LYMPH NODE FLAP TRANSFER FOR PATIENTS WITH SECONDARY LOWER LIMB LYMPHEDEMA CARLOS M. FARIA, M.D., Ph.D.,1,2 BERNARDO N. BATISTA, M.D.,1,2* MICHEL GERMAIN, M.D., Ph.D.,3 JOSE and CORINNE BECKER, M.D.3
Background: Previous authors have shown benefits from the use of lymph node flap transfer (LNFT) to treat lymphedema of the arms, but there is little evidence for its use for lower limb lymphedema. We performed a retrospective analysis of a series of patients suffering from secondary lower limb lymphedema treated with a free LNFT. Methods: 52 cases of LNFT to treat 41 legs in 38 patients with secondary lymphedema were retrospectively reviewed. The causes of the lymphedema included lymphedema secondary to hysterectomy for uterine cancer, melanoma resections on the leg, lymphoma treatment and testicular cancer, cosmetic surgery to the limb, lipoma resection at the inguinal region, and a saphenectomy. Patients had been suffering with lymphedema for an average of 9.1 6 7.3 years at the time of LNFT. Results: Eleven patients (28.9%) presented with minor complications treated conservatively. For 23 legs there was enough data to follow limb volume evolution after a single LNFT. Total volume reduction in eight legs (two patients with no measures of the healthy limb and three bilateral) was 7.1 6 8.6%. Another group of 15 patients with unilateral lymphedema had an average 46.3 6 34.7% reduction of excess volume. Better results (>30% REV) were associated with smaller preoperative excess volume (P 5 0.045). Conclusion: Patients with secondary leg lymphedema can benefit from LNFT. Results in patients with mild presentations seem to be better than in more severe C 2015 Wiley Periodicals, Inc. Microsurgery 00:000–000, 2015. cases. V
Lymphedema is one of the most poorly understood, relatively underestimated, and least researched complications of cancer treatment. In the developed world, cancer treatment is recognized as the primary cause of secondary lymphedema.1 It is an important complication and source of burden to patients.2 Inguinal lymph node dissection and radiotherapy to the groin exposes patients under oncological treatment of the legs or pelvic structures to similar risks of developing lymphedema as the breast cancer population.3 Large efforts have been made by the microsurgical community to generate better evidence to support reconstructive approaches to the lymphatic system. Many techniques have been proposed and have shown variable results.4–6 Lymphaticovenular bypass,7–10 lymph collector graft transposition11 and lymph node flap transfer (LNFT)12 are classified as physiologic procedures, as they are intended to increase the draining capacity of the limb lymphatic system. LNFT has been proposed by the senior author12 and performed extensively over the last 15–20 years.3,12–16 However, there is still very little evi-
1 ~o Paulo, Plastic Surgery Department, Medical School of the University of Sa ~o Paulo, Brazil Sa 2 ^s, Sa ~o Paulo, Brazil Instituto de Ensino e Pesquisa, Hospital Sırio-Libane 3 Lymphoedema Center, Clinique Jouvenet, Paris, France Presented as a free article at: 24th Congress of the International Society of Lymphology, Rome/Italy, September 16-20, 2013; ASPS 2013, San Diego/ USA, October 11-15, 2013. *Correspondence to: Bernardo Nogueira Batista, Rua Prof. Atılio Innocenti, ~o Paulo, CEP 045380-001, Brazil. E-mail: bernardonb@uol. 683, Itaim Bibi, Sa com.br Received 4 September 2014; Revision accepted 19 February 2015; Accepted 23 February 2015 Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/micr.22404
Ó 2015 Wiley Periodicals, Inc.
dence of its benefits for patients with lower limb lymphedema. We performed a retrospective analysis of a series of patients suffering from secondary lower limb lymphedema treated with a free LNFT. The purpose of this study was to evaluate postoperative complications and limb volume evolution after a single LNFT. PATIENTS AND METHODS
Thirty-eight patients with secondary leg lymphedema were included. Inclusion was determined by the documented registry of preoperative girth measurements and at least one postoperative registry for comparison. Incomplete surgical records were excluded from the sample. Three patients had bilateral lymphedema (total of 41 legs treated). All patients received at least one LNFT, performed by the same surgeon (C.B.) between 1990 and 2012. Data related to the lymphedema diagnosis, history and surgical treatment were collected. Postoperative complications reports were retrieved for safety assessment. The majority of patients treated were women (34 out of 38 patients). The average age at the time of lymph node transfer was 52.1 6 12.4 years (lowest 13 years and highest 74 years). Thirty-five patients presented with unilateral lymphedema while three patients had both limbs affected, with a total of 41 limbs treated. Lymphedema appeared at variable intervals after the primary surgery, ranging from a few days to up to 5 years. Patients had been suffering with lymphedema for an average of 9.1 6 7.3 years (1–26 years) at the time of LNFT. They were resistant to continuous physiotherapy, and had previously been subjected to multiple cycles of complex decongestive therapy and continuous use of compression garments.
2
Batista et al. Table 1. Population Demographics
Age Years with lymphedema Sex Side
Lymph Node Dissection Radiotherapy Infection status
Primary surgery
Mean 6 SD
Median
Range
52.1 6 12.4 9.1 6 7.3
55 6 N 5 38 4 34 3 18 17 41 30 8 27 11 23 11 2 2 22 3 4 1 3 1 1 3
13–74 1–26 % 10.5% 89.5%
Male Female Bilateral Left Right Total Yes No Yes No No records up to 2 episodes (year) 2–4 wpisodes (year) >4 episodes (year) Hysterectomy Melanoma Lymphoma Testicule Thigh lift Lipoma Saphenectomy NA
51.2% 48.8% 100% 78.9% 21.1% 71.1% 28.9% 60.5% 28.9% 5.3% 5.3% 57.9% 7.9% 10.5% 2.6% 7.9% 2.6% 2.6% 7.9%
For 3 patients, the primary cause of the lymphedema was not recorded. Twenty-two patients (57.9%) presented with lymphedema secondary to hysterectomy for uterine cancer, 3 (7.9%) for melanoma resections on the leg, 4 (10.5%) for lymphoma treatment, and 1 (2.6%) for testicular cancer. These 30 patients had inguinal lymph node dissections for their oncologic treatment and 27 of them had additional radiotherapy. The remaining 5 patients presenting with secondary leg lymphedema had been previously subjected to either cosmetic surgery to the limb after massive weight loss (3 patients), a lipoma resection at the inguinal region (1 patient) or a saphenectomy (1 patient). For this last patient, it remains unclear if the saphenectomy was the cause of a secondary lymphedema, or if it was performed in the setting of a mild case of congenital lymphedema that was worsened by the procedure. Fifteen of these patients had reports of infection episodes to the affected limb that needed medical treatment. Two of them had an average of 2–4 episodes a year and another two patients had infections more than 4 times a year, and received continuous antibiotic prophylaxis (Table 1). Surgical Technique
Over the past 20 years, technical aspects of LNFT have evolved. For lower limb lymphedema, the lateral thoracic region was the most common donor site. A free Microsurgery DOI 10.1002/micr
flap of subcutaneous fat tissue based on small branches of the thoracodorsal or the lateral thoracic vessels was harvested. Dissection was limited cranially to avoid the axillary region, and caudally by the inframamary fold. The flap included a group of lymph nodes located below the edge of the pectoralis muscle (level I for breast oncology surgeons) and above the lateral edge of the latissimus dorsi muscle. In situations where skin resurfacing was needed, these flaps were designed with a skin paddle. We did not include a skin paddle for flap surveillance since we believe that it can limit the final setting of the flap and consider that the risks and costs of a potential reintervention outweighs the chance of salvage in these small and short pedicled flaps. Fibrosis from the previous procedures was extensively removed and the flap transferred to the best size-match pedicle found in the recipient site. The flap was buried in the inguinal region beneath the superficial fascia, in an attempt to bridge the superficial and deep lymphatic system.3 A specialized physiotherapist usually administered postoperative decongestive therapy. Records of limb girth measured during pre-operative and follow-up consultations at six different levels (ankle, ankle 1 10 cm, knee 210 cm, knee, knee 110 cm, and knee 1 20 cm) were retrieved. Using the truncated cone volume formula, we were able to estimate the volume of part of the limb. These estimations were analyzed to evaluate lymphedema improvement after surgical treatment. In patients with unilateral lymphedema, measurements of the non-affected limb, when available, allowed for comparison with a healthy leg and determination of the percentage of excess volume (PEV) of the affected limb (PEV 5 volume of affected limb 2 volume of unaffected contralateral limb/volume of unaffected contralateral limb). Only data concerning the first LNFT was considered for analysis. Whenever the patient was submitted to a second intervention, follow-up was terminated and further data on girth measurement not considered. Excess volume reduction between preoperative and postoperative were defined by the following formula: REV 5 preoperative PEV 2 postoperative PEV/preoperative PEV. Statistical Analysis
Means, standard deviations, medians and ranges were used to summarize continuous variables. Frequencies and proportions were used to summarize categorical variables. We used a Wilcoxon signed rank test to compare preoperative and postoperative volumes of the affected and healthy limbs separately. A Wilcoxon-Mann Whitney test was used to determine if quantitative improvement (REV) was associated with the severity of disease or the time living with lymphedema. All tests were two-sided and values of p < 0.05 were considered significant. The
LNFT for Leg Lymphedema Table 2. Total Volume Variation of Lymphedematous Legs Treated with LNFT (No Available Information for Contralateral Limb) N58 Initial limb volume (L) Last limb volume (L) Volume variation (mL) Follow-up (m) Total volume reduction
Mean 6 SD
Median
Range
6.33 6 1 5.91 6 1.46 410 6 520 48.63 6 28.75 7.13 6 8.56%
6.15 5.65 (2600) 51 10%
4.8–8.2 3.9–8.5 [(2900) 21300] [4–85] [(23)217%]
Table 3. Excess Volume Reduction for Lymphedematous Legs Treated with LNFT Compared with a Healthy Contralateral Limb N 5 15
Mean 6 SD
Sick leg Preop. 7.2 6 1.5 Sick leg Postop. 6.3 6 1.3 Healthy leg Preop. 5 6 1.1 Healthy leg Postop. 5.1 6 1.1 Preop. PEV 40 6 20% Follow-up (m) 12.7 6 10.7 REV 46.3 6 34.7%
Median 7 6.3 4.8 4.9 42% 10 32%
Range
P
4.6–10.9 z 5 3128, 4.5–8.4 P < 0.002 3.5–8 z 5 0.746, 3.5–7.9 P 5 0.45 6–105% 3–36 1–100%
analyses were performed using Stata 13.1 statistical software (StataCorp, TX). RESULTS
Fifty-two lymph node flaps were performed in 41 legs. Eleven patients with unilateral lymphedema received two consecutive flaps at different levels of the leg. The remaining 30 legs, from 27 patients (3 bilateral), received a single lymph node transfer. Fifteen of the 38 patients (39.5%) had an additional liposuction performed to remove excessive fat tissue. Four of them presented with skin folds that were resected at the time of surgery. Thirty-nine (75%) of these flaps were transferred from the thoracic region. Another 10 (19.2%) were harvested at the contralateral inguinal side, and 3 cases (5.8%) had the flap harvested from the neck. Eleven patients (28.9%) presented with minor complications that involved small volume seroma or hematoma, of either the donor or recipient site, which were treated conservatively or drained by local puncture. Of these, one patient with a severe lymphedema of the lower left limb developed a wound dehiscence at the ankle (fold excision) that had to be skin grafted. No major complications were seen on this series. Of the 41 legs operated, we could follow volume evolution after a single LNFT in 23 legs of 20 patients. The remaining 18 legs had an additional intervention at the same procedure that could also influence volume changes (liposuction or skin fold resections). Whenever patients received a second flap or another intervention that could influence volume changes (secondary liposuction), follow-up analysis was discontinued.
3
Table 4. Comparison of Patients with Poor Results and Moderate/ Good Results
Variable Lymphedema Mean duration SD Sick leg Preop. Mean SD Preop. PEV Mean SD
Poor result Moderate/good result (30% REV) (>30% REV) N56 N59 4.83 1.17 7.07 1.38 58.67% 29.16%
11.00 8.60 7.21 1.61 32.11% 15.50%
P 5 0.34 P 5 0.59 P 5 0.045
Eight of these legs (3 bilateral and 2 unilateral without proper measurements of contralateral limb) could only be compared with themselves over time. An average reduction of 7.1 6 8.6% (412.5 6 520 mL) in overall leg volume was observed. Three legs from 2 patients with severe presentations did not present any volume reduction after the procedure. The other 5 legs, from 3 different patients, presented an average reduction of 12.8% (760 6 195 mL). The average follow-up for this group was 48.6 6 28.7 months (4–83 months; Table 2). There were 15 treated legs for which volume measurements could be compared with normal contralateral legs. The patients in this group received a single LNFT and were followed for an average time of 12.7 6 10.7 months (3–36 months). These patients presented with an average preoperative PEV of 42.7 6 24.9%. An average reduction of 46.3 6 34.7% in excess volume of the affected limbs was observed compared with the contralateral healthy legs. Two patients recovered completely and had lower estimated leg volumes of their affected legs than of their contralateral healthy ones. REV for these patients was considered 100% despite the larger relative change in volume. There was a statistically significant difference between the distribution of pre and post-operative volumes of the affected legs (Z 5 3128, p < 0.002). The same difference was not observed for the healthy legs (Z 5 0.7, p 5 0.45; Table 3). Lymphedema duration, total volume of the affected limb and pre-operative PEV distributions were compared between patients that presented a REV inferior to 30% (poor result) and those with an improvement superior to 30% (moderate/good result). There was a significant difference in distribution of preoperative PEV between these groups (p 5 0.045; Table 4). DISCUSSION
In this retrospective, observational study, we found evidence that suggests that patients suffering with secondary lymphedema to the leg can benefit from LNFT. Patients with less severe presentations had better results. The sample represents the demographically expected population consulting for secondary lymphedema to the lower limb at a lymphedema surgeon’s practice.17 Microsurgery DOI 10.1002/micr
4
Batista et al.
Oncological intervention to the groin for pelvic cancer was the most important cause of secondary lymphedema to the limb. This is consistent with the wider and deeper resection of inguinal lymph nodes performed for these patients. Other neoplasms were less frequently involved with this complication. Some patients presented with lymphedema secondary to interventions to the groin for benign conditions, especially after thigh lifts. This is probably a very rare complication of this widely used procedure for patients after massive weight loss, but these cases should raise awareness to those performing these resections. We were unable to find any reports in the literature of this severe complication. In this series, many patients had to live with lymphedema for a long time before referral to the lymphedema surgeon. As more physicians become familiar with these physiological surgical procedures for lymphedema treatment, we expect that earlier referral will become more frequent. Nevertheless, in our study we found that the length of time living with lymphedema was not associated with the clinical response to the procedure. This is consistent with findings for other reconstructive procedures of the lymphatic system.10 Minor complications were present in more than a third of the patients analyzed. In most cases, the management of these complications was simple. No references of persistent swelling to the donor site were found. A recent article from Vignes et al reported six cases of chronic lymphedema in a series of 26 patients who had undergone LNFT.18 These findings are not consistent with our impressions and might be due to a biased sampling. Pons et al. reported one case of swelling in the donor thigh from a series of 42 consecutive LNFT.19 Although we believe that these complications are rare, they support the concept that careful dissection of the flap must be carried out, avoiding damage to the more medial part of the lymphatic system.20 We acknowledge the importance of these papers and support the development of surgical strategies to reduce these risks. The combination of ICG lymphography and intraoperative use of nuclear medicine has been recently reported to help with flap dissection.21 Volume variation of the affected limb is the main outcome when evaluating lymphedema treatment. Many strategies have been described to evaluate this volume, but most require complicated tools and are time consuming. In common clinical practice, girth measurement has been recognized as the most applicable tool for volume estimation.22 The truncated cone formula has been shown by other authors to strongly correlate with direct volume measurements.23 The measurements used in this study did not allow for the estimation of the volume of the entire limb, as the volume of the middle part of the leg, corresponding to the calf, could not be calculated. Wider Microsurgery DOI 10.1002/micr
adoption of a single set of measurements would allow for better evaluation and comparison of results among different approaches to lymphatic reconstruction. Overall, patients presented with a significant reduction of the excess volume of their legs. Of a series of 15 patients, moderate improvement (REV between 30 and 80%) was seen in 5 and good results (>80% REV) were found in another 4 legs. Better results were statistically significant in patients with less severe presentations. In another group of 8 legs, in which the volume of the affected limb could only be compared to itself, 5 legs showed volume decrease over time. Higher volume variation was observed in patients with lighter limbs and possibly less severe cases. These observations are similar to reports for other forms of physiological reconstructions of the lymphatic system, where less severe forms of lymphedema have shown better response to surgical intervention.17,24 In more severe cases, sclerotic degeneration of lymph collectors and loss of their pumping ability could explain these findings. Other authors have suggested that even when an important objective volume reduction is not observed, patients report a relevant subjective improvement of their lymphedema-associated symptoms.19 In our experience, improvements in skin quality and softness of the affected limb are common observations, even when a volume reduction is not very noticeable. We believe that this would be the result of the well-known phenomenon of fat deposition in lymphedematous limbs (lipoedema), which would keep overall volume larger, even if the excess lymph is effectively removed. Magnetic resonance imaging is a promising tool for the evaluation of lymphedema and one that we have recently incorporated in our clinical practice. Although we designed this study to evaluate the effect of a single LNFT, the current approach of the senior author for the treatment of these patients involves a management protocol that evolved with experience over the past 20 years. Patients with iatrogenic lymphedema who are considered good candidates for the procedure are normally given a first LNFT to the inguinal site, after adequate resection of the scar tissue resulting from previous interventions. Some receive simultaneous liposuction depending on the clinical diagnosis of lipedema. The flap can be harvested from the patient at multiple locations, but preferably at the lateral thoracic area.3 It is thought that the transferred flap may improve the clearance of lymph by stimulating lymphatic growth and reconnection of the limb lymphatic system; however, it would be unreasonable to think that it could regenerate distal lymphatic ducts. Patients with more severe presentations might be good candidates for a second lymphatic flap at a more distant site if the excess fluid persists distally. Selective liposuction will be performed when physical
LNFT for Leg Lymphedema
examination on postoperative follow-up reveals any degree of fibrotic degeneration with fat deposition (lipoedema). Decisions on the management and indications of these procedures are still based on personal experience of the surgeon, and more critical evaluation of results is needed to ensure reproducibility of outcomes. Our sample was too small to undertake a more complete analysis of this multiple procedure approach. A recent report has also shown benefits from the combination of LNFT and an excisional procedure to the dorsum of the foot for more severe presentations of lymphedema.25 In this study, we have demonstrated volume reduction of lymphedematous legs after a LNFT. We limited the analysis to the results of a single LNFT to provide a more realistic estimate of the procedure effect. Despite the growing interest that microsurgeons have dedicated to this exciting field of lymphedema surgery, there is very little objective evidence about its benefits. This study has several limitations. It is a retrospective observational study of data generated and recorded in an uncontrolled manner. Many sources of bias and possible confounders cannot be addressed effectively with this design. Prospective randomized trials comparing the outcome of this procedure to more traditional approaches to lymphedema treatment, such as complex decongestive therapy, are still needed for definite validation. CONCLUSION
Patients with secondary leg lymphedema can benefit from lymphatic flap transfer. Results in patients with mild presentations seem to be better than results in more severe cases. Further prospective studies with proper controls will provide additional information on this promising procedure’s safety and efficacy. FINANCIAL DISCLOSURES
None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript.
REFERENCES 1. Framework L. Best Practice for the Management of Lymphoedema. International consensus. London: MEP Ltd; 2006. 2. Becker C, Pham DN, Assouad J, Badia A, Foucault C, Riquet M. Postmastectomy neuropathic pain: Results of microsurgical lymph nodes transplantation. Breast 2008;17:472–476. 3. Becker C, Arrive L, Saaristo A, Germain M, Fanzio P, Batista BN, Piquilloud G. Surgical treatment of congenital lymphedema. Clin Plast Surg 2012;39:377–384. 4. Suami H, Chang DW. Overview of surgical treatments for breast cancer-related lymphedema. Plast Reconstr Surg 2010;126: 1853–1863. 5. Onoda S, Todokoro T, Hara H, Azuma S, Goto A. Minimally invasive multiple lymphaticovenular anastomosis at the ankle for the prevention of lower leg lymphedema. Microsurgery 2014;34:372–376.
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6. Boccardo F, Casabona F, DeCian F, Friedman D, Murelli F, Puglisi M, C CC, Molinari L, Spinaci S, Dessalvi S, Campisi C. Lymphatic microsurgical preventing healing approach (LYMPHA) for primary surgical prevention of breast cancer-related lymphedema: Over 4 years follow-up. Microsurgery 2014;34:421–424. 7. Yamamoto T, Kikuchi K, Yoshimatsu H, Koshima I. Ladder-shaped lymphaticovenular anastomosis using multiple side-to-side lymphatic anastomoses for a leg lymphedema patient. Microsurgery 2014;34: 404–408. 8. Boccardo F, Fulcheri E, Villa G, Molinari L, Campisi C, Dessalvi S, Murdaca G, Campisi C, Santi PL, Parodi A, Puppo F, Campisi C. Lymphatic microsurgery to treat lymphedema: techniques and indications for better results. Ann Plast Surg 2013;71:191–195. 9. Koshima I, Nanba Y, Tsutsui T, Takahashi Y, Itoh S, Fujitsu M. Minimal invasive lymphaticovenular anastomosis under local anesthesia for leg lymphedema: Is it effective for stage III and IV? Ann Plast Surg 2004;53:261–266. 10. Chang DW, Suami H, Skoracki R. A prospective analysis of 100 consecutive lymphovenous bypass cases for treatment of extremity lymphedema. Plast Reconstr Surg 2013;132:1305–1314. 11. Baumeister RG, Seifert J. Microsurgical lymphvessel-transplantation for the treatment of lymphedema: Experimental and first clinical experiences. Lymphology 1981;14:90. 12. Becker C, Hidden G. Transfer of free lymphatic flaps. Microsurgery and anatomical study. J Mal Vasc 1988;13:119–122. 13. Batista BN, Becker C, Germain M. Vascularized lymph node transfer for patients with secondary inferior limb lymphedema. Plast Reconstr Surg 2013;132:32–33. 14. Becker C, Vasile JV, Levine JL, Batista BN, Studinger RM, Chen CM, Riquet M. Microlymphatic surgery for the treatment of iatrogenic lymphedema. Clin Plast Surg 2012;39:385–398. 15. Becker C, Assouad J, Riquet M, Hidden G. Postmastectomy lymphedema: Long-term results following microsurgical lymph node transplantation. Ann Surg 2006;243:313–315. 16. Assouad J, Becker C, Hidden G, Riquet M. The cutaneo-lymph node flap of the superficial circumflex artery. Surg Radiol Anat 2002;24: 87–90. 17. 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. 18. Vignes S, Blanchard M, Yannoutsos A, Arrault M. Complications of autologous lymph-node transplantation for limb lymphoedema. Eur J Vasc Endovasc Surg 2013;45:516–520. 19. Pons G, Masia J, Loschi P, Nardulli ML, Duch J. A case of donorsite lymphoedema after lymph node-superficial circumflex iliac artery perforator flap transfer. J Plast Reconstr Aesthet Surg 2014; 67:119–123. 20. Viitanen TP, Maki MT, Seppanen MP, Suominen EA, Saaristo AM. Donor-site lymphatic function after microvascular lymph node transfer. Plast Reconstr Surg 2012;130:1246–1253. 21. Dayan JH, Dayan E, Smith ML. Reverse lymphatic mapping: a new technique for maximizing safety in vascularized lymph node transfer. Plast Reconstr Surg 2015;135:277–285. 22. 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. 23. Brorson H, Hoijer P. Standardised measurements used to order compression garments can be used to calculate arm volumes to evaluate lymphoedema treatment. J Plast Surg Hand Surg 2012;46:410–415. 24. Yamamoto T, Matsuda N, Doi K, Oshima A, Yoshimatsu H, Todokoro T, Ogata F, Mihara M, Narushima M, Iida T, Koshima I. The earliest finding of indocyanine green lymphography in asymptomatic limbs of lower extremity lymphedema patients secondary to cancer treatment: The modified dermal backflow stage and concept of subclinical lymphedema. Plast Reconstr Surg 2011;128:314e–321e. 25. Sapountzis S, Ciudad P, Lim SY, Chilgar RM, Kiranantawat K, Nicoli F, Constantinides J, Wei MY, Sonmez TT, Singhal D, Chen HC. Modified Charles procedure and lymph node flap transfer for advanced lower extremity lymphedema. Microsurgery 2014;34:439– 447.
Microsurgery DOI 10.1002/micr
Background: Previous authors have shown benefits from the use of lymph node flap transfer (LNFT) to treat lymphedema of the arms, but there is little evidence for its use for lower limb lymphedema. We performed a retrospective analysis of a series of patients suffering from secondary lower limb lymphedema treated with a free LNFT. Methods: 52 cases of LNFT to treat 41 legs in 38 patients with secondary lymphedema were retrospectively reviewed. The causes of the lymphedema included lymphedema secondary to hysterectomy for uterine cancer, melanoma resections on the leg, lymphoma treatment and testicular cancer, cosmetic surgery to the limb, lipoma resection at the inguinal region, and a saphenectomy. Patients had been suffering with lymphedema for an average of 9.1 6 7.3 years at the time of LNFT. Results: Eleven patients (28.9%) presented with minor complications treated conservatively. For 23 legs there was enough data to follow limb volume evolution after a single LNFT. Total volume reduction in eight legs (two patients with no measures of the healthy limb and three bilateral) was 7.1 6 8.6%. Another group of 15 patients with unilateral lymphedema had an average 46.3 6 34.7% reduction of excess volume. Better results (>30% REV) were associated with smaller preoperative excess volume (P 5 0.045). Conclusion: Patients with secondary leg lymphedema can benefit from LNFT. Results in patients with mild presentations seem to be better than in more severe C 2015 Wiley Periodicals, Inc. Microsurgery 00:000–000, 2015. cases. V
Lymphedema is one of the most poorly understood, relatively underestimated, and least researched complications of cancer treatment. In the developed world, cancer treatment is recognized as the primary cause of secondary lymphedema.1 It is an important complication and source of burden to patients.2 Inguinal lymph node dissection and radiotherapy to the groin exposes patients under oncological treatment of the legs or pelvic structures to similar risks of developing lymphedema as the breast cancer population.3 Large efforts have been made by the microsurgical community to generate better evidence to support reconstructive approaches to the lymphatic system. Many techniques have been proposed and have shown variable results.4–6 Lymphaticovenular bypass,7–10 lymph collector graft transposition11 and lymph node flap transfer (LNFT)12 are classified as physiologic procedures, as they are intended to increase the draining capacity of the limb lymphatic system. LNFT has been proposed by the senior author12 and performed extensively over the last 15–20 years.3,12–16 However, there is still very little evi-
1 ~o Paulo, Plastic Surgery Department, Medical School of the University of Sa ~o Paulo, Brazil Sa 2 ^s, Sa ~o Paulo, Brazil Instituto de Ensino e Pesquisa, Hospital Sırio-Libane 3 Lymphoedema Center, Clinique Jouvenet, Paris, France Presented as a free article at: 24th Congress of the International Society of Lymphology, Rome/Italy, September 16-20, 2013; ASPS 2013, San Diego/ USA, October 11-15, 2013. *Correspondence to: Bernardo Nogueira Batista, Rua Prof. Atılio Innocenti, ~o Paulo, CEP 045380-001, Brazil. E-mail: bernardonb@uol. 683, Itaim Bibi, Sa com.br Received 4 September 2014; Revision accepted 19 February 2015; Accepted 23 February 2015 Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/micr.22404
Ó 2015 Wiley Periodicals, Inc.
dence of its benefits for patients with lower limb lymphedema. We performed a retrospective analysis of a series of patients suffering from secondary lower limb lymphedema treated with a free LNFT. The purpose of this study was to evaluate postoperative complications and limb volume evolution after a single LNFT. PATIENTS AND METHODS
Thirty-eight patients with secondary leg lymphedema were included. Inclusion was determined by the documented registry of preoperative girth measurements and at least one postoperative registry for comparison. Incomplete surgical records were excluded from the sample. Three patients had bilateral lymphedema (total of 41 legs treated). All patients received at least one LNFT, performed by the same surgeon (C.B.) between 1990 and 2012. Data related to the lymphedema diagnosis, history and surgical treatment were collected. Postoperative complications reports were retrieved for safety assessment. The majority of patients treated were women (34 out of 38 patients). The average age at the time of lymph node transfer was 52.1 6 12.4 years (lowest 13 years and highest 74 years). Thirty-five patients presented with unilateral lymphedema while three patients had both limbs affected, with a total of 41 limbs treated. Lymphedema appeared at variable intervals after the primary surgery, ranging from a few days to up to 5 years. Patients had been suffering with lymphedema for an average of 9.1 6 7.3 years (1–26 years) at the time of LNFT. They were resistant to continuous physiotherapy, and had previously been subjected to multiple cycles of complex decongestive therapy and continuous use of compression garments.
2
Batista et al. Table 1. Population Demographics
Age Years with lymphedema Sex Side
Lymph Node Dissection Radiotherapy Infection status
Primary surgery
Mean 6 SD
Median
Range
52.1 6 12.4 9.1 6 7.3
55 6 N 5 38 4 34 3 18 17 41 30 8 27 11 23 11 2 2 22 3 4 1 3 1 1 3
13–74 1–26 % 10.5% 89.5%
Male Female Bilateral Left Right Total Yes No Yes No No records up to 2 episodes (year) 2–4 wpisodes (year) >4 episodes (year) Hysterectomy Melanoma Lymphoma Testicule Thigh lift Lipoma Saphenectomy NA
51.2% 48.8% 100% 78.9% 21.1% 71.1% 28.9% 60.5% 28.9% 5.3% 5.3% 57.9% 7.9% 10.5% 2.6% 7.9% 2.6% 2.6% 7.9%
For 3 patients, the primary cause of the lymphedema was not recorded. Twenty-two patients (57.9%) presented with lymphedema secondary to hysterectomy for uterine cancer, 3 (7.9%) for melanoma resections on the leg, 4 (10.5%) for lymphoma treatment, and 1 (2.6%) for testicular cancer. These 30 patients had inguinal lymph node dissections for their oncologic treatment and 27 of them had additional radiotherapy. The remaining 5 patients presenting with secondary leg lymphedema had been previously subjected to either cosmetic surgery to the limb after massive weight loss (3 patients), a lipoma resection at the inguinal region (1 patient) or a saphenectomy (1 patient). For this last patient, it remains unclear if the saphenectomy was the cause of a secondary lymphedema, or if it was performed in the setting of a mild case of congenital lymphedema that was worsened by the procedure. Fifteen of these patients had reports of infection episodes to the affected limb that needed medical treatment. Two of them had an average of 2–4 episodes a year and another two patients had infections more than 4 times a year, and received continuous antibiotic prophylaxis (Table 1). Surgical Technique
Over the past 20 years, technical aspects of LNFT have evolved. For lower limb lymphedema, the lateral thoracic region was the most common donor site. A free Microsurgery DOI 10.1002/micr
flap of subcutaneous fat tissue based on small branches of the thoracodorsal or the lateral thoracic vessels was harvested. Dissection was limited cranially to avoid the axillary region, and caudally by the inframamary fold. The flap included a group of lymph nodes located below the edge of the pectoralis muscle (level I for breast oncology surgeons) and above the lateral edge of the latissimus dorsi muscle. In situations where skin resurfacing was needed, these flaps were designed with a skin paddle. We did not include a skin paddle for flap surveillance since we believe that it can limit the final setting of the flap and consider that the risks and costs of a potential reintervention outweighs the chance of salvage in these small and short pedicled flaps. Fibrosis from the previous procedures was extensively removed and the flap transferred to the best size-match pedicle found in the recipient site. The flap was buried in the inguinal region beneath the superficial fascia, in an attempt to bridge the superficial and deep lymphatic system.3 A specialized physiotherapist usually administered postoperative decongestive therapy. Records of limb girth measured during pre-operative and follow-up consultations at six different levels (ankle, ankle 1 10 cm, knee 210 cm, knee, knee 110 cm, and knee 1 20 cm) were retrieved. Using the truncated cone volume formula, we were able to estimate the volume of part of the limb. These estimations were analyzed to evaluate lymphedema improvement after surgical treatment. In patients with unilateral lymphedema, measurements of the non-affected limb, when available, allowed for comparison with a healthy leg and determination of the percentage of excess volume (PEV) of the affected limb (PEV 5 volume of affected limb 2 volume of unaffected contralateral limb/volume of unaffected contralateral limb). Only data concerning the first LNFT was considered for analysis. Whenever the patient was submitted to a second intervention, follow-up was terminated and further data on girth measurement not considered. Excess volume reduction between preoperative and postoperative were defined by the following formula: REV 5 preoperative PEV 2 postoperative PEV/preoperative PEV. Statistical Analysis
Means, standard deviations, medians and ranges were used to summarize continuous variables. Frequencies and proportions were used to summarize categorical variables. We used a Wilcoxon signed rank test to compare preoperative and postoperative volumes of the affected and healthy limbs separately. A Wilcoxon-Mann Whitney test was used to determine if quantitative improvement (REV) was associated with the severity of disease or the time living with lymphedema. All tests were two-sided and values of p < 0.05 were considered significant. The
LNFT for Leg Lymphedema Table 2. Total Volume Variation of Lymphedematous Legs Treated with LNFT (No Available Information for Contralateral Limb) N58 Initial limb volume (L) Last limb volume (L) Volume variation (mL) Follow-up (m) Total volume reduction
Mean 6 SD
Median
Range
6.33 6 1 5.91 6 1.46 410 6 520 48.63 6 28.75 7.13 6 8.56%
6.15 5.65 (2600) 51 10%
4.8–8.2 3.9–8.5 [(2900) 21300] [4–85] [(23)217%]
Table 3. Excess Volume Reduction for Lymphedematous Legs Treated with LNFT Compared with a Healthy Contralateral Limb N 5 15
Mean 6 SD
Sick leg Preop. 7.2 6 1.5 Sick leg Postop. 6.3 6 1.3 Healthy leg Preop. 5 6 1.1 Healthy leg Postop. 5.1 6 1.1 Preop. PEV 40 6 20% Follow-up (m) 12.7 6 10.7 REV 46.3 6 34.7%
Median 7 6.3 4.8 4.9 42% 10 32%
Range
P
4.6–10.9 z 5 3128, 4.5–8.4 P < 0.002 3.5–8 z 5 0.746, 3.5–7.9 P 5 0.45 6–105% 3–36 1–100%
analyses were performed using Stata 13.1 statistical software (StataCorp, TX). RESULTS
Fifty-two lymph node flaps were performed in 41 legs. Eleven patients with unilateral lymphedema received two consecutive flaps at different levels of the leg. The remaining 30 legs, from 27 patients (3 bilateral), received a single lymph node transfer. Fifteen of the 38 patients (39.5%) had an additional liposuction performed to remove excessive fat tissue. Four of them presented with skin folds that were resected at the time of surgery. Thirty-nine (75%) of these flaps were transferred from the thoracic region. Another 10 (19.2%) were harvested at the contralateral inguinal side, and 3 cases (5.8%) had the flap harvested from the neck. Eleven patients (28.9%) presented with minor complications that involved small volume seroma or hematoma, of either the donor or recipient site, which were treated conservatively or drained by local puncture. Of these, one patient with a severe lymphedema of the lower left limb developed a wound dehiscence at the ankle (fold excision) that had to be skin grafted. No major complications were seen on this series. Of the 41 legs operated, we could follow volume evolution after a single LNFT in 23 legs of 20 patients. The remaining 18 legs had an additional intervention at the same procedure that could also influence volume changes (liposuction or skin fold resections). Whenever patients received a second flap or another intervention that could influence volume changes (secondary liposuction), follow-up analysis was discontinued.
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Table 4. Comparison of Patients with Poor Results and Moderate/ Good Results
Variable Lymphedema Mean duration SD Sick leg Preop. Mean SD Preop. PEV Mean SD
Poor result Moderate/good result (30% REV) (>30% REV) N56 N59 4.83 1.17 7.07 1.38 58.67% 29.16%
11.00 8.60 7.21 1.61 32.11% 15.50%
P 5 0.34 P 5 0.59 P 5 0.045
Eight of these legs (3 bilateral and 2 unilateral without proper measurements of contralateral limb) could only be compared with themselves over time. An average reduction of 7.1 6 8.6% (412.5 6 520 mL) in overall leg volume was observed. Three legs from 2 patients with severe presentations did not present any volume reduction after the procedure. The other 5 legs, from 3 different patients, presented an average reduction of 12.8% (760 6 195 mL). The average follow-up for this group was 48.6 6 28.7 months (4–83 months; Table 2). There were 15 treated legs for which volume measurements could be compared with normal contralateral legs. The patients in this group received a single LNFT and were followed for an average time of 12.7 6 10.7 months (3–36 months). These patients presented with an average preoperative PEV of 42.7 6 24.9%. An average reduction of 46.3 6 34.7% in excess volume of the affected limbs was observed compared with the contralateral healthy legs. Two patients recovered completely and had lower estimated leg volumes of their affected legs than of their contralateral healthy ones. REV for these patients was considered 100% despite the larger relative change in volume. There was a statistically significant difference between the distribution of pre and post-operative volumes of the affected legs (Z 5 3128, p < 0.002). The same difference was not observed for the healthy legs (Z 5 0.7, p 5 0.45; Table 3). Lymphedema duration, total volume of the affected limb and pre-operative PEV distributions were compared between patients that presented a REV inferior to 30% (poor result) and those with an improvement superior to 30% (moderate/good result). There was a significant difference in distribution of preoperative PEV between these groups (p 5 0.045; Table 4). DISCUSSION
In this retrospective, observational study, we found evidence that suggests that patients suffering with secondary lymphedema to the leg can benefit from LNFT. Patients with less severe presentations had better results. The sample represents the demographically expected population consulting for secondary lymphedema to the lower limb at a lymphedema surgeon’s practice.17 Microsurgery DOI 10.1002/micr
4
Batista et al.
Oncological intervention to the groin for pelvic cancer was the most important cause of secondary lymphedema to the limb. This is consistent with the wider and deeper resection of inguinal lymph nodes performed for these patients. Other neoplasms were less frequently involved with this complication. Some patients presented with lymphedema secondary to interventions to the groin for benign conditions, especially after thigh lifts. This is probably a very rare complication of this widely used procedure for patients after massive weight loss, but these cases should raise awareness to those performing these resections. We were unable to find any reports in the literature of this severe complication. In this series, many patients had to live with lymphedema for a long time before referral to the lymphedema surgeon. As more physicians become familiar with these physiological surgical procedures for lymphedema treatment, we expect that earlier referral will become more frequent. Nevertheless, in our study we found that the length of time living with lymphedema was not associated with the clinical response to the procedure. This is consistent with findings for other reconstructive procedures of the lymphatic system.10 Minor complications were present in more than a third of the patients analyzed. In most cases, the management of these complications was simple. No references of persistent swelling to the donor site were found. A recent article from Vignes et al reported six cases of chronic lymphedema in a series of 26 patients who had undergone LNFT.18 These findings are not consistent with our impressions and might be due to a biased sampling. Pons et al. reported one case of swelling in the donor thigh from a series of 42 consecutive LNFT.19 Although we believe that these complications are rare, they support the concept that careful dissection of the flap must be carried out, avoiding damage to the more medial part of the lymphatic system.20 We acknowledge the importance of these papers and support the development of surgical strategies to reduce these risks. The combination of ICG lymphography and intraoperative use of nuclear medicine has been recently reported to help with flap dissection.21 Volume variation of the affected limb is the main outcome when evaluating lymphedema treatment. Many strategies have been described to evaluate this volume, but most require complicated tools and are time consuming. In common clinical practice, girth measurement has been recognized as the most applicable tool for volume estimation.22 The truncated cone formula has been shown by other authors to strongly correlate with direct volume measurements.23 The measurements used in this study did not allow for the estimation of the volume of the entire limb, as the volume of the middle part of the leg, corresponding to the calf, could not be calculated. Wider Microsurgery DOI 10.1002/micr
adoption of a single set of measurements would allow for better evaluation and comparison of results among different approaches to lymphatic reconstruction. Overall, patients presented with a significant reduction of the excess volume of their legs. Of a series of 15 patients, moderate improvement (REV between 30 and 80%) was seen in 5 and good results (>80% REV) were found in another 4 legs. Better results were statistically significant in patients with less severe presentations. In another group of 8 legs, in which the volume of the affected limb could only be compared to itself, 5 legs showed volume decrease over time. Higher volume variation was observed in patients with lighter limbs and possibly less severe cases. These observations are similar to reports for other forms of physiological reconstructions of the lymphatic system, where less severe forms of lymphedema have shown better response to surgical intervention.17,24 In more severe cases, sclerotic degeneration of lymph collectors and loss of their pumping ability could explain these findings. Other authors have suggested that even when an important objective volume reduction is not observed, patients report a relevant subjective improvement of their lymphedema-associated symptoms.19 In our experience, improvements in skin quality and softness of the affected limb are common observations, even when a volume reduction is not very noticeable. We believe that this would be the result of the well-known phenomenon of fat deposition in lymphedematous limbs (lipoedema), which would keep overall volume larger, even if the excess lymph is effectively removed. Magnetic resonance imaging is a promising tool for the evaluation of lymphedema and one that we have recently incorporated in our clinical practice. Although we designed this study to evaluate the effect of a single LNFT, the current approach of the senior author for the treatment of these patients involves a management protocol that evolved with experience over the past 20 years. Patients with iatrogenic lymphedema who are considered good candidates for the procedure are normally given a first LNFT to the inguinal site, after adequate resection of the scar tissue resulting from previous interventions. Some receive simultaneous liposuction depending on the clinical diagnosis of lipedema. The flap can be harvested from the patient at multiple locations, but preferably at the lateral thoracic area.3 It is thought that the transferred flap may improve the clearance of lymph by stimulating lymphatic growth and reconnection of the limb lymphatic system; however, it would be unreasonable to think that it could regenerate distal lymphatic ducts. Patients with more severe presentations might be good candidates for a second lymphatic flap at a more distant site if the excess fluid persists distally. Selective liposuction will be performed when physical
LNFT for Leg Lymphedema
examination on postoperative follow-up reveals any degree of fibrotic degeneration with fat deposition (lipoedema). Decisions on the management and indications of these procedures are still based on personal experience of the surgeon, and more critical evaluation of results is needed to ensure reproducibility of outcomes. Our sample was too small to undertake a more complete analysis of this multiple procedure approach. A recent report has also shown benefits from the combination of LNFT and an excisional procedure to the dorsum of the foot for more severe presentations of lymphedema.25 In this study, we have demonstrated volume reduction of lymphedematous legs after a LNFT. We limited the analysis to the results of a single LNFT to provide a more realistic estimate of the procedure effect. Despite the growing interest that microsurgeons have dedicated to this exciting field of lymphedema surgery, there is very little objective evidence about its benefits. This study has several limitations. It is a retrospective observational study of data generated and recorded in an uncontrolled manner. Many sources of bias and possible confounders cannot be addressed effectively with this design. Prospective randomized trials comparing the outcome of this procedure to more traditional approaches to lymphedema treatment, such as complex decongestive therapy, are still needed for definite validation. CONCLUSION
Patients with secondary leg lymphedema can benefit from lymphatic flap transfer. Results in patients with mild presentations seem to be better than results in more severe cases. Further prospective studies with proper controls will provide additional information on this promising procedure’s safety and efficacy. FINANCIAL DISCLOSURES
None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript.
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Microsurgery DOI 10.1002/micr
