RECONSTRUCTIVE Outcomes Article
Operative Treatment of Peripheral Lymphedema: A Systematic Meta-Analysis of the Efficacy and Safety of Lymphovenous Microsurgery and Tissue Transplantation Marten N. Basta, B.A. Lin Lin Gao, M.D. Liza C. Wu, M.D. Philadelphia, Pa.
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Background: The purpose of this study was to quantify the efficacy and safety of microsurgery for lymphedema through a systematic meta-analysis, which has not been described before. Methods: A literature search was conducted to identify all articles involving microsurgical treatment of lymphedema. Studies meeting criteria for inclusion were rated on methodologic quality based on the American Society of Plastic Surgeons levels of evidence. Demographic information, cause of lymphedema, and surgical technique were recorded. Quantitative change in lymphedema and perioperative complications were noted. Results: Twenty-seven studies were included, with 24 offering level IV evidence and three offering level III evidence. Lymphovenous shunt procedures were performed in 22 studies and lymph node transplantation was performed in five. Excess circumference was reduced by 48.8 ± 6.0 percent, and absolute circumference was reduced by 3.31 ± 0.73 cm. Studies reporting change in volume demonstrated reduction in excess volume by 56.6 ± 9.1 percent, and absolute volume was reduced by 23.6 ± 2.1 percent. The incidence of no improvement in lymphedema postoperatively was 11.8 percent, and 91.2 percent of patients reported subjective improvement. Approximately 64.8 percent of patients discontinued compression garments at follow-up. Complications included operative-site infection (4.7 percent), lymphorrhea (7.7 percent), reexploration for flap congestion (2.7 percent), and additional procedures (22.6 percent). Conclusions: Operative interventions for peripheral lymphedema appear to provide consistent quantitative improvements postoperatively, with a relatively wide safety margin. Lymph node transplantation may provide better outcomes compared with lymphovenous shunt, but well-designed head-to-head comparisons are needed to evaluate this further. (Plast. Reconstr. Surg. 133: 905, 2014.) CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
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eripheral lymphedema represents a complex physiologic manifestation of disrupted lymphatic drainage systems. The disease may be congenital, caused by agenesis or dysplasia of any component of the lymphatic network; From the Division of Plastic Surgery, Perelman School of Medicine at the University of Pennsylvania; the Division of Plastic Surgery, Hospital of the University of Pennsylvania; and the Division of Plastic Surgery, University of Pennsylvania Health Systems. Received for publication August 29, 2013; accepted September 26, 2013. Copyright © 2014 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000000010
or acquired, most commonly secondary to surgical disruption or recurrent infection.1 Regardless of pathophysiologic cause, the clinical presentation is characterized by chronic swelling, accompanied by localized pain, atrophic skin findings, and recurrent infections, all of which contribute to gradual functional decline. Treatment for lymphedema begins with combined decongestive physiotherapy.2 Although this alone may afford patients enough symptomatic relief, conservative therapy relies on a Disclosure: The authors have no financial interest to declare in relation to the content of this article.
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Plastic and Reconstructive Surgery • April 2014 substantial amount of patient compliance and ability to tolerate the burdens of lifelong physical therapy appointments and compression garments. As our understanding of the underlying etiopathology and surgical experience evolves, so too has the approach to operative treatment. Specifically, reductive surgery has given way to lymphovenous shunt and more recently, lymphatic tissue or lymph node transplantation, which have become popularized with advances in microsurgical techniques. Numerous studies have reported successful experiences with operative management of peripheral lymphedema, whereas others have demonstrated rather disappointing outcomes. As current literature reviews on the topic have generally cited heterogeneity in patient selection and outcomes reporting, there have been no systematic meta-analyses able to quantify what, if any, benefit is evidenced by surgical therapy.3,4 With the inconclusive results of these studies, much controversy surrounds indications for operative intervention, which surgical techniques provide the best outcomes, and which patients are likely to benefit from conservative versus operative management. The purpose of this study, therefore, was to quantify the efficacy and safety of various operative treatments for peripheral lymphedema.
PATIENTS AND METHODS Literature Search A literature search was conducted to identify all articles involving microsurgical interventions to treat lymphedema. Ovid MEDLINE was searched using the following headings and keyword terms: “lymphedema,” “microsurgery,” “lymphovenous,” “lympholymphatic,” “shunt,” and “anastomosis.” Search results were limited to English articles only, yielding 124 results. Titles and abstracts were examined and selected for full article review based on appropriate scope of study and patient population. In addition, selected study references and review articles were examined for further article sources. Study Selection and Methodologic Quality After identifying relevant studies through title and abstract information, studies were selected for inclusion based on the following criteria: 1. The study involved lymphatic reconstruction with lymphovenous shunt or lymphatic tissue transplant and described the
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surgical protocol and methodology of patient evaluation. 2. The study was published between 1985 and 2013. 3. The study reported relevant outcomes data. 4. The study was not limited to single case reports. 5. The study was in English. Studies were not included if they did not meet the above criteria and/or if multiple publications were from the same group; only studies that reported data from nonoverlapping time periods were included. Studies were then rated on methodologic quality based on the American Society of Plastic Surgeons Evidence Rating Scale for Therapeutic Studies.5 Data Extraction Baseline patient characteristics such as age, cause of lymphedema, and anatomical sites of involvement were recorded. Surgical protocols were categorized as either lymphovenous shunt or vascularized lymph node transplantation, and the configuration(s) of microsurgical anastomosis was recorded. Outcomes collected included both objective and subjective preoperative to postoperative change in lymphedema, average patient follow-up, and incidence of complications. Objective methods for measuring change in lymphedema included serial circumferential limb measurements and volumetric water displacement. Measurements were grouped as either change in absolute limb circumference or volume or change in excess limb circumference or volume relative to the contralateral, unaffected limb. When multiple levels of circumferential measurements were reported, measurements were averaged for each patient. For studies missing data such as standard deviations, the study authors were contacted and data were retrieved as available or qualitative analysis was performed alternatively. Statistical Analysis Data was input to RevMan5.2 (The Cochrane Collaboration, Copenhagen, Denmark) for analysis.6 Continuous variables, such as age, were compared by means of standard summary statistics. Outcomes for improvement of lymphedema were compared in forest plots and summarized with mean differences, and the confidence interval was set to 95 percent. Separate comparisons were made for improvement in studies reporting
Volume 133, Number 04 • Surgery for Lymphedema Meta-Analysis circumferential change and volumetric change. Patient populations were subdivided into those with upper limb lymphedema or lower limb lymphedema, and the effect size was calculated separately and with both populations combined when possible. Dichotomous data, such as the incidence of complications, were summarized with Fisher’s exact test, with significance set to p < 0.05. Heterogeneity of comparison data was judged by means of the I2 statistic when applicable, ranging from 0 to 99 percent (judged acceptable for I2, 75 percent). Publication bias was inspected routinely by means of funnel plots for each comparison.
RESULTS Study Characteristics A total of 27 studies were included in this systematic review. Twenty-four studies were retrospective case series presenting level IV evidence, two studies were cohort studies with level III evidence, and one was a case-control study with level III evidence (Table 1).7–33 Twenty studies provided sufficient data to be included in quantitative meta-analysis, and the remaining seven studies were included for qualitative summary.
Both upper and lower extremity populations were included in this meta-analysis. There were 10 studies that examined upper extremity lymphedema reduction, 11 studies that examined lower extremity reduction, and five studies that examined both upper and lower extremities. One study involved external genitalia lymphedema. Patient Characteristics Overall, the study population consisted of 1619 patients, with a female-to-male ratio of approximately 3:2. Patient age ranged from 7 to 92 years of age; however, the majority of patients were aged between 45 and 60 years. Although cause of lymphedema included both congenital and acquired, the vast majority of patients suffered from postsurgical lymphedema associated with oncologic conditions, including breast cancer and various gynecologic cancers. The staging system of lymphedema was inconsistent across studies. Of those studies reporting stage, either the Campisi lymphedema classification or the International Society of Lymphology classification system was used.2,34 Of studies reporting International Society of Lymphology classification, approximately 50 percent of patients were stage II, 25 percent were stage III, and the remaining 25 percent were stage I or IV. Average
Table 1. Summary of Included Studies Reference Felmerer et al., 2012 Huang et al., 19858 Matsubara et al., 20069 Yamamoto et al., 200310 Koshima et al., 200311 Koshima et al., 200012 Cheng et al., 201213 Furukawa et al., 201114 Lin et al., 200915 Yamamoto et al., 201116 Narushima et al., 201017 Auba et al., 201218 Ipsen et al., 198819 Demirtas et al., 201020 O’Brien et al., 199021 Chang et al., 201022 Baumiester and Siuda, 199023 Weiss et al., 200224 Becker et al., 200625 Olszewski, 201326 Maegawa et al., 201227 Maegawa et al., 201028 Mukenge et al., 201129 Yamamoto and Sugihara, 199830 Cheng et al., 201331 Gharb et al., 201132 Damstra et al., 200933 7
Design
Lymphedema Site
Operative Technique
No.
F/U (yr)
LOE
R-CS R-CS R-CS P-CS R-COH R-COH R-CS P-CS R-CS R-CS R-CS R-CS R-CS R-CS R-CS P-CS R-CS R-CS R-CS R-CS R-CS R-CS R-CS R-CS P-CC R-CS P-CS
U+L L L U L U L U U L L U+L L L U+L U U+L U U L L L O U+L U U U
E-E E-E, sleeve E-S E-E, sleeve E-E E-E LN-T E-E, sleeve LN-T E-E, S-E, E-S, lambda E-E, E-S, DE-E, S-E E-E S-E E-E E-E E-E E-E E-E, E-S LN-T E-E, E-S S-E S-E E-E, S-E E-E LN-T LN-T E-S
12 91 9 18 13 12 7 9 13 20 14 9 7 78 52 20 48 12 24 960 57 111 5 7 20 21 10
2.6 2.0 5.7 2.0 4.6 2.2 0.7 1.2 4.7 NA 0.7 1.5 1.0 1.1 4.2 1.5 1.3 7.7 8.3 5.0 1.2 NA 0.6 1.5 3.3 3.6 8
IV IV IV IV III III IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV III IV IV
LN-T, vascularized lymph node transfer; LOE, level of evidence; DE-E, double end-to-end; U, upper limb; L, lower limb; O, other (external genitalia lymphedema); R, retrospective; P, prospective; CS, case series; COH, cohort; CC, case-control; F/U, follow-up; NA, not applicable.
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Plastic and Reconstructive Surgery • April 2014 follow-up among all studies was 3.3 years, with individual cohort follow-up ranging from 8 months to 10 years. Patient Selection Criteria Although the majority of studies described factors taken into consideration for operative treatment of lymphedema, parameters for patient selection were inconsistently specified. All studies indicated that patients who underwent operative management had previously failed conservative therapy. In general, this criterion was fulfilled with less than 50 percent reduction of lymphedema with a minimum of 6 months of conservative therapy. Other indications were recurrent or severe cellulitis inadequately treated with antibiotics and functional impairment secondary to lymphedema. Important exclusion criteria reported included chronic venous insufficiency and severe fibrosclerotic lymphedema diagnosed on preoperative lymphoscintigraphy, and most studies were composed of patients with secondary lymphedema only. Operative Technique Lymphovenous Shunt The majority of studies used lymphovenous shunt as the operative approach to treatment. A variety of configurations were described for reconstructing the lymphedematous limb. The most popular was the lymphaticovenous end-to-end anastomosis. In this technique, patent blue dye can be injected intraoperatively to identify patent lymphatics. Subdermal venules are selected as the proximal recipient of lymphatic vessels. Specific advantages of these vessels cited by numerous authors included less size discrepancy, which facilitates more precise anastomosis, and a relatively lower intraluminal pressure compared with cutaneous veins, which prevents backflow from the venous system. Operative microscopes were uniformly used, and anastomosis was completed with 11-0 or 12-0 suture. Variations on the end-to-end configuration were frequently used in different studies. These included lymphaticovenous end-to-side, side-to-end, and double end-to-side shunts. Furthermore, Yamamoto et al. described the “lambda-shaped” configuration, which joined the proximal end of the lymphatic vessel to the side of the vein and the distal end of the lymphatic vessel to the end of the same vein.16 Finally, the end-to-end or sleeve anastomosis has been used in creating the lymphaticovenous shunt by multiple authors.8,10,14 The indication
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for this configuration was the inability to identify a suitable lymphatic vessel of appropriate size for microsurgical anastomosis. As such, multiple lymphatics and their surrounding soft-tissue adventitia are implanted into the end of a larger, cutaneous vein and anastomosed with 10-0 or 11-0 sutures in an interrupted fashion. Vascularized Lymph Node Transplantation Vascularized lymph node transplantation was the method of reconstruction in five of the included articles. Both Lin et al.15 and Becker et al.25 used the groin as a donor site in the treatment of upper limb lymphedema. The recipient sites were the distal wrist and the axilla, respectively. Cheng et al.13 recently proposed the submental vascularized lymph node flap as the donor for lower limb lymphedema, and the ankle served as the recipient site. In 2013, this same group described a groin flap designed off of perforators, with the wrist or elbow serving as the recipient site.31 Similarly, Gharb et al. used the same design in a 2011 study.32 Intraoperative lymphatic dye staining with methylene blue or indocarmine was reported in 19 studies, and lymphatic patency was assessed by means of lymphoscintigraphy or lymphography in 19 studies as well. Postoperative Care Postoperative management was assessed for each study. Six studies specified routine postoperative antibiotic prophylaxis for 1 week in patients without a history of recurrent cellulitis and 6 months or more in patients with a history of recurrent or severe cellulitis. Six studies detailed perioperative anticoagulation, with two studies using low-molecular-weight heparin, two using dextran, and two using low-dose aspirin. The duration of anticoagulation was approximately 1 month for heparin or dextran and 3 months for aspirin. The protocol for use of compression stockings was reported variably, with 14 studies initiating compression garments either in the immediate postoperative period or within 1 month of surgery, continued on an as-needed basis, and seven studies in which use of compression garments postoperatively was not recommended. Primary Outcomes Objective improvement of lymphedema postoperatively was reported heterogeneously, with studies presenting either change in limb circumference or volume as either absolute difference or difference of excess size relative to the contralateral limb in patients with unilateral lymphedema.
Volume 133, Number 04 • Surgery for Lymphedema Meta-Analysis Table 2 summarizes the four major parameters reported, and measures of heterogeneity indicate that circumferential measurements were homogenous and reliable, although all parameters demonstrated statistically significant improvement in lymphedema postoperatively. Specifically, excess circumference and volume were reduced by 49 percent and 57 percent of preoperative values, respectively; absolute volume was reduced by 23.6 percent; and absolute circumference was reduced by 3.31 cm (8.5 percent) of preoperative values. Figure 1 depicts the forest plots of the four major parameters (Fig. 1). Secondary Outcomes Results were comparable between patients with upper and lower limb lymphedema, and in studies of lymphovenous shunt procedures versus lymph node transplantation (Fig. 2). Overall, the incidence of no change or worsening of lymphedema postoperatively was approximately 11.8 percent; only studies detailing each patient’s outcomes were included in this statistic. Subjective improvement of lymphedema was documented in 13 studies, and overall, 92.7 percent of patients related symptomatic improvement after operative intervention. However, only two studies used a validated patientreported outcomes scale in assessing subjective improvement. Finally, the proportion of patients able to discontinue compression therapy was 78 percent in lymph node transplantation studies, compared with 56.3 percent in lymphovenous shunt studies (p = 0.04). Complications Complications are listed in Table 3. Postoperative wound-site infection occurred in 4.7
percent of patients, all of which resolved with antibiotic administration. In four studies reporting wound infection, the protocol did not include prophylactic antibiotics, whereas in two others, no wound infections occurred after the authors began administering prophylactic antibiotics routinely. The incidence of lymphorrhea was 7.7 percent overall; however, duration of symptoms and management were not reported. Furthermore, all lymph node transplantation studies reported this outcome, whereas only nine of 21 lymphovenous shunt studies did so. Operative reexploration for vascularized lymph node flap venous congestion was required in two of 75 patients. Finally, 35 patients underwent additional elective procedures to improve lymphedema subsequent to the initial procedure, including donor-site split-thickness skin grafting, liposuction, and excess skin excision.
DISCUSSION This systematic meta-analysis attempts to quantify the efficacy and safety of operative treatment of peripheral lymphedema. Of the 27 studies included, only three were level III evidence and the remainder were level IV. As such, interpretation of the findings of this review mandates evaluation of the evidence in light of the methodologic flaws inherent in the studies included. However, a number of observations can be ascertained from our results and deserve consideration. Of the four outcome measures presented here, change in excess circumference as a percentage of preoperative excess was most frequently reported. It follows that this measure was also the most homogenous and therefore most reliable of the pooled outcomes. We demonstrated
Table 2. Primary Outcomes* Parameter Excess circumference reduction, % All ULL LLL LV shunt LN-T Absolute circumference reduction, cm All ULL LLL Excess volume reduction, % All Absolute volume reduction, % All
No. of Studies
No.
Mean (95% CI)
I2 (%)
11 7 4 7 4
131 90 34 80 51
48.8 (42.8–54.8) 46.0 (39.0–53.0) 57.4 (44.5–70.3) 48.9 (40.7–57.2) 48.5 (35.3–61.6)
0 0 0 0 49
11 6 5
138 79 52
3.31 (2.58–4.04) 2.73 (1.63–3.83) 3.52 (2.28–4.75)
0 16 0
4
165
56.6 (47.5–65.6)
78
2
60
23.6 (21.5–25.7)
42
ULL, upper limb lymphedema; LLL, lower limb lymphedema; LV, lymphovenous, LN-T, lymph node transplantation. *p < 0.00001 for all endpoints (or p < 0.05).
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Fig. 1. Primary outcomes. (Above) Excess circumference reduction (values are percentages). (Second row) Circumference reduction (in centimeters). (Third row) Excess volume reduction (values are percentages). (Below) Absolute volume reduction (values are percentages).
an average reduction in excess circumference of approximately 48.8 percent across 11 studies with 131 patients. Although there is no existing literature with which to compare this result, it appears as though surgical treatment does consistently lead to a substantial improvement in this parameter. Furthermore, circumference reduction (in centimeters) consistently supports this finding, with an average 3.31-cm reduction across 11 studies. Admittedly, few studies reported on volume reduction, and an immediate consequence of this is an unacceptably high heterogeneity statistic.
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Although this brings into question the validity of the result, the magnitude of change in volume is very similar to that found for circumferential measurements. Notably, secondary outcomes were promising. Specifically, the incidence of no postoperative quantifiable improvement in lymphedema was only 11.8 percent, suggesting that a great majority of patients derived benefit from surgery. In an attempt to translate this benefit into a clinically relevant parameter, the ability to discontinue conservative therapy was investigated and found
Volume 133, Number 04 • Surgery for Lymphedema Meta-Analysis
Fig. 2. Secondary outcomes compared by operative technique (*p = 0.04, lymph node transplantation versus lymphovenous shunt). LV, lymphovenous; LN-T, lymph node transplantation.
to be 65 percent across all studies reporting this outcome. Moreover, lymph node transplantation was superior to lymphovenous shunt, affording a 20 percent greater chance of discontinuing conservative treatment. Complication rates were relatively low throughout, and major complications such as operative reexploration had an incidence of less than 3 percent and a concomitant flap salvage rate of 100 percent. It appears, in general, that these procedures are safe for most patients. A comparison of lymph node transplantation to lymphovenous shunt operative techniques demonstrates similar preoperative to postoperative improvements in lymphedema. There are, however, notable differences in secondary outcomes and complication rates. Patients undergoing lymph node transplantation procedures tended to have greater subjective improvement and were more likely to discontinue compression garments.
Although complication rates were higher for lymph node transplantation procedures, a reporting bias likely contributed to this finding, as all lymph node transplantation studies reported complications whereas several lymphovenous shunt studies did not. Furthermore, the additional procedures were elective and minimally invasive—circumferential liposuction and split-thickness skin grafting. It appears that lymph node transplantation procedures may offer the most benefit to patients. A recently published review on outcomes of microsurgery for secondary upper limb lymphedema concluded that there was consistent benefit to surgery and further indicates that lymphatic tissue transplantation was the more successful operative modality.4 Although more investigation into this claim is certainly warranted, our findings suggest that this may in fact be true. Perhaps the most apparent observation and pressing limitation of our study is the
Table 3. Complications LV Shunt Complication Infection Lymphorrhea Reexploration Additional procedure
LN-T
Overall
Studies
Incidence (%)
Studies
Incidence (%)
Studies
Incidence (%)
p*
11 9 0 7
8/207 (3.9) 6/145 (4.1) NA 8/80 (10.0)
4 5 5 5
4/51 (7.8) 11/75 (14.7) 2/75 (2.7) 27/75 (36.0)
15 14 5 12
12/258 (4.7) 17/220 (7.7) 2/75 (2.7) 35/155 (22.6)
0.26 0.008 NA 0.0001
LV, lymphovenous; LN-T, lymph node transplantation; NA, not applicable. *Fisher’s exact test p value.
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Plastic and Reconstructive Surgery • April 2014 heterogeneity of the patient population, assessment modalities, and inconsistent reporting of complications of included studies. Although the validity of our findings is subject to careful interpretation, there is a clear message to be gleaned. Future studies must attempt to standardize every aspect of management, from consistent clinical staging of lymphedema at initial consultation to uniform evaluation of postoperative evolution of disease. The International Society of Lymphology Consensus provides specific recommendations for grading lymphedema in a three- or four-point standardized grading system. Furthermore, a discussion of the various assessment modalities for documenting efficacy of surgery is provided. Ideally, preoperative measurements would be taken both before initiating and after finishing conservative therapy, and immediately preoperatively. Postoperatively, measurements should be taken at routine follow-up, with attention paid to both short-term and long-term outcomes.2 These measures may serve to better delineate whether surgical intervention is indicated, and if so, which patients are most likely to benefit from surgery. As study populations were diverse, it was not possible to compare outcomes for patients with primary lymphedema to those with acquired lymphedema. Furthermore, acquired lymphedema is frequently encountered in association with two different clinical contexts: postsurgical and in the setting of chronic elephantiasis.2 As the pathophysiologic basis and natural history is different for all three of these conditions, it may be that surgical intervention is more appropriate for some patients and more likely to fail in others. Although this study did not differentiate between primary and secondary lymphedema, the great majority of patients had postsurgical lymphedema, and as such, the results are most reflective of operative treatment for this patient population.
CODING PERSPECTIVE
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Lymphovenous Shunt, Upper Extremity 35206 Repair blood vessel, upper extremity 69990 Use of operating microscope Lymphovenous Shunt, Lower Extremity 35226 Repair blood vessel, lower extremity 69990 Use of operating microscope Lymphatic Tissue Transplant 15758 Free flap • Lymphovenous shunts are microvascular procedures. The following blood vessel repair codes are used: 35206 for the upper extremity; 35226 for the lower extremity. • These codes are used whether the anastomosis is end to end, end to side, side to side, sleeve, or lambda. • Codes 35206 and 35226 are macrovascular codes. To report the techniques of microsurgery, code 69990 is used. • Code 69990 is an add-on code, so the multiple procedure modifier, 51, is not appended. • These codes are used for each anastomosis performed. Thus, in the case of the lambda procedure (if performed in the upper extremity), the procedure is reported as follows: 35206 Repair blood vessel, upper extremity 35206-59 Repair blood vessel, upper extremity 69990 Use of operating microscope • Code 69990 is used only once per operative session. • The lymph node transfer is a free flap, so code 15758 is used. Free flap codes include use of the operating microscope, so code 69990 is not reported.
CONCLUSIONS Microsurgical interventions for peripheral lymphedema appear to provide consistent quantitative improvements postoperatively and have a relatively wide safety margin. These quantitative improvements have clinical relevance, as a substantial number of patients are able to discontinue conservative therapy. Lymphatic tissue transplantation may provide better outcomes compared with lymphovenous shunt; however, well-designed head-to-head comparisons are still needed to evaluate this more definitively.
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This information provided by Dr. Raymond Janevicius is intended to provide coding guidance.
Liza C. Wu, M.D. University of Pennsylvania Health Systems 3400 Spruce Street 10 Penn Tower Philadelphia, Pa. 19104 [email protected]
ACKNOWLEDGMENT
This study was funded by the Department of Surgery of the Perelman School of Medicine at the University of Pennsylvania.
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18. Auba C, Marre D, Rodríguez-Losada G, Hontanilla B. Lymphaticovenular anastomoses for lymphedema treatment: 18 months postoperative outcomes. Microsurgery 2012;32: 261–268. 19. 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. 20. Demirtas Y, Ozturk N, Yapici O, Topalan M. Comparison of primary and secondary lower-extremity lymphedema treated with supermicrosurgical lymphaticovenous anastomosis and lymphaticovenous implantation. J Reconstr Microsurg. 2010;26:137–143. 21. O’Brien BM, Mellow CG, Khazanchi RK, Dvir E, Kumar V, Pederson WC. Long-term results after microlymphaticovenous anastomoses for the treatment of obstructive lymphedema. Plast Reconstr Surg. 1990;85:562–572. 22. Chang DW. Lymphaticovenular bypass for lymphedema management in breast cancer patients: A prospective study. Plast Reconstr Surg. 2010;126:752–758. 23. Baumeister RG, Siuda S. Treatment of lymphedemas by microsurgical lymphatic grafting: What is proved? Plast Reconstr Surg. 1990;85:64–74; discussion 75. 24. Weiss M, Baumeister RG, Hahn K. Post-therapeutic lymphedema: Scintigraphy before and after autologous lymph vessel transplantation: 8 years of long-term follow-up. Clin Nucl Med. 2002;27:788–792. 25. Becker C, Assouad J, Riquet M, Hidden G. Postmastectomy lymphedema: Long-term results following microsurgical lymph node transplantation. Ann Surg. 2006;243:313–315. 26. Olszewski WL. Lymphovenous microsurgical shunts in treatment of lymphedema of lower limbs: A 45-year experience of one surgeon/one center. Eur J Vasc Endovasc Surg. 2013;45:282–290. 27. Maegawa J, Yabuki Y, Tomoeda H, Hosono M, Yasumura K. Outcomes of lymphaticovenous side-to-end anastomosis in peripheral lymphedema. J Vasc Surg. 2012; 55:753–760. 28. Maegawa J, Mikami T, Yamamoto Y, Satake T, Kobayashi S. Types of lymphoscintigraphy and indications for lymphaticovenous anastomosis. Microsurgery 2010;30:437–442. 29. Mukenge SM, Catena M, Negrini D, et al. Assessment and follow-up of patency after lymphovenous microsurgery for treatment of secondary lymphedema in external male genital organs. Eur Urol. 2011;60:1114–1119. 30. Yamamoto Y, Sugihara T. Microsurgical lymphaticovenous implantation for the treatment of chronic lymphedema. Plast Reconstr Surg. 1998;101:157–161. 31. 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. 32. Gharb BB, Rampazzo A, di Spilimbergo SS, 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. 33. Damstra RJ, Voesten HG, van Schelven WD, van der Lei B. Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema: A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature. Breast Cancer Res Treat. 2009;113:199–206. 34. Campisi C, Boccardo F. Microsurgical techniques for lymphedema treatment: Derivative lymphatic-venous microsurgery. World J Surg. 2004;28:609–613.
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Operative Treatment of Peripheral Lymphedema: A Systematic Meta-Analysis of the Efficacy and Safety of Lymphovenous Microsurgery and Tissue Transplantation Marten N. Basta, B.A. Lin Lin Gao, M.D. Liza C. Wu, M.D. Philadelphia, Pa.
cpt
Background: The purpose of this study was to quantify the efficacy and safety of microsurgery for lymphedema through a systematic meta-analysis, which has not been described before. Methods: A literature search was conducted to identify all articles involving microsurgical treatment of lymphedema. Studies meeting criteria for inclusion were rated on methodologic quality based on the American Society of Plastic Surgeons levels of evidence. Demographic information, cause of lymphedema, and surgical technique were recorded. Quantitative change in lymphedema and perioperative complications were noted. Results: Twenty-seven studies were included, with 24 offering level IV evidence and three offering level III evidence. Lymphovenous shunt procedures were performed in 22 studies and lymph node transplantation was performed in five. Excess circumference was reduced by 48.8 ± 6.0 percent, and absolute circumference was reduced by 3.31 ± 0.73 cm. Studies reporting change in volume demonstrated reduction in excess volume by 56.6 ± 9.1 percent, and absolute volume was reduced by 23.6 ± 2.1 percent. The incidence of no improvement in lymphedema postoperatively was 11.8 percent, and 91.2 percent of patients reported subjective improvement. Approximately 64.8 percent of patients discontinued compression garments at follow-up. Complications included operative-site infection (4.7 percent), lymphorrhea (7.7 percent), reexploration for flap congestion (2.7 percent), and additional procedures (22.6 percent). Conclusions: Operative interventions for peripheral lymphedema appear to provide consistent quantitative improvements postoperatively, with a relatively wide safety margin. Lymph node transplantation may provide better outcomes compared with lymphovenous shunt, but well-designed head-to-head comparisons are needed to evaluate this further. (Plast. Reconstr. Surg. 133: 905, 2014.) CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
P
eripheral lymphedema represents a complex physiologic manifestation of disrupted lymphatic drainage systems. The disease may be congenital, caused by agenesis or dysplasia of any component of the lymphatic network; From the Division of Plastic Surgery, Perelman School of Medicine at the University of Pennsylvania; the Division of Plastic Surgery, Hospital of the University of Pennsylvania; and the Division of Plastic Surgery, University of Pennsylvania Health Systems. Received for publication August 29, 2013; accepted September 26, 2013. Copyright © 2014 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000000010
or acquired, most commonly secondary to surgical disruption or recurrent infection.1 Regardless of pathophysiologic cause, the clinical presentation is characterized by chronic swelling, accompanied by localized pain, atrophic skin findings, and recurrent infections, all of which contribute to gradual functional decline. Treatment for lymphedema begins with combined decongestive physiotherapy.2 Although this alone may afford patients enough symptomatic relief, conservative therapy relies on a Disclosure: The authors have no financial interest to declare in relation to the content of this article.
www.PRSJournal.com
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Plastic and Reconstructive Surgery • April 2014 substantial amount of patient compliance and ability to tolerate the burdens of lifelong physical therapy appointments and compression garments. As our understanding of the underlying etiopathology and surgical experience evolves, so too has the approach to operative treatment. Specifically, reductive surgery has given way to lymphovenous shunt and more recently, lymphatic tissue or lymph node transplantation, which have become popularized with advances in microsurgical techniques. Numerous studies have reported successful experiences with operative management of peripheral lymphedema, whereas others have demonstrated rather disappointing outcomes. As current literature reviews on the topic have generally cited heterogeneity in patient selection and outcomes reporting, there have been no systematic meta-analyses able to quantify what, if any, benefit is evidenced by surgical therapy.3,4 With the inconclusive results of these studies, much controversy surrounds indications for operative intervention, which surgical techniques provide the best outcomes, and which patients are likely to benefit from conservative versus operative management. The purpose of this study, therefore, was to quantify the efficacy and safety of various operative treatments for peripheral lymphedema.
PATIENTS AND METHODS Literature Search A literature search was conducted to identify all articles involving microsurgical interventions to treat lymphedema. Ovid MEDLINE was searched using the following headings and keyword terms: “lymphedema,” “microsurgery,” “lymphovenous,” “lympholymphatic,” “shunt,” and “anastomosis.” Search results were limited to English articles only, yielding 124 results. Titles and abstracts were examined and selected for full article review based on appropriate scope of study and patient population. In addition, selected study references and review articles were examined for further article sources. Study Selection and Methodologic Quality After identifying relevant studies through title and abstract information, studies were selected for inclusion based on the following criteria: 1. The study involved lymphatic reconstruction with lymphovenous shunt or lymphatic tissue transplant and described the
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surgical protocol and methodology of patient evaluation. 2. The study was published between 1985 and 2013. 3. The study reported relevant outcomes data. 4. The study was not limited to single case reports. 5. The study was in English. Studies were not included if they did not meet the above criteria and/or if multiple publications were from the same group; only studies that reported data from nonoverlapping time periods were included. Studies were then rated on methodologic quality based on the American Society of Plastic Surgeons Evidence Rating Scale for Therapeutic Studies.5 Data Extraction Baseline patient characteristics such as age, cause of lymphedema, and anatomical sites of involvement were recorded. Surgical protocols were categorized as either lymphovenous shunt or vascularized lymph node transplantation, and the configuration(s) of microsurgical anastomosis was recorded. Outcomes collected included both objective and subjective preoperative to postoperative change in lymphedema, average patient follow-up, and incidence of complications. Objective methods for measuring change in lymphedema included serial circumferential limb measurements and volumetric water displacement. Measurements were grouped as either change in absolute limb circumference or volume or change in excess limb circumference or volume relative to the contralateral, unaffected limb. When multiple levels of circumferential measurements were reported, measurements were averaged for each patient. For studies missing data such as standard deviations, the study authors were contacted and data were retrieved as available or qualitative analysis was performed alternatively. Statistical Analysis Data was input to RevMan5.2 (The Cochrane Collaboration, Copenhagen, Denmark) for analysis.6 Continuous variables, such as age, were compared by means of standard summary statistics. Outcomes for improvement of lymphedema were compared in forest plots and summarized with mean differences, and the confidence interval was set to 95 percent. Separate comparisons were made for improvement in studies reporting
Volume 133, Number 04 • Surgery for Lymphedema Meta-Analysis circumferential change and volumetric change. Patient populations were subdivided into those with upper limb lymphedema or lower limb lymphedema, and the effect size was calculated separately and with both populations combined when possible. Dichotomous data, such as the incidence of complications, were summarized with Fisher’s exact test, with significance set to p < 0.05. Heterogeneity of comparison data was judged by means of the I2 statistic when applicable, ranging from 0 to 99 percent (judged acceptable for I2, 75 percent). Publication bias was inspected routinely by means of funnel plots for each comparison.
RESULTS Study Characteristics A total of 27 studies were included in this systematic review. Twenty-four studies were retrospective case series presenting level IV evidence, two studies were cohort studies with level III evidence, and one was a case-control study with level III evidence (Table 1).7–33 Twenty studies provided sufficient data to be included in quantitative meta-analysis, and the remaining seven studies were included for qualitative summary.
Both upper and lower extremity populations were included in this meta-analysis. There were 10 studies that examined upper extremity lymphedema reduction, 11 studies that examined lower extremity reduction, and five studies that examined both upper and lower extremities. One study involved external genitalia lymphedema. Patient Characteristics Overall, the study population consisted of 1619 patients, with a female-to-male ratio of approximately 3:2. Patient age ranged from 7 to 92 years of age; however, the majority of patients were aged between 45 and 60 years. Although cause of lymphedema included both congenital and acquired, the vast majority of patients suffered from postsurgical lymphedema associated with oncologic conditions, including breast cancer and various gynecologic cancers. The staging system of lymphedema was inconsistent across studies. Of those studies reporting stage, either the Campisi lymphedema classification or the International Society of Lymphology classification system was used.2,34 Of studies reporting International Society of Lymphology classification, approximately 50 percent of patients were stage II, 25 percent were stage III, and the remaining 25 percent were stage I or IV. Average
Table 1. Summary of Included Studies Reference Felmerer et al., 2012 Huang et al., 19858 Matsubara et al., 20069 Yamamoto et al., 200310 Koshima et al., 200311 Koshima et al., 200012 Cheng et al., 201213 Furukawa et al., 201114 Lin et al., 200915 Yamamoto et al., 201116 Narushima et al., 201017 Auba et al., 201218 Ipsen et al., 198819 Demirtas et al., 201020 O’Brien et al., 199021 Chang et al., 201022 Baumiester and Siuda, 199023 Weiss et al., 200224 Becker et al., 200625 Olszewski, 201326 Maegawa et al., 201227 Maegawa et al., 201028 Mukenge et al., 201129 Yamamoto and Sugihara, 199830 Cheng et al., 201331 Gharb et al., 201132 Damstra et al., 200933 7
Design
Lymphedema Site
Operative Technique
No.
F/U (yr)
LOE
R-CS R-CS R-CS P-CS R-COH R-COH R-CS P-CS R-CS R-CS R-CS R-CS R-CS R-CS R-CS P-CS R-CS R-CS R-CS R-CS R-CS R-CS R-CS R-CS P-CC R-CS P-CS
U+L L L U L U L U U L L U+L L L U+L U U+L U U L L L O U+L U U U
E-E E-E, sleeve E-S E-E, sleeve E-E E-E LN-T E-E, sleeve LN-T E-E, S-E, E-S, lambda E-E, E-S, DE-E, S-E E-E S-E E-E E-E E-E E-E E-E, E-S LN-T E-E, E-S S-E S-E E-E, S-E E-E LN-T LN-T E-S
12 91 9 18 13 12 7 9 13 20 14 9 7 78 52 20 48 12 24 960 57 111 5 7 20 21 10
2.6 2.0 5.7 2.0 4.6 2.2 0.7 1.2 4.7 NA 0.7 1.5 1.0 1.1 4.2 1.5 1.3 7.7 8.3 5.0 1.2 NA 0.6 1.5 3.3 3.6 8
IV IV IV IV III III IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV III IV IV
LN-T, vascularized lymph node transfer; LOE, level of evidence; DE-E, double end-to-end; U, upper limb; L, lower limb; O, other (external genitalia lymphedema); R, retrospective; P, prospective; CS, case series; COH, cohort; CC, case-control; F/U, follow-up; NA, not applicable.
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Plastic and Reconstructive Surgery • April 2014 follow-up among all studies was 3.3 years, with individual cohort follow-up ranging from 8 months to 10 years. Patient Selection Criteria Although the majority of studies described factors taken into consideration for operative treatment of lymphedema, parameters for patient selection were inconsistently specified. All studies indicated that patients who underwent operative management had previously failed conservative therapy. In general, this criterion was fulfilled with less than 50 percent reduction of lymphedema with a minimum of 6 months of conservative therapy. Other indications were recurrent or severe cellulitis inadequately treated with antibiotics and functional impairment secondary to lymphedema. Important exclusion criteria reported included chronic venous insufficiency and severe fibrosclerotic lymphedema diagnosed on preoperative lymphoscintigraphy, and most studies were composed of patients with secondary lymphedema only. Operative Technique Lymphovenous Shunt The majority of studies used lymphovenous shunt as the operative approach to treatment. A variety of configurations were described for reconstructing the lymphedematous limb. The most popular was the lymphaticovenous end-to-end anastomosis. In this technique, patent blue dye can be injected intraoperatively to identify patent lymphatics. Subdermal venules are selected as the proximal recipient of lymphatic vessels. Specific advantages of these vessels cited by numerous authors included less size discrepancy, which facilitates more precise anastomosis, and a relatively lower intraluminal pressure compared with cutaneous veins, which prevents backflow from the venous system. Operative microscopes were uniformly used, and anastomosis was completed with 11-0 or 12-0 suture. Variations on the end-to-end configuration were frequently used in different studies. These included lymphaticovenous end-to-side, side-to-end, and double end-to-side shunts. Furthermore, Yamamoto et al. described the “lambda-shaped” configuration, which joined the proximal end of the lymphatic vessel to the side of the vein and the distal end of the lymphatic vessel to the end of the same vein.16 Finally, the end-to-end or sleeve anastomosis has been used in creating the lymphaticovenous shunt by multiple authors.8,10,14 The indication
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for this configuration was the inability to identify a suitable lymphatic vessel of appropriate size for microsurgical anastomosis. As such, multiple lymphatics and their surrounding soft-tissue adventitia are implanted into the end of a larger, cutaneous vein and anastomosed with 10-0 or 11-0 sutures in an interrupted fashion. Vascularized Lymph Node Transplantation Vascularized lymph node transplantation was the method of reconstruction in five of the included articles. Both Lin et al.15 and Becker et al.25 used the groin as a donor site in the treatment of upper limb lymphedema. The recipient sites were the distal wrist and the axilla, respectively. Cheng et al.13 recently proposed the submental vascularized lymph node flap as the donor for lower limb lymphedema, and the ankle served as the recipient site. In 2013, this same group described a groin flap designed off of perforators, with the wrist or elbow serving as the recipient site.31 Similarly, Gharb et al. used the same design in a 2011 study.32 Intraoperative lymphatic dye staining with methylene blue or indocarmine was reported in 19 studies, and lymphatic patency was assessed by means of lymphoscintigraphy or lymphography in 19 studies as well. Postoperative Care Postoperative management was assessed for each study. Six studies specified routine postoperative antibiotic prophylaxis for 1 week in patients without a history of recurrent cellulitis and 6 months or more in patients with a history of recurrent or severe cellulitis. Six studies detailed perioperative anticoagulation, with two studies using low-molecular-weight heparin, two using dextran, and two using low-dose aspirin. The duration of anticoagulation was approximately 1 month for heparin or dextran and 3 months for aspirin. The protocol for use of compression stockings was reported variably, with 14 studies initiating compression garments either in the immediate postoperative period or within 1 month of surgery, continued on an as-needed basis, and seven studies in which use of compression garments postoperatively was not recommended. Primary Outcomes Objective improvement of lymphedema postoperatively was reported heterogeneously, with studies presenting either change in limb circumference or volume as either absolute difference or difference of excess size relative to the contralateral limb in patients with unilateral lymphedema.
Volume 133, Number 04 • Surgery for Lymphedema Meta-Analysis Table 2 summarizes the four major parameters reported, and measures of heterogeneity indicate that circumferential measurements were homogenous and reliable, although all parameters demonstrated statistically significant improvement in lymphedema postoperatively. Specifically, excess circumference and volume were reduced by 49 percent and 57 percent of preoperative values, respectively; absolute volume was reduced by 23.6 percent; and absolute circumference was reduced by 3.31 cm (8.5 percent) of preoperative values. Figure 1 depicts the forest plots of the four major parameters (Fig. 1). Secondary Outcomes Results were comparable between patients with upper and lower limb lymphedema, and in studies of lymphovenous shunt procedures versus lymph node transplantation (Fig. 2). Overall, the incidence of no change or worsening of lymphedema postoperatively was approximately 11.8 percent; only studies detailing each patient’s outcomes were included in this statistic. Subjective improvement of lymphedema was documented in 13 studies, and overall, 92.7 percent of patients related symptomatic improvement after operative intervention. However, only two studies used a validated patientreported outcomes scale in assessing subjective improvement. Finally, the proportion of patients able to discontinue compression therapy was 78 percent in lymph node transplantation studies, compared with 56.3 percent in lymphovenous shunt studies (p = 0.04). Complications Complications are listed in Table 3. Postoperative wound-site infection occurred in 4.7
percent of patients, all of which resolved with antibiotic administration. In four studies reporting wound infection, the protocol did not include prophylactic antibiotics, whereas in two others, no wound infections occurred after the authors began administering prophylactic antibiotics routinely. The incidence of lymphorrhea was 7.7 percent overall; however, duration of symptoms and management were not reported. Furthermore, all lymph node transplantation studies reported this outcome, whereas only nine of 21 lymphovenous shunt studies did so. Operative reexploration for vascularized lymph node flap venous congestion was required in two of 75 patients. Finally, 35 patients underwent additional elective procedures to improve lymphedema subsequent to the initial procedure, including donor-site split-thickness skin grafting, liposuction, and excess skin excision.
DISCUSSION This systematic meta-analysis attempts to quantify the efficacy and safety of operative treatment of peripheral lymphedema. Of the 27 studies included, only three were level III evidence and the remainder were level IV. As such, interpretation of the findings of this review mandates evaluation of the evidence in light of the methodologic flaws inherent in the studies included. However, a number of observations can be ascertained from our results and deserve consideration. Of the four outcome measures presented here, change in excess circumference as a percentage of preoperative excess was most frequently reported. It follows that this measure was also the most homogenous and therefore most reliable of the pooled outcomes. We demonstrated
Table 2. Primary Outcomes* Parameter Excess circumference reduction, % All ULL LLL LV shunt LN-T Absolute circumference reduction, cm All ULL LLL Excess volume reduction, % All Absolute volume reduction, % All
No. of Studies
No.
Mean (95% CI)
I2 (%)
11 7 4 7 4
131 90 34 80 51
48.8 (42.8–54.8) 46.0 (39.0–53.0) 57.4 (44.5–70.3) 48.9 (40.7–57.2) 48.5 (35.3–61.6)
0 0 0 0 49
11 6 5
138 79 52
3.31 (2.58–4.04) 2.73 (1.63–3.83) 3.52 (2.28–4.75)
0 16 0
4
165
56.6 (47.5–65.6)
78
2
60
23.6 (21.5–25.7)
42
ULL, upper limb lymphedema; LLL, lower limb lymphedema; LV, lymphovenous, LN-T, lymph node transplantation. *p < 0.00001 for all endpoints (or p < 0.05).
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Fig. 1. Primary outcomes. (Above) Excess circumference reduction (values are percentages). (Second row) Circumference reduction (in centimeters). (Third row) Excess volume reduction (values are percentages). (Below) Absolute volume reduction (values are percentages).
an average reduction in excess circumference of approximately 48.8 percent across 11 studies with 131 patients. Although there is no existing literature with which to compare this result, it appears as though surgical treatment does consistently lead to a substantial improvement in this parameter. Furthermore, circumference reduction (in centimeters) consistently supports this finding, with an average 3.31-cm reduction across 11 studies. Admittedly, few studies reported on volume reduction, and an immediate consequence of this is an unacceptably high heterogeneity statistic.
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Although this brings into question the validity of the result, the magnitude of change in volume is very similar to that found for circumferential measurements. Notably, secondary outcomes were promising. Specifically, the incidence of no postoperative quantifiable improvement in lymphedema was only 11.8 percent, suggesting that a great majority of patients derived benefit from surgery. In an attempt to translate this benefit into a clinically relevant parameter, the ability to discontinue conservative therapy was investigated and found
Volume 133, Number 04 • Surgery for Lymphedema Meta-Analysis
Fig. 2. Secondary outcomes compared by operative technique (*p = 0.04, lymph node transplantation versus lymphovenous shunt). LV, lymphovenous; LN-T, lymph node transplantation.
to be 65 percent across all studies reporting this outcome. Moreover, lymph node transplantation was superior to lymphovenous shunt, affording a 20 percent greater chance of discontinuing conservative treatment. Complication rates were relatively low throughout, and major complications such as operative reexploration had an incidence of less than 3 percent and a concomitant flap salvage rate of 100 percent. It appears, in general, that these procedures are safe for most patients. A comparison of lymph node transplantation to lymphovenous shunt operative techniques demonstrates similar preoperative to postoperative improvements in lymphedema. There are, however, notable differences in secondary outcomes and complication rates. Patients undergoing lymph node transplantation procedures tended to have greater subjective improvement and were more likely to discontinue compression garments.
Although complication rates were higher for lymph node transplantation procedures, a reporting bias likely contributed to this finding, as all lymph node transplantation studies reported complications whereas several lymphovenous shunt studies did not. Furthermore, the additional procedures were elective and minimally invasive—circumferential liposuction and split-thickness skin grafting. It appears that lymph node transplantation procedures may offer the most benefit to patients. A recently published review on outcomes of microsurgery for secondary upper limb lymphedema concluded that there was consistent benefit to surgery and further indicates that lymphatic tissue transplantation was the more successful operative modality.4 Although more investigation into this claim is certainly warranted, our findings suggest that this may in fact be true. Perhaps the most apparent observation and pressing limitation of our study is the
Table 3. Complications LV Shunt Complication Infection Lymphorrhea Reexploration Additional procedure
LN-T
Overall
Studies
Incidence (%)
Studies
Incidence (%)
Studies
Incidence (%)
p*
11 9 0 7
8/207 (3.9) 6/145 (4.1) NA 8/80 (10.0)
4 5 5 5
4/51 (7.8) 11/75 (14.7) 2/75 (2.7) 27/75 (36.0)
15 14 5 12
12/258 (4.7) 17/220 (7.7) 2/75 (2.7) 35/155 (22.6)
0.26 0.008 NA 0.0001
LV, lymphovenous; LN-T, lymph node transplantation; NA, not applicable. *Fisher’s exact test p value.
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Plastic and Reconstructive Surgery • April 2014 heterogeneity of the patient population, assessment modalities, and inconsistent reporting of complications of included studies. Although the validity of our findings is subject to careful interpretation, there is a clear message to be gleaned. Future studies must attempt to standardize every aspect of management, from consistent clinical staging of lymphedema at initial consultation to uniform evaluation of postoperative evolution of disease. The International Society of Lymphology Consensus provides specific recommendations for grading lymphedema in a three- or four-point standardized grading system. Furthermore, a discussion of the various assessment modalities for documenting efficacy of surgery is provided. Ideally, preoperative measurements would be taken both before initiating and after finishing conservative therapy, and immediately preoperatively. Postoperatively, measurements should be taken at routine follow-up, with attention paid to both short-term and long-term outcomes.2 These measures may serve to better delineate whether surgical intervention is indicated, and if so, which patients are most likely to benefit from surgery. As study populations were diverse, it was not possible to compare outcomes for patients with primary lymphedema to those with acquired lymphedema. Furthermore, acquired lymphedema is frequently encountered in association with two different clinical contexts: postsurgical and in the setting of chronic elephantiasis.2 As the pathophysiologic basis and natural history is different for all three of these conditions, it may be that surgical intervention is more appropriate for some patients and more likely to fail in others. Although this study did not differentiate between primary and secondary lymphedema, the great majority of patients had postsurgical lymphedema, and as such, the results are most reflective of operative treatment for this patient population.
CODING PERSPECTIVE
cpt
Lymphovenous Shunt, Upper Extremity 35206 Repair blood vessel, upper extremity 69990 Use of operating microscope Lymphovenous Shunt, Lower Extremity 35226 Repair blood vessel, lower extremity 69990 Use of operating microscope Lymphatic Tissue Transplant 15758 Free flap • Lymphovenous shunts are microvascular procedures. The following blood vessel repair codes are used: 35206 for the upper extremity; 35226 for the lower extremity. • These codes are used whether the anastomosis is end to end, end to side, side to side, sleeve, or lambda. • Codes 35206 and 35226 are macrovascular codes. To report the techniques of microsurgery, code 69990 is used. • Code 69990 is an add-on code, so the multiple procedure modifier, 51, is not appended. • These codes are used for each anastomosis performed. Thus, in the case of the lambda procedure (if performed in the upper extremity), the procedure is reported as follows: 35206 Repair blood vessel, upper extremity 35206-59 Repair blood vessel, upper extremity 69990 Use of operating microscope • Code 69990 is used only once per operative session. • The lymph node transfer is a free flap, so code 15758 is used. Free flap codes include use of the operating microscope, so code 69990 is not reported.
CONCLUSIONS Microsurgical interventions for peripheral lymphedema appear to provide consistent quantitative improvements postoperatively and have a relatively wide safety margin. These quantitative improvements have clinical relevance, as a substantial number of patients are able to discontinue conservative therapy. Lymphatic tissue transplantation may provide better outcomes compared with lymphovenous shunt; however, well-designed head-to-head comparisons are still needed to evaluate this more definitively.
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This information provided by Dr. Raymond Janevicius is intended to provide coding guidance.
Liza C. Wu, M.D. University of Pennsylvania Health Systems 3400 Spruce Street 10 Penn Tower Philadelphia, Pa. 19104 [email protected]
ACKNOWLEDGMENT
This study was funded by the Department of Surgery of the Perelman School of Medicine at the University of Pennsylvania.
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