lower urinary tract symptoms (LUTS)

M

Macroplastique, 156–157

Magnetic resonance imaging systems, 378

Male incontinence

and bladder neck contracture

ﬁ brosis in, 438

sphincteric function in, 438

nerve damage

bladder trigonal biopsies, 437

preservation, 437

pathophysiology, 435

patient evaluation, 438

pharmacotherapy

overﬂ ow incontinence (OI), 418

postprostatectomy incontinence, 417–418

sphincter, surgical anatomy and innervation

bladder neck and prostatic urethra, 434

mechanisms, 433–434

surgical options, 441

Male sling procedures, 433

Malignant transformation, 239–240

Marshall–Marchetti–Krantz (MMK) procedure

cure rates, 134

complication rates, 135

sagittal section, 134

sutures, 133

Martius ﬂ ap, transvaginal urethrolysis, 504

Martius grafts, 456

Maximum urethral closure pressure (MUCP), 477

McCall–Mayo culdoplasty, 330–331

Mesh grafts

in anterior vaginal wall, 484

cadaveric fascia lata and polypropylene comparison, 484

classiﬁ cation, 484

Marlex mesh used in, 484

synthetic biomaterials/ mesh, 321

classiﬁ cation and host remodeling, 321–322

erosion/extrusion, 324–325

synthetic mesh types

polyglactin 910, 322

polypropylene, 322–323

prolapse recurrence, 324

in vaginal vault prolapse, 484

Micturition neurophysiology

central control, 17–18

neurophysiological basis

painful bladder, 26–27

urgency, 27–28

peripheral control

adenosine triphosphate (ATP), 23, 25

afferent axons, 19

detrusor overactivity, 19–20

bladder suburothelium, 26

immunohistochemical studies, 20

lamina propria space, electron micrograph, 25, 26

muscarinic and nicotinic ACh receptors, 23

myoﬁ broblasts, 25–26

SP and CGRP, 21–22

suburothelial nerve immunoreactivity, 21–22

TRPV1-and P2X3 mice, 20–21

ultrastructural components of human bladder, 21

unmyelinated suburothelial nerves, electron

micrographs, 23–24

reﬂ ex mechanisms, 18–19

Midurethra, Integral Theory, 37–38

Midurethral slings, 126

Midurethral synthetic slings techniques, 494, 496, 498

erosion of, 499

loosening/incision

right-angle clamp, use of, 500

TVT sling, 500–501

Muscarinic acetylcholine receptors (MAChRs), 23

Muscarinic receptor antagonists

adverse effects, 194

efﬁ cacy and tolerability meta-analysis, 196

randomized clinical trials, 195

subtypes, 192

tolterodine, 196

Myelinated Aδ-ﬁ bers, 19

N

National Association for Continence (NAFC), USA,

522, 527

bathroom-related attitudes, 522–523

continence awareness and, 524

public forums, 527

538 Index

National continence organizations, 527

Natural biomaterials. See Biological grafts

Needle suspension surgery, 517

Neurogenic bladder dysfunction (NBD), 231–232, 445

Neurogenic detrusor overactivity (NDO), 20–22,

261–262

New Zealand Continence Foundation (NZCA), 527

Nicotinic acetylcholine receptors (nAChRs), 23

O

Obliterative procedures, colpocleisis

contemporary series of, 488

partial schematic representation, 487

total schematic representation, 485–486

Obstructive voiding disorders, 494

ObTryx sling system, 166

OI. See Overﬂ ow incontinence

Open retropubic suspensions

Burch colposuspension

arcus tendineus fascia pelvis, 135

Burch suture, 136

cure rate, 137

foley catheter, 136

lateral vaginal fornix elevation, 136

postoperative complications, 137

Marshall–Marchetti–Krantz (MMK) procedure

cure rates, 134

complication rates, 135

sagittal section, 134

Overactive bladder syndrome, peripheral

neuromodulation

action mechanism, 228

electrical stimulation, 228

indications, 228

simulation procedure, 228–229

study results, 229–230

Overﬂ ow incontinence (OI), 418

P

Painful bladder syndrome interstitial cystitis (PBS/IC), 27

Pelvic ﬂ oor dysfunction, 475

Pelvic ﬂ oor electrical stimulation (PFES), 204

Pelvic ﬂ oor exercises (PFE), 440

Pelvic ﬂ oor muscle exercise (PFME)

active exercise, 293

Colpexin sphere, 294

regular exercises, 292

Pelvic ﬂ oor muscle training (PFMT), 512

biofeedback, 89–90

effective training, 88–89

factors affecting outcome, 95

improvement and cure rates, 88

long-term effects, 92–94

motivation, 95

randomized controlled trials, 87, 88

rehabilitation method adverse effect, 91–92

SUI prevention, 94

vaginal cones, 90–91

Pelvic ﬂ oor physiotherapy, iatrogenic obstruction, 498

Pelvic ﬂ oor prolapse

anatomy, 53–54

causes

decompensating events, 57–58

inciting events, 55–56

predisposing events, 54–55

promoting events, 56–57

risk factors, 53–55

effects

anatomic symptoms, 58–59

functional symptoms, 59–60

sexual symptoms, 60

symptoms of, 58

Pelvic ﬂ oor, three-dimensional surgical anatomy

bony pelvis, 41, 42

endopelvic fascia

anterior and posterior pelvic triangles, 48–49

DeLancey’s functional level description, 46

Denonvilliers’ fascia, 48

external urethral sphincter, 47

ligaments, 44–46

proximal and distal urethra, 47

vagina and supportive structures, 46, 47

viscerofascial layer, 43

neurovascular anatomy, 51–52

obturator foramen (OF), 41–43

soft tissues, 42–45

tissue planes

paravesical and pararectal space, 51

rectovaginal space, 51–52

Retzius space, 51

vesicovaginal space, 49

vaginal anatomy, 49

Pelvic irradiation

ﬁ brosis and necrosis, 462

neoplastic cells and, 461

Pelvicol®, 319

Pelvic organ prolapse (POP). See also Pelvic ﬂ oor prolapse

abdominal hysterectomy, 306, 307

Amreich–Richter procedures, 309

cervical amputation, 307

colporrhaphy, 308

cystocele vaginal repair, 307

degree and severity, 310

genital tract description, 303

goals and paradigm, 277–278

ICS classiﬁ cation, 309

intestinovaginal hernia, 308

paravaginal defect, 307

pessary, 301, 306

recurrent incontinence

Index 539

mesh graft, 484

MeSH search methods, 475–476

obliterative procedures, 485

role of biofeedback

home training programs, 295

training technique, 294

role of pessaries

behavioral treatments, 292

complications and contraindications, 290–291

conservative management, 279

ﬁ tting and insertion techniques, 281–282

historical perspective, 278

patient satisfaction, 291–292

suction mechanism, 280

types, 280, 283, 286

sacrocolpopexy, 309

surgical management, 277

symptomatic posterior vaginal wall prolapse surgical

treatment

abdominal open/laparoscopic procedures, 381

allografts and xenografts, 380

pelvic ﬂ oor symptoms, 378–379

surgical approach, 379–380

surgical literature analysis, 379

transanal/transperineal approaches, 381

transvaginal approach, 380–381

vaginal hysterectomy, 302, 306

vaginal speculum, 306

Pelvic radiation

bladder dysfunction

management of, 465

radical hysterectomy and pelvic irradiation, 463

complications of

urinary bladder rupture, 462

urological, 462

intrinsic sphincter deﬁ ciency and stress urinary

incontinence, 465–466

radiation therapy, 464

Pelvic reconstruction, abdominal approach

abdominal sacrocolpopexy, 341

complications, 346

concomitant procedures, 345–346

cul-de-sac closure, 345

efﬁ cacy of, 346

pelvic anatomy, 342

sacral dissection, 344

surgical steps, 343

surgical technique, 342–343

ligament suspensions

cul-de-sac closure, 347–348

uterosacral ligament vaginal apex suspension, 347

objectives of, 341

paravaginal repair

cystoceles, 349–350

surgical technique, 350–351

Pelvic reconstruction, vaginal approach

anterior wall repairs, 332

anterior colporrhaphy, 333–334

paravaginal defect repair, 334

grafted apical procedures, 336

McCall–Mayo culdoplasty, 330–331

posterior reconstruction, 334–335

surgical approach, 329–330

vaginal apical suspensions

iliococcygeus suspension, 331,

sacrospinous ligament ﬁ xation, 332

uterosacral ligament suspension, 331

Percutaneous nerve evaluation (PNE) test

patient selection, 218

sacral neuromodulation technique, 219

Peripheral nerve stimulation (PNS)

action mechanism, 228

simulation procedure, 228–229

Peripheral neuromodulation

action mechanism, 228

electrical stimulation, 228

indications, 228

simulation procedure, 228–229

study results, 229–230

Pessaries

behavioral treatments, 292

complications and contraindications,

290–291

conservative management, 279

ﬁ tting and insertion techniques

self-management, 282

urination and defecation, 281

Valsalva maneuver, 281–282

historical perspective, 278

patient satisfaction, 291–292

suction mechanism, 280

types

ring with supportive membrane, 283

space-ﬁ lling pessaries, 280, 286

PFES. See Pelvic ﬂ oor electrical stimulation

PFMT. See Pelvic ﬂ oor muscle training

Pharmacotherapy, UUI

alpha blockers, 400–401

5 alpha reductase inhibitors, 401

antimuscarinics, 401–402

clinical data interpretation

biometrical issue, 194

patient population characteristics, 193

randomized controlled trial vs.real-life practice,

194–195

secondary subgroup analysis, 194

solifenacin, 193

concepts, 191

drugs and properties, 191–193

muscarinic receptor antagonists

540 Index

Pharmacotherapy, UUI (Continued)

efﬁ cacy and tolerability meta-analysis, 196

randomized clinical trials, 195

tolterodine, 196

neuromodulation, 403–404

treatment strategy

efﬁ cacy and tolerability, 197

trospium, 196

PNTML. See Pudendal nerve terminal motor latencies

Polyglactin 910, 322

Polypropylene, 322–323

Polytetraﬂ uoroethylene (PFTE), 155–156

Posterior compartment prolapse, 372–373

Posterior tibial nerve stimulation (PTNS), 403

Postpartum urinary incontinence, 4–5

Postprostatectomy incontinence (PPI), 5–6, 417–418, 435

biofeedback and, 441

bladder instability

capacities and compliance values on, 437

concomitant sphincteric weakness, 436

radical prostatectomy in, 437

patients history and examination for, 438

sphincter and bladder dysfunction in, 435–436

urine leakages, 436

Postvoid residual (PVR) urine volume, 398, 497

Pressure-regulating balloon (PRB), 435

Prostate adjustable continence therapy (ProAct)

procedures and devices in, 447

Pudendal nerve terminal motor latencies, 375–376

Pumpkin seed oil, 207

Q

Q-tip test, urethral mobility, 497

Qualityadjusted life years (QALYs), 511

R

Radical hysterectomy (RH), 464

Radio frequency (RF) tissue interaction theory

fascial hammock laxity and elasticity, 109

microremodeling, 113

technique

fascia visual blanching, 112

Foley catheter, 111

laparoscopic, 112

SURx transvaginal system, 111

tissue temperature and impedance, 112

therapeutic results

clinical efﬁ cacy, 112

three-dimensional thermal effect, 110

Recurrent urinary incontinence, AUS

Cuff erosion in, 471

device malfunction, valve problems, 472

female patient, evaluation and treatment

risk factors in, 469–470

urinary symptom assessment in, 469

male patient, evaluation and treatment, 470

resulting urethral atrophy, 471

surgical treatments for, 469

Reﬂ ex continence mechanism, 437

Resiniferatoxin (RTX), 20–21, 262–264

Retropubic suspensions, 120

Retropubic urethrolysis, 502

paravaginal defect, 505

Retropubic urethropexy, 494. See also Burch

colposuspension, MMK procedures

Rhus aromatica. See Sweet sumach

Robotic-assisted laparoscopic sacrocolpopexy

da Vinci robot, 355

vs. open series, 360, 362–363

S

Sacral nerve stimulation, 382

clinical results, 221–222

complications, 222–223

expanding indications, 223–224

intravesical electrostimulation, 217

micturition reﬂ ex, 217–218

patient selection, 218–219

sacral neuromodulation technique

percutaneous nerve evaluation test, 219

S3 stimulation, 219–220

unilateral/bilateral stimulation, 220–221

Scrotal activating/deactivating mechanism, 442

Selective estrogen receptor modulator, 58

Serotonin and norepinephrine reuptake inhibitors

acetic acid-induced model, 102

demographic characteristics and comorbidities, 104

DRUDP, 105

micturition cycle neural control, 101

mixed urinary incontinence, 104

randomized clinical trial, 103

Silicone pessaries, 279

Simon Foundation for Continence (USA), 524

Sling materials, 165

Sling procedures, pubovaginal slings, 165,

493–494

autologous and synthetic sling in, 477–479

biomaterials

allograft tissues, 123–124

autlogous fascia, 123

synthetic, 124–126

xenografts, 124

costs and diagnostic tests, 516

effectiveness of, 477

failure reasons for, 479

Goebell–Frangenheim–Stoeckel technique, 122

materials for, 477

paradigm shift, 123

salvage therapy, 479

tension-free vaginal tape (TVT), 515

Index 541

SNAP-25. See Synaptosomal-associated protein-25

SNS. See Sacral nerve stimulation

Soluble N-ethylmaleimide-sensitive factor attachment

protein receptors, 258–259

Stapled transanal rectal resection, 384

Stress urinary incontinence (SUI), 4–5

α-adrenoceptor agonists, 100–101, 415

artiﬁ cial urinary sphincter (AUS), 482

assessment and treatment of, 482–484

anterior vaginal wall laxity, 118, 119

autologous blood and fat, 154

autologous tissue, 160

β-adrenoceptor antagonists and agonists, 101

bioglass, 160

bulking agent injection, 480–482

bulking materials

calcium hydroxyapatite, 158–159

carbon-coated zirconium beads, 157–158

ethylene vinyl alcohol copolymer, 158

polytetraﬂ uoroethylene (PFTE), 155–156

silicone polymers, 156–157

Burch colposuspension, 476–477

conservative vs. surgical management

in men, 518

in women, 517

and costs

direct, 511–512

indirect and intangible, 512

deﬁ nition, 415

dextranomer microspheres, 159

diagnostic testing

conservative management in, 514

pelvic organ prolapse in, 513

pharmaceutical management for, 514

treatments and symptoms in, 513

drug efﬁ cacy and safety issues, 105

duloxetine, 416

economic burden

annual direct medical costs, 512

indirect costs for, 513

storage conditions and controls for, 512–513

electrical stimulation, 91

glutaraldehyde cross-linked bovine collagen (GAX-

collagen), 154–155

Green/McGuire/Blaivas classiﬁ cation, 118

hormone replacement therapy, 99–100

hyaluronic acid, 159

injectable agents, 153

laparoscopic retropubic suspensions

artiﬁ cial urinary sphincter, 141–143

pubovaginal sling, 138–141

maintenance and surgical treatment for, 518

mechanism, 149

MeSH search methods, 476

microballoons, 160

obstruction incidence

and urinary retention, 493

voiding dysfunction, 494

open retropubic suspensions

Burch colposuspension, 135–137

Marshall–Marchetti–Krantz (MMK) procedure,

133–135

pelvic ﬂ oor muscle training

biofeedback, 89–90

effective training, 88–89

factors affecting outcome, 95

improvement and cure rates, 88

long-term effects, 92–94

motivation, 95

randomized controlled trials, 87, 88

rehabilitation method adverse effect, 91–92

vaginal cones, 90–91

periurethral injection, 152

postoperative care, 153

pubovaginal slings, 477–479

radical retropubic prostatectomy, 416

radio frequency (RF) tissue interaction theory

fascial hammock laxity and elasticity, 109

microremodeling, 113

potential salubrious effect, 111

technique, 111–112

therapeutic results, 112–113

three-dimensional thermal effect, 110

serotonin and norepinephrine reuptake inhibitors,

101–105

surgical management

cost-effectiveness, 515–516

cost of illness analysis, 514–515

cost utility, 516–517

surgical treatment

ﬁ xation techniques, 126–127

laparoscopic retropubic urethropexy,

120–121

midurethral slings, 126

pubovaginal sling, 122–126

retropubic suspensions, 120

sphincter prosthesis, 127

transvaginal needle suspension, 121–122

transvaginal plication, 119–120

tension-free vaginal tape (TVT), 119, 479–480

transurethral injection, 151–152

tricyclic antidepressants, 101

ultrasound guidance, 153

SUI. See Stress urinary incontinence

Suprapubic pubic arch sling (SPARC)

components, 171

evidence-based clinical outcome, 172–173

procedures and complications, 172

Sweet sumach, 210

Synaptosomal-associated protein-25, 258

542 Index

T

Tandem-Cube pessaries, 290

TCA. See Tricyclic antidepressants

Teas

Camellia sinensis, 209

chamomile, 209–210

Tension-free vaginal tape (TVT), 119, 126, 515

kit and procedure for, 516

midurethral approach

composition, 167

evidence-based clinical outcome, 169

polypropylene mesh tape, 166–167

procedures and complications, 168

SPARC approach

components, 171

evidence-based clinical outcome, 172–173

procedures and complications, 172

transobturator approach

complications, 170–171

evidence-based clinical outcome, 171

procedures, 169–170

urinary retention and, 494

voiding difﬁ culties after, 495

Tension-free vaginal tape-Secur (TVT-S), 173–174

Tibial nerve stimulation, 229

Transient receptor potential vanilloid 1 (TRPV1)

ATP, 2 5

P2X3, 20–21

Transobturator tape (TOT), 493

Transvaginal needle suspension, 121–122

Transvaginal plication, 119–120

Transvaginal sling incision, 502

cystoscopy, 501

segmental resection for sling identiﬁ cation, 501

sling isolation, 501

Transvaginal urethrolysis, 501

endoscopic examination, 502

midline or inverted U incision, 503

suprameatal approach, 504

Tricyclic antidepressants (TCA), 101

Tutoplast®, 318

TVT. See Tension-free vaginal tape

U

United Kingdom’s National Health Service, 512

Unmyelinated C-ﬁ bers, 19

Ureterovaginal ﬁ stula (UVF), 454

Urethra, 47, 68

Urethral hypermobility, 36

Urethrolysis, 497, 504

Urge urinary incontinence (UUI), 4–5

acupuncture

b-endorphins, 204

evidence reviewing, 204–205

peripheral circulation, 204

acute urinary retention, 413

antimuscarinics and a1-receptor antagonists, 414–415

behavioral therapy, 399–400

biofeedback therapy, 183–184

bladder contractility index, 414

bladder training

cochrane database meta-analysis, 181

randomized control trials, 182

urodynamic testing, 180

voiding diary, 180botulinum toxin (BTX), 404

C-ﬁ ber desensitization, 404

deﬁ nition, 179

dietary modiﬁ cation

caffeine, 179, 180

OAB, 179

retrospective study, 180

evaluation, 398–399

functional electrical stimulation (FES), 184–185

functional magnetic stimulation (FMS), 185–186

herbology

bladderwort, 206–207

bladderwrack, 207–209

dimethylsulfoxide, 211–212

goldenrod, 210–211

lower urinary tract symptoms, 206

pumpkin seed oil, 207

sweet sumach, 210

teas, 209–210

lower urinary tract symptoms (LUTS), 412

management, 399

muscarinic responsiveness, 413

neurogenic bladder or detrusor muscle instability, 412

nomenclature

diagnoses, 394–395

signs, 394

storage symptoms, 394

overactive bladder syndrome (OAB), 203–204, 412

pelvic ﬂ oor electrical stimulation (PFES),

204pathophysiology

extravesical, 397–398

intravesical, 397

myogenic, 397

neurogenic, 396–397

pelvic ﬂ oor muscle exercises

pubococcygeus muscle, 182

randomized controlled trial, 182, 183

stress strategy, 182

pharmacotherapy

alpha blockers, 400–401

5 alpha reductase inhibitors, 401

antimuscarinics, 401–402

augmentation cystoplasty, 403–404

clinical data interpretation, 193–195

concepts, 191

drugs and properties, 191–193

Index 543

muscarinic receptor antagonists, 195–196

neuromodulation, 403–404

surgical procedure, 402–403

treatment strategy, 196–197

tolterodine, 413

TURP, 404–405

Urge urinary incontinence, surgical treatment

augmentation cystoplasty, 233–234

”Clam” ileocystoplasty, 236–237

complications, 238–242

contraindication, 235–236

enterocystoplasty results, 242–243

lifelong follow-up, 237

nonpharmacological options, 243–244

patient selection and evaluation, 234–235

bladder autoaugmentation

autoaugmentation results, 246–247

complications, 247

demucosalized gastrointestinal segments, 245

detrusor myectomy–myotomy, 244–245

surgical technique, 245–246

detrusor overactivity, 231

Ingelman–Sundberg bladder denervation, 232–233

neurogenic bladder dysfuntion (NBD), 231–232

urinary diversion, 248–251

Urinary diversion, 248–251

Urinary incontinence (UI) and community awareness

and Australia, 529–530

continence awareness

bladder health mobile, 524

inﬂ uence leaders, role, 524

public education, promotion program, 523–524

help-seeking behavior

barriers, 521

self-care practices, 522

treatment seeking, 521

urine leakage and, 521–522

and older persons, 522

patient advocacy continence organizations, 525

public awareness campaigns, evaluation

health promotion project, 528

stigmatization

incontinence and, 522

terms and usage, 523

websites on, 524

Urinary incontinence epidemiology

and mortality, 10

population prevalence, 3–4

quality of life, 10

risk factors

age, 6

caffeine and alcohol intake, 10

cognitive and functional impairment, 8–9

depression, 9

diabetes mellitus, 9–10

estrogen–hormone replacement, 9

hysterectomy and menopause, 8

mode of delivery, 7–8

obesity, 8

obstetrical factors, 7–8

parity, 7

race and ethnicity, 6–7

smoking, 9

seeking help, 10

speciﬁ c population prevalence

communities and long-term care facilities, 4

postprostatectomy incontinence, 5–6

pregnancy-related and postpartum UI, 4–5

type prevalence, 4

Urinary tract

bladder function, 68

collagen, 68

dysfunction

clinical results, 221–222

complications, 222–223

expanding indications, 223–224

intravesical electrostimulation, 217

micturition reﬂ ex, 217–218

patient selection, 218–219

sacral neuromodulation technique, 219–220

unilateral/bilateral stimulation, 220–221

imaging, 385

infection, 67

prolapse impact on, 386

symptoms

hormonal inﬂ uence, 67

urinary incontinence, 68–69

urogenital atrophy, 69

urethra, 68

Urinary tract infections (UTIs), 239, 495

Urodynamics, 167

decision–analytic approach, 513

postincontinence surgery, 497–498

symptoms recording in, 439

tracing and evaluation in, 438–439

videourodynamics and, 497

UTI. See Urinary tract infections

Utricularia vulgaris. See Bladderwort

UUI. See Urgency urinary incontinence

V

Vaginal pessaries, 286

Vaginal prolapse surgical repair

anterior wall repairs, 332

anterior colporrhaphy, 333–334

paravaginal defect repair, 334

McCall–Mayo culdoplasty, 330–331

posterior reconstruction, 334–335

surgical approach for, 329–330

uterosacral ligament suspension, 331

544 Index

Vaginal surgery

grafted apical procedures, 336

mesh and grafts in, 335–336

prolapse repair kits, 336–338

Valsalva leak point pressure (VLPP), 439, 480

Vesicovaginal ﬁ stula (VVF), 455

benign and malignant, 456

conservative treatment, 454–455

cystoscopy of, 455

diagnosis, 462

diluted contrast media, use of, 463

etiology in adults

latrogenic, 453

noniatrogenic, 454

presentation and diagnosis, 454

ﬂ ouroscopy of, 454

history of, 453

hysterectomy, 463

postradiation, 463

surgical repairs

postoperative care, 458

surgical approach, 456–457

surgical timing, 456

Voiding cystourethrogram, 498

Voiding dysfunction and female anti-incontinence

surgery

cystourethroscopy and imaging, 498

diagnostic evaluation

obstruction, duration, 496

storage symptoms, 496

etiology, 494

history and physical examination, 496–497

irritative symptoms, 495, 496, 499

postoperative risk factors

detrusor pressure, 495

pelvic organ prolapse, 496

urethrolysis and sling incision/loosening

treatment, 500

urodynamics, 497–498

X

Xenografts, 319–321

Continence: Bladder Neck versus Mid-Urethra

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