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Iqbal A, Salinas V, Filipi CJ. Endoscopic therapies of
gastroesophageal reflux disease.
World J Gastroenterol
2006; 12(17): 2641-2655
http://www.wjgnet.com/1007-9327/12/2641.asp
INTRODUCTION
Gastroesophageal refl ux disease affects millions of people
worldwide. The prevalence of heartburn in a randomly
selected adult population is approximately 20%. It is
estimated that approximately one third of the adult
population in the United States suffers from heartburn
[1]
.
Of these, approximately 7% have refl ux esophagitis. The
management of GERD has gained increasing attention
during the past two decades due to a high prevalence
in Western societies, a better understanding of the
pathophysiology, new potent anti-secretory drug therapies,
the advent of minimally invasive surgery and new transoral
endoscopic therapies. We attempt to determine the true
efficacy and benefit of these therapies. The relative
advantage of one over the other is enlightened by objective
comparison of study outcomes. The potential for use by
clinicians in daily practice and the underlying mechanisms
of action are also explored.
It is important to understand the pathophysiology
of GERD although much controversy remains. The
effi cacy of the antirefl ux barrier at the GEJ is dependent
upon three factors. These include the “lower esophageal
sphincter complex”, the geometric profile of the cardia
and the changes within each as a result of gastric
distension. Other factors such as gravity, intra-peritoneal
pressure, esophageal motility and the mucosal barrier also
play a role in refl ux prevention. Refl ux can be precipitated
by a decrease in either the length or the pressure of the
lower esophageal sphincter (LES) and/or obliteration or
diminishment of the angle of His. Both these factors are
present during periods of gastric distension. It is believed
that transient LES relaxations (tLESR), i.e. intermittent
spontaneous decreases in LESP, are responsible for refl ux
events in patients with a normal LES
[2-5]
. In the early
stages of disease and in the absence of a hiatal hernia,
the geometry and integrity of the cardia are normal.
However, during periods of gastric distension such as after
meals, gastric distension alters the anatomy and makes the
sphincter incompetent due to sphincter shortening, which
some term transient lower esophageal sphincter shortening
(tLESS)
[6]
. Such patients appear to be the ideal population
EDITORIAL
Endoscopic therapies of gastroesophageal refl ux disease
Atif Iqbal, Vanessa Salinas, Charles J Filipi
Atif Iqbal,
Department of Surgery, University of Missouri
Columbia, One Hospital Drive, Columbia, MO 65211,
United States
Vanessa Salinas, Charles J Filipi,
Department of Surgery,
Creighton University, 601 N 30
th
Street, Omaha NE 68131,
United States
Correspondence to:
Charles J Filipi, MD, Professor of Surgery,
Department of Surgery, Suite 3740, Creighton University School
of Medicine, 601 N. 30
th
street, Omaha, Nebraska 68131,
United States. cjfi lipi@creighton.edu
Telephone:
+1-402-2804213
Fax:
+1-402-2804278
Received:
2005-08-08
Accepted:
2005-08-30
Abstract
The high prevalence of gastroesophageal refl ux disease
(GERD) in Western societies has accelerated the need
for new modalities of treatment. Currently, medical and
surgical therapies are widely accepted among patients
and physicians. New potent antisecretory drugs and
the development of minimally invasive surgery for the
management of GERD are at present the pivotal and
largely accepted approaches to treatment. The minimally
invasive treatment revolution, however, has stimulated
several new endoscopic techniques for GERD.
Up to now, the data is limited and further studies are
necessary to compare the advantages and disadvantages
of the various endoscopic techniques to medical and
laparoscopic management of GERD. New journal articles
and abstracts are continuously being published. The Food
and Drug Administration has approved 3 modalities, thus
gastroenterologists and surgeons are beginning to apply
these techniques. Further trials and device refi nements
will assist clinicians.
This article will present an overview of the various
techniques that are currently on study. This review will
report the effi cacy and durability of various endoscopic
therapies for gastroesophageal reflux disease (GERD).
The potential for widespread use of these techniques
will also be discussed. Articles and abstracts published in
English on this topic were retrieved from Pubmed. Due
to limited number of studies and remarkable differences
between various trials, strict criteria were not used for
the pooled data presented, however, an effort was made
to avoid bias by including only studies that used off-PPI
scoring as baseline and intent to treat.
© 2006 The WJG Press. All rights reserved.
Key words:
Endoscopic; Treatment; Gastroesophageal
refl ux disease
PO Box 2345, Beijing 100023, China World J Gastroenterol 2006 May 7; 12(17): 2641-2655
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World Journal of Gastroenterology
ISSN 1007-9327
wjg@wjgnet.com © 2006 The WJG Press. All rights reserved.
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for endoscopic antirefl ux procedures.
In the light of the above described pathophysiologic
factors, endoscopic therapies should prevent refl ux in the
following ways; (1) alter the compliance of the cardia and
prevent tLES shortening/relaxation, (2) increase baseline
LES tone or (3) increase baseline LES length. None of the
endoluminal therapies reduce the distal esophagus into the
abdomen and effect a hiatal hernia repair.
The majority of patients with GERD are best treated
by proton pump inhibitors (PPI’s). However, symptom
relapse is common after cessation of treatment
[7]
and
lifelong therapy is often necessary. Even while on therapy,
up to 33% of patients have recurrent symptoms within
the first two years. Almost 50% of patients continue to
exhibit objective evidence of acid regurgitation despite
complete symptomatic control on PPI therapy. Although,
a fundoplication is a good treatment option
[8]
, laparoscopic
anti-reflux surgery requires a general anesthetic,
hospitalization, postoperative lifestyle limitations for days
to weeks, is expensive and is associated with post-operative
morbidity and even a mortality rate. In addition, patients
may return to medical therapy
[9]
. These limitations created
the need to develop less invasive but effective procedures.
These procedures are listed here (1) Endoscopic Suturing
devices: Endoluminal Gastroplication (ELGP/Endocinch);
Endoluminal full-thickness plicator (NDO plicator);
Syntheon ARD Plicator; (2) Radiofrequency energy
delivery device: Stretta; (3) Synthetic Implants/Injections:
Implantable biopolymer (Enteryx); Implantable Prosthesis
(Gatekeeper); Implantable plexiglass microspheres
(PMMA). Of these, 3 novel endoscopic therapies have
been approved for use by the FDA. All procedures can
be safely performed in an outpatient setting utilizing
conscious sedation.
The general selection criteria that have been used
in most trials are shown in Figure 1. In addition to this,
specifi c patient selection, if any, is mentioned under the
respective procedures.
ENDOLUMINAL GASTROPLASTY
Initially, Swain
et al
developed a mechanical aid which
allowed passage of a needle and subsequent suture via the
biopsy channel of an endoscope
[10]
. Later, the technique
was modifi ed to create plications endoscopically below and
at the GEJ for the prevention of GERD.
Procedure
The procedure requires a suturing capsule, suture tags
and an anchoring system that secures the suture and cuts
the strands (Figure 2). A short, 18 mm-outer-diameter
overtube allows repeated intubations (approximately 12)
while avoiding trauma to the esophageal mucosa. Usually
patients tolerate the procedure with conscious sedation.
However monitored anesthesia or general anesthesia may
be used as necessary. Two to four plications are placed
either longitudinally (one above the other), radially (next
to each other) or spirally within the cardia. Each plication
is formed by two stitches that are placed into the gastric
submucosa, approximately one centimeter apart and then
pulled together. The procedure is completed within 40 to
60 minutes.
The application of cautery on opposing mucosal
surfaces prior to plication may secure tissue apposition
and promote long-term adherence. Its efficacy has been
proved in pilot studies
[11]
and needs to be tested in a larger
randomized controlled trial.
Effi cacy
The overall results with ELGP are tabulated in Table
1. This is a pooled data obtained from 11 studies. Two
multicenter trials are included in the table and will be
highlighted. In the fi rst trial 64 patients were randomized
between a circumferential and a linear plication
configuration
[12]
. All patients were dependent on anti-
Symptomatic GERD
Inclusion criteria:
1 Patients dependent on PPI’s
2 Good response to PPI’s
3 Patient fi t for surgery
4 Surgically adverse
Exclusion criteria:
1 Patients < 18 yr
2 BMI > 35
3 Esophageal varices
4 Barrett’s esophagus
5 Esophagitis (grade C or
higher)
6 Hiatal hernia > 2 cm
1
7 Motility disorder
8 Dysphagia
GERD confi rmed on 24-h pH-study
manometry
Esophagitis (grade B or lower) on
endoscopy
Endoscopic therapy for GERD
PPI’s or surgical therapy
1
Recently some studies have included patients with a hiatal hernias > 3 cm
and Barrett’s esophagus.
↓
↓
↓↓
↓
Figure 1 Inclusion/exclusion criteria for endoluminal therapies of GERD.
AB
C
D
E
F
Figure 2 A: Drawing of the suturing device which is equipped with a vacuum
chamber and a hollow needle in which there is a suture attached to a tag; B:
Tissue is drawn into the chamber by suction. The needle passes through the tissue
and the tag is captured in the distal chamber; C: The suction is then released; D:
The procedure is repeated on an adjacent piece of tissue; E: On tightening the
knot, the pieces of tissues are approximated; F: The knot, tied outside the animal,
is advanced by a knot pusher which is attached to the tip of the endoscope.
←←
←
←
←
2642 ISSN 1007-9327 CN 14-1219/ R World J Gastroenterol May 7, 2006 Volume 12 Number 17
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secretories and had proven refl ux by 24-h pH monitoring.
Manometry and endoscopy was performed to exclude
patients with Barrett’s esophagus, grade 3 or 4 esophagitis,
large hiatal hernias and an esophageal dysmotility disorder.
There was no difference found between the plication
configuration groups and post-procedure manometry
and endoscopy showed no improvement in LES pressure
or grade of esophagitis. A significant improvement in
heartburn and regurgitation scores from baseline was
found but the pH monitoring results although signifi cantly
improved showed only a 30% normalization rate.
In a second multicenter study, 85 symptomatic GERD
patients when off PPIs and with proven reflux on 24-h
pH monitoring were included
[13]
. Upper endoscopy and
manometry were also performed at baseline. Follow up
was scheduled at 3, 6, 12, and 24 mo. Symptom scores
and medication usage were assessed at each follow
up and pH-metry was done at 3 mo follow up. This
study was different from others with respect to their
inclusion criteria as it included patients with esophagitis
grade 3 (
n
= 10), hiatal hernia >2 cm (
n
= 9), Barrett’
s esophagus (
n
= 4), failed fundoplication (
n
= 3) and
those with pulmonary symptoms (
n
= 10). The majority
of the patients had 2 plications performed (range, 1-3)
and most had a circumferential plication (65%) with the
remaining receiving a linear confi guration (35%). Twenty-
four-mo follow up data demonstrated durable functional
improvement and a sustained reduction in anti-secretory
medication. Heartburn scores were reduced at both 1 (94%)
and 2 yr (78%) follow up. At 2 yr follow up, complete
resolution for heartburn was seen in 52% of patients and
77% for patients with regurgitation. Likewise, PPI usage
decreased with 69% of patients using <50% of their
baseline medication and 41% were completely off PPI’s
at 2 yr follow up. The duration and number of esophageal
acid exposures at 3-6 mo post-procedure were signifi cantly
reduced. There was no change in LES length or pressure
when measured at 3 mo.
A sham-controlled, randomized, blinded single
institution study (
n
= 34) is underway and 3 mo follow-up
is available
[14]
. The study nurse and patients were blinded to
the procedure performed. An overtube and 2 endoscopes
were exchanged in all patients and the conscious sedation
dosing was similar. Four circumferential plications were
placed when performing the ELGP. At 3 mo follow up,
heartburn frequency (69%
vs
31%,
P
= 0.03) and severity
(47%
vs
17%,
P
= NS) were improved in patients with
ELGP in comparison to those with the sham procedure.
A significantly greater number of patients discontinued
their daily PPI/H
2
B (75%
vs
25%,
P
= 0.03) in the plication
group. A signifi cant reduction in % time pH < 4 was also
observed, however, no difference was seen between groups
regarding normalization of pH, median LESP or quality
of life. Limitations of this study include a probable type
II error, a larger than expected sham effect, inadequate
follow-up length and lack of technique standardization.
A randomized controlled trial of larger size with longer
follow up is needed for objective evidence of durable
benefi t.
Other studies of note have demonstrated a markedly
improved quality of life at one year follow up
[15]
, reduction
of the rate of tLESRs by 37% at 6 mo in a single-center
study
[16]
, in baboons
[17]
a significant increase in LES
length, and Kadirkamanathan
et al
reported an increase
in intra-abdominal, but not total, length of the LES after
placement of three linear plications in dogs
[10]
. A double
blind pilot study with 18 patients randomized to either
ELGP alone or ELGP with cautery (10 in cautery group, 8
in no cautery group) showed numerically improved patient
plication persistence, decreased esophageal exposure
and improved symptoms at 1 year in the cautery group.
However, the benefits were not sustained at 2-yr follow
Table 1 Endotherapy result comparisons: pooled data
Trial result ELGP NDO Plicator Stretta Enteryx Gatekeeper
1
HDQRL improvement 55% 70% 65% 70% 74%
1
Heartburn improvement 74% - 61% 71% -
Off PPI’s
At 1 yr 40% 75% 55% 72% 58%
1
At > 2 yr 33% - 63% 65% -
≥
50% reduction in PPI 51% - 67% 80% 54%
1
Quality of life improvement
SF-36 Physical 17% 31% 20% 12% 17%
1
SF-36 Mental None 10% 14% 3% 1.4%
1
Time pH < 4 improvement 16% None 36% 33% 32%
1
No. of refl ux episode improvement 33% - None 31% 45%
1
pH normalization 25% - - 38% 40%
1
LESP improvement None None None None None
LES length improvement None None None None None
tLESR improvement Yes No Yes No No
Healing of esophagitis None None None None None
Sham Trial 3-mo FU Being planned 1-yr FU Underway Underway
1
6 mo follow-up. None: Change not statistically signifi cant. All results are at 1-yr follow-up except Gatekeeper. Highlighted cell
indicate controversy regarding results but the results mentioned above are the ones shown by the majority of studies.
Iqbal A
et al.
Endoscopic therapies of GERD 2643
www.wjgnet.com
up
[11]
. Plication persistence at 1 year was 37% in the cautery
group
vs
15% in the no-cautery group. Further studies are
required to elucidate the effi cacy of cautery with ELGP.
Changes in selection criteria
A significant improvement in symptom scores and pH
study results has been observed in 19 patients refractory to
medications, although, this improvement was less than that
seen in other studies
[18]
.
Short term studies suggest that
ELGP can be used as an effective salvage procedure for
failed surgical fundoplication
[19,20]
, however, this indication
requires further study.
Mechanism of action
The mechanism by which ELGP improves competence
of the gastroesophageal junction remains unclear. Feitoza
et al
demonstrated lack of fusion between the folds when
sutures were placed intra-luminally in the stomach of
rabbits, irrespective of suture depth
[21]
. The symptomatic
improvement can be explained by a lower volume
of refluxate reaching the more “sensitive” proximal
esophagus. The decreased volume might signify a decreased
frequency of tLESR’s, probably due to scar formation.
Secondary scarring may also impair distensibility of the
proximal stomach. This when combined with the fact
that ELGP has been shown to stimulate localized circular
muscle hypertrophy in both humans and animals
[22]
may
lead to an increased basal tensile tone and increased
resistance to gastric distension. This explanation does not
negate, however, the deleterious effect of the acid within
the distal esophagus and the chance for progression to
complications such as stricture formation or even Barrett’s
esophagus.
Complications
Endoluminal gastroplasty is generally safe over long term
follow up and free of serious immediate side effects. The
major and minor complications are shown in Table 2.
Esophageal perforations can occur. Two perforations have
been seen so far, one of whom required a thoracotomy
and the other hospitalization and antibiotics. To avoid a
perforation, which is usually due to placement of a full-
thickness suture within the esophageal wall, all stitches and
plications should be placed below the squamocolumnar
junction. If the suturing capsule needle does not retract
after penetrating the tissue, the handle with pusher rod
should be disassembled rather than pulling the capsule
away from the esophageal wall. Occasionally, the suture
loops and locks at the tissue level as the second stitch is
being placed. The needle literally goes through a loop and
the suture will not slide through the tissue on removal of
the endoscope. In this circumstance the suture should
be cut with an endoscopic scissors, however, this can
be difficult and pull out may be necessary. If tissue
accompanies the knot, it should be sent to pathology
for frozen section analysis. If the muscularis propria is
Table 2 Procedure characteristics and complications: Pooled data
NA: not available.
Variable Endocinch NDO Plicator Stretta Enteryx Gatekeeper
Procedure duration (mean)
68 min 20 min 69 min 33 min 35-60 min
Personnel required 1 physician and
2 assistants
1 physician and
2 assistants
1 physician and
2 assistants
1 physician and
2 assistants
1 physician and
2-3 assistants
Sedation required
Conscious
sedation 82%
NA Conscious
sedation 100%
Conscious
sedation 100%
NA
Approximate no. of
procedures performed
4000 NA 4000 2600 225
Major complication
Perforation 0.08% 0.00% 0.13% 0% 0.40%
Bleeding 0.05% NA 0.05% 0% 0%
Hypoxemia 0.08% 0% 0% 0% 0%
Pleural effusion 0% 0% 0.03% 0.08% 0%
Pericardial effusion 0% 0% 0% 0.08% 0%
Aspiration
pneumonia
0% 0% 0.05% 0% 0%
Esophageal abscess 0% 0% 0% 0.04% 0%
Ulceration over
prostheses
0% 0% 0% 0% 0.40%
Death 0% 0% 0.05% 0.04% 0%
Minor complications
• Sore throat
(0.35%)
• Chest soreness
(0.17%)
• Abdominal
pain
• (0.15%)
• Bloating
(0.02%)
• Transient
dysphagia
(0.05%)
• Bronchospasm
(0.01%)
- • Superfi cial mucosal injury
• Burn at pad site (0.02%)
• Transient A. fi b (0.02%)
• Bloating (0.02%)
• Gastroparesis and ulcerative
esophagitis (0.02%)
• Low grade fever
• Transient dysphagia
• Transient chest pain
• Topical anesthesia-related
complications
(eg. Allergy, hypotension)
• Garlic odor
for several hours
(due to DMSO)
• Chest pain (82%)
• Transient dysphagia
(13%)
• Belching/ burping
• Bloating/ fl atulence
• Fever
• Sore throat (15%)
• Chest pain (5%)
• Nausea/ vomiting
(0.8%)
• Erosive duodenitis
(0.8%)
• Retrosternal pain
(0.4%)
• Poor sleep (0.4%)
• Abdominal pain
(0.4%)
• Rash (0.4%)
• Cough (0.4%)
2644 ISSN 1007-9327 CN 14-1219/ R World J Gastroenterol May 7, 2006 Volume 12 Number 17
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ePTFE
Pledgets
Wall retractor
Standard
Gastroscope
←
←
←
←
included within the specimen, an esophagram should be
performed followed by hospitalization.
Procedure failure
Studies demonstrate that laparoscopic Nissen fundoplica-
tion (LNF) is feasible and effective after failed ELGP
[23,24]
.
Patients should undergo upper GI endoscopy before
surgery but suture removal is not necessary. No signifi cant
scarring or adhesions have been noted in the esophageal
hiatus or inferior mediastinum at LNF. This may be due
to the stitches not penetrating beyond the muscularis
propria, as penetration of the serosa has been shown to
induce more scarring
[21]
. This in itself might contribute to
the lack of durability in post-ELGP results. Although the
technique is initially effective, long-term symptom control
has yet to be established.
Alternatively, patients who experience recurrent
GERD symptoms post-ELGP may benefi t from a second
procedure. However, one study demonstrates a signifi cant
trend toward earlier onset of recurrent symptoms after
repeat ELGP
[25]
.
Advantages
Easy repeatability, short operative time, early discharge, no
morbidity and symptomatic improvement make ELGP an
attractive option. Endoscopic gastroplication has proven
short term effi cacy and has been demonstrated to be cost-
effective for one to two years
[26]
.
Disadvantages
The absence of objective improvement after ELGP is
disconcerting. No studies have shown improvement in
LES pressure or length and grade of esophagitis. pH
monitoring results are mixed but the rate of normalization
is only 30%-40% between studies. Several studies have
compared ELGP with LNF
[27-29]
. Comparable improvement
in symptom scores,
reduction in PPI intake and QOL
assessments has been seen, however, surgery is superior to
ELGP in patient satisfaction and objective improvement
in refl ux.
Recently, Chang
et al
showed that ELGP with cautery
did not improve LESP, Gastric yield volumes, pressures
or GEJ compliance in a porcine model, however, limited
sample size (
n
= 5) precludes defi nitive analysis
[30]
. Lack of
durability is another reason for concern as shown by many
authors. Lepoutre
et al
reported loss of 51% plications in
60 patients at one year follow up
[31]
.
The optimal confi guration for plications is not known.
In a small and unfortunately underpowered study by Davis
et al
22 patients with proven GERD were randomized
between a helical and circumferential plication pattern.
No difference in outcome was observed between
configurations at 18 mo although a trend in objective
results favored the helical pattern
[32]
. At 18-mo follow
up, only 15%
of patients being asymptomatic and off
antisecretory medication. The prevalence and persistence
of these possible advantages are currently subject to
investigation. Increasing the number of plications, when
using the helical pattern, did not show a signifi cant benefi t
at either 6- or 12- mo follow-up
[32]
.
ENDOSCOPIC FULL-THICKNESS PLICATOR
Current endoscopic suturing techniques usually involve
submucosal suture placement, which may limit potential
procedure-related complications but may also lead to
early suture dehiscence and loss of long term efficacy.
This problem may be theoretically solved by full thickness
suturing or stapling devices, which include pledgets. Such
an approach may, however, increase the risk of subsequent
perforation. A novel technique of applying a full-thickness
plication endoscopically has been developed and recently
underwent clinical study in a U.S. multicenter trial.
Selection criteria were similar to that shown in Figure 1.
Procedure
The (NDO) plicator (Figure 3A) is designed to apply a
full thickness pledget reinforced U stitch tissue near the
1: Plicator and gastroscope
retrofl exed
2: Arms opened, tissue
retractor advanced to serosa
3: Gastric wall retracted,
arms closed
4: Single pre-tied implant is
deployed, securing serosa-to-
serosa plication
5: Full thickness plication
restructures normal anti-refl ux
barrier.
A
B
1
B
4
B
2
B
5
B
3
Figure 3 A: The NDO plicator mounted on a small diameter endoscope; B: Schematic representation of the procedure for application of a full-thickness plication by NDO
plicator.
Iqbal A
et al.
Endoscopic therapies of GERD 2645
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GE junction with serosa to serosa apposition. The system
consists of a reusable instrument and a single-use suture-
based implant. Additionally, a proprietary endoscopic
tissue retractor and a 5 mm diameter endoscope are
used to perform the procedure
[33]
. The tissue retractor
is designed to engage the deep gastric wall, allowing for
creation of the serosa to serosa plication.
With the patient under conscious sedation, a
gastroscope is passed into the stomach for endoscopic
inspection and passage of a guidewire. The gastroscope
fi tted with the plication device is passed into the stomach
over the guidewire. The suture applicator is retroflexed
and properly positioned under endoscopic vision. The
endoscopic tissue retractor is then inserted to within 1 cm
of the GE junction and advanced to the level of the serosa
which is judged by visible tenting of the tissues around
the entry point of the retractor. The gastric wall is then
retracted and instrument arms are closed upon it. The pre-
tied implant is deployed to secure a full-thickness plication.
The tissue retractor is removed from the greater curvature
side of the GEJ, the jaws opened and entire assembly is
removed from the stomach followed by removal of the
overtube (Figure 3B 1-5). The approximate procedural
time is 15-20 min.
Effi cacy
Pooled results for NDO plicator are shown in Table 1. A
multi-center study enrolled 64 patients with symptomatic
GERD who were dependent on antisecretory medication
and showed evidence of esophageal acid exposure (pH-
metry) without an underlying motility disorder. Follow
up was completed at 1, 3 and 6 mo post-procedure.
It showed a significant reduction in GERD symptom
scores, medication usage and esophageal acid exposure
on 24-h pH-study, which persisted at one year follow up.
No significant changes in esophageal manometry were
noted
[34]
. At 6-mo follow up, there was a 63% symptom
score improvement with elimination of PPI therapy in
74% and normalization of pH in 30% patients. No patient
required re-treatment during the 6-mo follow up. In this
initial trial, one full thickness plication was used. A pilot
study on 7 patients also showed similar results but failed to
show objective improvement of refl ux
[35]
. Further studies
with single
vs
multiple plications are anticipated. No sham
controlled trial has yet been completed but one is being
organized.
Mechanism of action
This procedure aims at inducing fusion of the opposed
gastric tissue and thereby reducing distensibility at the GEJ.
Feitoza
et al
[21]
showed maximal fi brosis with incorporation
of serosa in the plication when compared to other depths
of suture plication. Theoretically, the suture retention
rate and thus, durability of results should also improve.
Lengthening of the intra-abdominal segment of the LES
[33]
is expected.
Complications
The most common complication was sore throat (spon-
taneously resolving within several days post-procedure).
One gastric perforation did occur during the multi-center
trial and was managed conservatively.
SYNTHEON ARD PLICATOR
This is a promising new endoluminal suturing/com-
pression implant device that has the capacity to place
two titanium plications at once, thus, decreasing technical
variability between operators (Figure 4). The distance
between the two stitches is pre-determined. The plications
are removable within the first 48 h. Withdrawal of the
device is not necessary after each stitch which may decrease
the procedure time and anesthesia related complications.
Implantation is performed using a standard endoscope
and no overtube is required. The mean procedure time is
21 min. Initial results show the device to be safe and time-
effi cient. An expanded multicenter pivotal phase I study is
ongoing and will help clarify the procedure results.
Effi cacy
The results of feasibility trials involving 8 patients with
symptomatic GERD, abnormal pH scores, normal motility
and responsiveness to daily PPI use have been published.
Patients with large hiatal hernias (>2 cm), esophagitis (grade
II or more) and Barretts esophagus were excluded. At 6
mo follow up, 75% were off PPI’s, 68% improved GERD-
HRQL score and 40% improved GSRS:GERD score.
However, 24-h pH and manometry showed no signifi cant
improvement. (S1199)
Complications
Serious complications have not been encountered. Minor
adverse effects seen to date are sore throat, epigastric/
referred chest pain and the gas bloat syndrome.
THE STRETTA PROCEDURE
Radiofrequency energy (RFe) has been extensively utilized
in medicine since 1921 and is currently being used in
the treatment of benign prostatic hypertrophy, cardiac
arrythmias and metastatic liver lesions. The possibility of
RFe being used for GERD therapy was explored after
successful treatment of snoring and sleep apnea.
Patient selection
Radiofrequency augmentation of the LES has been widely
used. Over 3500 procedures have been performed in
the United States alone. The indications in the past have
Figure 4 Syntheon device.
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been confined to patients with early reflux disease. The
Stretta procedure may have specific utility in morbidly
obese patients, those with a previous gastric resection, a
gastric bypass, after a failed LNF
[36]
or as an alternative
to re-operation after fundoplication disruption. In a
porcine fundoplication disruption model, fluoroscopic
guidance improved RF lesion accuracy therefore it has
been suggested that fl uoroscopic guidance be utilized to
ensure probe placement
[37]
. Patients with failed anti-refl ux
surgery and subsequent RF therapy have experienced non-
significant symptomatic improvement (heartburn score
from 3.33 pre-procedure to 2.75 post-procedure), however,
patient satisfaction scores are significantly improved
[38]
.
The role of the Stretta procedure in postoperative
fundoplication patients remains unclear.
Procedure
The Stretta catheter (Figure 5A) is a flexible, handheld,
disposable 20F Savary-style dilator that is used in con-
junction with the Curon (Sunnyvale, California) control
module. It is comprised of a balloon basket assembly,
4 nickel titanium electrodes, suction and irrigation. The
balloon basket deploys 4 radially arranged electrodes
into the smooth muscle of the GE junction. Tiny
thermocouple temperature sensors within the electrodes
provide temperature feedback to the radiofrequency
generator. A target temperature is pre-selected and the
power is automatically discontinued if the temperature
exceeds the predetermined threshold. The needles also
provide feedback on impedance which allows the operator
to know if the needles are positioned correctly into the
tissue.
Under conscious sedation, the catheter is placed
over the guidewire into the stomach and withdrawn
to the position of needle deployment. After removal
of the guidewire, the balloon at the distal end of the
catheter is inflated, the electrodes are deployed and RF
is applied for a specifi c period of time while monitoring
the temperature and impedance levels (Figure 5B). A
fi rst treatment ring of 8 lesions is created by rotating the
catheter 45º and repeating the same. Four such antegrade
rings, each with 8 lesions, are created at 0.5 cm intervals
to a distance of 1cm below the GE junction. Two further
gastric “pull-back” rings, of 12 lesions each (3 sets of
deployment each), complete a set of thermal lesions
(Figure 5C). Halfway through the procedure, an endoscope
is reintroduced to verify the location of treatments with
subsequent adjustment distally or proximally to prevent
superimposition of lesions. Following recovery, patients
continue their usual anti-reflux medication for 3 wk. A
modified technique has been proposed in the presence
of a large hiatal hernia (>3 cm) or a failed Nissen
fundoplication
[39]
. The modified technique creates 6
anterograde treatment levels instead of 4, beginning 1 cm
above the squamocolumnar junction with 5mm between
levels and placing 2 sets of lesions at each of the 4
proximal levels and 3 sets at the distal 2 levels.
Effi cacy
In the initial US open label trial
[40]
, one year follow up
showed a signifi cant decrease in symptom scores. Gastro-
esophageal refl ux disease-specifi c quality of life satisfaction
scores and distal acid exposure were signifi cantly improved
over the baseline on-medication scores as well. However,
normalization of pH monitoring scores did not occur in
the majority of patients. In addition, LES pressures did
not increase and esophagitis did not improve signifi cantly
at 6 mo endoscopic follow-up.
The sham-controlled trial
[41]
showed significant
improvement in symptom scores and quality of life at 6
and 12 mo, but at 6 mo there was no difference between
groups in medication usage. Esophagitis grade did not
show improvement, and in fact grade 2 esophagitis
increased in severity in both groups. Similarly, pH scores
also failed to show significant improvement, unlike the
previous uncontrolled studies
[40,42]
. The explanation for
these findings may be altered sensitivity of the distal
esophagus or unusual persistence of the sham effect.
In a registry series
[43]
, 558 patients underwent the
Stretta procedure and showed a signifi cant improvement in
GERD symptom control (from 50% to 90%) and patient
satisfaction (from 23% to 86% at a mean follow up of 8
mo. The onset of GERD relief was in less than 2 mo in
most patients (69%). The treatment effect was durable
beyond 1 year and most patients (51% at one year
vs
96%
pre-procedure) were off all antisecretory drugs at follow-
up.
Most studies are limited to short term follow up (up to
12 mo). For the fi rst time, Torquati
et al
reported long term
results in 41 patients with 83% being highly satisfi ed at a
mean follow up of 27 mo
[44]
. Proton pump inhibitor usage
was discontinued in 56% patients and was significantly
reduced in 87%. Similarly, Reymunde
et al
demonstrated
significant and sustained improvement in anti-secretory
drug discontinuation (88%), GERD symptom scores (82%)
and QOL scores (44%) at more than 3 years of follow-
up
[45]
. This is encouraging evidence and suggests that
durability of results is the distinguishing attribute for the
Stretta procedure.
Significant improvement in symptom scores and
quality of life have also been observed in shorter term
studies
[40,43,46,47]
. Similarly, decreased PPI use and increased
patient satisfaction have been consistently seen
[46,40,47]
. Most
studies fail to demonstrate a beneficial effect of Stretta
A
BC
Figure 5 A: The Stretta catheter with guidewire; B: The balloon assembly with
struts and electrodes extending into the muscularis propria; C: A total of 56 lesions
are applied as seen in this diagram.
Iqbal A
et al.
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on esophagitis but Triadofilopoulos
et al
[42]
showed an
improvement in esophagitis grade, from 21% with grade
2 esophagitis to 9.3% post-procedure in 43 patients at 6
mo
.
The role of Stretta in improving extra-esophageal
manifestations of GERD is still not clear, however, one
study
[36]
suggests that respiratory benefi t can be achieved
if strict patient selection (abnormal pH study) is followed.
Pooled results are shown in Table 1.
Mechanism of action
Multiple changes may be responsible for the effect seen
in the Stretta procedure. First, a mechanical alteration and
thickening of the LES musculature leads to diminished
reflux, as shown in the canine model
[48]
. Secondly,
progressive tissue remodeling and scar formation observed
after Stretta could contribute to the decreased compliance
and an increased tensile strength of the GE junction which
also exerts its effect in decreasing tLESRs. This decrease in
tLESRs has been shown in both animals and humans
[48,49]
.
Histologically normal muscle with occasional focal areas
of collagen deposition at 8 wk follow up has been shown
in the porcine model.
The disparity between symptomatic improvement and
acid exposure seen in the sham trial was surprising and
might be explained by a residual sham effect on symptoms
or altered visceral sensitivity
[41]
. The later would explain
the striking dichotomy between symptom relief and
minimal to moderate improvement in acid refl ux profi les.
A diminished sensitivity may be due to destruction of
chemosensitive or mechanosensitive nerve endings
[50]
.
However, some studies contradict this contention
[44]
by
showing signifi cant improvement in pH results at 27 mo in
patients who had responded to therapy.
Complications
The major and minor complications are shown in Table
2. The 5 perforations and 2 deaths occurred during the
learning curve and were due to poor patient selection
and technical errors. No major complications were seen
in the multi-center trial and subsequent studies have not
shown adverse effects on vagal nerve function or gastric
emptying. The complication rate after Stretta has been
< 0.6% since the introduction of the new technology and
0.13% in the last 12 mo.
Recommended precautions
Operators should check the position if abnormal
impedance/temperatures are observed, use correct balloon
pressures, control the mucosal temperature carefully,
minimize balloon pull back pressure and avoid NG tube
placement for one month post-procedure
Alternatives after treatment failure
In the US open label trial, 5% of the patients elected
to undergo fundoplication 6-12 mo after Stretta due
to incomplete or recurrent symptom response. In each
case, there was no evidence of extra-esophageal tissue
abnormality and the anti-refl ux operation was performed
in a normal manner and without diffi culty. Richards
et al
[36]
compared the outcome of patients who had the Stretta
procedure and a laparoscopic fundoplication at 6 mo
and found a comparable and signifi cant improvement in
QOLRAD, SF-12 and pH scores in both groups. However,
medication usage was signifi cantly less in patients who had
surgery (97%
vs
58% off PPI’s). Both groups were highly
satisfi ed with their procedure. A repeat Stretta procedure is
not recommended.
ENTERYX
Enteryx consists of a biocompatible polymer (80 g/L
EVOH with a radioopaque contrast agent dissolved in an
organic liquid carrier [DMSO]). Upon contact with tissues
or body fl uids after injection, the solvent, DMSO, rapidly
diffuses resulting in precipitation of the polymer (EVOH)
as a spongy mass. It is not biodegradable and has no
antigenic properties. Migration through blood vessels or
lymphatics nor prosthetic contraction after injection have
been observed
[51]
.
The three components of Enteryx, ethylene vinyl
alcohol polymer (EVOH), dimethyl sulfoxide DMSO, and
tantalum, have been previously used together medically
as a vascular embolization agent and a membrane for
hemodialysis and plasmapheresis.
Patient selection
Enteryx is a treatment with promise but, like other
endoluminal therapies, is lacking objective supportive
data. Patients must understand that the procedure is
irreversible
[52]
. The possible future indications for En-
teryx include primary therapy for GERD in patients
who respond to PPI’s but prefer not to take medications
daily, salvage therapy for PPI responders to reduce or
eliminate daily medications and salvage therapy for surgical
failures
[52]
. Recently, Enteryx has been attempted in pos-
fundoplication patients
[53]
.
Enteryx therapy is clearly contraindicated in any
individual who does not have physiologically documented
GERD by pH study or endoscopic findings. It is also
contraindicated in individuals who cannot undergo or
tolerate endoscopy and those who have esophageal varices.
There is no reported experience with this procedure in
individuals with esophageal motility disorders, prior gastric
or GERD surgery, scleroderma, Barrett’s esophagus,
hiatal hernias >3cm, BMI >35 or patients who use
anticoagulants other than aspirin
[52]
.
Procedure
The procedure is performed in an endoscopy suite
equipped with fluoroscopy under conscious sedation.
A long needle catheter is fi lled with Enteryx after it has
been fl ushed with DMSO, to keep it liquefi ed as long as
it stays within the catheter. The prepared injection needle
is placed into the muscularis propria at the appropriate
level of the esophageal wall. The prosthesis is injected
at a rate no greater than 1mL/s under combined
fluoroscopic and endoscopic guidance (Figure 6). The
EVOH solidifies within the esophageal wall as the
generated heat causes DMSO to dissipate. The injection
is stopped if either a submucosal or transmural injection
is observed. Submucosal accumulation of material is
seen endoscopically as a black bulge and an extramural
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injection is demonstrated on fluoroscopy as either flow
of material beyond the muscularis into the mediastinum
or the abdominal cavity, or lack of a visible deposit
in the esophageal wall. If a circumlinear transverse
path of material is visualized under florosocopy, the
injection is completed at this stie using a total of 1 to
2 mL. The procedure is considered satisfactory if 6 to
8 mL of Enteryx is delivered to the muscularis propria
circumferentially without a submucosal or transmural
injection. After the injection is complete at one site, the
needle remains in place for 20 s allowing the material to
stabilize and solidify. This maneuver prevents leakage of
the prosthesis into the esophageal lumen. Patients are
usually discharged 2 to 4 h after recovery.
Robert
et al
reported Enteryx implantation in 5 pigs
without the use of fl uoroscopy. Enteryx was consistently
deposited into the deep esophageal wall with a high
degree of accuracy in a minimal amount of time. The
placement was accurate in 85% and was transmural in just
one instance. A human trial is underway to confi rm these
fi ndings
[54]
.
Effi cacy
Enteryx implantation significantly improves the QOL
scores and medication usage
[51,52]
. No change has been seen
in the severity of esophagitis at endoscopy after Enteryx
implantation. In general, the structural characteristics of
the LES, including its length and pressure, are not altered
signifi cantly. Pooled results are shown in Table 1.
The 2 year follow up results of this U.S multicenter
trial, which included 85 patients, were recently published
[55]
and showed PPI use to be eliminated in 74% of patients
at 6 mo follow up. This effect was maintained in 64% of
subjects at 2 years while 74% were maintained on less
than half of their baseline PPI dosage. The improvement
in symptom scores was 82% at 6 mo and 70% at 2-yr.
Quality of life (SF-36) questionnaires demonstrated an
improvement of 6% from baseline at 3 mo and 3% at 12
mo for the mental score while the improvement in the
physical score was maintained at 12% at both 6 and 12 mo
follow up. pH scores improved with 30% normalization
and there was a small but significant LES length
augmentation (1 cm) following therapy
[56]
. No signifi cant
change in LES pressure was observed. The absence of
change in LES resting pressure contrasts with findings
from the pilot study, in which a significant increase in
the LES pressure was observed at 6 mo. This may have
been due to the inclusion of patients with a normal LES
pressure at baseline or the smaller sample size in the
pilot study. Importantly, most of the decline in treatment
responders during follow-up occurred between 1 and 6
mo. Between 6 and 12 mo, the proportion of treatment
responders remained stable. There was no evidence that
the reduction in PPI usage after the implant procedure was
due to medication shifting.
The decline in residual implant volume seen after
one month was attributable to sloughing of superfi cially
implanted material until encapsulation was complete.
There was no radiographic evidence of implant migration
and after 3 mo, residual volume remained stable (
P
> 0.1)
[57]
.
Twenty two percent of patients were re-treated at 3 mo
follow up of which, 63% improved at 12 mo follow
up with 58% completely off PPI’s and 5% of patients
reducing their PPI usage by more than 50% of baseline
[56]
.
The multicenter randomized controlled sham trials with
“cross-over” option starting at 3 mo post-randomization
are currently underway in both Europe and the United
States
[58]
. An interim report on 56 out of the 64 total
Figure 6 Enteryx
injection under
fluoroscopic
control with
a resultant
prosthetic cuff.
ABC
DE F
Iqbal A
et al.
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European patients has been announced with 3 mo follow
up. An improvement in GERD HQRL was seen in 65%
patients in the Enteryx arm
vs
21% in the sham arm. The
median change in symptom scores was 15 for the Enteryx
group and 4 for the sham group. There was also a greater
reduction in PPI usage (64%
vs
33%) and a lower cross-
over/re-treatment incidence (21%
vs
71%) in the Enteryx
group when compared to the sham group. Criteria for
both cross over (for controls) and re-treatment (for the
Enteryx group) were the same i.e. an off-PPI HQRL score
> 15
[58]
.
Johnson
et al
reported that the likelihood of a successful
clinical outcome is higher with more residual implant
volume. He showed that all patients who retained
≥
5
mL of implant material eliminated or reduced PPI use
by
≥
50% and the majority of subjects who retained > 5
mL of Enteryx achieved a GERD-HRQL score of < 15.
Lehman
et al
reported the procedure to be equally effective
irrespective of the radiologic pattern evident at the time
of implantation
[59]
. In a study evaluating predictors of
outcome for Enteryx, Deviere
et al
[60]
showed there was
no statistically significant difference in PPI usage or pH
outcome by gender, but GERD-HRQL symptom scores
were signifi cantly more likely to improve in males (86%;
57/66) than in females (67%; 32/48) (
P
= 0.01). Finally,
Ganz
et al
compared the endoscopic fi ndings of patients
from the multicenter study at 1 yr follow up with their
baseline values (on PPI’s) and reported that treatment
with Enteryx provided improvement in esophagitis
scores comparable to that provided by PPI medication
[61]
.
This finding, however, has not been supported by other
studies. A pilot study determining the effi cacy of Enteryx
in post-fundoplication patients (
n
= 19) and reported no
apparent diffi culty due to the distorted anatomy during the
procedure. Post-fundoplication patients with refractory
symptoms on high dose PPI therapy were enrolled and
‘improvement’ was seen in 89% of patients, however,
this study primarily addressed the technical feasibility
rather than the efficacy of post-fundoplication Enteryx
implantation
[53]
.
Mechanism of action
Both gross and histological examination in animals have
shown that the implants persist as encapsulated, firm,
smooth, slightly mobile ovoid masses, several weeks after
implantation. No evidence of pathologic inflammatory
changes in the surrounding tissues have been observed.
However, the implants lead to a signifi cant increase in the
yield pressure and yield volume with a raised threshold for
transient relaxations after implantation
[62]
.
Fibrous encapsulation may functionally lengthen
the LES. The encapsulation/scarring is the probable
mechanism of effect but the exact mechanism in
humans remains to be fully characterized. The “bulking”
effect, seen with some injectable treatments for urinary
incontinence, is not apparent for Enteryx because follow-
up endoscopies reveal no evidence of luminal narrowing.
Sloughing of superficially injected material may be the
reason for inadequate clinical outcome and lack of
durability seen in some patients
[57]
.
Complications
The complications are shown in Table 2. Recently,
one death was reported in a patient due to inadvertent
injection of Enteryx into the aorta. Further details are
not yet available. Two patients experienced a pericardial
effusion after injection of the prosthesis and subsequently
underwent a pericardial window. Two additional patients
developed a pleural effusion but no other problems
were recognized. Although, the cause of the effusions
is not clear, extension of an infl ammatory process from
the esophagus to the surrounding structures namely
pericardium and pleura and the possibility of an allergic or
infectious process cannot be ruled out.
Recommended precautions
All operators are required to receive hands on laboratory
training prior to clinical utilization. Injection techniques
when using fluoroscopy are emphasized and guidelines
for prostheses preparation are given. Most centers place
patients on a liquid diet followed by a soft diet, the day
of the procedure followed by normal diet the day after.
Maintenance therapy with PPI’s is continued for 10-14 d
after implantation.
GATEKEEPER
Gatekeeper is a dehydrated hydrogel prosthesis implanted
into the submucosa of the cardia/LES. It hydrates to
6 mm × 15 mm cylinder shaped soft pliable cushions and
is removable by endoscopy
[63]
.
Patient selection
In addition to the general selection criteria already
described, patients with esophageal varices, a peptic
stricture and morbid obesity were excluded from the trials
for Gatekeeper.
Procedure
The Gatekeeper device consists of an overtube with
separate channels for passage of an endoscope and a
long delivery sheath (Figure 7). After placement of the
overtube, the injection capsule is placed through the
overtube to straddle the squamocolumnar junction. A
vacuum is created to stabilize the device and to draw
the mucosa in. The injection needle is advanced into the
submucosa followed by injection of 3-6 mL of sterile
saline until blanching is observed. This is followed by
removal of the injection needle and advancement of the
needle assembly and the delivery sheath into the mucosa,
leaving the delivery sheath in the submucosal plane. After
the needle assembly has been retracted, the prosthesis
is inserted into the proximal end of the delivery sheath
and advanced to the submucosal level using a pushrod
assembly. Up to 6 hydrogel implants are placed. The
implants are small and “sliver”-like when introduced but
swell to full size within 24 h, when hydrated.
Effi cacy
In a limited number of patients the Gatekeeper procedure
has been shown to significantly decrease heartburn,
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improve quality of life, 24-h pH-metry scores and decrease
medication usage
[64]
. The success rate for implantation is
93% while the procedural success rate was reported at
98.7%
[65]
. Pooled results for Gatekeeper are shown in Table 1.
After completion of a 6 mo pilot study
[66]
with
favorable results, a European multicenter study was
initiated
[67]
. Patients underwent manometry, endoscopy,
24-hr pH-metry and symptom scoring before and after
the procedure. The average number of prostheses
implanted was 4.3 (2-6). Final results showed significant
improvement in symptom scores (HRQL score from 24
to 5), quality of life, pH parameters (% time pH < 4, 9.1%
to 6.1%) and LESP (8.8 to 13.8 mmHg) at 6 mo
[65]
. The
prosthesis retention was 70% at 6 mo. Other studies with
smaller numbers of patients have failed to show signifi cant
improvement in LESP, however, symptom scores and pH
results show consistent improvement
[64,67]
.
An international, prospective multi-center (US/
European) randomized, sham-controlled Gatekeeper trial
has recently commenced
[68]
. One hundred and forty four
patients with symptomatic GERD dependent on PPI
with evidence of refl ux on 24-h pH study and a symptom
score of > 20 off medications are being included in the
study. Patients with Barretts esophagus, hiatal hernia > 3
cm, esophagitis (garde II or higher), stricture formation,
varices or prior antireflux surgery will be excluded.
Randomization will be attempted with a sealed envelope
at a rate of 2:1 implant
vs
sham. Four implants will be
placed circumferentially in the distal LES/cardia with re-
treatment offered to individuals if GERD symptoms
persist. Sham patients will be offered Gatekeeper therapy
at 6 mo. Patients will take anti-secretory medications on a
PRN basis. Outcome parameters are HRQL, esophagitis,
medication use, 24 hr pH monitoring and implant
persistence. To date, 52 subjects have been enrolled
and randomized, 21 of whom have been implanted.
Enrollment completion is anticipated in April, 2005
[69]
.
Mechanism of action
The mechanism of action is probably similar to Enteryx in
addition to bulking. The prosthesis narrows the lumen as
seen at 6 mo follow-up endoscopy and is self contained.
Complications
The complications reported at 6 mo follow-up are shown
in Table 2
[65]
. In the largest multicenter study, 2 out of
40 patients (5%) developed severe complications which
included esophageal perforation caused by overtube
placement and severe postprandial nausea (1 wk post-
procedure) leading to endoscopic removal of the
prosthesis at 3 wk
[65]
.
Advantages
The Gatekeeper prosthesis is removable by endoscopic
means. A needle knife can be used to incise over the
edge of the implant which is then suctioned from its
submucosal pocket
[63]
. Endoscopic ultrasound may be used
for exact localization of the prosthesis. Of note, one of
the two patients who had the prostheses removed was 7
mo post-procedure. All 3 prostheses were removed in the
other patient, 3 wk post-procedure. No complication was
encountered with either patient.
PLEXIGLASS
A trial of gelatinous plexiglass (polymethylmethacrylate,
PMMA) microsphere implants has been published by
Feretis
et al
[70]
. A mean volume of 32 mL was implanted
submucosally, 1-2 cm proximal to the squamocolumnar
junction, in 10 patients with a 21-gauge needle. Transient
dysphagia was noted in one patient due to excessive
implant volume. At a mean follow-up of 7.2 mo, there
was signifi cant improvement of GERD-related symptoms
and 24-h pH-studies (decreased from 24.5 to 7.2) but pH
normalization was not seen. Ninety percent of patients
were completely off PPI’s at 6 mo follow-up. The
procedure was found to be safe at short term follow-up.
Minor and self-limited complications occurred in
4 of 10 patients (40%). Transient dysphagia and the
gas-bloat syndrome (10%) were thought to be due to
excessive treatment with an implantation volume of 39
mL. The plexiglass injection was not associated with
local or systemic complications and is not antigenic.
Polymethylmethacrylate (PMMA) is highly viscous and
Figure 7 Gatekeeper procedure. Sequence of the procedure: A. Stabilization B.
Create space C. Access space D. Delivery E. Gatekeeper.
↓
↓
A
C
E
B
D
Iqbal A
et al.
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therefore a sigmoidoscope with a larger biopsy channel
that accommodates a large caliber catheter was used for
implantation. Longer follow-up studies are needed
[70]
. A
multicenter study is currently being planned.
In addition, to these bulk-forming implants, injection
therapy with sclerosing agents which induce focal necrosis
and fibrosis similar have been tried. Sodium Morrhuate
was used in 15 refractory GERD patients but after a year
of follow up, the authors concluded that the therapy was
ineffective
[71]
.
COMBINATION THERAPIES
The use of endoscopic therapies after a failed fun-
doplication has been seen with ELGP, Stretta and Enteryx
and their preliminary results have been discussed above.
A combination of two different endoscopic therapies may
be a solution to the lack of durability and objective benefi t
seen with these procedures. Anderson reported results of
a pilot study done on 5 patients who were symptomatic
and had radiological or pH probe evidence of refl ux after
prior ELGP procedure. These patients underwent Enteryx
implantation and 3 of the 5 patients were off medication
(60%) at a mean follow up of 7.6 mo. Transient dysphagia
was seen after implantation in two patients but no major
adverse effects were observed. Larger studies with longer
follow up and objective documentation of improvement
will help elucidate the efficacy of the combination
approach
[72]
.
Summary
The endpoints studied in most of the trials are GERD
symptoms scores (HRQL), medication usage, manometric
fi ndings, grade of esophagitis and 24 hr pH-study results.
In general, the procedures are safe with 3 deaths in
9000-10 000 cases. At present, the overall complication rate
reported for ELGP, Stretta, Enteryx and Gatekeeper is
11%, 6%, 6.7% and 15% respectively
[65]
. All studies, to date,
allow use of PPI’s and most gauge success by the number
of patients decreasing PPI dosage and symptomatic
improvement. Meaningful conclusions cannot be made in
this instance. There is evidence of symptomatic relief with
decreased medication usage but with failure of an increase
in LES length and pressure, healing of esophagitis and
improvement in pH scores. An overview of the procedure
for different endotherapies for GERD is shown in Table
2. A comparison of results in patients with Endocinch,
Stretta and Enteryx at various follow-up intervals is also
depicted in graphic format (Figures 8A-D).
In conclusion the scientifi c community needs to wait
6 mo 12 mo 24 mo
80
70
60
50
40
30
20
10
0
53
65
76
40
55
72
33
63
66
Percentage of total patients
Percentage improvement
6 mo 12 mo 6 mo 12 mo
20
18
16
14
12
10
8
6
4
2
0
16
17
12
17
20
12
9
15
6
14
3
NS
6 mo 12 mo 24 mo
100
90
80
70
60
50
40
30
20
10
0
69
53
83
55
65
70
32
95
73
Percentage improvement
6 mo 12 mo
45
40
35
30
25
20
15
10
5
0
26
43
27
17
36
33
Percentage improvement
ELGP
Stretta
Enteryx
ELGP
Stretta
Enteryx
ELGP
Stretta
Enteryx
ELGP
Stretta
Enteryx
Figure 8 A: Percentage
of total patients off PPI’s
at 6, 12 and 24 mo post-
procedure; B: Improvement
in quality of life scores
(SF-36), both physical and
mental, at various follow-
up intervals; C: Degree of
symptomatic improvement
at various follow-up
intervals; D: Improvement
in % time pH <4 at 6- and
12- mo follow-up.
AB
CD
Graph showing percentage of total patients completely off PPI
medication. Comparison of ELGP, Stretta and Enteryx at various follow-
up intervals is shown. All changes are signifi cant when compared to
baseline. Pooled data was obtained from following references: 18, 20,
21, 23, 26, 31, 39, 41, 44, 45, 47, 49, 58, 74, 77, 82, 84.
Graph showing the degree of improvement in quality of life assessment
scores (SF-36) in patients with ELGP, Stretta and Enteryx at various
follow-up intervals. NS, not signifi cant. All other changes are signifi cant
when compared to baseline. Pooled data was obtained from the following
references: 17, 21, 45, 46, 47, 58, 59, 74.
SF-36 (physical) SF-36 (mental)
Graph showing the degree of improvement of symptom scores in
patients with ELGP, Stretta and Enteryx at various follow-up intervals.
All changes are signifi cant when compared to baseline. Pooled data was
obtained from the following references: 17, 18, 20, 21, 23, 26, 41, 45,
46, 47, 57, 58, 74, 77, 78, 80, 81, 82, 83.
Graph showing the degree of improvement of pH scores in
patients with ELGP, Stretta and Enteryx at various follow-up
intervals. Only studies showing signifi cant improvement in pH
scores are considered. Pooled data was obtained from the
following references: 17, 21, 39, 45, 47, 58, 74, 79, 81, 83.
GERD-HRQL score
2652 ISSN 1007-9327 CN 14-1219/ R World J Gastroenterol May 7, 2006 Volume 12 Number 17
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% time pH < 4
for industry-independent trials showing endoscopic and
24 hour pH monitoring follow-up data that establishes
long term efficacy and prolonged symptomatic benefit.
Cost-effectiveness and post-marketing documentation of
complications will better defi ne the “true” role of these
procedures in the management of GERD patients.
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S- Editor
Pan BR
E- Editor
Liu WF
Iqbal A
et al.
Endoscopic therapies of GERD 2655
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