Evidence-Based Outcomes




Key Points





  • The surgical treatment of lymphedema has not been evaluated in randomized clinical trials; therefore, the level of current evidence does not justify the widespread adoption of surgery as the standard of care for lymphedema.



  • Complete decongestive therapy remains the only lymphedema treatment that is supported at the highest level of evidence.



  • Health-related quality of life is a multidimensional construct that encompasses physical, functional, emotional, and social well-being parameters.



  • A variety of quality of life instruments have been used to capture outcomes in lymphedema patients, but some of these instruments were not sensitive to lymphedema-specific outcomes.



  • Lymphedema-specific symptom assessment tools may be more sensitive than other instruments to clinically meaningful changes in patients with lymphedema.





Introduction


Lymphedema continues to be a significant health issue for cancer survivors, as shown by the 2006 and 2010 LiveStrong Cancer Survivor Surveys. Among the 6593 survivors of various types of cancer who completed the questionnaires, lymphedema was the sixth most-frequently reported physical issue; lymphedema was an increasing concern for 21% of respondents in 2006 and for 25% of respondents in 2010. Of the respondents, 53% had their cancer treated with surgery or radiation, with or without adjuvant systemic therapy.


Standard-of-care lymphedema treatment is a management-based program providing symptomatic relief but requiring lifelong compression, self-massage, and in some cases regular visits to a lymphedema therapist for bandaging, education, and manual lymphatic drainage. Although some surgical management techniques for the treatment of lymphedema offer patients an opportunity to forgo lifelong treatment and in some cases to forgo ongoing compression, little evidence exists for the long-term efficacy of these relatively novel procedures.


Because quality of life (QOL) outcomes have become a subject of increasing focus as primary or secondary outcomes in most clinical trials, a variety of general, malignancy-specific, and symptom-specific self-report instruments have been developed and used to assess QOL and symptoms in patients who have or are at risk for lymphedema. This chapter will provide an overview of the levels of evidence used in plastic surgery research, the published evidence for the surgical treatment of lymphedema, the assessment of patient-centered outcomes, and specific QOL and symptom assessment tools that have been used to evaluate patients with lymphedema.




Level of Evidence


Definitions


The Center for Evidence-Based Medicine has created a document that categorizes the levels of evidence available for current clinical practices. The highest level of evidence is level 1A, which is evidence derived from a systematic review of randomized controlled trials, and the lowest level of evidence is level 5, which is expert opinion without clinical basis. Each level has clearly defined criteria ( Table 22.1 ).



Table 22.1

Level of Evidence Scoring System





































Level Evidence for Therapy/Treatment/Prevention
1a Systematic review with homogeneity of randomized controlled trials
1b Individual randomized controlled trials with narrow confidence intervals
1c All-or-none case series
2a Systematic review with homogeneity of cohort studies
2b Individual cohort study
2c Outcomes research; ecological studies
3a Systematic review with homogeneity of case studies
3b Individual case-control study
4 Case-series and poor-quality cohort or case-control studies
5 Expert opinion without explicit critical appraisal

From Sullivan et al. Plast Reconstr Surg 2011 Jul;128(1):311–4.


These levels of evidence have been modified to specifically address the levels of evidence used in plastic and reconstructive surgery articles. This modified schema first classifies articles as diagnostic, therapeutic, or prognostic and then further classifies them using the Center for Evidence-Based Medicine levels 1 through 5. The highest-level evidence is defined as evidence arising from a high-quality cohort study with adequate power or from a systematic review of multiple studies, and the lowest-level evidence is defined as expert opinion. The levels vary between the diagnostic, therapeutic, and prognostic-associated sub-classifications but share general characteristics. For therapeutic studies, the highest level of evidence comes from high-quality single- or multicenter randomized controlled trials with appropriate power; for diagnostic studies, the highest level of evidence comes from cohort studies validating a diagnostic test using a gold-standard test as a comparison; and for prognostic/risk studies, the highest level of evidence comes from prospective cohort or comparative analyses. In each category, a systematic review of the study types at the highest level for that category can also be classified as the highest level of evidence. The lowest level of evidence in each category comes from expert opinions or consensus documents based on the evaluation of case studies ( Table 22.2 ).



Table 22.2

Plastic Surgery-Specific Criteria for Levels of Evidence











































Level Therapeutic Studies Diagnostic Studies Prognostic/Risk Studies
I High-quality, multicenter or single-center randomized controlled trial with adequate power High-quality, multicenter or single-center cohort study validating a diagnostic test with a ‘gold’ standard as a reference in a series of consecutive patients High-quality, multicenter prospective cohort or comparative study with adequate power
Systematic Review of the Above Studies Qualifies as Level I Evidence
II Lesser-quality randomized controlled trial, prospective cohort or comparative study Exploratory cohort study developing diagnostic criteria (with a ‘gold’ standard as a reference) in a series of consecutive patients Lesser-quality prospective cohort or comparative study; retrospective cohort or comparative study; untreated controls from a randomized controlled trial
Systematic Review of the Above Studies Qualifies as Level II Evidence
III Retrospective cohort or comparative study Diagnostic study in non-consecutive patients without consistently applied ‘gold’ standard Case-control study
Systematic Review of the Above Studies Qualifies as Level III Evidence
IV Case series with pre/post-test or post-test only Case-control study or any above-mentioned study without a ‘gold’ standard Case series with pre/post-test or post-test only
V Expert opinion developed via consensus; case report or clinical example; evidence based on physiology, bench research, or ‘first principles’ Expert opinion developed via consensus; case report or clinical example; evidence based on physiology, bench research, or ‘first principles’ Expert opinion developed via consensus; case report or clinical example; evidence based on physiology, bench research, or ‘first principles’

Adapted from Sullivan et al. Plast Reconstr Surg 2011 Jul;128(1):311–4.


NonSurgical Treatment of Lymphedema


The traditional, gold-standard treatment for lymphedema remains complete decongestive therapy (CDT). In the treatment phase of CDT, trained lymphedema therapists apply multiple modalities including manual lymph drainage, multilayer short-stretch compression bandaging, therapeutic exercises, skin care, elastic compression, and education in self-maintenance. After the treatment phase, which usually lasts three to eight weeks, the patient is expected to continue into the maintenance phase, which includes self-administered lymphatic drainage, exercise, skin care, and compression garments.


A recent systematic review by Lasinksi et al. includes eight randomized controlled trials and 10 prospective cohort studies that examined the outcomes associated with CDT, placing this review at the highest level of evidence. This study utilized both data collected from studies and data described in previously published reviews. The authors concluded that those studies were moderately strong but lacked consistent, objectively collected data and that several of the studies that did describe consistent interventions often bundled CDT with other interventions. Findings from these data indicate that CDT is effective in reducing limb volume. However, many treatments are only evaluated as a bundled therapy (e.g., manual lymph drainage and bandaging) which makes it difficult to determine the overall efficacy of a single component of the CDT treatment schema.


Nonsurgical treatments other than CDT can be considered for the treatment of lymphedema. A systematic review of complementary, alternative, and other non-CDT lymphedema treatments found that treatments like these were widespread but poorly supported by evidence. In this review, the lymphedema therapies were categorized as either physical agents or modalities of contemporary value. The physical agent modalities included ultrasound therapy, electrically stimulated lymphatic drainage, high-voltage electrical stimulation, diathermy, low-level laser therapy, hyperbaric oxygen therapy, elastic taping, and acupuncture. Among the modalities of contemporary value were internationally designed at-home units devised to complete manual lymph drainage through circular massage motions, aqualymphatic therapy, and extracorporeal shockwave therapy. The evidence supporting the use of any of these therapies remains limited. Most of these studies were completed with a small convenience sample (level 2) or a case series (level 4) and have not been replicated. Also, very few of these studies used completely objective measures of limb volume reduction, such as circumference, perometry, water displacement, or bioimpedance; subjective measures including symptom assessment and clinical examination were used to identify the pre- and post-treatment changes which limit the validity of the data.


Surgical Treatment of Lymphedema


Surgical treatment of lymphedema has become more widely available and is used primarily in the treatment of chronic, progressive lymphedema that remains refractory to standard treatment protocols. Because of the paucity of published high-level studies evaluating the long-term outcomes following surgical treatment of lymphedema, this type of treatment remains controversial and is considered experimental in many countries, including the US.


In 2011, a systematic review on the surgical treatment of lymphedema cited a lack of evidence due primarily to small patient populations, failure to use objective measurement criteria for limb volume change, and a lack of long-term follow-up. Summaries of the literature included in the systematic review have been updated through February 2014 and are presented in Tables 22.3–22.6 . Subsequent systematic reviews have been published evaluating the efficacy of microsurgery and tissue transplantation in treating lymphedema; these reviews have found mixed outcome results.



Table 22.3

Summary of Published Literature Related to Excisional Procedures for the Treatment of Lymphedema










































































Author (Year) Study Design Number of Patients Lymphedema Site Specific Surgical Procedure Follow-Up Time, Months Measurement Technique Volume Reduction, % QOL Tool Used
Kim et al. (2004) Retrospective 20 Lower extremity Excision 17.8 Volumeter 16% None
Modolin et al. (2006) Prospective 17 Penis/scrotum Excision 72 NR NR None
Lee et al. (2008) Retrospective 22 Lower extremity Excision 48 Infrared optometric volumetry and circumference NR Mentions QOL but no instrument
Salgado et al. (2009) Prospective 11 Upper extremity Excision with preservation of perforators 17.8 Circumference 21 None
van der Walt et al. (2009) Retrospective 8 Lower extremity Modified Charles procedure 27 NR 8.5 kg None
Karri et al. (2011) Retrospective 27 Lower extremity Charles procedure 48 NR NR None

NR: not reported; QOL: quality of life.

Modified from Cormier et al., Cancer 2010 Nov 15;116(22):5138–49.


Table 22.4

Summary of Published Literature Related to Liposuction Procedures for the Treatment of Lymphedema



































































Author (Year) Study Design Number of Patients Lymphedema Site Specific Surgical Procedure Follow-Up Time, Months Measurement Technique Volume Reduction, %
Liu et al. (2005) Prospective 11 Upper extremity Liposuction Circumference
Brorson et al. (2006) Prospective 35 Upper extremity Liposuction 12 Water displacement 103
Qi et al. (2009) Prospective 11 Upper extremity Liposuction, myocutaneous flap transfer 26 Circumference 18
Damstra et al. (2009) Prospective 37 Upper extremity Suction-assisted lipectomy 12 Water displacement 118
Schaverien et al. (2012) Prospective 12 Upper extremity Liposuction 36 Water displacement 123
Granzow ∗∗ (2014) Retrospective 10 Upper extremity (n=6), lower extremity (n=4) Suction-assisted lipectomy 32 Circumference 111% (UE), 87% (LE)

UE: upper extremity, LE: lower extremity.

Modified from Cormier et al., Cancer 2010 Nov 15;116(22):5138–49.

Abstract only available.


∗∗ Study included a discussion of patients who had tissue transfer and lymphatic venous anastomosis.



Table 22.5

Summary of Published Literature Related to Tissue Transfer Procedures for the Treatment of Lymphedema






























































































Author (Year) Study Design Number of Patients Lymphedema Site Specific Surgical Procedure Follow-Up Time, Months Measurement Technique Volume Reduction, %
Weiss et al. (2002) Prospective 12 Upper extremity Autologous lymphatic tissue transplantation 96 Circumference 22 to 31
Wongtrungkapun (2004) Prospective 10 Lower extremity Lymphonodovenous implantation 4.5 Circumference 3.5 cm at knee, 7.37 cm at 16 cm below knee, 2.75 at metatarsal level
Becker et al. (2006) Retrospective 24 Upper extremity Lymph node transplantation 96 Circumference Reduction to normal (n=10), some reduction (n=10), no change (n=2)
Belcaro et al. (2008) Retrospective case-control 9 Lower extremity Autologous lymphatic tissue transplantation (n=9) vs. control (n=8) 120 Water displacement Increase of 13
Hou et al. (2008) Randomized controlled trial 15 Upper extremity Autologous bone marrow stromal cell transplantation (n=15) vs. CDT (n=35) 12 Circumference 81
Lin et al. (2009) Retrospective 13 Upper extremity Vascularized lymph node transfer 56 Circumference 51
Gharb et al. (2011) Prospective 21 Upper extremity Vascularized lymph node transfer 40 Circumference NR
Cheng et al. (2012) Prospective 6 Lower extremity Vascularized lymph node transfer 8.7 Circumference 64% above knee, 64% below knee, 67% above ankle
Cheng et al. (2013) Prospective 10 Upper extremity Vascularized lymph node transfer 39 Circumference 40

NR: not reported

Modified from Cormier et al., Cancer 2010 Nov 15;116(22):5138–49.


Table 22.6

Summary of Published Literature Related to Lymphatic Reconstructive Procedures for the Treatment of Lymphedema












































































































































Author (Year) Study Design Number of Patients Lymphedema Site Follow-Up Time, Months Measurement Technique Volume Reduction, %
Koshima et al. (2004) Retrospective 52 Lower extremity 15 Water displacement 42
Matsubara et al. (2006) Retrospective 9 Lower extremity 21 to 87 Circumference >5 cm (n=6), 2 cm (n=2), no effect (n=3)
Damstra et al. (2009) Prospective 10 Upper extremity 12 Water displacement 2
Demirtas et al. (2009) Retrospective 42 Lower extremity 12 Circumference 59
Campisi et al. (2010) Retrospective 1800 Upper and lower extremities 120 Water displacement 56 (83% with 67% reduction)
Chang (2010) Prospective 20 Upper extremity 18 Perometer 35
Maegawa et al. (2010) Retrospective 111 Lower extremity NR Circumference Percentage not reported average 872 ml reduction
Mihara et al. (2010) Retrospective 11 Lower extremity 23.6 Circumference 92
Narushima et al. (2010) Prospective 14 Upper extremity (n=2), lower extremity (n=12) 809 Circumference 11
Furukawa et al. (2011) Prospective 9 Upper extremity 17 Circumference >50 in 77.8% of patients
Yamamoto et al. (2011) Retrospective 20 Lower extremity 8.9 Circumference 11
Auba et al. (2012) Prospective 12 Upper extremity (n=7), lower extremity (n=5) 24 Circumference 1.18 cm circumference
Mihara et al. (2012) Prospective 6 Lower extremity 10 Circumference NR
Ayestaray et al. (2013) Prospective 4 Head and neck 12 Circumference 3.7
Boccardo et al. (2013) Retrospective 23 ∗∗ Lower extremity 42 Circumference 80
Chang et al. (2013) Prospective 100 Upper extremity (n=89), lower extremity (n=11) 12 to 36 Perometer 42 (upper extremity)
7 to 42 (lower extremity)

NR: not reported.

Modified from Cormier et al., Cancer 2010 Nov 15;116(22):5138–49.

Selected among duplicate studies with overlapping patients.


∗∗ Study included patients treated in a preventative manner, lymphedema patients included.



Surgical intervention for lymphedema has been widely reported in the literature, but only two such studies were found to use any patient-reported QOL metrics. Among reports of excisional surgical procedures to treat lymphedema, only one study reported any assessment of QOL; however, this study did not report what instrument was used. In a study of 35 patients who received liposuction for the treatment of chronic lymphedema, QOL was evaluated using the Psychological General Well-Being Index (22 items) and the Hospital Anxiety and Depression Scale (14 items). Six months after liposuction, the patients’ total scores and general health scores in the Psychological Well-Being Index had improved since baseline measurements, but this change was not statistically significant. Scores on the Hospital Anxiety and Depression Scale decreased, although the change was not statistically significant, at six months after the surgery but returned to their baseline levels at 12 months after the surgery.

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Apr 10, 2019 | Posted by in General Surgery | Comments Off on Evidence-Based Outcomes
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