Surgical Treatment of Lymphedema: A Systematic Review and Meta-Analysis of Controlled Trials. Results of a Consensus Conference : Plastic and Reconstructive Surgery

Journal Logo

Advanced Search
Plastic Surgery Focus: Special Topics

Surgical Treatment of Lymphedema: A Systematic Review and Meta-Analysis of Controlled Trials. Results of a Consensus Conference

Chang, David W. M.D.; Dayan, Joseph M.D.; Greene, Arin K. M.D.; MacDonald, John K. M.A.; Masia, Jaume M.D.; Mehrara, Babak M.D.; Neligan, Peter C. M.D.; Nguyen, Dung M.D.

Author Information

Chicago, Ill.; New York, N.Y.; Boston, Mass.; London, Ontario, Canada; Barcelona, Spain; Seattle, Wash.; and Palo Alto, Calif.

From the University of Chicago Medicine and Biological Sciences; Memorial Sloan Kettering Cancer Center; Boston Children’s Hospital; University of Western Ontario; Sant Pau Hospital; University of Washington Medical Center; and Stanford University Medical Center.

Received for publication July 22, 2019; accepted August 28, 2020.

Related digital media are available in the full-text version of the article on www.PRSJournal.com.

Disclosure:None of the authors has a financial interest in any of the products or devices mentioned in this article.

David W. Chang, M.D., Section of Plastic and Reconstructive Surgery, Department of Surgery, University of Chicago Medicine and Biological Sciences, 5841 S. Maryland Avenue, MC 6035, Room J-641, Chicago, Ill. 60637, [email protected], Twitter: @UChicagoPRS, Instagram: @uchicagoprs

Plastic and Reconstructive Surgery 147(4):p 975-993, April 2021. | DOI: 10.1097/PRS.0000000000007783

Abstract

Background: 

The goal of this consensus conference, sponsored by the American Association of Plastic Surgeons, was to perform a systematic review and meta-analysis of controlled trials to examine both the benefits and risks of surgical treatment and surgical prevention of upper and lower extremity lymphedema.

Methods: 

The panel met in Boston for a 3-day, face-to-face meeting in July of 2017. After an exhaustive review of the existing literature, the authors created consensus recommendations using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Important directions for future research were also identified.

Results: 

There is evidence to support that lymphovenous anastomosis can be effective in reducing severity of lymphedema (grade 1C). There is evidence to support that vascular lymph node transplantation can be effective in reducing severity of lymphedema (grade 1B). Currently, there is no consensus on which procedure (lymphovenous bypass versus vascular lymph node transplantation) is more effective (grade 2C). A few studies show that prophylactic lymphovenous bypass in patients undergoing extremity lymphadenectomy may reduce the incidence of lymphedema (grade 1B). More studies with longer follow-up are required to confirm this benefit. Debulking procedures such as liposuction are effective in addressing a nonfluid component such as fat involving lymphedema (grade 1C). There is a role for liposuction combined with physiologic procedures although the timing of each procedure is currently unresolved (grade 1C).

Conclusions: 

Many studies seem to support some efficacy of lymphovenous bypass and vascular lymph node transplantation. Many studies show the important role of lymphedema therapy and other procedures such as liposuction and debulking. The management of lymphedema is a challenging field with many promising advances. However, many questions remain unanswered.

There is no cure for lymphedema and the optimal treatment is unknown. The purpose of this consensus conference was to develop evidence-based consensus statements and recommendations for surgical treatment and prevention of secondary lymphedema by performing a meta-analysis of randomized and nonrandomized clinical trials. The objectives included the following:

  1. To assess the effectiveness and safety of surgical treatment of lymphedema. Surgical treatments included lymphovenous bypass, vascular lymph node transplantation, and liposuction. Comparators included surgery (i.e., lymphovenous bypass, vascular lymph node transplantation, or liposuction) and compression therapy.
  2. To assess the effectiveness and safety of surgical treatment to prevent secondary lymphedema. Surgical treatments included lymphovenous bypass. The comparator was no surgery.
  3. To develop consensus statements and recommendations for surgical treatment of lymphedema.

PATIENTS AND METHODS

Consensus panel members were selected based on content and methodologic expertise. After considering the evidence, the consensus panel made recommendations regarding surgical treatment for patients with lymphedema and for surgical prevention of lymphedema in high-risk patients. The Grading of Recommendations, Assessment, Development and Evaluation framework was used to assess the overall quality of evidence and the strength of recommendations.1–3 Randomized trials start as high-quality evidence and nonrandomized studies start as low-quality evidence. Studies may be downgraded because of risk of bias, indirectness, heterogeneity, imprecision, and publication bias. The overall quality of evidence was determined after considering each of these elements and categorized as high, moderate, low, or very low quality. The Grading of Recommendations, Assessment, Development and Evaluation criteria were used to classify recommendations as strong (grade 1) or weak (grade 2).1 Recommendations were further classified as A, B, or C based on the quality of evidence informing the recommendation. Recommendations to use or not use an intervention are made on the basis of tradeoffs between benefits, risks, and burdens. If the benefits clearly outweigh risks and burdens, a strong recommendation is made. If the benefits, risks, and burdens are finely balanced, or uncertainty exists regarding the extent of benefits or risks, a weak recommendation is made.

Search Methods for Identification of Studies

The MEDLINE, Embase, and Cochrane Library databases were searched from inception to September 20, 2019. (See Appendix, Supplemental Digital Content 1, which shows the MEDLINE, Embase, and Cochrane Library search strategy, https://links.lww.com/PRS/E392.)

Inclusion Criteria

Randomized controlled trials and observational studies including prospective and retrospective cohort and case-control studies were considered for inclusion. Case series that reported on preoperative and postoperative outcomes of interest were also included.

Adult patients with secondary lymphedema (stages 1, 2, 3, or 4) were considered for inclusion. Surgical interventions for treatment of lymphedema included lymphovenous bypass (lymphaticovenular anastomosis), vascular lymph node transplantation, and liposuction. Studies that used combined procedures (e.g., vascular lymph node transplantation plus liposuction) were also considered for inclusion. The comparison group for surgical treatment studies included surgery and/or compression therapy. Eligible surgical comparators included lymphovenous bypass, vascular lymph node transplantation, and liposuction. Compression therapy could include graduated compression stockings, sequential compression devices, complex decongestive therapy, and physiotherapy.

We were also interested in the effectiveness and safety of surgical treatment to prevent lymphedema. Thus, studies that assessed surgical treatment for prevention of secondary lymphedema in high-risk patients were also considered for inclusion. Surgical interventions for the prevention of lymphedema included lymphaticovenular anastomosis (Lymphatic Microsurgical Preventive Healing Approach technique). The comparison group for surgical prevention studies included a no-surgery control group.

Exclusions

Studies published in abstract form only were excluded. Pediatric patients were excluded. Other types of surgery (e.g., excisional) and microsurgery (e.g., lymph vessel transplant) used for the treatment of lymphedema were excluded.

The primary outcomes for surgical treatment of lymphedema were reduction in limb volume (as a percentage or in milliliters) as measured by a validated system for limb volume measurement (e.g., truncated cone and water displacement) and reduction in limb circumference (as a percentage or in centimeters). The primary outcome for surgical prevention was the proportion of patients who developed lymphedema within 1 year of surgery. Secondary outcomes included surgical complications, ability to discontinue lymphedema interventions (e.g., pressure therapy), and patient-reported outcomes using validated questionnaires (e.g., quality of life).

The Cochrane risk-of-bias tool was used to assess the methodologic quality of randomized controlled trials.4 The methodologic quality of cohort and case control studies was assessed using the Newcastle-Ottawa Scale.5

Data Extraction and Analysis

Meta-analysis was conducted if the interventions, patient groups, and outcomes were sufficiently similar. We calculated the odds ratio and 95 percent confidence interval for dichotomous outcomes obtained from case-control and cohort studies. For dichotomous outcomes from randomized controlled trials, we calculated the risk ratio and 95 percent confidence interval. For continuous outcomes, we calculated the mean difference and 95 percent confidence interval. Heterogeneity was assessed using the chi-square test. A value of p = 0.10 was considered statistically significant. The I2 statistic was used to quantify heterogeneity.6 If statistically significant heterogeneity was detected, we visually inspected the forest plots for outliers and conducted sensitivity analyses to explore potential explanations for the heterogeneity. Meta-analysis was carried out using a random-effects model. We planned subgroup analysis by location of lymphedema (i.e., upper extremity lymphedema versus lower extremity lymphedema). We used the software Review Manager (computer program) Version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark).

RESULTS

Two hundred fifty-eight studies were excluded. Common reasons for exclusion included lack of usable data, no reporting of prespecified outcomes, ineligible surgical comparators or surgery, and abstract publications. Seventy-one articles reporting the results of 66 studies met the predefined inclusion criteria.7–77 (See Figure, Supplemental Digital Content 2, which shows the study flow chart, https://links.lww.com/PRS/E393.) Two studies were randomized controlled trials13,28; seven included studies were prospective cohort studies8,16,17,24,47,52,65; 14 retrospective cohort studies were included21,25,29,31,34,40,42,44,60–64,66; 43 included studies were case series; eight studies reported on liposuction and compression therapy for treatment of lymphedema7,15,20,26,36,43,57,74; 16 studies reported on lymphovenous bypass and compression therapy9–11,14,22,32,33,37–39,46,48,51,58,71,77; and 17 studies reported on vascular lymph node transplantation and compression therapy.23,24,27,35,45,49,50,53,56,59,67,69,70,72,73,75,76 Three case series reported on combination therapy.12,55,68 The characteristics of included studies are described in Table 1 and results are described in Table 2.7–78

Table 1. - Characteristics of Included Studies
Reference Methods No. of Participants/ISL/Campisi Stage Interventions Outcomes Follow-Up (mo)
Agarwal et al., 19987 Case series; grade 2 8 patients with LEL; compression stockings; physical therapy Liposuction; circumference (cm) Volume reduction (ml) 24
Akita et al., 20158 Prospective cohort 46 patients with LEL; I–II (ISL) LNT (n = 13); LVA (n = 33); compression stockings Lymphatic function; hospitalization days; complications; BMI; LEL index LNT, 15.1; LVA, 18.3
Aljaaly et al., 201960 Retrospective cohort 15 patients with UEL; II–IV (Cheng) Dorsal wrist: LNT (n = 7)
Volar wrist: LNT (n = 8)		 Circumferential difference (%); circumferential reduction rate (%); cellulitis 12
Asuncion et al., 201867 Case series 5 patients with UEL; 10 patients with LEL; stage NR LNT Circumferential difference (cm); cellulitis 12
Auba et al., 20129 Case series 4 patients with LEL; 6 patients with UEL; II–V (Campisi) LVA; compression garments Circumference (cm) 24
Ayestaray et al., 201310 Case series 20 patients with UEL; II–V (Campisi) LVA; compression garments Circumference (cm); volume reduction (%); use of compression 6
Ayestaray and Bekara, 201411 Case series 12 patients with UEL; 8 patients with LEL; II–V (Campisi) LVA; compression garments Circumference (cm); volume reduction (%); use of compression 12
Batista et al., 201712 Case series 38 with LEL; stage NR LNT; physiotherapy; compression stockings; liposuction (n = 15) Volume (ml) 48.6
Boccardo et al., 201113 RCT 49 patients with axillary dissection for breast cancer LVA, LYMPHA (n = 23); no surgery (n = 23) Postoperative lymphedema 18
Boccardo et al., 201414 Case series 7 patients with LEL; stage NR LVA; compression stockings Volume (ml); use of compression 12
Boyages et al., 201515 Case series 15 patients with UEL; 6 patients with LEL; II–III (ISL) Liposuction; compression garments Excess volume (ml); excess volume (%); PSFS functional/emotional domains; BMI 9
Brorson et al., 199818 Prospective cohort 20 patients with UEL; II (ISL) Liposuction plus CCT (n = 11); CCT (n = 9) Volume (ml); volume reduction (%); 12
Brorson et al., 200617 Prospective cohort 49 patients with UEL; II (ISL) Liposuction plus CCT (n = 35); CCT (n = 14) Volume (ml); volume reduction (%); QoL 12
Campisi et al., 201720 Case series 63 patients with UEL; 83 patients with LEL; IIB–IIIB (Campisi) Liposuction; compression bandages; compression garments Volume (ml); volume reduction (%) 12
Casabona et al., 200921 Retrospective cohort 72 patients with sentinel lymph node biopsy for breast cancer LVA, LYMPHA (n = 9); no surgery (n = 63) Postoperative lymphedema 9
Chang et al., 201768 Case series 49 patients with LEL Liposuction plus LVA Circumference (cm); volume (ml); cellulitis 12
Chen et al., 201622 Case series 13 patients with UEL; 8 patients with LEL; II–IV (Campisi) LVA (n = 18); LNT (n = 3); NR QoL; UEL index; LEL index 12
Cheng et al., 201223 Case series 7 patients with LEL; II–III (ISL) LNT Reduction rate (%); volume differentiation; LYMQOL; cellulitis 8.7
Cheng et al., 201324 Prospective cohort 20 patients with UEL; II (ISL) LNT (n = 10); physical therapy (n = 10) Infection; cellulitis; circumferential reduction; circumferential differentiation; BMI 39.1
Ciudad et al., 201725 Retrospective cohort 41 patients with UEL; 69 patients with LEL; II–III (ISL) S-LNT (n = 54); G-LNT (n = 20); O-RG-LNT (n = 19); L-RG-LNT (n = 17) Hospital stay; BMI; flap harvest time; complications S-LNT, 33; G-LNT, 31.4; O-RG, 26.6; RG-LNT, 25.6
Ciudad et al., 201761 Retrospective cohort 30 patients with UEL; 53 patients with LEL; II–III (ISL) S-LNT (n = 25) G-LNT (n = 13); Gas-LNT (n = 42); A-LNT (n = 1); I-LNT (n = 2) Circumferential reduction (%); infections; complications 32.8
Ciudad et al., 201769 Case series 4 patients with UEL; 3 patients with LEL; III (ISL) DG-LNT Circumferential reduction (%); infections; complications 9.7
Ciudad et al., 201970 Case series 6 patients with UEL; 10 patients with LEL; III (ISL) LNT plus modified radical reduction; conservative therapy Circumferential reduction (%); complications; infections; QoL LYMQOL 14.2
Damstra et al., 200926 Case series 37 patients with UEL; stage NR Liposuction; limb compression; compression garments Excess volume (ml) 12
De Brucker et al., 201627 Case series 25 patients with UEL; I–II (ISL) LNT; physiotherapy; compression garments QoL (ULL-27Q); discontinue physiotherapy 29
Dionyssiou et al., 201628 RCT 36 patients with UEL; II (ISL) LNT plus physiotherapy (n = 18); physiotherapy (n = 18); compression Excess volume (%); circumferential differentiation; infection; pain; heaviness; overall function; BMI 18
Engel et al., 201862 Retrospective cohort 124 patients with UEL; I–IV (Cheng) LVA (n = 27); LNT (n = 45); CDT (n = 52) Circumferential difference (%); reduction rate (%); cellulitis 19.1
Feldman et al., 201529 Retrospective cohort 32 patients with axillary dissection for breast cancer LVA, LYMPHA (n = 24); no surgery (n = 8) Postoperative lymphedema; complications 6
Gentileschi et al., 201771 Case series 16 patients with UEL; IIa, IIb (ISL) LVA; compression garments Circumference difference (cm); QoL LYMQOL 12.13
Gharb et al., 201131 Retrospective cohort 21 patients with UEL; II (ISL) G-LNT (n = 11); I-LNT (n = 10); limb elevation; compression garments; decongestive treatment Circumference (cm); complications; cellulitis; seroma; necrosis; required further procedures G-LNT, 46; I-LNT, 40
Gong-Kang et al., 198132 Case series 11 patients with LEL; 2 patients with UEL; stage NR LVA; bandages; antibiotics Circumference (cm); cellulitis 6
Huang et al., 198533 Case series 91 patients with LEL; stage NR LVA; elastic bandages; limb elevation Excess volume (ml); excess volume (%); cellulitis 24
Granzow et al., 201434 Retrospective cohort; stage NR 26 patients with UEL or LEL; LNT (n = 8); compression garments; lymphedema therapy Liposuction (n = 10); LVA (n = 8) Excess volume (ml); cellulitis; need for compression or lymphedema therapy; clinical improvement at 24 mo; complications 25
Gratzon et al., 201735 Case series 50 patients with UEL; I–II (ISL) LNT; CDT Volume reduction (%); CDT use; cellulitis; QoL LYMQOL; complications
Gustafsson et al., 201872 Case series 35 patients with LEL; I–IV (Cheng) LNT; CDT Circumferential difference; cellulitis 30.3
Hahamoff et al., 201763 Retrospective cohort 87 patients with axillary dissection for breast cancer LVA, LYMPHA (n = 8); no surgery (n = 10) Postoperative lymphedema 15
Ho et al., 201973 Case series 76 patients with UEL (n = 30) or LEL (n = 46); I–IV (Cheng) LNT; compression Circumferential difference; excess volume (%) 50.1
Hoffner et al., 201736 Case series 60 patients with UEL; I–III (ISL) Liposuction plus CCT Excess volume (ml); QoL: SF-36 12
Hoffner et al., 201874 Case series 105 patients with UEL; stage NR Liposuction plus CCT; compression garments Excess volume (ml) 60
Ipsen et al., 198837 Case series 9 patients with LEL; 1 patient with UEL; stage NR LVA; none Circumference (cm); subjective symptoms 12
Ito et al., 201638 Case series 5 patients with LEL; I–II (Cheng) LVA; CDT; Compression garments Circumferential differentiation; cellulitis; compression garment use; BMI
Koshima et al., 199639 Case series 6 patients with UEL; 8 patients with LEL; moderate/severe LVA; NR Excess circumference (cm) UEL, 25.5; LEL, 23.4
Koshima et al., 200040 Restrospective cohort 24 patients with UEL; severe LVA plus pressure (n = 12); pressure (n = 12) Circumferential differentiation; circumference reduction 12
Koshima et al., 200342 Retrospective cohort 25 patients with LEL; stage NR LVA plus pressure (n = 13); pressure (n = 12) Circumferential differentiation; circumference reduction 55
Lamprou et al., 201743 Case series 41 patients with LEL; III end-stage Liposuction plus compression Volume difference 24
Lee et al., 201144 Retrospective cohort 32 patients with LEL; I–III (ISL) LVA (n = 19); LNT (n = 13); CDT Clinical improvement at 12, 24, and 48 mo 48
Leppapuska et al., 201964 Retrospective cohort 48 patients with UEL; I–II LNT plus liposuction (n = 21); LNT (n = 27); compression garments Excess volume (ml); complications; use of compression garments 48.9
Lin et al., 200945 Case series 13 patients with UEL; stage NR G-LNT; CDT Circumference reduction (%);Circumference reduction (cm) 56.3
Lin et al., 201965 Prospective cohort 180 patients with UEL; P1–P3, T4–T6 (TLS) LNT (n = 100); CDT (n = 80) Circumferential difference (%);QoL LYMQOL; cellulitis; lymphedema knowledge scale; PHCA seeking 6
Maruccia et al., 201966 Retrospective cohort 39 patients with UEL; II–III (ISL) LNT plus scar release (n = 18); LNT (n = 21) Reduction rate (%);Infectious episodes LNT plus scar, 29; LNT, 32
Matsubara et al., 200646 Case series 9 patients with LEL; II (ISL) LVA; physiotherapy; limb elevation; manual lymph drainage; pneumatic compression; compression stocking Circumference reduction (%);Circumference reduction (cm); cellulitis 68
Montag et al., 201975 Case series 24 patients with UEL; II–III (ISL) LNT; CDT; Compression Volume reduction (cm); volume reduction (%); cellulitis 18
Morotti et al., 201347 Prospective cohort 15 patients with vulvar cancer undergoing ILND LVA, LYMPHA (n = 8); no surgery (n = 7) Postoperative lymphedema; Complications 16.7
Mousavi et al., 201976 Case series 24 patients with UEL; stage NR LNT; compression garments Circumferential difference; cellulitis 12
Narushima et al., 201048 Case series 12 patients with LEL; 2 patients with UEL; II–IV (Campisi) LVA; compression garments Circumference reduction(cm) 8.9
Nguyen et al., 201749 Case series 19 patients with UEL; 24 patients with LEL; III–V (Chang) O-LNT; CDT Volume reduction (%);subjective improvement; complications; cellulitis 14
Nicoli et al., 201550 Case series 10 patients with UEL; II (ISL) S-LNT or G-LNT plus liposuction; arm elevation; compression garments Circumference (cm) 6
O’Brien et al., 197951 Case series 37 patients with UEL; Stage NR LVA; elevation; elastic stockings; pumping Limb volume; subjective improvement; cellulitis 19.9
Orefice et al., 198852 Prospective cohort 114 patients undergoing ilioinguinal dissection for breast cancer LVA (n = 30); no surgery (n = 84) Postoperative lymphedema; hospital stay; complications 29
Patel et al., 201553 Case series 15 patients with UEL; 10 patients with LEL; Late-stage G-LNT (n = 13) or SLNT (n = 12) Excess circumference (%); cellulitis; LYMQOL UEL, 25.4; LEL, 16.1
Qi et al., 200955 Case series 11 patients with UEL LNT plus liposuction; elastic bandage; compression garment Circumference (cm); cellulitis 26
Saaristo et al., 201256 Case series 9 patients with UEL; stage NR G-LNT; manual drainage; elastic compression dressing Circumference (cm) 6
Schaverien et al., 201257 Case series 12 patients with UEL; stage NR Liposuction; antibiotics; pressure garments Volume (ml); anxiety; depression; 12
Shi et al., 201558 Case series 11 patients with UEL; moderate/severe LVA; NR Circumference (cm) 38.4
Viitanen et al., 201359 Case series 19 patients with UEL; Stage NR LNT; physiotherapy; elastic compression Circumference (cm); transport index 27.5
Winters et al., 201777 Case series 29 patients with UEL; Ib-IIa (Campisi) LVA; compression garment Excess volume (%);Qol: LYMQOL 12
ISL, International Society of Lymphology; LEL, lower extremity lymphedema; LNT, lymph node transfer; LVA, lymphaticovenular anastomosis; UEL, upper extremity lymphedema; RCT, randomized controlled trial; CCT, controlled compression therapy; QoL, quality of life; ULL-27Q, Upper Limb Lymphedema-27 Questionnaire; LYMQOL, Lymphoedema Quality-of-Life; PSFS, Patient-Specific Functional Scale; BMI, body mass index; S-LNT, supraclavicular lymph node transfer; G-LNT, groin lymph node transfer; O-RG-LNT, open right gastroepiploic lymph node transfer; L-RG-LNT, laparoscopic right gastroepiploic lymph node transfer; Gas-LNT, gastroepiploic lymph node transfer; A-LNT, appendicular lymph node transfer; DG-LNT, double gastroepiploic lymph node transfer; I-LNT, ileocecal lymph node transfer; I-LNT-HP, inguinal lymph nodes with hilar perforators; SF-36, 36-Item Short-Form Health Survey; ILND, inguinofemoral lymph node dissection; O-LNT, omental lymph node transfer; SLNT, submental lymph node transfer; SEKI-LVA, superior edge of knee incision LVA; SE-LVA, side to-end LVA; NR, not reported; CDT, complex decongestive therapy; LDB, leg dermal backflow; ADB, arm dermal backflow; PHCA, professional health care advice.

Table 2. - Results and Methodologic Quality of Included Studies
Reference No. of Patients/Intervention Volume Reduction [MD (range) or OR (95% CI)] Circumference Reduction [MD (range) or OR (95% CI)] Complications QoL
Agarwal et al., 19987 8 with LEL; liposuction 2736.6 ml (1767–3706.2 ml) 5 cm (−0.58 to 10.58 cm) Hyperpigmentation (n = 2); cellulitis (n = 1) NR; NR
Akita et al., 20158 46 with LEL; LNT (n = 13); LVA (n = 33) NR NR LNT (n = 3); LVA (n = 0); skin paddle congestion (n = 3); venus thrombosis (n = 1) NR
Aljaaly et al., 201960 15 with UEL; dorsal LNT (n = 7); volar LNT (n = 8) NR 12.1% (−24.05 to 48.25%) NR 2.0 (1.31–2.69)
Asuncion et al., 201867 5 with UEL; 10 with LEL; LNT NR 3.2 ± 0.4 cm NR 4.9 ± 0.3
Auba et al., 20129 4 with LEL; 6 with UEL; LVA NR 0.70 cm (−4.36 to 5.76 cm) None NR
Ayestaray et al., 201310 20 with UEL; LVA 22.8% (7.2–48.8%) 4.2 cm (2.39–6.01 cm) Partial skin ulceration (n = 1) 18/20 had improved QoL at 6 mo
Ayestaray and Bekara, 201411 12 with UEL; 8 with LEL; LVA 504 ml (32.06–975.94 ml); 22.9% (4.9–46.3%) 5 cm (0.71–9.29 cm); 13.1% (3.5–28.1) Hypertrophic scar (n = 1); 19/20 had improved QoL at 12 mo
Batista et al., 201712 38 with LEL; LNT 900 ml (−104.5 to 1904.5 ml) NR Complications (n = 11); seroma; hematoma; wound dehiscence (n = 1) NR
Boccardo et al., 201113 49 with axillary dissection; LVA (n = 23); no surgery (n = 23) NR NR Lymphedema; OR, 0.10 (0.01–0.93); LVA, 1/23; no surgery, 7/23 NR
Boccardo et al., 201414 7 with LEL; LVA 1858.6 ml (1721.5–1995.7 ml) NR None NR
Boyages et al., 201515 15 with UEL; 6 with LEL; liposuction UEL, 40.6% (31.89–49.31%); LEL, 43% (25.55–60.45%) NR None Improved; PSFS
Brorson et al., 199818 20 with UEL; liposuction plus CCT (n = 11); CCT (n = 9) 61% (38.53–83.47%); −968 ml (−1335.14 to −600.86 ml) NR None NR
Brorson et al., 200617 49 with UEL; liposuction plus CCT (n = 35); CCT (n = 14) 66% (47.29–84.71%); −838 ml (−1166.53 to −509.47 ml) NR None Improved ROM; symptoms; ADL; NHP; PGWB; HAD
Campisi et al., 201720 63 with UEL; 83 with LEL; liposuction UEL, 17.51% (14.58–20.44%); LEL, 18.64% (15.96–21.32%); UEL, 261.32 ml (152.0–370.44 ml) NR None NR
Casabona et al., 200921 72 with sentinel lymph node biopsy; LVA, LYMPHA (n = 9); no surgery (n = 63) NR NR Lymphedema; LVA, 0/9; no surgery, 0/63 NR
Chang et al., 201768 49 with LEL; liposuction plus LVA 1840 ml (1389.98–2290.02 ml) 3.34 cm (2.59–4.09 cm) NR NR
Chen et al., 201622 13 with UEL; 8 with LEL; LVA (n = 18); LNT (n = 3) NR NR Flap congestion (n = 1) MD, 12.80 (7.6–18.00)
Cheng et al., 201223 7 with LEL; LNT NR NR Flap congestion (n = 1) MD, 5.3 (4.60–6.00)
Cheng et al., 201324 20 with UEL; LNT (n = 10); physical therapy (n = 10) NR 32.1% (8.39–55.81%) None NR
Ciudad et al., 201725 41 with UEL; 69 with LEL; S-LNT (n = 54); G-LNT (n = 20); O-RG-LNT (n = 19); L-RG-LNT (n = 17) NR NR S-LNT, hematoma (n = 1); S-LNT, lymphatic leakage (n = 1); G-LNT, lymphatic leakage (n = 1); O-RG-LNT, none; L-RG-LNT, none NR
Ciudad et al., 201761 30 with UEL; 53 with LEL; S-LNT (n = 25); G-LNT (n = 13); Gas-LNT (n = 42); A-LNT (n = 1); I-LNT (n = 2) NR; −2.3% (−10.06 to 5.46%); S-LNT vs. Gas-LNT; −4.2% (−10.91 to 2.51%); G-LNT vs. Gas-LNT; −1.9% (−7.52 to 3.72%) S-LNT vs. G-LNT Delayed wound healing; lymphatic leak; flap infection; venous congestion; wound infection; flap loss; partial loss of skin graft; hematoma NR
Ciudad et al., 201970 4 with UEL; 3 with LEL; LNT NR 43.7 ± 2.5% None NR
Ciudad et al., 201970 6 with UEL; LNT NR 74.5 ± 6.9% Numbness (n = 3); hyperesthesia (n = 1); seroma (n = 1); lymphatic leakage (n = 1) −4.3 (−5.34 to −3.26)
Damstra et al., 200926 37 with UEL; liposuction 1548 ml (1338.11–1757.89 ml) NR None NR
De Brucker et al., 201627 25 with UEL; LNT NR NR Seroma (n = 3); donor-site wound breakdown (n = 4); axilla infection and flap loss (n = 1) MD, 18 (8.56–27.44)
Dionyssiou et al., 201628 36 with UEL; LNT (n = 18); physiotherapy (n = 18) −15% (−22.03 to −7.97%) NR Mild discomfort donor side lower limb (n = 2); lymphorrhea at donor site (n = 2) Improved pain, heaviness, overall function
Engel et al., 201862 124 with UEL; LVA (n = 27); LNT (n = 45); CDT (n = 52) NR LVA vs. CDT, 5.2% (3.96–6.44%); LNT vs. CDT, 24.2% (21.71–26.69%); LNT vs. LVA, 15.7% (12.73–18.67%) NR NR
Feldman et al., 201529 32 with axillary dissection; LVA (n = 24); no surgery (n = 8) NR NR Lymphedema; OR, 0.14 (0.02–0.90); LVA, 3/24; no surgery, 4/8; no complications NR
Gentileschi et al., 201771 16 with UEL; LVA NR 1.80 (0.90–2.70) NR Improved QoL; preoperatively, 5.5; postoperatively, 7.9
Gharb et al., 201131 21 with UEL; G-LNT (n = 11); I-LNT (n = 10) NR NR G-LNT, cellulitis (n = 2); seroma (n = 2); I-LNT, cellulitis (n = 1) NR
Gong-Kang et al., 198132 11 with LEL; 2 with UEL; LVA NR 6.2 cm (range, 2.5–11 cm) Cellulitis (n = 1) NR
Huang et al., 198533 91 with LEL; LVA 703 ± 850 ml; 59.2 ± 29.5% 6.4 cm (range, 1–17 cm) Cellulitis (n = 19) NR
Granzow et al., 201434 26 with UEL or LEL Liposuction arm, 111% (98–120%) NR Liposuction, none; LVA, pulmonary embolus (n = 1) NR
Liposuction (n = 10); LVA (n = 8); LNT (n = 8) Liposuction leg, 86% (81–97%); LVA, NR; LNT, NR Sciatic neurapraxia (n = 1); LNT, seroma (n = 1); delayed flap healing (n = 2)
Gratzon et al., 201735 50 with UEL; LNT 58.68% NR Seroma (n = 6); wound dehiscence (n = 4); surgical-site infection (n = 9); hematoma (n = 1); nonhealing wound (n = 1); bleeding (n = 1) Improved QoL; function; appearance; symptoms; mood; pain; heaviness
Gustafsson et al., 201872 35 with LEL NR; LNT 19.8 ± 9.2 Cellulitis NR
Hahamoff et al., 201763 18 with axillary dissection; LVA (n = 8); no surgery (n = 10) NR NR Lymphedema; OR, 0.10 (0.01–0.93); LVA, 0/8; no surgery, 4/10 NR
Ho et al., 201973 30 with UEL; 46 with LEL; LNT 8.9% (7.12–10.68%); 13% (11.89–14.11%) 14% (6.47–21.53%); 20.8% (15.00–26.60%) NR NR
Hoffner et al., 201736 60 with UEL; liposuction 1578 ml (1419.33–1736.67 ml) NR None Improved; physical functioning; bodily pain; social functioning; mental health; vitality; PCS; MCS
Hoffner et al., 201874 105 with UEL 1761 ml (1624.94–1897.06 ml) NR None NR
Ipsen et al., 198837 9 with LEL; 1 with UEL; LVA NR 2.2 cm (−2.47 to 6.87 cm) Erysipelas (n = 2); hypoplasia (n = 1); thrombophlebitis (n = 1) NR
Ito et al., 201638 5 with LEL; LVA NR 63.8 ± 20.2% NR NR
Koshima et al., 199639 6 with UEL; 8 with LEL; LVA NR 3.6 cm (0.16–7.04 cm); UEL, 5.3 cm (3.12–7.48 cm); LEL, 2.6 cm (−3.63 to 8.83 cm) NR NR
Koshima et al., 200040 24 with UEL; LVA (n = 12); pressure (n = 12) NR LVA, 4.1 cm (47.3%); pressure, 0.8 cm (11.7%) NR NR
Koshima et al., 200342 25 with LEL; LVA (n = 13); pressure (n = 12) NR LVA: 4.7 cm, 55.6%; pressure, 0.6 cm (8%) NR NR
Lamprou et al., 201743 41 with LEL; liposuction 101%; −38 ml (−1151 to 1135 ml) NR Decubitus ulcer (n = 1) NR
Lee et al., 201144 32 with LEL; LVA (n = 19); LNT (n = 13) NR NR; NR LVA, none; LNT, transient lymphedema in donor limb (n = 3)
Leppapuska et al., 201964 48 with UEL; LNT plus liposuction (n = 21); LNT (n = 27) −201.4 ml (−331.55 to −71.25 ml) NR Postoperative numbness; wound infection; skin necrosis; seroma NR
Lin et al., 200945 13 with UEL; G-LNT NR 3.6 cm (−0.47 to 7.67 cm); 50.6% (35.79–65.41%) Wound infection (n = 1); venous congestion (n = 1) NR
Lin et al., 201965 180 with UEL; LNT (n = 100); CDT (n =80) NR 3.7 cm (2.59–4.81 cm) NR NR
Maruccia et al., 201966 39 with UEL; LNT plus scar release (n = 18); LNT (n = 21) NR LNT plus scar, 51.3 ± 6.3%; LNT, 50.2 ± 5.5% NR NR
Matsubara et al., 200646 9 with LEL; LVA; NR 3.44 cm (0.56–6.32 cm); 37.7% (2.04–73.36%) None NR
Montag et al., 201975 24 with UEL; LNT 20.1 ± 44.89% NR Cellulitis (n = 3) NR
Morotti et al., 201347 15 with vulvar cancer had ILND; LVA, LYMPHA (n = 8); no surgery (n = 7) NR NR Lymphedema; OR, 0.36 (0.02–5.11); LVA, 1/8; no surgery, 2/7; LVA, wound dehiscence (n = 1), lymphocele (n = 1), lymphangitis (n = 1); no surgery, DVT (n = 1); lymphangitis (n = 1) NR
Mousavi et al., 201976 24 with UEL; LNT NR 20.9% (14.24–27.56%) NR NR
Narushima et al., 201048 12 with LEL; 2 with UEL; LVA NR 3.6 cm (1.56–5.64 cm) Dehiscence (n = 1) NR
Nguyen et al., 201749 19 with UEL; 24 with LEL; O-LNT 22% (−35 to 74%) NR Flap loss (n = 1); cellulitis (n = 2); hematoma (n = 2); seroma (n = 2) NR
Nicoli et al., 201550 10 with UEL; S-LNT; or G-LNT plus liposuction NR 2.4 cm (1.00–3.80 cm) None NR
O’Brien et al., 197951 37 with UEL; LVA 15% NR Cellulitis (n = 9) NR
Orefice et al., 198852 114 had ilioinguinal dissection; LVA (n = 30); no surgery (n = 84) NR NR Lymphedema; OR, 0.15 (0.05–0.43); LVA, 7/23; No surgery, 39/52; LVA, lymphocele (n = 7), skin necrosis (n = 5), wound infection (n = 3); no surgery, lymphocele (n = 53), skin necrosis (n = 23), wound infection (n = 3) NR
Patel et al., 201553 15 with UEL; 10 with LEL; G-LNT (n = 13); S-LNT (n = 12) NR UEL, 6% (2.58–9.42%); LEL, 10.1% (−1.87 to 22.07%) NR UEL: MD, 3.7 (3.26–4.14)
LEL: MD, 4.1 (3.48–5.82)
Qi et al., 200955 11 with UEL; LNT plus liposuction NR 6.23 cm (4.77–7.69 cm) Partial wound disruption (n = 2); numbness in fingers (n = 2); dorsal foot edema of donor leg (n = 1); slight edema at medial side of knee (n = 1) NR
Saaristo et al., 201256 9 with UEL; G-LNT; 12 with UEL; liposuction NR; 101% (69–148%); 1381 ml (489–1971 ml) 1.00 cm (−1.18 to 3.18 cm); NR Seroma (n = 3); delayed wound closure (n = 2); none NR; improved anxiety and depression
Seki et al., 201578 30 with LEL; LVA (n = 15); EK-LVA (n = 15) NR NR NR NR
Shi et al., 201558 11 with UEL; LVA NR 3.00 cm (−0.01 to 6.01 cm) Delayed healing (n = 1) NR
Viitanen et al., 201359 19 with UEL; LNT NR 1.20 cm (−0.01 to 2.41 cm) Donor-site infection (n = 4); seroma (n = 5); delayed wound closure (n = 5) NR
Winters et al., 201777 29 with UEL; LVA 234 ml (43.74–424.26 ml) NR None −1.71 (−2.32 to −1.10)
MD, mean difference; QoL, quality of life; LEL, lower extremity lymphedema; NR, not reported; LNT, lymph node transfer; LVA, lymphaticovenular anastomosis; UEL, upper extremity lymphedema; PSFS, Patient-Specific Functional Scale; CCT, controlled compression therapy; ROM, range of motion; ADL. activities of daily living; NHP, Nottingham Health Profile; PGWB, Psychological General Well-Being Index; HAD, Hospital Anxiety Depression Test; LYMQOL, Lymphoedema Quality-of-Life; BMI, body mass index; S-LNT, supraclavicular lymph node transfer; G-LNT, groin lymph node transfer; O-RG-LNT, open right gastroepiploic lymph node transfer; L-RGLNT, laparoscopic right gastroepiploic lymph node transfer; Gas-LNT, gastroepiploic lymph node transfer; A-LNT, appendicular lymph node transfer; I-LNT, ileocecal lymph node transfer; I-LNT-HP, inguinal lymph nodes with hilar perforators; SF-36, 36-Item Short-Form Health Survey; ILND, inguinofemoral lymph node dissection; O-LNT, omental lymph node transfer; SLNT, submental lymph node transfer; SEKI-LVA, superior edge of knee incision; SE-LVA, side to-end LVA; CDT, complex decongestive therapy; LDB, leg dermal backflow; ADB, arm dermal backflow; EK-LVA, XXX lymphaticovenular anastomosis.

The risk of bias assessment is summarized. (See Figure, Supplemental Digital Content 3, which shows the risk of bias assessment, https://links.lww.com/PRS/E394.) The quality assessment of the cohort and case-control studies (Newcastle-Ottawa scale) is reported in Table 3.

Table 3. - Quality Assessment of Cohort and Case-Control Studies (Newcastle-Ottawa Scale)
Reference Selection Comparability Outcomes
Akita et al., 20158 4 0 3
Aljaaly et al., 201960 4 0 2
Brorson et al., 199816 4 1 3
Brorson et al., 200617 4 0 3
Casabona et al., 200921 3 0 2
Cheng et al., 201324 4 0 3
Ciudad et al., 201725 4 0 3
Ciudad et al., 201761 4 0 3
Engel et al., 201862 4 0 2
Feldman et al., 201529 3 0 2
Gharb et al., 201131 4 0 2
Granzow et al., 201434 4 0 2
Hahamoff et al., 201963 4 0 3
Koshima et al., 200040 4 0 2
Koshima et al., 200342 4 0 2
Lee et al., 201144 4 0 2
Leppapuska et al., 201964 4 0 3
Lin et al., 201965 4 1 2
Maruccia et al., 201966 4 0 3
Morotti et al., 201347 3 0 2
Orefice et al., 198852 4 0 2

Liposuction

A pooled analysis of two studies (n = 48 patients) showed that the combination of liposuction and controlled compression therapy was significantly superior to controlled compression therapy for reducing edema volume in patients with stage II (International Society of Lymphology) upper extremity lymphedema.16,17 On average, patients who had liposuction and controlled compression therapy had a 63.95 percent greater reduction in volume compared to patients who had controlled compression therapy only (95 percent CI, 49.57 to 78.33; very low-quality evidence). [See Figure, Supplemental Digital Content 4, which shows the liposuction versus controlled compression therapy; outcome = reduction in limb volume (percent), https://links.lww.com/PRS/E395.] Similarly, a pooled analysis of two studies (n = 69 patients) showed that the combination of liposuction and controlled compression therapy was significantly superior to controlled compression therapy for reducing the volume of edema (in milliliters) in patients with stage II (International Society of Lymphology) upper extremity lymphedema. On average, patients who had liposuction and controlled compression therapy reduced their lymphedema volume by 895 ml more than controlled compression therapy patients (95 percent CI, −1140.63 to 650.98; very low-quality evidence). [See Figure, Supplemental Digital Content 5, which shows the liposuction versus controlled compression therapy; outcome = percentage reduction in limb volume (in milliliters), https://links.lww.com/PRS/E396.]

Two case series (163 patients) reported on liposuction for reducing percentage excess limb volume in patients with stage II to III (International Society of Lymphology) lymphedema.15,20 Liposuction combined with compression therapy significantly reduced excess limb volume by an average 26.59 percent (95 percent CI, 18.64 to 34.54; very low-quality evidence). [See Figure, Supplemental Digital Content 6, which shows the liposuction; reduction in excess limb volume (percentage), https://links.lww.com/PRS/E397.] This benefit was significant for patients with upper extremity lymphedema (mean difference, 28.68; 95 percent CI, 6.06 to 51.29) and lower extremity lymphedema (mean difference, 29.23; 95 percent CI, 5.56 to 52.90). A high degree of heterogeneity was detected (I2 = 91 percent), which likely reflects differences in surgical technique, patients, and lymphedema. Six case series (294 patients) reported on liposuction for reducing excess limb volume (in milliliters) in patients with stage I to III (International Society of Lymphology) upper extremity lymphedema or lower extremity lymphedema.7,17,26,36,68,74 Liposuction combined with compression therapy significantly reduced excess limb volume by an average 1702.44 ml (95 percent CI, 1558.64 to 1846.23 ml). [See Figure, Supplemental Digital Content 7, which shows the liposuction; reduction in volume (in milliliters), https://links.lww.com/PRS/E398.] This benefit was significant for patients with upper extremity lymphedema (mean difference, 1666.04 ml; 95 percent CI, 1543.97 to 1788.10 ml) and lower extremity lymphedema (mean difference, 2181.22 ml; 95 percent CI, 1328.00 to 3034.44 ml). A moderate degree of heterogeneity was detected (I2 = 51 percent). One case series of 10 patients with upper extremity lymphedema and lower extremity lymphedema reported on preoperative and postoperative cellulitis.34 Cellulitis was significantly reduced after treatment with liposuction and compression therapy. The incidence of severe cellulitis before surgery was 70 percent (seven of 10) compared to 10 percent (one of 10) after surgery (OR, 21.00; 95 percent CI, 1.78 to 248.10).

Lymphovenous Bypass

Three studies (102 patients) compared lymphovenous bypass to pressure therapy in patients with upper extremity lymphedema or lower extremity lymphedema.40,42,62 Two studies reported significantly higher circumference reduction in lymphovenous bypass patients compared to patients who received compression alone. Koshima et al. reported that leg circumference decreased by a mean 4.7 cm in the lymphovenous bypass group compared to 0.6 cm in the compression therapy group (p < 0.05). This corresponded to a 55.6 percent reduction in leg circumference in the lymphovenous bypass group compared to an 8 percent reduction in the compression therapy group.42 Koshima et al. reported that arm circumference decreased by a mean 4.1 cm in the lymphovenous bypass group compared to 0.8 cm in the compression therapy group (p < 0.05). This corresponded to a 47.3 percent reduction in arm circumference in the lymphovenous bypass group compared to a 11.7 percent reduction in the compression therapy group.40 Engel et al. reported a 17.3 percent reduction in arm circumference in the lymphovenous bypass group compared to a 9.8 percent reduction in the complex decongestive therapy group (mean difference, 7.50 percent; 95 percent CI, 4.89 to 10.11 percent; p < 0.00001).62

Ten studies (134 patients) reported on lymphovenous bypass for reducing limb circumference in patients with stage II to V (Campisi or International Society of Lymphology) upper extremity lymphedema or lower extremity lymphedema.9–11,37,39,40,42,46,48,58 Lymphovenous bypass combined with compression garments significantly reduced circumference by an average of 3.8 cm (95 percent CI, 2.93 to 4.67 cm; p < 0.00001; very low-quality evidence) (Fig. 1) after surgery. Two studies39,71 also reported a significantly reduced circumference difference after lymphovenous bypass combined with compression garments in 29 patients (mean difference, 3.26 cm; 95 percent CI, 0.44 to 6.08 cm; p = 0.02). This benefit was significant for patients with upper extremity lymphedema (six patients) (mean difference, 5.30 cm; 95 percent CI, 3.12 to 7.48 cm; p < 0.00001) and lower extremity lymphedema (23 patients) (mean difference, 1.82 cm; 95 percent CI, 0.92 to 2.71 cm; p < 0.0001). Similarly, Ito et al.38 found no significant difference in postoperative excess circumference reduction in five patients with lower extremity lymphedema who received lymphovenous bypass with compression garments (mean difference, 3.50 percent; 95 percent CI, −6.89 to 13.89 percent; p = 0.51). Ayestaray and Bekara11 reported a significant reduction in limb volume of 504 ml (95 percent CI, 32.06 to 975.94 ml; p < 0.05) after lymphovenous bypass combined with compression garment use in 20 patients with upper and lower extremity lymphedema. Similarly, Boccardo et al.14 reported a large and significant excess volume reduction of 1858.6 ml (95 percent CI, 1721.48 to 1995.72 ml; p < 0.00001) after lymphovenous bypass combined with compression garment use in seven patients with lower extremity lymphedema. Winters et al.77 reported a significant volume reduction of 234 ml (95 percent CI, 43.74 to 424.26 ml; p = 0.02) after lymphovenous bypass and compression garments in 29 patients with upper extremity lymphedema. Five studies (81 patients) reported on the proportion of patients who were able to discontinue compression garment use postoperatively.10,11,14,38,77 Although 81 of 81 of patients (100 percent) used compression garments before lymphovenous bypass, 39 of 81 (48 percent) were able to stop using compression garments after surgery (OR, 0.03; 95 percent CI, 0.01 to 0.11; p < 0.00001).

F1
Fig. 1.:
Lymphovenous bypass; reduction in circumference (in centimeters).

Three case series (14 lower extremity lymphedema and 23 upper extremity lymphedema patients) reported on the mean number of cellulitis infections per year before and after surgery.38,46,62 Mean cellulitis infections were significantly reduced after treatment with lymphovenous bypass and compression therapy (mean difference, 2.57; 95 percent CI, 1.75 to 3.38). Three case series (141 upper or lower extremity lymphedema patients) reported on preoperative and postoperative cellulitis.32,33,51 Cellulitis was significantly reduced after lymphovenous bypass and compression therapy. The incidence of cellulitis before surgery was 67 percent (95 of 141) compared to 21 percent (29 of 141) after surgery (OR, 9.11; 95 percent CI, 2.31 to 35.97). A high degree of heterogeneity was detected (I2 = 75 percent), which could reflect differences in surgical technique, patients, and lymphedema stage.

Vascularized Lymph Node Transfer

Four studies (300 patients) reported usable data for the comparison of vascularized lymph node transfer versus physiotherapy.24,28,62,65 Dionyssiou et al.28 reported significantly reduced percentage excess arm volume in patients who had vascularized lymph node transfer and physiotherapy compared to physiotherapy alone (mean difference, −15.00 ml; 95 percent CI, −22.0 to −7.97 ml; p < 0.001). Similarly, a pooled analysis of two studies showed a significant improvement in both circumferential differentiation (mean difference, 3.99 cm; 95 percent CI, 2.62 to 5.32 cm; 200 patients),24,65 and circumferential reduction (mean difference, 24.29 percent; 95 percent CI, 21.81 to 26.76 percent; 84 patients),24,62 in patients who underwent vascularized lymph node transfer and physiotherapy compared to physiotherapy alone. A pooled analysis of two studies (56 patients) shows a nonsignificant reduction in the number of infections per year in patients who underwent vascularized lymph node transfer and physiotherapy compared to physiotherapy alone (mean difference, −0.48; 95 percent CI, −1.25 to 0.29; p = 0.22). Patients who underwent vascularized lymph node transfer and physiotherapy had significantly reduced pain (36 patients) (mean difference, −4.00; 95 percent CI, −5.09 to −2.91; p < 0.00001) and heaviness (36 patients) (mean difference, −4.17; 95 percent CI, −5.62 to −2.72; p < 0.00001) and significantly improved overall function (36 patients) (mean difference, −3.39; 95 percent CI, −5.08 to −1.70; p < 0.00001) compared to physiotherapy patients.

Five studies (72 patients) reported on vascularized lymph node transfer for reducing limb circumference in stage II (International Society of Lymphology) upper extremity lymphedema.31,45,50,56,59 Vascularized lymph node transfer combined with compression garments and complex decongestive therapy significantly reduced circumference by an average of 1.64 cm (95 percent CI, 0.87 to 2.42 cm; p < 0.0001; very low-quality evidence) (Fig. 2). Two studies (28 patients with upper extremity lymphedema) reported on circumference difference.56,59 Circumference difference was significantly lower after vascularized lymph node transfer combined with compression garments and complex decongestive therapy (mean difference, 1.15 cm; 95 percent CI, 0.09 to 2.21 cm; p = 0.03). Two studies53,73 reported on percentage excess volume reduction after vascularized lymph node transfer in 101 patients. Vascularized lymph node transfer significantly reduced excess limb volume by an average 9.60 percent (95 percent CI, 5.98 to 13.22 percent; p < 0.00001). This benefit was significant for patients with upper extremity lymphedema (45 patients) (mean difference, 7.83 percent; 95 percent CI, 5.09 to 10.57 percent; p < 0.00001) and lower extremity lymphedema (56 patients) (mean difference, 12.98 percent; 95 percent CI, 11.87 to 14.08 percent; p < 0.00001). Batista et al.12 reported on preoperative and postoperative volume (in milliliters) in 15 lower extremity lymphedema patients. Vascularized lymph node transfer combined with physiotherapy and compression stockings reduced leg volume by an average of 900.0 ml (95 percent CI, −104.50 to 1904.50 ml; p = 0.08). Some of these patients also received liposuction. Leppapuska et al.64 reported on preoperative and postoperative excess volume (in milliliters) in 27 upper extremity lymphedema patients. Vascularized lymph node transfer combined with compression stockings reduced arm volume by an average of 112.6 ml (95 percent CI, −81.61 to 306.81 ml; p = 0.26). Three studies (175 upper extremity lymphedema patients) reported on the proportion of patients who required physiotherapy and complex decongestive therapy postoperatively.27,35,65 Although 104 of 175 patients (59 percent) required physiotherapy and complex decongestive therapy before vascularized lymph node transfer, 57 of 175 (33 percent) required physiotherapy and complex decongestive therapy after surgery (OR, 45.37; 95 percent CI, 8.73 to 235.78; p < 0.00001).

F2
Fig. 2.:
Lymph node transplantation; reduction in circumference (in centimeters).

Eight case series (248 patients) reported on the mean number of cellulitis infections per year before and after surgery.23,53,60,65–67,72,73 Cellulitis infections were significantly reduced after vascularized lymph node transfer (mean difference, 2.34; 95 percent CI, 1.82 to 2.85; p < 0.00001). This benefit was significant for upper extremity lymphedema (181 patients) (mean difference, 2.68; 95 percent CI, 1.94 to 3.41; p < 0.00001) and for lower extremity lymphedema (67 patients) (mean difference, 2.01; 95 percent CI, 1.12 to 2.91; p < 0.001). Six case series (233 patients with upper extremity lymphedema or lower extremity lymphedema) reported on the proportion of patients with preoperative and postoperative cellulitis.35,49,61,64,69,75 Cellulitis was significantly reduced after vascularized lymph node transfer. The incidence of cellulitis before surgery was 53 percent (124 of 233) compared to 18 percent (42 of 233) after surgery (OR, 9.37 percent; 95 percent CI, 5.39 to 16.27 percent; p < 0.0001). Patel et al.53 reported on quality of life using the Lymphoedema Quality-of-Life tool. Quality of life improved significantly after vascularized lymph node transfer (25 patients) (mean difference, −3.95; 95 percent CI, −4.33 to −3.57; p < 0.00001). This benefit was significant for upper extremity lymphedema (15 patients) (mean difference, −3.70; 95 percent CI, −4.14 to −3.26; p < 0.00001) and lower extremity lymphedema (10 patients) (mean difference, −4.10; 95 percent CI, −4.30 to −3.90; p < 0.00001).

Vascularized Lymph Node Transfer and Donor Site

Ciudad et al.25 compared the morbidity of different donor sites for vascularized lymph node transfer in 110 patients with stage II to III (International Society of Lymphology) lymphedema. Donor sites included groin (n = 20), supraclavicular (n = 54), and right gastroepiploic, where an open (n = 19) or laparoscopic approach (n = 17) was used. No significant differences in complications were found across donor sites. Ciudad et al.61 compared the circumference reduction rates across different donor sites for vascularized lymph node transfer in 45 patients with stage II (International Society of Lymphology) lymphedema. Donor sites included groin (n = 10), supraclavicular (n = 10), and gastroepiploic (n = 25). No significant differences in circumference reduction rates were found across donor sites.

Lymphovenous Bypass versus Vascularized Lymph Node Transfer

Three studies (161 patients) compared the efficacy and safety of lymphovenous bypass to vascularized lymph node transfer in stage I to III upper extremity lymphedema or lower extremity lymphedema patients.8,34,44,62 A pooled analysis of two studies8,44 showed no significant difference in lymphatic function at 12- to 18-month follow-up. Seventeen of 26 patients (65 percent) who underwent vascularized lymph node transfer had improved lymphatic function at 12- to 18-month follow-up compared to 26 of 62 patients (42 percent) who underwent lymphovenous bypass (OR, 1.73; 95 percent CI, 0.29 to 10.15). Similarly, a pooled analysis of two studies,34,44 showed no significant difference in clinical improvement (lymphatic function) at 24-month follow-up. Fourteen of 21 patients (67 percent) who underwent vascularized lymph node transfer had improved lymphatic function at 24-month follow-up compared to 15 of 27 patients (56 percent) who underwent lymphovenous bypass (OR, 1.57; 95 percent CI, 0.48 to 5.17). Lee et al. also reported 48-month follow-up data.44 Although the difference was not significant, more patients in the vascularized lymph node transfer group continued to experience improved lymphatic function at 48-month follow-up. Six of 13 patients (46 percent) who underwent vascularized lymph node transfer still had improved lymphatic function at 48 months compared to three of 19 lymphovenous bypass patients (16 percent) (OR, 4.57; 95 percent CI, 0.88 to 23.71; p = 0.07). Engel et al.62 compared circumferential reduction rates, and patients who underwent vascularized lymph node transfer had a 16.7 percent (95 percent CI, 13.32 to 20.08 percent) greater reduction in circumference than patients who underwent lymphovenous bypass.

Two studies reported on postoperative complications.8,34 Postoperative complications were reported in two of 41 lymphovenous bypass patients (5 percent), compared to six of 21 vascularized lymph node transfer patients (29 percent) (OR, 4.86; 95 percent CI, 0.99 to 23.86 percent; p = 0.05). Engel et al. compared cellulitis rates and, on average, patients who underwent vascularized lymph node transfer had 1.2 more episodes of cellulitis per year than patients who underwent lymphovenous bypass (95 percent CI, 0.42 to 1.98; p = 0.02). Granzow et al.34 reported on compression garment use at 24-month follow-up. Six of eight vascularized lymph node transfer patients (75 percent) reported no compression garment use at 24 months compared to three of eight lymphaticovenous anastomosis patients (38 percent) (OR, 5.00; 95 percent CI, 0.58 to 42.80; p = 0.14). Akita et al. reported a significantly shorter hospital stay among lymphovenous bypass patients compared to vascularized lymph node transfer patients.8 The mean hospital stay in the vascularized lymph node transfer group was 15.2 ± 1.6 days compared to 8.9 ± 2.9 days in the lymphovenous bypass group (mean difference, 6.30 days; 95 percent CI, 5.07 to 7.53 days).

Lymphatic Microsurgical Preventive Healing Approach

Three studies (154 patients) reported on the development of lymphedema at greater than 15-month follow-up in cancer patients who underwent lymphovenous bypass for prevention of lymphedema compared to a no-surgery control.13,47,52,63 Significantly fewer lymphedemas developed in patients who underwent preventive lymphovenous bypass. Nine of 62 patients (14 percent) who underwent lymphovenous bypass developed lymphedema at 15 to 29 months’ follow-up compared to 52 of 92 control patients (56 percent) (OR, 0.15; 95 percent CI, 0.06 to 0.35; p < 0.0001; very low-quality evidence). (See Figure, Supplemental Digital Content 8, which shows the lymphaticovenous anastomosis versus no preventive surgery; outcome = lymphedema at >18-month follow-up, https://links.lww.com/PRS/E399.) Two studies (140 patients) reported on complications.47,52 Patients who had lymphovenous bypass and lymph node dissection were not at increased risk of developing complications compared to patients who only had lymph node dissection.

DISCUSSION

Limitations of Meta-Analysis

This meta-analysis has several limitations. Only two randomized controlled trials were included. The majority of included studies were observational studies, which are at high risk of bias, and the conclusions that can be drawn from these studies are limited. It was difficult to report a meta-analysis on these studies because of the variation in outcome measurements and lack of reported standard deviations. Although there was a lack of standardization in outcomes measurements, the magnitude of limb volume reduction was large for some procedures, particularly for liposuction.

Physiologic Surgery (Lymphovenous Bypass and Vascularized Lymph Node Transfer)

A lymphedema therapist is recommended for patients undergoing lymphatic surgery. However, the failure of conservative management is not a prerequisite for physiologic surgery. This is based on a plurality of studies demonstrating that patients with earlier stage disease have better outcomes.

There is level I evidence demonstrating vascularized lymph node transfer and 6 months of compression and physiotherapy was more effective in reducing limb volume (grade 1B) and incidence of cellulitis than compression and physiotherapy alone.28 Further studies that provide a nonsurgical control group are needed in this field. Mapping of the lymphatics is encouraged when harvesting lymph nodes adjacent to the limbs such as reverse lymphatic mapping to avoid lymphatics draining the limb and to minimize the risk of donor-site lymphedema.

A few studies compared lymphovenous bypass to vascularized lymph node transfer, but because of heterogeneous patient populations, there is currently no consensus regarding which procedure is more effective. We understand that patients with more advanced disease who may be offered vascularized lymph node transfer may not be candidates for lymphovenous bypass, and there may be inherent selection bias in these studies.

A few studies show that prophylactic lymphovenous bypass in patients undergoing lymphadenectomy may reduce the incidence of lymphedema. Prophylactic lymphovenous bypass should be avoided in cases of extremity malignancy. Lymphovenous bypass after mastectomy or inguinal dissection may reduce the incidence of lymphedema (grade 1B). The potential for hematogenous spread of extremity malignancies is unknown.

Liposuction

Liposuction is indicated for moderate to advanced lymphedema with a significant component of fat hypertrophy (grade 1C). Evidence of fat hypertrophy of the limb can be provided either by physical examination or by imaging. There is sufficient evidence that liposuction is safe with a large benefit in terms of limb volume reduction (grade 1C). There is a role for liposuction combined with physiologic procedures, although the timing of each procedure is currently unresolved.

Unresolved Questions

Is there a body mass index cutoff for offering physiologic procedures given the correlation with elevated body mass index and impaired lymphatic function? What is the role of scar release? Do physiologic procedures respond better in patients with preserved lymphatic architecture/early stage? Do physiologic procedures work better in upper extremity lymphedema or lower extremity lymphedema? We agree that the International Society of Lymphology staging system is a limited staging system that does not incorporate physiologic measures but is useful in communicating in general terms with the patient population.

CONSENSUS and RECOMMENDATIONS

  • There is evidence to support that lymphaticovenous anastomosis can be effective in reducing severity of lymphedema (grade 1C). A plurality of studies demonstrates that patients with earlier stage disease have better outcomes. There is no evidence that lymphovenous bypass can cure lymphedema.
  • There is evidence to support that vascularized lymph node transfer can be effective in reducing the severity of lymphedema (grade 1B). There is no evidence that vascularized lymph node transfer can cure lymphedema.
  • Currently, there is no consensus on which procedure (lymphovenous bypass versus vascularized lymph node transfer) is more effective (grade 2C).
  • A few studies show that prophylactic lymphovenous bypass in patients undergoing extremity lymphadenectomy may reduce the incidence of lymphedema (grade 1B). More studies with longer follow-up are required to confirm this benefit.
  • Debulking procedures such as liposuction are effective in addressing nonfluid component such as fat involving lymphedema (grade 1C).
  • There is a role for liposuction combined with physiologic procedures, although the timing of each procedure is currently unresolved (grade 1C).
  • Lymphatic procedures are highly complex, and anyone contemplating performing lymphatic surgery is encouraged to visit a high-volume center. To decrease the incidence of complications, microsurgical training is encouraged.
  • A consensus on staging of lymphedema and preoperative and postoperative evaluation would be helpful.
  • There is a need for more quantitative methods for measuring fat, fluid, and physiologic measures and immunologic function.
  • There is a need for better designed studies that include more objective reporting of outcomes and longer follow-up.

CONCLUSIONS

The role of surgery in the treatment of lymphedema has evolved from debulking procedures to those that aim to counteract the pathophysiology of lymphedema using microsurgical techniques. Many studies seem to support some efficacy of lymphovenous bypass and vascularized lymph node transfer. Many studies show the important role of lymphedema therapy and other procedures such as liposuction and debulking. The management of lymphedema is a challenging field with many promising advances. However, many questions remain unanswered.

ACKNOWLEDGMENTS

The Consensus Panel acknowledges the support of the American Association of Plastic Surgeons, and Aurelie Alger and Rebecca Bonsaint, for their substantial contribution to this project. The authors appreciate additional data that were kindly provided by Håkan Brorson, M.D., Ph.D., and John Boyages, M.D., Ph.D.

REFERENCES

1. Guyatt G, Gutterman D, Baumann MH, et al. Grading strength of recommendations and quality of evidence in clinical guidelines: Report from an American College of Chest Physicians task force. Chest. 2006;129:174–181.
2. Guyatt GH, Oxman AD, Vist GE, et al.; GRADE Working Group. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–926.
3. Schünemann HJ, Oxman AD, Vist GE, et al. Higgins JPT, Green S, eds. Chapter 12: Interpreting results and drawing conclusions. In: Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. 2011.London: Cochrane Collaboration;
4. Higgins JPT, Altman DG, Sterne JAC. Higgins JPT, Green S, eds. Chapter 8: Assessing risk of bias in included studies. In: Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. 2011.London: Cochrane Collaboration;
5. Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2019Ottawa, Ontario, Canada: Department of Epidemiology and Community Medicine, University of Ottawa; Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed February 25, 2021.
6. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560.
7. Agarwal R, Bhatnagar SK, Chandra R. Lymphosuction: A new treatment modality for chronic filarial lymphedema. Eur J Plast Surg. 1998;21:113–117.
8. Akita S, Mitsukawa N, Kuriyama M, et al. Comparison of vascularized supraclavicular lymph node transfer and lymphaticovenular anastomosis for advanced stage lower extremity lymphedema. Ann Plast Surg. 2015;74:573–579.
9. Auba C, Marre D, Rodríguez-Losada G, Hontanilla B. Lymphaticovenular anastomoses for lymphedema treatment: 18 months postoperative outcomes. Microsurgery. 2012;32:261–268.
10. Ayestaray B, Bekara F, Andreoletti JB. Patent blue-enhanced lymphaticovenular anastomosis. J Plast Reconstr Aesthet Surg. 2013;66:382–389.
11. Ayestaray B, Bekara F. π-Shaped lymphaticovenular anastomosis: The venous flow sparing technique for the treatment of peripheral lymphedema. J Reconstr Microsurg. 2014;30:551–560.
12. Batista BN, Germain M, Faria JC, Becker C. Lymph node flap transfer for patients with secondary lower limb lymphedema. Microsurgery. 2017;37:29–33.
13. Boccardo FM, Casabona F, Friedman D, et al. Surgical prevention of arm lymphedema after breast cancer treatment. Ann Surg Oncol. 2011;18:2500–2505.
14. Boccardo F, Dessalvi S, Campisi C, et al. Microsurgery for groin lymphocele and lymphedema after oncologic surgery. Microsurgery. 2014;34:10–13.
15. Boyages J, Kastanias K, Koelmeyer LA, et al. Liposuction for advanced lymphedema: A multidisciplinary approach for complete reduction of arm and leg swelling. Ann Surg Oncol. 2015;22(Suppl 3):S1263–S1270.
16. Brorson H, Svensson H, Norrgren K, Thorsson O. Liposuction reduces arm lymphedema without significantly altering the already impaired lymph transport. Lymphology. 1998;31:156–172.
17. Brorson H, Ohlin K, Olsson G, Långström G, Wiklund I, Svensson H. Quality of life following liposuction and conservative treatment of arm lymphedema. Lymphology. 2006;39:8–25.
18. Brorson H, Svensson H. Liposuction combined with controlled compression therapy reduces arm lymphedema more effectively than controlled compression therapy alone. Plast Reconstr Surg. 1998;102:1058–1067, discussion 1068.
19. Brorson H. Liposuction gives complete reduction of chronic large arm lymphedema after breast cancer. Acta Oncol. 2000;39:407–420.
20. Campisi CC, Ryan M, Boccardo F, Campisi C. Fibro-lipo-lymph-aspiration with a lymph vessel sparing procedure to treat advanced lymphedema after multiple lymphatic-venous anastomoses: The complete treatment protocol. Ann Plast Surg. 2017;78:184–190.
21. Casabona F, Bogliolo S, Valenzano Menada M, Sala P, Villa G, Ferrero S. Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients. Ann Surg Oncol. 2009;16:2459–2463.
22. Chen WF, Zhao H, Yamamoto T, Hara H, Ding J. Indocyanine green lymphographic evidence of surgical efficacy following microsurgical and supermicrosurgical lymphedema reconstructions. J Reconstr Microsurg. 2016;32:688–698.
23. Cheng MH, Huang JJ, Huang JJ, et al. A novel approach to the treatment of lower extremity lymphedema by transferring a vascularized submental lymph node flap to the ankle. Gynecol Oncol. 2012;126:93–98.
24. Cheng MH, Chen SC, Henry SL, Tan BK, Lin MC, Huang JJ. Vascularized groin lymph node flap transfer for postmastectomy upper limb lymphedema: Flap anatomy, recipient sites, and outcomes. Plast Reconstr Surg. 2013;131:1286–1298.
25. Ciudad P, Manrique OJ, Date S, et al. A head-to-head comparison among donor site morbidity after vascularized lymph node transfer: Pearls and pitfalls of a 6-year single center experience. J Surg Oncol. 2017;115:37–42.
26. Damstra RJ, Voesten HG, Klinkert P, Brorson H. Circumferential suction-assisted lipectomy for lymphoedema after surgery for breast cancer. Br J Surg. 2009;96:859–864.
27. De Brucker B, Zeltzer A, Seidenstuecker K, Hendrickx B, Adriaenssens N, Hamdi M. Breast cancer-related lymphedema: Quality of life after lymph node transfer. Plast Reconstr Surg. 2016;137:1673–1680.
28. Dionyssiou D, Demiri E, Tsimponis A, et al. A randomized control study of treating secondary stage II breast cancer-related lymphoedema with free lymph node transfer. Breast Cancer Res Treat. 2016;156:73–79.
29. Feldman S, Bansil H, Ascherman J, et al. Single institution experience with Lymphatic Microsurgical Preventive Healing Approach (LYMPHA) for the primary prevention of lymphedema. Ann Surg Oncol. 2015;22:3296–3301.
30. Bansil HA, Rohde C, Ascherman J, et al. Single-institution experience with lymphatic microsurgical preventive healing approach (LYMPHA) for the primary prevention of lymphedema. Ann Surg Oncol. 2015;22(Suppl 1):3296–3301.
31. Gharb BB, Rampazzo A, Spanio di Spilimbergo S, Xu ES, Chung KP, Chen HC. Vascularized lymph node transfer based on the hilar perforators improves the outcome in upper limb lymphedema. Ann Plast Surg. 2011;67:589–593.
32. Gong-Kang H, Ru-Qi H, Zong-Zhao L, Yao-Liang S, Tie-De L, Gong-Ping P. Microlymphaticovenous anastomosis for treating lymphedema of the extremities and external genitalia. J Microsurg. 1981;3:32–39.
33. Huang GK, Hu RQ, Liu ZZ, Shen YL, Lan TD, Pan GP. Microlymphaticovenous anastomosis in the treatment of lower limb obstructive lymphedema: Analysis of 91 cases. Plast Reconstr Surg. 1985;76:671–685.
34. Granzow JW, Soderberg JM, Kaji AH, Dauphine C. An effective system of surgical treatment of lymphedema. Ann Surg Oncol. 2014;21:1189–1194.
35. Gratzon A, Schultz J, Secrest K, Lee K, Feiner J, Klein RD. Clinical and psychosocial outcomes of vascularized lymph node transfer for the treatment of upper extremity lymphedema after breast cancer therapy. Ann Surg Oncol. 2017;24:1475–1481.
36. Hoffner M, Bagheri S, Hansson E, Manjer J, Troëng T, Brorson H. SF-36 shows increased quality of life following complete reduction of postmastectomy lymphedema with liposuction. Lymphat Res Biol. 2017;15:87–98.
37. Ipsen T, Pless J, Frederiksen PB. Experience with microlymphaticovenous anastomoses for congenital and acquired lymphoedema. Scand J Plast Reconstr Surg Hand Surg. 1988;22:233–236.
38. Ito R, Wu CT, Lin MC, Cheng MH. Successful treatment of early-stage lower extremity lymphedema with side-to-end lymphovenous anastomosis with indocyanine green lymphography assisted. Microsurgery. 2016;36:310–315.
39. Koshima I, Kawada S, Moriguchi T, Kajiwara Y. Ultrastructural observations of lymphatic vessels in lymphedema in human extremities. Plast Reconstr Surg. 1996;97:397–405; discussion 406–407.
40. Koshima I, Inagawa K, Urushibara K, Moriguchi T. Supermicrosurgical lymphaticovenular anastomosis for the treatment of lymphedema in the upper extremities. J Reconstr Microsurg. 2000;16:437–442.
41. Koshima I, Inagawa K, Etoh K, Moriguchi T. Supramicrosurgical lymphaticovenular anastomosis for the treatment of lymphedema in the extremities (in Japanese). Nihon Geka Gakkai Zasshi. 1999;100:551–556.
42. Koshima I, Nanba Y, Tsutsui T, Takahashi Y, Itoh S. Long-term follow-up after lymphaticovenular anastomosis for lymphedema in the leg. J Reconstr Microsurg. 2003;19:209–215.
43. Lamprou DA, Voesten HG, Damstra RJ, Wikkeling OR. Circumferential suction-assisted lipectomy in the treatment of primary and secondary end-stage lymphoedema of the leg. Br J Surg. 2017;104:84–89.
44. Lee BB, Laredo J, Neville R. Reconstructive surgery for chronic lymphedema: A viable option, but. Vascular. 2011;19:195–205.
45. Lin CH, Ali R, Chen SC, et al. Vascularized groin lymph node transfer using the wrist as a recipient site for management of postmastectomy upper extremity lymphedema. Plast Reconstr Surg. 2009;123:1265–1275.
46. Matsubara S, Sakuda H, Nakaema M, Kuniyoshi Y. Long-term results of microscopic lymphatic vessel-isolated vein anastomosis for secondary lymphedema of the lower extremities. Surg Today. 2006;36:859–864.
47. Morotti M, Menada MV, Boccardo F, et al. Lymphedema microsurgical preventive healing approach for primary prevention of lower limb lymphedema after inguinofemoral lymphadenectomy for vulvar cancer. Int J Gynecol Cancer. 2013;23:769–774.
48. Narushima M, Mihara M, Yamamoto Y, Iida T, Koshima I, Mundinger GS. The intravascular stenting method for treatment of extremity lymphedema with multiconfiguration lymphaticovenous anastomoses. Plast Reconstr Surg. 2010;125:935–943.
49. Nguyen AT, Suami H, Hanasono MM, Womack VA, Wong FC, Chang EI. Long-term outcomes of the minimally invasive free vascularized omental lymphatic flap for the treatment of lymphedema. J Surg Oncol. 2017;115:84–89.
50. Nicoli F, Constantinides J, Ciudad P, et al. Free lymph node flap transfer and laser-assisted liposuction: A combined technique for the treatment of moderate upper limb lymphedema. Lasers Med Sci. 2015;30:1377–1385.
51. O’Brien BM, Das SK. Microlymphatic surgery in management of lymphoedema of the upper limb. Ann Acad Med Singap. 1979;8:474–480.
52. Orefice S, Conti AR, Grassi M, Salvadori B. The use of lympho-venous anastomoses to prevent complications from ilio-inguinal dissection. Tumori. 1988;74:347–351.
53. Patel KM, Lin CY, Cheng MH. A prospective evaluation of lymphedema-specific quality-of-life outcomes following vascularized lymph node transfer. Ann Surg Oncol. 2015;22:2424–2430.
54. Patel KM, Lin CY, Cheng MH. From theory to evidence: Long-term evaluation of the mechanism of action and flap integration of distal vascularized lymph node transfers. J Reconstr Microsurg. 2015;31:26–30.
55. Qi F, Gu J, Shi Y, Yang Y. Treatment of upper limb lymphedema with combination of liposuction, myocutaneous flap transfer, and lymph-fascia grafting: A preliminary study. Microsurgery. 2009;29:29–34.
56. Saaristo AM, Niemi TS, Viitanen TP, Tervala TV, Hartiala P, Suominen EA. Microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patients. Ann Surg. 2012;255:468–473.
57. Schaverien MV, Munro KJ, Baker PA, Munnoch DA. Liposuction for chronic lymphoedema of the upper limb: 5 years of experience. J Plast Reconstr Aesthet Surg. 2012;65:935–942.
58. Shi P, Zhang W, Zhao G, Li L, Haifeng C. Treatment of post-mastectomy upper limb lymphedema by modified side-to-end lymphaticovenular anastomosis (in Chinese). Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2015;29:339–342.
59. Viitanen TP, Visuri MT, Hartiala P, et al. Lymphatic vessel function and lymphatic growth factor secretion after microvascular lymph node transfer in lymphedema patients. Plast Reconstr Surg Glob Open. 2013;1:1–9.
60. Aljaaly HA, Fries CA, Cheng MH. Dorsal wrist placement for vascularized submental lymph node transfer significantly improves breast cancer-related lymphedema. Plast Reconstr Surg Glob Open. 2019;7:e2149.
61. Ciudad P, Agko M, Perez Coca JJ, et al. Comparison of long-term clinical outcomes among different vascularized lymph node transfers: 6-year experience of a single center’s approach to the treatment of lymphedema. J Surg Oncol. 2017;116:671–682.
62. Engel H, Lin CY, Huang JJ, Cheng MH. Outcomes of lymphedema microsurgery for breast cancer-related lymphedema with or without microvascular breast reconstruction. Ann Surg. 2018;268:1076–1083.
63. Hahamoff M, Gupta N, Munoz D, et al. A lymphedema surveillance program for breast cancer patients reveals the promise of surgical prevention. J Surg Res. 2019;244:604–611.
64. Leppäpuska IM, Suominen E, Viitanen T, et al. Combined surgical treatment for chronic upper extremity lymphedema patients: Simultaneous lymph node transfer and liposuction. Ann Plast Surg. 2019;83:308–317.
65. Lin CY, Liu HE, Cheng MH. Factors associated with professional healthcare advice seeking in breast cancer-related lymphedema. J Surg Oncol. 2019;121:67–74.
66. Maruccia M, Elia R, Ciudad P, et al. Postmastectomy upper limb lymphedema: Combined vascularized lymph node transfer and scar release with fat graft expedites surgical and patients’ related outcomes. A retrospective comparative study. J Plast Reconstr Aesthet Surg. 2019;72:892–901.
67. Asuncion MO, Chu SY, Huang YL, Lin CY, Cheng MH. Accurate prediction of submental lymph nodes using magnetic resonance imaging for lymphedema surgery. Plast Reconstr Surg Glob Open. 2018;6:e1691.
68. Chang K, Xia S, Sun YG, Xin JF, Shen WB. Liposuction combined with lymphatico-venous anastomosis for treatment of secondary lymphedema of the lower limbs: A report of 49 cases (in Chinese). Zhonghua Wai Ke Za Zhi. 2017;55:274–278.
69. Ciudad P, Manrique OJ, Date S, et al. Double gastroepiploic vascularized lymph node transfers to middle and distal limb for the treatment of lymphedema. Microsurgery. 2017;37:771–779.
70. Ciudad P, Manrique OJ, Adabi K, et al. Combined double vascularized lymph node transfers and modified radical reduction with preservation of perforators for advanced stages of lymphedema. J Surg Oncol. 2019;119:439–448.
71. Gentileschi S, Servillo M, Albanese R, De Bonis F, Tartaglione G, Salgarello M. Lymphatic mapping of the upper limb with lymphedema before lymphatic supermicrosurgery by mirroring of the healthy limb. Microsurgery. 2017;37:881–889.
72. Gustafsson J, Chu SY, Chan WH, Cheng MH. Correlation between quantity of transferred lymph nodes and outcome in vascularized submental lymph node flap transfer for lower limb lymphedema. Plast Reconstr Surg. 2018;142:1056–1063.
73. Ho OA, Chu SY, Huang YL, Chen WH, Lin CY, Cheng MH. Effectiveness of vascularized lymph node transfer for extremity lymphedema using volumetric and circumferential differences. Plast Reconstr Surg Glob Open. 2019;7:e2003.
74. Hoffner M, Ohlin K, Svensson B, et al. Liposuction gives complete reduction of arm lymphedema following breast cancer treatment: A 5-year prospective study in 105 patients without recurrence. Plast Reconstr Surg Glob Open. 2018;6:e1912.
75. Montag E, Okada AY, Arruda EGP, et al. Influence of vascularized lymph node transfer (VLNT) flap positioning on the response to breast cancer-related lymphedema treatment. Rev Col Bras Cir. 2019;46:e2156.
76. Mousavi SR, Akbari ME, Zarrintan S. Vascularized gastroepiploic lymph node transfer significantly improves breast cancer-related lymphedema. J Surg Oncol. 2020;121:163–167.
77. Winters H, Tielemans HJP, Hameeteman M, et al. The efficacy of lymphaticovenular anastomosis in breast cancer-related lymphedema. Breast Cancer Res Treat. 2017;165:321–327.
78. Seki Y, Kajikawa A, Yamamoto T, Takeuchi T, Terashima T, Kurogi N. Single lymphaticovenular anastomosis for early-stage lower extremity lymphedema treated by the superior-edge-of-the-knee incision method. Plast Reconstr Surg Glob Open. 2018;6:e1629.

Supplemental Digital Content

Copyright © 2021 by the American Society of Plastic Surgeons