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The management of secondary lower limb lymphoedema in cancer patients: A systematic review

August 2014
Palliative Medicine 29(2)

August 2014
29(2)

DOI:10.1177/0269216314545803

Source
PubMed

Authors:

Elaine YL Leung

University of Birmingham

Seema A Tirlapur

Queen Mary, University of London

Catherine Meads

Anglia Ruskin University

Background: Lower limb lymphoedema is a recognised complication of cancer commonly encountered in palliative care, associated with reduced mobility and poor quality of life. Aim: To evaluate the available evidence for the treatment of secondary lower limb lymphoedema in patients with malignancies. Design: A systematic review of the literature. Data sources: The MEDLINE, Embase, LILACS, Science Citation Index, Cochrane Databases and conference proceedings for published data from date of inception to July 2014 were searched. Relevant unpublished studies via relevant databases, Internet searches and hand-searches of the bibliographies of relevant papers were performed. Results: From 1617 citations, 32 papers were selected for full-text assessment. Two randomised trials and five observational studies were identified. The two randomised controlled trials evaluated graded compression stockings and Coumarin capsules, respectively. The five observational studies evaluated lymphovenous microsurgical shunts, pneumatic compression devices, compression bandages alone, manual lymphatic drainage with compression and a herbal remedy combining Coumarin, Ginkgo and Melitoto (with or without manual lymphatic drainage), respectively. The extracted studies showed substantial heterogeneity. Hence, a meta-analysis was inappropriate and not performed. Conclusion: Few studies have evaluated the clinical effectiveness and potential side effects of treatments for lower limb lymphoedema. Moreover, symptoms and quality-of-life assessments were inconsistently reported. All included studies report lower limb volume reduction after treatment, which includes complex decongestion therapy, graded compression stockings and lymphovenous microsurgical shunts. Adequately powered randomised controlled trials of these interventions are recommended. Effort should be made to establish standardised outcomes, to minimise bias and to improve reporting quality in future trials of treatment for lower limb lymphoedema.

PRISMA flow chart.

…

Assessment of the risks of bias: (a) randomised controlled trial assessed by Jadad's Score 21 and (b) observational studies assessed by Newcastle–Ottawa Scale. 22,23

…

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published online 18 August 2014Palliat Med

Elaine YL Leung, Seema A Tirlapur and Catherine Meads

The management of secondary lower limb lymphoedema in cancer patients: A systematic review

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What is already known about the topic?

 Lower limb lymphoedema (LLL) is a recognised complication of cancer and a common symptom encountered in palliative

care worldwide, associated with reduced mobility and poor quality of life.

 The prevalence of LLL and its best treatment in patients with cancer are unclear.

 The efficacy of the existing treatments is unclear.

What this paper adds?

 All included studies in the systematic review evaluated conservative treatments, including pneumatic compression devices,

manual lymphatic drainage (MLD), compression bandages and herbal remedy combining Coumarin, Ginkgo and Melitoto

(with or without MLD) achieved short-term reduction of limb volume.

The management of secondary lower

limb lymphoedema in cancer patients:

A systematic review

Elaine YL Leung1, Seema A Tirlapur1 and Catherine Meads2

Abstract

Background: Lower limb lymphoedema is a recognised complication of cancer commonly encountered in palliative care, associated

with reduced mobility and poor quality of life.

Aim: To evaluate the available evidence for the treatment of secondary lower limb lymphoedema in patients with malignancies.

Design: A systematic review of the literature.

Data sources: The MEDLINE, Embase, LILACS, Science Citation Index, Cochrane Databases and conference proceedings for

published data from date of inception to July 2014 were searched. Relevant unpublished studies via relevant databases, Internet

searches and hand-searches of the bibliographies of relevant papers were performed.

Results: From 1617 citations, 32 papers were selected for full-text assessment. Two randomised trials and five observational studies

were identified. The two randomised controlled trials evaluated graded compression stockings and Coumarin capsules, respectively.

The five observational studies evaluated lymphovenous microsurgical shunts, pneumatic compression devices, compression bandages

alone, manual lymphatic drainage with compression and a herbal remedy combining Coumarin, Ginkgo and Melitoto (with or without

manual lymphatic drainage), respectively. The extracted studies showed substantial heterogeneity. Hence, a meta-analysis was

inappropriate and not performed.

Conclusion: Few studies have evaluated the clinical effectiveness and potential side effects of treatments for lower limb lymphoedema.

Moreover, symptoms and quality-of-life assessments were inconsistently reported. All included studies report lower limb volume

reduction after treatment, which includes complex decongestion therapy, graded compression stockings and lymphovenous microsurgical

shunts. Adequately powered randomised controlled trials of these interventions are recommended. Effort should be made to establish

standardised outcomes, to minimise bias and to improve reporting quality in future trials of treatment for lower limb lymphoedema.

Keywords

Lower extremities, lymphoedema, neoplasm, systematic review

1Women’s Health Research Unit, Centre of Public Health and Primary

Care, Queen Mary University of London, London, UK

2Health Economics Research Group, Brunel University, London,

545803PMJ0010.1177/0269216314545803Palliative MedicineLeung et al.

research-article2014

Original Article

Corresponding author:

Elaine YL Leung, Women’s Health Research Unit, Centre of Public

Health and Primary Care, Queen Mary University of London, Yvonne

Carter Building, 58 Turner Street, London E1 2AB, UK.

Email: elaine.leung@qmul.ac.uk

at Glasgow University Library on August 19, 2014pmj.sagepub.comDownloaded from

2 Palliative Medicine

 Surgical management of LLL (lymphovenous microsurgical shunts) can be an effective treatment with long-term improve-

ments reported.

 These studies were heterogeneous and with moderate to high risks of bias.

Implications for practice, theory or policy

 Improving methodological quality of future studies requires minimising the risks of bias, standardising measured outcomes

and improving reporting quality.

 Adequately powered randomised trials of complex decongestion therapy, graded compression stockings and microvascular

lymphovenous shunts evaluating risks, benefits and cost-effectiveness are recommended.

Background

Lower limb lymphoedema (LLL) is a recognised compli-

cation of cancers and its treatment.1–4 LLL presents as

chronic unilateral or bilateral swelling of the lower limbs,

which may be accompanied with pain, tissue fibrosis and

associated skin changes (e.g. skin thickening and hyper-

pigmentation). It is associated with reduced mobility, psy-

chosexual dysfunction and poor quality of life (QoL).4–6 It

was estimated that the majority (70%–80%) of all signifi-

cant lymphoedema referred to specialist units are cancer-

related.7,8 Moreover, more than one-third (36%) have

lymphoedema on admission to a specialist palliative care

unit,9 but only a few get referred to specialist lymphoe-

dema services.10 Although the commonest cause of LLL in

developing countries is filarial infection,11 more than half

of the new cancer cases reported worldwide were diag-

nosed in low- and middle-income countries (LMIC).12

Patients diagnosed with cancers in LMIC often have lim-

ited access to surgery and medical and radiological man-

agement of cancer.13 Palliative care, including the

management of LLL, is therefore an important part of

comprehensive cancer care that should be incorporated

early in a patient’s journey.14

The risk of LLL in cancer patients and its best manage-

ment strategy are unknown.1,3 Moreover, previous reports

suggested that clinicians had often shown inadequate

knowledge and lack of interest in the evidence-based man-

agement of lymphoedema,15 particularly lymphoedema

secondary to non-breast malignancies.16–19 Standardised

assessments of LLL exist (e.g. the International Society of

Lymphology lymphoedema staging system10) and are rou-

tinely used by specialist management units of lymphoe-

dema.10 Clinical progress can be monitored by standardised

pro forma including both symptomatic progress and limb

circumference measurements.10

Physical therapies promoting lymph drainage are com-

monly used to treat lymphoedema, with varying success.10

However, the majority of interventional studies were per-

formed on patients with upper limb lymphoedema second-

ary to breast cancer.17–19

None of the previous systematic reviews have specifi-

cally evaluated the evidence available for the treatment of

patients with non-infective secondary LLL.16–19 This study

systematically reviewed the current evidence for the treat-

ment of patients with LLL secondary to malignancies and

their treatment.

Methods

This systematic review was performed in accordance with

Preferred Reporting Items for Systematic Reviews and

Meta-Analyses (PRISMA) guideline.20

Identifications of studies

We searched the MEDLINE, Embase, LILACS, Science

Citation Index, Cochrane Central Register of Controlled

Trials (CENTRAL) and International Society of Lymphology

and the Australian Lymphoedema Association congress pro-

ceedings from inception to 5 July 2014 to identify relevant

citations. We looked for relevant unpublished studies and

those reported in the grey literature in databases such as

Systems for Information in Grey Literature (SIGLE). We

looked for systematic reviews in the area to find any primary

studies they might have included. The search term combina-

tion captured the concept ‘secondary lower limb lymphoe-

dema’ and ‘therapy’ incorporating Medical Subject Headings

(MeSH), free text and word variants (Appendix 2, available

online). Language restrictions were not applied.

Inclusion and exclusion criteria

Included were all randomised controlled studies with any

number of participants, as well as comparative observa-

tional studies (cohort and case-control) with more than 50

participants with secondary LLL. Only studies that have

included patients with malignancies or patients who had

undergone treatment for their malignancies were included.

Excluded were studies of lymphatic flow, biochemical

markers, mixed cohorts with no description of the particu-

lar effects of treatment on LLL and those exclusively on

infective LLL and/or non-malignant (e.g. orthopaedic)

conditions.

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Leung et al. 3

Study selection

The electronic searches were scrutinised and full manu-

scripts of all citations likely to meet the predefined selec-

tion criteria were selected. Independent reviewers

(E.Y.L.L. and S.A.T.) examined these manuscripts and

made the final decisions regarding inclusion or exclusion.

In cases of duplicate publications, we selected the most

recent and complete versions.

Data extraction and assessment of the

risks of bias

Two independent reviewers (E.Y.L.L. and S.A.T.) extracted

data using pre-designed and piloted data extraction forms.

The risks of bias of each study were assessed by different

methods according to study design. Randomised con-

trolled trials (RCTs) were assessed by Jadad’s Score,21 and

observational studies were assessed by Newcastle–Ottawa

Scale (NOS).22,23

Results

Paper selection

From 1617 citations, 32 were deemed to be relevant for

full-text assessment (Appendix 1, available online). Two

randomised trials and five observational studies were

identified after full-text assessment (Figure 1). One eligi-

ble Italian-language study was identified and translated

by a native Italian speaker. Two studies exclusively

included patients who had undergone gynaecological

operations24,25 or Classic Kaposi-sarcoma.26 Other stud-

ies included patients with mixed aetiologies,27–30 that is,

participants with malignant and non-malignant conditions.

Unfortunately, only pooled results were available for these

studies (Table 1). None of the studies explicitly stated the

stages of malignancies of their participants. No LLL stud-

ies retrieved exclusively recruited participants within a

palliative care population.

Summary of results

In total, 778 participants with LLL were included in

seven studies (two focused on patients with gynaecologi-

cal malignancy, one on classic Kaposi lymphoma and

four included LLL patients with different aetiologies).

The two randomised trials evaluated graded compression

stockings (GCSs; n = 10)24 compared to conservative

management without GCSs (n = 8) and Coumarin cap-

sules (n = 10) compared to placebo (n = 11).27 The five

observational studies evaluated pneumatic compression

devices (PCDs)28 (n = 196), lymphovenous microsurgical

shunts (LMS)29 (n = 260), manual lymphatic drainage

(MLD) with compression (n = 65),26 compression band-

ages alone (n = 50)25 and a herbal remedy combining

Coumarin, Ginkgo and Melitoto (with or without MLD)

(n = 133).30 The summaries of all eligible studies are

described in Table 1.

Different methods were used to evaluate lymphoedema,

and only one study evaluated the impact of observer vari-

ability (Table 1).

Assessment of the risks of bias

The included studies showed substantial clinical heteroge-

neity (Table 1). Hence, a meta-analysis was inappropriate

and not performed. In addition, the included studies also

showed significant risks of bias. We have summarised the

risk of bias assessments of these studies in Figure 2, and a

detailed breakdown was described in Appendix 3, availa-

ble online.

Effects of the treatments

Different volumetric outcomes were used (Table 1). All

included studies reported favourable outcomes of the man-

agement evaluated. GCS was reported to reduce excess

volume by 6.9%26 and mean lower limb volumes by

350 mL.24 PCD achieved a mean lower limb volume reduc-

tion of 8% or 1150 mL, although the range of response was

wide.28 Complex decongestion therapy reduced the mean

percentage excess volume by 20%.25 Herbal remedies

including Coumarin were also reported to reduce limb cir-

cumference by 7.8%–17.6%30 and by 1.39% per month.27

Microsurgical lymphovenous shunts consistently reduced

the mean circumferences ratio of oedematous versus nor-

mal limb by 20%–30%.29 None of the included studies

reported confidence intervals of their results.

Patient-reported outcomes and side effects of

treatments

Four studies reported QoL assessments,24,25,27,28 using dif-

ferent instruments and surveys. Only two used validated

Figure 1. PRISMA flow chart.

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4 Palliative Medicine

Table 1. Summaries of all included studies.

Paper Design; participants Methods used to measure lymphoedema Treatment; duration Treatment (n);

Control (n);

Volumetric outcome and

follow-up

Brambilla et al.26

Case-control; Classic

Kaposi-sarcoma

 Circumferences were measured from

the base of the great toe to the knee at

1.5-cm intervals

 Mean lower limb volumes were

estimated as if limbs were truncated

cones

Custom-made

stockings; 15 months

50; 15 Mean percentage excess volume

difference

Treatment group: 30/50

showed reduced excess

volume 6.9%; 20/50 showed

increased volume of 6.7%

Control group: all had

increased limb volume of

5.82%

Median follow-up: 65 weeks

Lost to follow-up: 2 (no

further details provided)

Casley-Smith et al.27

RCT; mixed

aetiologiesa

 Each limb was measured twice at

each follow-up by means of a water-

displacement tank

 Limb circumferences were measured at

up to eight points at 10-cm intervals

5,6-benzo-[alpha]-

pyrone (Coumarin);

12 months

10; 11 (participants

with LLL)

Monthly percentage volume

difference

Results: volume reduced by

1.39% per month (SE 0.22;

95% CI 0.93–1.85, p < 0.001)

Last follow-up: 6 months

Lost to follow-up: 6 (unclear

allocated group)

Kim and Park25

Cohort; gynae-

oncology post-

treatment (unilateral

LLL)

 Circumferences were measured at six

locations: mid-foot ankle, calf, knee and

two along the thigh

 Circumferences were average and

the mean percentage excess volume

calculated

 Unaffected limb used as normal control

Complex

decongestion therapy;

2–4 weeks (intensive),

plus maintenance

65; 0 Mean percentage excess volume

difference (p < 0.05)

Baseline: 55.93 (compared to

normal limb)

At follow-up: 31.56

Last follow-up: 1 month

Lost to follow-up: 8

Muluk et al.28

Cohort; mixed

aetiologiesa

 Circumferences were measured

from the ankle to the groin at 10 cm

increments

 Mean lower limb volumes were

estimated as if limbs were truncated

cones

Pneumatic

compression devices;

median of 55 days

196; 0 Mean lower limb volumes (LLV)

Mean reduction: 8% or

1150 mL (−1241 to +3084;

p < 0.0001)

Median follow-up: 60 days

Lost to follow-up: 60

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Leung et al. 5

Paper Design; participants Methods used to measure lymphoedema Treatment; duration Treatment (n);

Control (n);

Volumetric outcome and

follow-up

Olszewski29

Cohort; mixed

aetiologiesa (unilateral

LLL)

 Circumferences were measured at

three locations: dorsum of foot, mid-calf

and mid-thigh

 Limb volume was not estimated

 Unaffected limb used as normal control

Microsurgical

lymphovenous shunts;

operative procedure

260; 0 Mean circumferences ratio (CR)

of oedematous leg versus normal

(CR; p < 0.05)

At foot level: CR from 1.3

to 1.1

At mid-calf level: CR from 1.8

to 1.6

At mid-thigh level: CR from

2.0 to 1.7

Median follow-up: 5 years

(pooled data at 10–40 years)

Lost to follow-up: 64

Sawan et al.24

RCT; vulval cancer  Observer identities recorded Graded compression

stocking (GCSs);

180 days

10; 8 Mean LLV

 Circumferences were measured from

2 cm above the lateral malleolus to 4 cm

below the perineum at 4-cm intervals

 Mean lower limb volumes were

estimated as if limbs were cylinders

Treatment group: +607 mL

Control group: +953 mL

(p = 0.010)

Last follow-up: 6 months

Lost to follow-up: 3 in control

group, 1 in treatment group

Vettorello et al.30

Cohort; mixed

aetiologiesa

 Circumferences were measured from

the malleoli and feet

 Limb volume was not estimated

Coumarin, Ginkgo

and Melitoto ± manual

lymphatic draining;

8 months

133; 10 Percentage circumference

reduction

Results (3 months): 7.8% at

malleoli, 10.3% at feet

Results (8 months): 12.3% at

malleoli and 17.6% at feet

Last follow-up: 8 months

Lost to follow-up: 67 (no

further details provided)

RCT: randomised controlled trial; LLL: lower limb lymphoedema; SE: standard error; CI: confidence interval.

aStudies of mixed aetiologies included participants with malignant and non-malignant conditions.

Table 1. (Continued)

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6 Palliative Medicine

QoL instruments.25,27 One of these two studies reported

significant improvement of QoL in the treatment group,

while the other was a pilot trial with insufficient power to

detect any difference in QoL.

All evaluated treatments appeared to be safe, although

three studies did not state whether side effects were specifi-

cally assessed.24,26,30 Reported side effects of physical com-

pression treatments include muscle cramps28 and limb

erythema.28 No side effect was reported from decongestive

physical therapy.25 Herbal remedies containing Coumarin

was associated with mild gastrointestinal upset.27 No surgi-

cal complication was reported after LMS.29

Discussion

Main findings, strengths and limitations

All included studies reported overall volumetric and symp-

tomatic improvements of LLL after treatment, with mini-

mal side effects. Few studies24–30 have investigated the

effects of different treatments for LLL secondary to malig-

nancies. Although it is not possible to disaggregate infor-

mation specifically in the end-of-life palliative care

populations from the studies, our results highlight the lack

of evidence in such population and the potential impact of

well-designed research in this area. This systematic review

included all randomised controlled studies and observa-

tional studies participated by patients with LLL secondary

to malignancies. No time and language restrictions were

applied to our literature search. A comprehensive list of

databases, including grey literature databases, was

searched. Moreover, previous systematic reviews only

included conservative management of lymphoedema.17–19

We also included a study on surgical management of LLL

in this systematic review.29

However, the included studies showed clinical hetero-

geneity and often included participants with LLL second-

ary to different aetiologies (Table 1 and Figure 2). In

addition, all included studies showed moderate to high

risks of bias. As a result of these limitations, it was impos-

sible to accurately estimate the overall effect size of each

evaluated treatment for patients with LLL, and whether

any one treatment is superior compared to the others.

Different definitions and verification methods of LLL

were used to identify participants (Table 1). In addition,

various outcome measurements were used to evaluate vol-

umetric changes in these studies (Table 1). In the majority

of studies, inter-observer and intra-observer variability of

outcome measurements were not taken into account

(Table 1). Although five included studies evaluated sub-

jective changes of symptoms,24,25,27,28,30 only one study29

specifically evaluated the complications of the treatment.

Recommendations for future studies on the

management of LLL

This review suggested that the effectiveness of the treat-

ments for LLL and their side effect profiles are currently

unclear. Although our results provided limited evidence to

support current clinical decision-making, the included

studies24–30 could guide the planning of future studies.

Patients. A number of included studies recruited partici-

pants with LLL secondary to different aetiologies and

combining patients with and without malignancies in the

same reported cohort. It is unclear whether the aetiologies

of lymphoedema have any implications on the response to

treatment. For example, in malignancies, lymphoedema

can be secondary to both the tumours and their surgical

treatment. Studies evaluating the effects of treatment on

clinically relevant subgroups will be helpful.

Multiple diagnostic criteria were used to define lym-

phoedema in the included studies, and often, they were not

clearly defined (Table 1). Grading systems for the diagno-

sis of lymphoedema exist10 and should be used in future

studies.

Interventions and comparison. Although the pharmacological

interventions used were well described, studies using other

interventions such as GCSs and PCDs provided insufficient

methodological details for replication in different popula-

tions. In the included case-control studies, information

about the control was limited and potential confounding fac-

tors could not be satisfactorily evaluated. Sufficient meth-

odological details are needed in future studies.

Outcomes. Only two out of the seven included studies used

the same volumetric outcomes (Table 1). Moreover, each

study used a different method to measure the limbs, and

only one study considered observer variability (Table 1).

Figure 2. Assessment of the risks of bias: (a) randomised

controlled trial assessed by Jadad’s Score21 and (b)

observational studies assessed by Newcastle–Ottawa Scale.22,23

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Leung et al. 7

The results between these studies were difficult to com-

pare and impossible to combine.

In addition, it is established that immobility leads to

morbidities and mortalities through complications such as

infection and thromboembolism. Since LLL can lead to

reduced mobility, there may be additional adverse effects

secondary to LLL that are clinically important. None of the

included studies had evaluated these risks. Moreover, the

potential side effects of the treatment for LLL have not

been evaluated in the existing studies. Finally, long-term

outcomes of lymphoedema treatment have rarely been

investigated.17–19

In 2010, the Core Outcome Measures in Effectiveness

Trials (COMET) initiative was launched to develop agreed

standardised sets of outcomes to represent the minimum

set that should be measured and reported in all randomised

trials of a specific condition.31 We believe core outcomes

set should be developed for future trials of LLL. The pro-

posed core outcomes set should not simply focus on volu-

metric measurements by trained assessors (to reduce

inter-observer and intra-observer variability). It should

also assess side effects of the evaluated treatment, compli-

cations of LLL (including fibrosis and incidence of deep

vein thrombosis) and use validated instruments to assess

pain and QoL of participants.

Study design. RCT is the most appropriate primary study

design to evaluate an intervention.32 However, only two

ongoing clinical trials on the treatment of LLL have been

registered – one is investigating a new PCD33 and the other

is evaluating pelvic and lower extremity exercises.34 Suf-

ficiently powered randomised trials using standardised

assessment of LLL and validated outcome measures are

needed for improving the treatment of LLL.

Reporting of future studies. It is recognised that RCTs or

controlled trials are often not available.35 Observational

studies with comparators are acceptable study designs to

evaluate the effects of an intervention. The reporting qual-

ity of the observational studies included in this review was

poor, which made the assessment of the risks of bias

difficult.

Similar to the Consolidated Standards of Reporting

Trials (CONSORT) statement36 for reporting clinical tri-

als, recommendations also exist for the reporting of obser-

vational studies. The STrengthening the Reporting of

OBservational studies in Epidemiology (STROBE) initia-

tive37 helps support the reporting of observational studies

by encouraging comprehensive description of methodol-

ogy, recognition and reporting of bias and limitations and

inclusion of numeric data and unadjusted estimates. We

believe the adoption of STROBE can help readers to deter-

mine the impact of bias and confounders of studies, as well

as allowing appropriate secondary data analysis (e.g. meta-

analysis) of similar studies.

Conclusion

Few studies have evaluated the clinical effectiveness and

potential side effects of treatments for LLL, a common

and disabling symptom in palliative care not only

restricted to those who are at the end of life. All studies to

date report a reduction of lower limb volume after treat-

ment, but symptom and QoL assessments were inconsist-

ently reported. In this review, complex decongestion

therapy, GCSs and LMSs have been shown to produce

larger reduction of limb volume. Adequately powered

RCTs of these interventions are recommended. Effort

should also be made to establish standardised outcomes,

to minimise bias and to improve reporting quality in

future trials of treatment for LLL.

Acknowledgements

E.Y.L.L. contributed to the conception of the research question,

acted as the first reviewer and compiled the first draft. C.M. pro-

vided initial methodological guidance. S.A.T. contributed as the

second reviewer. All authors have contributed to this manuscript

and approved the final version.

Declaration of conflicting interests

The authors declare that there is no conflict of interest.

Ethics/research governance approvals

This is a systematic review of primary studies. Further ethical

approval is not applicable.

Funding

This research received no specific grant from any funding agency

in the public, commercial or not-for-profit sectors.

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Reconfiguring life: A grounded theory study on living with lower limb lymphoedema

Thesis

Full-text available

Jul 2023

Claire Doole

This thesis presents the theory of Reconfiguring Life which explains how adults live with moderate to severe lower limb lymphoedema. Lymphoedema is a long-term, progressively deteriorating condition; with associated symptoms such as limb swelling, heaviness, changes in personal appearance, reduced mobility and complications that are disruptive, debilitating, and, on occasions, life threatening. Lymphoedema may affect one or two limbs and adjacent areas but can occur anywhere in the body. Left untreated the condition leads to significant physical and psychosocial incapacity. Lymphoedema is a health issue in lower- and higher-income countries, through differing causal factors. Lymphoedema is an under researched area. Most lymphoedema in higher-income countries, such as Aotearoa New Zealand, is acquired through treatment for cancer. As cancer rates increase, so too does the risk of lymphoedema. The literature is dominated by breast cancer related lymphoedema which affects the upper limb (arms). This research set out to give voice to those living with the more burdening lower limb lymphoedema. The research question was “How do people live with moderate to severe lower limb lymphoedema?” A constructivist grounded theory study informed by Charmaz was undertaken. Twelve participants who lived with primary or secondary lower leg lymphedema were interviewed. Data collection and analysis followed a constructivist approach. The resulting theory provides an in-depth view into how people live following the onset of moderate to severe lower limb lymphoedema. This thesis proposes that there are three phases in adapting to living with lymphoedema which leads to transformative change. Transformation is initiated in phase one through physical changes termed ‘being led by the body.’ During this time, moderate to severe lower limb lymphoedema often dominates life experience with a loss of previous normality. There is a subsequent fracturing of the previous identity, which precipitates phase two termed ‘being led by feelings.’ A turning point is reached, and transformative change is triggered. Phase three, termed ‘leading with the mind,’ reconfigures the new normal through ‘what I learn,’ ‘what I do’, and through ‘how I come to be.’ Through this process, lymphoedema assumes an appropriate place as a condition to be managed. The main motivator for the process is managing disruption which refers to responding to the demands of an unstable condition which alters and disrupts ordinary life. ii My study identified that lymphoedema therapists are critical to the process of supporting transformative change for those adapting to living with lower limb lymphoedema. Those who receive self-care support are positioned to learn how to manage disruptions, mitigate the disruptions of lymphoedema, and place the condition within the context of their lives. Without sufficient support for self-care, achieving self-management is highly problematic. The implications for clinical practice relate to providing an explanatory framework for lymphoedema therapists to convey the transformative reconfiguring through which people move. The framework may be useful for advocating for policy change and to those working alongside lymphoedema therapists such as oncologists, surgeons, nurses, and general practitioners. The framework may be useful for supporting people living with lymphoedema to understand their own journey; and for friends, family, and support people to gain an insight into this under researched, under recognised, and misunderstood condition.

Research Progress on Postoperative Limb Lymphedema in Breast Cancer

Article

Full-text available

Dec 2023

This article reviews the mechanisms, factors, and preventive measures of upper limb lymphedema following breast cancer surgery. Methods: Extensive review of recent research literature on factors and prevention of upper limb lymphedema after breast cancer surgery in the past five years, followed by analysis and summary. Conclusion: Postoperative upper limb lymphedema significantly impacts the function and mobility of the affected limb. The formation of upper limb lymphedema is a chronic process, and to date, there is no treatment that can fully restore the affected limb. Therefore, early detection, preventive measures, and the proactive adoption of effective strategies have become a new approach to treatment. By systematically elucidating the mechanisms, factors, and preventive measures of postoperative upper limb lymphedema in breast cancer, adopting effective preventive measures can reduce the occurrence of upper limb lymphedema, alleviate patient suffering, and improve the quality of life.

Primary Prevention of Cancer-Related Lymphedema Using Preventive Lymphatic Surgery: Systematic Review and Meta-analysis

Article

Full-text available

Feb 2022

Background Several studies have proven prophylactic lymphovenous anastomosis (LVA) performed after lymphadenectomy can potentially reduce the risk of cancer-related lymphedema (CRL) without compromising the oncological treatment. We present a systematic review of the current evidence on the primary prevention of CRL using preventive lymphatic surgery (PLS). Patients and Methods A comprehensive search across PubMed, Cochrane-EBMR, Web of Science, Ovid Medline (R) and in-process, SCOPUS, and ScienceDirect was performed through December 2020. A meta-analysis with a random-effect method was accomplished. Results Twenty-four studies including 1547 patients fulfilled the inclusion criteria. Overall, 830 prophylactic LVA procedures were performed after oncological treatment, of which 61 developed lymphedema. The pooled cumulative rate of upper extremity lymphedema after axillary lymph node dissection (ALND) and PLS was 5.15% (95% CI, 2.9%–7.5%; p < 0.01). The pooled cumulative rate of lower extremity lymphedema after oncological surgical treatment and PLS was 6.66% (95% CI < 1–13.4%, p-value = 0.5). Pooled analysis showed that PLS reduced the incidence of upper and lower limb lymphedema after lymph node dissection by 18.7 per 100 patients treated (risk difference [RD] – 18.7%, 95% CI – 29.5% to – 7.9%; p < 0.001) and by 30.3 per 100 patients treated (RD – 30.3%, 95% CI – 46.5% to – 14%; p < 0.001), respectively, versus no prophylactic lymphatic reconstruction. Conclusions Low-quality studies and a high risk of bias halt the formulating of strong recommendations in favor of PLS, despite preliminary reports theoretically indicating that the inclusion of PLS may significantly decrease the incidence of CRL.

EFFICACY OF MULTI-LAYER BANDAGING WITH AN ADDITIONAL PADDING DURING INTENSIVE PHASE OF DECONGESTIVE LYMPHATIC THERAPY ON LYMPHEDEMA POST MASTECTOMY

Article

Full-text available

Dec 2021

Esraa Hany Rostom

Factors Predicting Limb Volume Reduction Using Compression Bandaging Within Decongestive Lymphatic Therapy in Lymphedema: A Multicountry Prospective Study

Article

Full-text available

Oct 2021

Objectives: To identify predictive factors associated with limb volume reduction using different decongestive lymphatic therapy (DLT) systems in patients with lymphoedema, over a period of up to 28 days. Methods: A multicountry (Canada, France, Germany, the United Kingdom) prospective cohort study using (DLT): skin care, exercise, compression bandaging, and manual lymphatic drainage for up to 4 weeks. Reduction in limb volume comparing DLT with (1) standard multilayer bandaging with inelastic material, and with (2) multilayer bandaging with Coban2, together with the identification of factors associated with limb volume changes. Results: Out of 264 patients with upper or lower limb lymphedema, 133 used Coban2 and 131 used standard care. Following DLT, mean limb volume reduction was 941 mL using Coban2 compared with 814 mL using standard care. A difference of 127 mL was found (95% confidence interval -275 to 529 mL, p = 0.53). Of the 176 patients with leg swelling, 166 (94.3%) had a limb volume measurement after 28 days and were included in the risk factor analysis. Of these, 132 (79.5%) were female, with overall mean age of 60.1 years (standard deviation = 14.7), with secondary lymphedema in 102/163 (62.6%). Duration of lymphedema was >10 years in 75/161 (46.6%) and 99/166 (59.7%) were International Society of Lymphology late-stage II/III, indicating longstanding and/or a high frequency of patients with advanced stages of lymphedema. Ninety-one (54.8%) received Coban2 and 75 (45.2%) had standard care. Multivariable factors for a greater leg volume reduction were large initial leg volume (p < 0.001), DLT treatment duration of 4 weeks compared with 2 weeks (p = 0.01), and peripheral arterial disease (p = 0.015). Conclusion: Limb volume changes were found to be similar between groups. Lack of standardization of DLT makes interpretation of effectiveness problematic. There is an urgent need for randomized-controlled trials. Despite this, severe lymphedema with a large limb volume responded well to DLT in this study.

Physiotherapy in Breast and Gynecological Cancer Recommendations for Physiotherapy in Breast and Gynecological Cancer during COVID-19 Pandemic: Literature Review

Article

Full-text available

Jun 2021

Introdução: Considerando a pandemia de Covid-19 e a assistência fisioterapêutica nos cânceres de mama e ginecológico, o desafio tem sido continuar ou iniciar a fisioterapia para prevenir ou tratar complicações. Objetivo: Oferecer recomendações voltadas à fisioterapia para os cânceres de mama e ginecológico durante o período de Covid-19. Método: Estudo descritivo produzido após consulta pública sobre o tema, baseado na revisão da literatura e nas considerações de grupo de especialistas. Para graduar a força das recomendações para os desfechos incluídos, utilizou-se o sistema GRADE. Resultados: Oitenta e dois fisioterapeutas de diferentes regiões brasileiras responderam à pesquisa, remotamente. A maioria (36,6%) relatou necessidade de informação sobre equipamento de proteção individual e sua higiene; 18,3% sobre controle e prevenção de linfedema, enfaixamento compressivo e cuidados com a pele; e 17,1% sobre disfunção do assoalho pélvico. A análise da consulta pública, revisão da literatura e considerações dos especialistas resultaram nas recomendações sobre: impacto da pandemia de Covid-19 no acompanhamento fisioterapêutico das mulheres submetidas ao tratamento oncológico mamário ou ginecológico; acompanhamento das complicações mais prevalentes por meio da telefisioterapia; atenção às mulheres em cuidados paliativos; e segurança na assistência após retorno presencial. Aspectos da tomada de decisão em relação ao formato das sessões e critérios de retorno à rotina presencial foram discutidos. Conclusão: Este manuscrito recomenda a continuidade da fisioterapia durante e após a pandemia de Covid-19, destacando componentes educativos e de autoaplicação, priorizando um plano de atividade física e exercícios específicos para contribuir para melhor qualidade de vida das mulheres.

Phospholipase A2 (PLA2) injured lymphatic endothelial cells leading to progression of secondary lymphoedema

Article

Mar 2023
Biotechnol Genet Eng Rev

Secondary lymphoedema is one of the common complications after lymph node dissection for gynecologic malignancies and breast cancer. In this study, the relationship between PLA2 and postoperative lymphoedema in cancer at the molecular level has been explored through transcriptomics and metabolomic assays. Transcriptome sequencing technology, as well as metabolomic assays, were utilized to explore the expression of PLA2 in lymphoedema patients, and search for potential pathways in the pathogenesis and exacerbation mechanism of lymphoedema. The effect of sPLA2 on human lymphatic endothelial cells was investigated by culturing human lymphatic endothelial cells. Secretory phospholipases A2 (sPLA2) showed high expression levels in lymphoedema tissues, however, cytoplasmic phospholipases A2 (cPLA2), showed low expression in lymphoedema, as demonstrated by RT-qPCR. By culturing human lymphatic vascular endothelial cells, the study found that sPLA2 causes HLEC vacuolization and has an inhibitory effect on HLEC proliferation and migration. By detecting sPLA2 in the serum of lymphoedema patients and analyzing clinical data, it was found that sPLA2 was positively correlated with the severity of lymphoedema. Secretory Phospholipase A2 (sPLA2) is highly expressed in lymphoedema tissue, damages lymphatic vessel endothelial cells, is strongly associated with disease severity, and can be used as a potential predictor of disease severity. Abbreviations: PLA2: Phospholipase A2; DEGs: differentially expressed genes; DMP: differential metabolic production

Obstipation

Chapter

Sep 2020

Leitliniengerechte Versorgung von Patienten mit malignen Wunden

Article

Feb 2022

The German Association of Palliative Care developed an evidence-based guideline about the management of malignant wounds in adult patients with incurable cancer. There is a lack of evidence-based guidelines about fungating wounds and a confusing wide range of available wound dressings. The goal of the guideline is to reduce the suffering of patients with malignant wounds and stabilize or improve their quality of life. The guideline is constructed following the German Instrument for Methodological Guideline Appraisal (DELBI): A systematic review was carried out for guidelines and reviews. A wound expert group discussed these research findings and suggested recommendations which were adapted and consented by representatives of 62 medical and health professionals associations. The guideline has 34 recommendations, thereof nine (26%) are evidence based with an evidence level from 2+ to 4 (according to SIGN). The assessment chapter comprises specific assessment tools for malignant wounds, odor and wound-related quality of life. Three recommendations address the psychosocial support of patients and their family caregivers and aim to reduce the impact of the wound on their emotional wellbeing, caregiver burden and social participation. The pain recommendations focus on a preventive atraumatic dressing change, positioning, systemic pain medication (anticipated, rescue and baseline) and local application of morphine or local anesthetics. The guideline gives recommendations on odor management (metronidazole, active coal and antiseptic dressings) and management of exudate (super absorber). The recommendations on prevention and management of bleeding (antifibrinolytica, haemostyptica) are vital for patients and caregivers. This guideline is one of the first evidence-based and consented guideline on malignant wound care and has the potential to improve the palliation of patients who suffer from there malignant wounds.

Genitale: Penis

Chapter

Aug 2021

Den benignen Erkrankungen des Penis unterliegen sehr unterschiedliche Ätiologien und Pathogenesen. Dementsprechend heterogen sind auch die Komplikationen und die ihrer Behandlungen. Insbesondere die Ansprüche an ein perfektes Timing der Therapie sind hoch, die Umstände oft schambehaftet und Grund für Verzögerungen. Einige Erkrankungen sind so selten und einzigartig z. B. im Verletzungsmuster, dass evidenzbasierte Empfehlungen nicht gegeben werden können. In vielen Fällen entscheidet daher die Erfahrung des Behandlers über den Erfolg der Therapie. In der Behandlung spielen funktionelle, kosmetische und psychosexuelle Aspekte eine Rolle. Dementsprechend sorgfältig sollte die Aufklärung bei einer realistisch formulierten Erwartungshaltung erfolgen. Organerhalt hat beim Peniskarzinom neben der Kuration die größte Bedeutung. Für die operative Therapie des Peniskarzinoms gilt, dass so wenig wie möglich und so viel wie nötig exzidiert werden soll. Knappe Schnittränder im Millimeterbereich sind ausreichend, dabei besteht aber ein erhöhtes Lokalrezidiv-Risiko. Diese werden wie ein Primärtumor erneut nach Möglichkeit organerhaltend therapiert. Die Prognose des Patienten wird durch das richtige und zeitgerechte Lymphknotenmanagement bestimmt. Die inguinale Lymphadenektomie bleibt trotz gewebeschonender Technik komplikationsträchtig.

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and Elaboration.

Article

Full-text available

Jan 2014
Int J Surg

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (http://www.strobe-statement.org/) should be helpful resources to improve reporting of observational research.

Assessing the quality of reports of RCT: is blinding necessary?

Article

Full-text available

Jan 1996

Contribution of an association of α and β benzopyrones, flavonoids and natural terpenes in the treatment of II stage lymphedema of the lover limbs

Article

Full-text available

Sep 1996

Hypothesis. To create a phlebolymphologic therapy in order: to activate venous system; to activate lymphatic system; to activate macrophagic system; to reduce the proteic lymphatic load. Experimental. A study was performed on the use of an ideal phlebolymphological association (Tonka Beans, Ginko Biloba, Melilotus Officinalis) as a practical standpoint in the treatment of lymphedema of lower limbs in order to create an efficace dose of Cumarin, Benzophirones and Ginkolidi. Clinical. We investigated a population of 76 patients treated in an open-label study for six-eigth months with a dosage of Cumarin 60 mg/daily + Ginko Biloba 40 mg/daily + Melilotus 40 mg/daily. Conclusion: This trilogy induced a very significant improvement in lymphedema (centimetry - aspect) both in functional symptoms (pain heaviness in affected limbs) and physical signs (edema, episodes of infection). Tolerance of long term treatment was good and the improvement was observed from the third month of treatment.

Integrated genomic characterization of endometrial carcinoma

Article

Full-text available

May 2013
NATURE

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

The COMET (Core Outcome Measures in Effectiveness Trials) initiative

Article

Full-text available