MICROSURGERY
Comparison of Vascularized Supraclavicular Lymph Node Transfer and Lymphaticovenular Anastomosis for Advanced Stage Lower Extremity Lymphedema Shinsuke Akita, MD, PhD,* Nobuyuki Mitsukawa, MD, PhD,† Motone Kuriyama, MD, PhD,‡ Yoshitaka Kubota, MD, PhD,† Masakazu Hasegawa, MD, PhD,† Hideki Tokumoto, MD,* Tatsuya Ishigaki, MD,† Takashi Togawa, MD, PhD,§ Junpei Kuyama, MD, PhD,§ and Kaneshige Satoh, MD, PhD† Background: Vascularized lymph node transfer has become a popular surgical option to improve lower extremity lymphedema (LEL), although potential donor sites are limited. The free supraclavicular flap with deep cervical lymph nodes has been recently associated with a minimal risk of secondary lymphedema caused by donor site dissection. However, the effectiveness of this procedure has not yet been evaluated. Methods: Vascularized supraclavicular lymph node transfer (VSLNT) was performed for patients with International Society of Lymphology late stage II or more severe LEL. The results were compared with lymphaticovenular anastomosis (LVA) performed for patients with the same stages of severity. To evaluate improvement in lymphatic function, indocyanine green lymphography and lymphoscintigraphy were performed. Results: Vascularized supraclavicular lymph node transfer was performed in 13 limbs of 13 patients. The results were compared with 43 limbs of 33 patients who underwent multiple LVA. No severe complications were observed in either group. Improvement in lymphatic function, as measured by the LEL index, was 26.5 ± 4.4 and 21.2 ± 2.0 in the VSLNT and LVA groups, respectively. Lymphatic function was improved in 7 cases in the VSLNT group and 10 cases in the LVA group. Conclusions: Vascularized supraclavicular lymph node transfer is an effective technique for the treatment of advanced stage LEL. Lymphaticovenular anastomosis is also effective, but to a lesser degree than VSLNT. However, LVA is less invasive and requires a shorter hospital stay. Key Words: lymphedema, lymphaticovenular anastomosis, vascularized supraclavicular lymph node transfer (Ann Plast Surg 2015;00: 00–00)
A
mong reconstructive surgery techniques for lower extremity lymphedema (LEL), 2 creditable procedures have recently emerged: vascularized lymph node transfer (VLNT) and lymphaticovenular anastomosis (LVA).1–22 However, potential VLNT donor sites for LEL are limited.16–22 The use of a free supraclavicular flap with deep cervical lymph nodes as a donor site has been recently associated with a minimal risk of secondary lymphedema caused by donor site dissection.22 The aim of this study was to compare the effectiveness of vascularized supraclavicular lymph node transfer (VSLNT) versus
Received December 10, 2014, and accepted for publication, after revision, February 2, 2015. From the *Department of Plastic and Reconstructive Surgery, Chiba Cancer Center; †Department of Plastic, Reconstructive and Aesthetic Surgery, Chiba University, Faculty of Medicine, Chiba; ‡Department of Plastic and Reconstructive Surgery in Kochi Medical School Hospital, Nankoku; and §Division of Nuclear Medicine, Chiba Cancer Center, Chiba, Japan. Conflicts of interest and sources of funding: none declared. Reprints: Shinsuke Akita, Department of Plastic and Reconstructive Surgery, Chiba Cancer Center 666-2, Nitona-cho, Chuo-ku, Chiba City, Chiba, Japan. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/15/0000–0000 DOI: 10.1097/SAP.0000000000000513
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LVA for the treatment of severe LEL. This is the first report to compare the results of different reconstructive surgical procedures for the treatment of lymphedema based on both lymphedematous volume and lymphatic function.
METHODS This study was carried out at the Chiba University Hospital (Chiba, Japan) and Chiba Cancer Center (Chiba, Japan) with approval of the institutional review board and permission from the ethics committee. Written permission for publication of photographs was obtained from all patients. Patients with severe LEL who underwent surgical treatment at the Chiba University and Chiba Cancer Center between January 2012 and February 2014 were included in this study. The clinical stages of lymphedema and lymphatic function were evaluated in all patients. The severity of lymphedema in all patients, except those with an allergy to iodine, was assessed via indocyanine green (ICG) lymphography. For those patients with secondary lymphedema, lymphatic function was categorized as stage I to V in accordance with the guidelines reported by Yamamoto et al23 (Table 1). For patients who were obese or diagnosed with advanced stage lymphedema, ICG lymphography may not be an ideal modality because it is insufficient for detecting lymphatic function greater than 15 mm from the skin surface. For this group of patients, lymphoscintigraphy proved more useful in assessing lymphatic function in the deeper layers.24 Cases of secondary lymphedema assessed by lymphoscintigraphy were categorized as type 0-V, as described by Maegawa et al25 (Table 2). Lymphatic function in all patients with primary lymphedema was assessed via ICG lymphography and lymphoscintigraphy. Vascularized lymph node transfer was not selected as a surgical option for patients with early-stage lymphedema. Lymphaticovenular anastomosis was recommended as the treatment of choice for all patients categorized as Internal Society of Lymphology (ISL) clinical stage I or early II with confirmed adequate lymphatic function.26 For patients with stage I or II secondary lymphedema, ICG lymphography was used to establish preserved lymphatic function, whereas lymphoscintigraphy was the diagnostic modality for patients with type I or II disease. A diagnosis of mild primary lymphedema was made by the visualization of functional lymphatics. For these individuals, LVA was recommended as the optimal treatment.27 Patients with secondary lymphedema graded as late ISL clinical stage II or worse and those with lymphatic function categorized as type III-V by lymphoscintigraphy or stage III-V by ICG lymphography were considered to have advanced stage lymphedema. Patients with ISL clinical stage II primary lymphedema or worse and those with undetectable functional linear lymphatics were deemed to have advanced stage primary lymphedema. All patients with advanced stage lymphedema received supervised compression therapy for at least 3 months. After the completion of compression therapy, the patients received counseling on the respective benefits of VLNT and LVA, both orally and in writing, www.annalsplasticsurgery.com
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TABLE 1. Indocyanine Green Lymphography Stage Stage
0 I II III IV V
Description
No dermal back flow pattern A splash pattern around the groin/axillary region A stardust pattern extending proximally to the superior border of the patella/elbow A stardust pattern extending distally to the superior border of the patella/elbow A stardust pattern extending to the entire limb The existence of a diffuse pattern with a stardust pattern in the background
by a single plastic surgeon. Based on this knowledge, each patient selected LVA or VLNT depending on the appropriateness of the procedure. No patient underwent simultaneous LVA and VLNT or the wedge resection of fibrotic subcutaneous adipose tissue. Although our LVA surgical technique includes some intricate procedures designed to prevent reflux within small subcutaneous veins, our method was essentially the same as that reported elsewhere.3–5,9,13,28 Multiple side-to-end anastomoses between the collecting lymphatics and small veins were preferable to end-to-end anastomosis. Most LVA procedures were performed under local anesthesia, unless the patient preferred general anesthesia. The average postoperative hospitalization period was approximately 7 days. The donor site for VLNT was selected from the thoracic (vascularized thoracic lymph node transfer [VTLNT]), groin (vascularized groin lymph node transfer [VGLNT]), or supraclavicular regions (VSLNT).17,18,21,22,29 Vascularized groin lymph node transfer was not selected if the patient exhibited any sign of secondary lymphedema after pelvic lymph node dissection. In the remaining cases, the normal lymphatic function of the contralateral leg was confirmed by lymphoscintigraphy and ICG lymphography before performing VGLNT. In our institution, the submental region was generally not recommended to the patient as a donor site.20 The VLNT recipient site was selected from the distal region of the thigh or the ankle, depending on the area most affected. If symptoms were most severe at the thigh, the distal thigh was selected. If symptoms at the lower leg were severe, the ankle was selected. If adequately sized collecting lymphatics were evident in both the recipient lesion and afferent lymphatics to the transferring lymph nodes, they were anastomosed to each other. In the VLNT group, all surgeries were performed under general anesthesia. For these patients, hospitalization was extended to 2 weeks postoperatively. All patients performed simple lymph drainage procedures by themselves after discharge. TABLE 2. Lymphoscintigraphy Type Type
0 I II III IV V
2
Description
Inguinal/axillary lymph nodes stained normally; no dermal back flow pattern is seen The number of visible inguinal/axillary lymph nodes is reduced Few or no inguinal/axillary lymph nodes are seen; dermal back flow is seen in the thigh/upper arm No inguinal/axillary lymph nodes are detected; dermal back flow is seen in the thigh and leg/upper arm and forearm Dermal back flow and lymph stasis are seen in the leg/forearm No dermal back flow is seen; no tracer migration is seen
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All patients with advanced stage lymphedema received supervised compression therapy for at least 3 months before surgery, and the preoperative lymphedematous volume of the limb was measured afterward. Changes in the postoperative volume were compared using the LEL index, which was calculated from the circumferences of 5 points on the limb (the superior edge of the patella, 10 cm above and below the patella, the lateral malleolus, and the dorsum of the foot) and the body mass index, which yielded an accurate quantitative assessment of the severity of lymphedema.30 Improvement achieved by surgical treatment was defined as the difference between the preoperative and postoperative LEL indices. The postoperative LEL index was measured for at least 3 months after surgery. Postoperative lymphatic function, assessed by ICG lymphography or lymphoscintigraphy, was compared with the preoperative findings. When an improvement in the ICG lymphography stage or lymphoscintigraphy type was confirmed, lymphatic function was regarded as improved. Even if the stage remained unchanged, dermal backflow was reduced by more than 25%, and lymphatic function was determined to have improved. The results of all patients treated for advanced stage lymphedema during the study period were collected. Improvements in the LEL index and the proportion of patients with improved lymphatic function after surgery were compared against the surgical methods. Hospital stay, operation time, anesthesia type (local or general), and postoperative complications were also compared between the surgical methods. Statistical analyses were performed using IBM SPSS Statistics 22 (IBM-SPSS, Inc., Chicago, IL). An unpaired t test was used to compare the level of improvement according to the LEL index, hospital stay, and operation time. A standard χ2 test and the Yates corrected χ2 test were used to compare the proportion of patients with improved lymphatic function after surgery, anesthesia type, and the incidence of postoperative complications. A probability (P) value less than 0.05 was considered statistically significant.
RESULTS During the study period, surgical treatment for LEL was performed in 127 limbs. In 63 limbs, lymphatic function was sufficiently preserved to meet our criteria of early-stage lymphedema. These patients were treated by LVA. The other 64 limbs exhibited advanced stage lymphedema. Of these patients, 43, 13, 4, and 4 underwent multiple LVA, VSLNT, VTLNT, and VGLNT procedures, respectively. For the cases that underwent VLNT, anastomoses between lymphatics could not be performed in 1 case that received VGLNT and in 2 cases that received VTLNT. These 3 cases were young patients with primary lymphedema and sizable collecting lymphatics that could not be detected at the recipient site. For cases that underwent VSLNT, anastomoses between lymphatics were performed in all cases. Because relatively few patients underwent VTLNT and VGLNT, the statistical comparisons were only performed for LVA and VSLNT. The characteristics of patients according to surgical treatment are listed in Table 3. Among the baseline characteristics, the patients' age was significantly lower in the LVA group (P = 0.03). A history of phlegmon was noted in 39 of 43 limbs (90.7%) in the LVA group and all 13 limbs (100%) in the VSLNT group. In the LVA group, the anastomoses were 5.1 ± 1.8 (mean ± standard deviation). The mean operation time was shorter in the LVA group than in the VSLNT group with significant difference (213 ± 68 vs. 414 ± 65 minutes, respectively; P < 0.01). In the LVA group, the operation was performed under general anesthesia in 8 of 43 limbs in accordance with the patients' wishes. The other 35 limbs underwent LVA under local anesthesia. All 13 patients in the VSLNT group underwent the operation under general anesthesia. There was a significant difference between the 2 groups regarding anesthesia type (P < 0.01). The mean hospital stay was shorter for the LVA group than the VSLNT © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Annals of Plastic Surgery • Volume 00, Number 00, Month 2015
TABLE 3. Surgical Treatments for Patients With Advanced Stage Lymphedema and Patients' Characteristics
Total no. limbs Female Secondary Age, y Postoperative follow-up period, mo Preoperative BMI
LVA
VSLNT
P
43 40 34 54.1 ± 14.8 18.3 ± 8.8 24.8 ± 5.8
13 13 11 63.7 ± 7.0 15.1 ± 1.9 23.0 ± 2.8
1.00 1.00 0.03 0.06 0.30
BMI indicates body mass index.
group with significant difference (8.9 ± 2.9 vs 15.2 ± 1.6 days, respectively; P < 0.01). The LVA group showed lower incidence of complications than the VSLNT group with significant difference (0 vs 3 cases, respectively; P < 0.01). No significant complications occurred in the LVA group, whereas congestion to the skin paddle was observed in three patients in the VSLNT group on the day of surgery. The patency of the anastomosed vessels and adequate blood circulation to the transferred lymph nodes at the deep layer were confirmed by re-exploration in 2 cases. In these cases, because the problem was believed to involve the venous drainage from the skin flap skin paddle via the perforators, the congested skin flaps were removed and the blood circulation to the transferred lymph nodes was monitored by color Doppler sonography. In both cases, the patency of the anastomosed vessels was monitored until the final examination 2 weeks after surgery. Venous thrombosis at the anastomosis site was observed in a third case, for which the vein was re-anastomosed and the flap salvaged. In these 3 complicated cases, hospitalization was extended for a few days beyond the preoperative plan. In all cases, the transferred lymph nodes survived. Perioperative improvement, as indicated by the mean value of the LEL index, was significantly better in the VSLNT group than in the LVA group (21.2 ± 2.0 vs 26.5 ± 4.4, respectively; P = 0.032). Lymphatic function improved in 10 cases (23.3%) in the LVA group and in 7 cases (53.8%) in the VSLNT group. A significant difference was observed between the LVA and VSLNT groups (P = 0.046) (Table 4). None of the 64 patients with advanced stage lymphedema regained normal lymphatic function or were completely free from compression therapy. Most of them wore elastic garments occasionally until the final follow-up.
CASE REPORTS
Comparison of VSLNT and LVA
Cases 8 (right), 9 (left) A 34-year-old woman presented with bilateral primary LEL with an onset at 17 years of age. After 6 months of follow-up with conservative treatment, she received multiple LVAs in both legs. One year after surgery, her legs were thinner, and she had managed to lose a total of 3 kg. After surgery, her LEL index improved from 258.8 to 245.2 for the right leg and from 292.5 to 265.5 for the left leg (Fig. 2, above). Preoperatively, the migration of the tracer was poor in both legs. Postoperatively, linear collecting lymphatics and lymph nodes were detected in her right leg, and lymphatic function on this side was determined to be improved. However, no significant improvement was observed in her left leg (Fig. 2, below).
Case 30 A 49-year-old woman presented with left LEL after pelvic lymph node dissection 2 years ago. After 6 months of follow-up with conservative treatment, she received VSLNT to the left thigh. One year after surgery, her legs were thinner, and she had managed to lose a total of 5 kg. The LEL index of her left limb improved from 317.6 to 292.0 perioperatively (Fig. 3, above). Lymphoscintigraphy findings improved from type IV to III after surgery (Fig. 3, below).
Case 56 A 64-year-old woman presented with left LEL after pelvic lymph node dissection 10 years ago. After 5 months of follow-up with conservative treatment, she received VSLNT to the left thigh. One year after surgery, her legs were thinner without losing any body weight. The LEL index of her left limb improved from 262.5 to 236.9 (Fig. 4, above). Lymphoscintigraphy findings improved from type V to III (Fig. 4, below).
DISCUSSION Both LVA and VLNT are recognized as effective reconstructive surgical treatments for extremity lymphedema. Marten et al31 performed a meta-analysis to compare the effectiveness of lymphovenous shunt procedures and VLNT from the results of 22 studies of lymphovenous shunt procedures and 5 studies of VLNT.31 They ultimately concluded that VLNT may provide better outcomes than lymphovenous shunting, although most of the studies about VLNTwere associated with upper extremity lymphedema. In contrast, the studies that involved lymphovenous shunting included both the upper and lower extremities. However, there are important differences in venous pressure and fat volume between the upper and lower extremities. To properly assess the effectiveness of surgical treatment, the upper and lower extremities should be separately evaluated because lymphedema is much more refractory in the lower extremities. In addition, because assessment modalities for lymphedema have not yet been standardized, the comparisons of the volume reduction among different studies appear unsound. Furthermore, the severity of the disease and
Cases 31 (right), 32 (left) A 50-year-old woman presented with bilateral LEL after pelvic lymph node dissection 10 years ago. Although she had received conservative therapy, the limb volume did not decrease. After a 12-month follow-up period with conservative treatments by specialists, she received multiple LVA in both legs. One year after surgery, her legs were thinner, and she had managed to lose a total of 8 kg (Fig. 1, above). After surgery, her LEL index improved from 285.9 to 257.7 for the right leg and from 258.9 to 233.0 for the left leg. Although the lymphoscintigraphy of the left leg showed improvement from type III to type II, the right leg remained as type V. The straight staining lines on the bilateral thighs in the postoperative lymphoscintigraphy image were the veins (Fig. 1, below). © 2015 Wolters Kluwer Health, Inc. All rights reserved.
TABLE 4. Results of Each Type of Treatment for the Patients With Advanced Stage Lymphedema
No. patients Days of hospitalization Preoperative LEL index Postoperative LEL index Improvement value of LEL index Improvement of lymphatic function
LVA
VSLNT
43 8.9 ± 2.9 292.2 ± 35.1 271.0 ± 33.1 21.2 ± 2.0 10
13 15.2 ± 1.6 288.2 ± 23.4 261.7 ± 26.3 26.5 ± 4.4 7
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FIGURE 1. A 50-year-old woman with bilateral lower extremity lymphedema. (above, left) After 12 months of follow-up with conservative treatments. (above, right) One year after multiple LVA in both legs. (below, left) Preoperative lymphoscintigraphy revealed type V lymphatic function in the right leg and type III in the left leg. (below, right) Postoperative lymphoscintigraphy findings for the right leg did not show any improvement. Dermal back flow at the left thigh was reduced significantly, and lymphatic function in the left leg was redesignated as type II. The straight staining lines on the bilateral thighs in the postoperative lymphoscintigraphy image were the veins. 4
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FIGURE 2. A 34-year-old woman with bilateral primary lower extremity lymphedema. (above, left) After 6 months of follow-up with conservative treatments. (above, right) One year after multiple LVA in both legs. (below, left) Preoperative lymphoscintigraphy showed minor migration of the tracer in both legs. (below, right) Postoperatively, linear collecting lymphatics and lymph nodes were detectable in the right leg, but no significant improvement was observed in the left leg.
effectiveness of conservative treatment may have influenced the surgical outcomes. When comparing one surgery for lymphedema against another, targeting of the limb to precisely assess disease severity and matching conservative therapy protocols are essential. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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FIGURE 3. A 49-year-old woman with left lower extremity lymphedema. (above, left) After 6 months of follow-up with conservative treatments. (above, right) 12 months after VSLNT to the left thigh. (below, left) Lymphoscintigraphy findings demonstrated type IV lymphatic function before surgery. (below, right) Dermal back flow was seen in both the thigh and lower leg after surgery; lymphatic function improved to type III. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Comparison of VSLNT and LVA
FIGURE 4. A 64-year-old woman with left lower extremity lymphedema. (above, left) After 12 months of follow-up with conservative treatments. (above, right) 12 months after VSLNT to the left thigh. (below, left) Lymphoscintigraphy findings demonstrated type V lymphatic function before surgery. (below, right) Dermal back flow was observed in the thigh and lower leg. Lymphatic function improved to type III after surgery. Note that the transferred lymph nodes were also stained (red arrow). www.annalsplasticsurgery.com
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In the present study, we adopted the LEL index to evaluate changes in limb volume because body mass index was factored into the formula.30 To compare the effectiveness of surgical treatments during a long-term follow-up, changes in body weight should be taken into consideration. Some patients successfully lose body weight whereas others do not. The LEL index appears to be a reasonable formula for case comparisons. In addition, this formula facilitates the evaluation of patients with bilateral lymphedema because it is not necessary to compare the circumferences of the affected and unaffected legs. For patients with upper extremity lymphedema, an upper extremity lymphedema index has also been described.32,33 We have previously reported the results of LVA in patients with early-stage lymphedema, who only had dermal backflow at the thigh and preserved lymphatic function of the lower leg.27 In this study, the LEL index improved from 255.7 ± 22.7 to 245.2 ± 19.0 and lymphatic function improved in 53.8% of the patients. Thus, we concluded that LVA can be recommended as the first surgical approach for patients with early-stage lymphedema because it is a minimally invasive surgical treatment that requires no donor sites, only a small skin incision, and a short hospital stay, and achieves good results. We have never performed VLNT for patients with early-stage lymphedema because it is too invasive. In this study, among patients with advanced stage lymphedema who received LVA, the improvement in the LEL index was greater than that among patients with early-stage lymphedema at our institution, which was similar to that reported in previous articles.34–36 However, improved lymphatic function was achieved in only 23.3% of cases. The supraclavicular area is a favorable donor site for VLNT because it is not likely to induce extremity lymphedema after donor site dissection.22 In the present study, the improvement in lymphedematous volume was greater among VSLNT cases than among LVA cases. In addition, improved lymphatic function was achieved more frequently in the VSLNT group than in the LVA group. However, in this study, none of the 64 patients with advanced stage lymphedema regained normal lymphatic function or were completely free from compression therapy. This was far different from our results regarding early-stage lymphedema, where 44.8% of our patients who received LVA no longer required daily compression therapy.27 Despite the encouraging outcomes of lymphedema treatment in clinical cases, the interactions between VLNT and the lymphatic system at the recipient site remain poorly understood.37 However, spontaneous reconnection between the recipient site and afferent lymphatic vessels of the transferred lymph node has been described.29,38 The results of experimental studies have shown that lymphangiogenesis can be enhanced by combining VLNT with the cytokine administration of vascular endothelial growth factor C or hepatocyte growth factor.39–44 In clinical settings, lymphangiogenesis among the lymphatics cannot be assured with current treatment modalities. Therefore, we anastomosed the collecting lymphatics to assist the affluence of lymph into the transferred lymph nodes. Lin et al and Cheng et al hypothesized that transferred lymph nodes act as “lymph pumps,” absorbing lymph fluid from the surrounding interstitial tissue and ejecting it into the venous circulation by means of lymphovenous communication within the nodes.18,20,21 In advanced stage lymphedema, the walls of the collecting lymphatics in the affected limb become thickened, resulting in functional decline because of increased concentrations in smooth muscle cells and collagen fibers.45 The effectiveness of LVA can be significantly reduced by the dysregulated pumping of the lymphatic vessels in patients with advanced stage lymphedema. Therefore, in advanced stage lymphedema, the pumping ability of the transferred lymph nodes may be more beneficial in VLNT than LVA. Vascularized supraclavicular lymph node transfer has some disadvantages compared with LVA, including longer hospital stay, longer operation time, necessity of general anesthesia, the risk of flap loss from 6
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thrombosis of anastomosed vessels, donor site morbidity (eg, abnormality of sensation at the subclavian region), and a visible donor site scar. In this study, younger patients tended to select LVA because they did not want the long hospital stay. We selected donor sites for VLNT after consideration about the possibility of donor site morbidity. Patients should be informed of the disadvantages of each donor site in advance and the relative efficacy of available treatments vis-à-vis potential donor sites should also be discussed. It remains unclear whether LVA or VLNT is the better treatment strategy for patients with advanced stage lymphedema. Besides discussing the advantages and disadvantages of each treatment modality, the patient should also be advised of the limited efficacy of each (a distinct possibility depending on preoperative lymphatic function) and given other choices for surgical intervention, such as liposuction or the wedge resection of the fibrotic and subcutaneous adipose tissue.46,47 In addition, combining treatments may achieve better results.48,49 Further studies to explore treatment strategies for advanced stage LEL may yield practicable results.
CONCLUSIONS Reconstructive surgery can improve both the lymphedematous volume and lymphatic function. The extent of volume decrease and degree of improvement in lymphatic function achievable by surgery may be greater in VSLNT than in LVA. However, none of the patients diagnosed with advanced stage LEL in this study were completely diseasefree after treatment. Depending on the individual case, both VSLNT and LVA can be recommended. However, LVA is less invasive and usually requires a shorter hospital stay. REFERENCES 1. O'Brien BM, Sykes P, Threlfall GN, et al. Microlymphaticovenous anastomoses for obstructive lymphedema. Plast Reconstr Surg. 1977;60:197–211. 2. O'Brien BM, Mellow CG, Khazanchi RK, et al. Long-term results after microlymphaticovenous anastomoses for the treatment of obstructive lymphedema. Plast Reconstr Surg. 1990;85:562–572. 3. Koshima I, Nanba Y, Tsutsui T, et al. Long-term follow-up after lymphaticovenular anastomosis for lymphedema in the leg. J Reconstr Microsurg. 2003;19:209–215. 4. Koshima I, Inagawa K, Urushibara K, et al. Supermicrosurgical lymphaticovenular anastomosis for the treatment of lymphedema in the upper extremities. J Reconstr Microsurg. 2000;16:437–442. 5. Koshima I, Nanba Y, Tsutsui T, et al. 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. 6. 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. 7. Nagase T, Gonda K, Inoue K, et al. Treatment of lymphedema with lymphaticovenular anastomoses. Int J Clin Oncol. 2005;10:304–310. 8. Damstra RJ, Voesten HG, van Schelven WD, et al. 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. 9. Chang DW. Lymphaticovenular bypass for lymphedema management in breast cancer patients: a prospective study. Plast Reconstr Surg. 2010;126:752–758. 10. Demirtas Y, Ozturk N, Yapici O, et al. Comparison of primary and secondary lower-extremity lymphedema treated with supermicrosurgical lymphaticovenous anastomosis and lymphaticovenous implantation. J Reconstr Microsurg. 2010; 26:137–143. 11. Auba C, Marre D, Rodríguez-Losada G, et al. Lymphaticovenular anastomoses for lymphedema treatment: 18 months postoperative outcomes. Microsurgery. 2012;32:261–268. 12. Maegawa J, Mikami T, Yamamoto Y, et al. Types of lymphoscintigraphy and indications for lymphaticovenous anastomosis. Microsurgery. 2010;30:437–442. 13. Maegawa J, Yabuki Y, Tomoeda H, et al. Outcomes of lymphaticovenous sideto-end anastomosis in peripheral lymphedema. J Vasc Surg. 2012;55:753–760.
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Annals of Plastic Surgery • Volume 00, Number 00, Month 2015
14. 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. 15. Yamamoto T, Narushima M, Kikuchi K, et al. Lambda-shaped anastomosis with intravascular stenting method for safe and effective lymphaticovenular anastomosis. Plast Reconstr Surg. 2011;127:1987–1992. 16. Becker C, Hidden G. Transfer of free lymphatic flaps. Microsurgery and anatomical study (in French). J Mal Vasc. 1988;13:119–122. 17. Becker C, Assouad J, Riquet M, et al. Postmastectomy lymphedema: long-term results following microsurgical lymph node transplantation. Ann Surg. 2006; 243:313–315. 18. Lin CH, Ali R, Chen SC, et al. Vascularized groin lymph node transfer using the wrist as a recipient site for management of postmastectomy upper extremity lymphedema. Plast Reconstr Surg. 2009;123:1265–1275. 19. Gharb BB, Rampazzo A, di Spilimbergo SS, et al. Vascularized lymph node transfer based on the hilar perforators improves the outcome in upper limb lymphedema. Ann Plast Surg. 2011;67:589–593. 20. Cheng MH, Huang JJ, Nguyen DH, et al. A novel approach to the treatment of lower extremity lymphedema by transferring a vascularized submental lymph node flap to the ankle. Gynecol Oncol. 2012;126:93–98. 21. Cheng MH, Chen SC, Henry SL, et al. Vascularized groin lymph node flap transfer for postmastectomy upper limb lymphedema: flap anatomy, recipient sites, and outcomes. Plast Reconstr Surg. 2013;131:1286–1298. 22. Althubaiti GA, Crosby MA, Chang DW. Vascularized supraclavicular lymph node transfer for lower extremity lymphedema treatment. Plast Reconstr Surg. 2013;131:133e–135e. 23. Yamamoto T, Matsuda N, Doi K, et al. 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. 24. Akita S, Mitsukawa N, Kazama T, et al. Comparison of lymphoscintigraphy and indocyanine green lymphography for the diagnosis of extremity lymphoedema. J Plast Reconstr Aesthet Surg. 2013;66:792–798. 25. Maegawa J, Mikami T, Yamamoto Y, et al. Types of lymphoscintigraphy and indications for lymphaticovenous anastomosis. Microsurgery. 2010;30:437–442. 26. International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology. Lymphology. 2013;46:1–11. 27. Akita S, Mitsukawa N, Kuriyama M, et al. Suitable therapy options for subclinical and early-stage lymphoedema patients. J Plast Reconstr Aesthet Surg. 2014;67:520–525. 28. Akita S, Mitsukawa N, Kuriyama M, et al. External valvuloplasty for subcutaneous small veins to prevent venous reflux in lymphaticovenular anastomosis for lower extremity lymphedema. Plast Reconstr Surg. 2013;132:1008–1014. 29. Becker C1, Vasile JV, Levine JL, et al. Microlymphatic surgery for the treatment of iatrogenic lymphedema. Clin Plast Surg. 2012;39:385–398. 30. Yamamoto T, Matsuda N, Todokoro T, et al. Lower extremity lymphedema index: a simple method for severity evaluation of lower extremity lymphedema. Ann Plast Surg. 2011;67:637–640.
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Comparison of VSLNT and LVA
31. Basta MN1, Gao LL, Wu LC. Operative treatment of peripheral lymphedema: a systematic meta-analysis of the efficacy and safety of lymphovenous microsurgery and tissue transplantation. Plast Reconstr Surg. 2014;133:905–913. 32. Yamamoto T, Yamamoto N, Hara H, et al. Upper extremity lymphedema index: a simple method for severity evaluation of upper extremity lymphedema. Ann Plast Surg. 2013;70:47–49. 33. Yamamoto N, Yamamoto T, Hayashi N, et al. Arm volumetry versus upper extremity lymphedema index: validity of upper extremity lymphedema index for body-type corrected arm volume evaluation. Ann Plast Surg. 2014. [Epub ahead of print]. 34. Yamamoto T, Kikuchi K, Yoshimatsu H, et al. Ladder-shaped lymphaticovenular anastomosis using multiple side-to-side lymphatic anastomoses for a leg lymphedema patient. Microsurgery. 2014;34:404–408. 35. Yamamoto T, Yoshimatsu H, Yamamoto N, et al. Modified lambda-shaped lymphaticovenular anastomosis with supermicrosurgical lymphoplasty technique for a cancer-related lymphedema patient. Microsurgery. 2014;34:308–310. 36. Yamamoto T, Yoshimatsu H, Yamamoto N, et al. Side-to-end lymphaticovenular anastomosis through temporary lymphatic expansion. PLoS One. 2013;8:e59523. 37. Ito R, Suami H. Overview of lymph node transfer for lymphedema treatment. Plast Reconstr Surg. 2014;134:548–556. 38. Chen HC, O'Brien BM, Rogers IW, et al. Lymph node transfer for the treatment of obstructive lymphedema in the canine model. Br J Plast Surg. 1990;43: 578–586. 39. Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997;276:1423–1425. 40. Lähteenvuo M, Honkonen K, Tervala T, et al. Growth factor therapy and autologous lymph node transfer in lymphedema. Circulation. 2011;123:613–620. 41. Honkonen KM, Visuri MT, Tervala TV, et al. Lymph node transfer and perinodal lymphatic growth factor treatment for lymphedema. Ann Surg. 2013;257: 961–967. 42. Saaristo AM, Niemi TS, Viitanen TP, et al. Microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patients. Ann Surg. 2012;255:468–473. 43. Saito Y, Nakagami H, Morishita R, et al. Transfection of human hepatocyte growth factor gene ameliorates secondary lymphedema via promotion of lymphangiogenesis. Circulation. 2006;114:1177–1184. 44. Saito Y, Nakagami H, Kaneda Y, et al. Lymphedema and therapeutic lymphangiogenesis. Biomed Res Int. 2013;43:804675. 45. Mihara M, Hara H, Hayashi Y, et al. Pathological steps of cancer-related lymphedema: histological changes in the collecting lymphatic vessels after lymphadenectomy. PLoS One. 2012;7:e41126. 46. Brorson H, Svensson H. Liposuction combined with controlled compression therapy reduces arm lymphedema more effectively than controlled compression therapy alone. Plast Reconstr Surg. 1998;102:1058–1067. 47. Brorson H. Liposuction in arm lymphedema treatment. Scand J Surg. 2003;92: 287–295. 48. Granzow JW, Soderberg JM, Kaji AH, et al. Review of current surgical treatments for lymphedema. Ann Surg Oncol. 2014;21:1195–1201. 49. Granzow JW, Soderberg JM, Kaji AH, et al. An effective system of surgical treatment of lymphedema. Ann Surg Oncol. 2014;21:1189–1194.
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Comparison of Vascularized Supraclavicular Lymph Node Transfer and Lymphaticovenular Anastomosis for Advanced Stage Lower Extremity Lymphedema Shinsuke Akita, MD, PhD,* Nobuyuki Mitsukawa, MD, PhD,† Motone Kuriyama, MD, PhD,‡ Yoshitaka Kubota, MD, PhD,† Masakazu Hasegawa, MD, PhD,† Hideki Tokumoto, MD,* Tatsuya Ishigaki, MD,† Takashi Togawa, MD, PhD,§ Junpei Kuyama, MD, PhD,§ and Kaneshige Satoh, MD, PhD† Background: Vascularized lymph node transfer has become a popular surgical option to improve lower extremity lymphedema (LEL), although potential donor sites are limited. The free supraclavicular flap with deep cervical lymph nodes has been recently associated with a minimal risk of secondary lymphedema caused by donor site dissection. However, the effectiveness of this procedure has not yet been evaluated. Methods: Vascularized supraclavicular lymph node transfer (VSLNT) was performed for patients with International Society of Lymphology late stage II or more severe LEL. The results were compared with lymphaticovenular anastomosis (LVA) performed for patients with the same stages of severity. To evaluate improvement in lymphatic function, indocyanine green lymphography and lymphoscintigraphy were performed. Results: Vascularized supraclavicular lymph node transfer was performed in 13 limbs of 13 patients. The results were compared with 43 limbs of 33 patients who underwent multiple LVA. No severe complications were observed in either group. Improvement in lymphatic function, as measured by the LEL index, was 26.5 ± 4.4 and 21.2 ± 2.0 in the VSLNT and LVA groups, respectively. Lymphatic function was improved in 7 cases in the VSLNT group and 10 cases in the LVA group. Conclusions: Vascularized supraclavicular lymph node transfer is an effective technique for the treatment of advanced stage LEL. Lymphaticovenular anastomosis is also effective, but to a lesser degree than VSLNT. However, LVA is less invasive and requires a shorter hospital stay. Key Words: lymphedema, lymphaticovenular anastomosis, vascularized supraclavicular lymph node transfer (Ann Plast Surg 2015;00: 00–00)
A
mong reconstructive surgery techniques for lower extremity lymphedema (LEL), 2 creditable procedures have recently emerged: vascularized lymph node transfer (VLNT) and lymphaticovenular anastomosis (LVA).1–22 However, potential VLNT donor sites for LEL are limited.16–22 The use of a free supraclavicular flap with deep cervical lymph nodes as a donor site has been recently associated with a minimal risk of secondary lymphedema caused by donor site dissection.22 The aim of this study was to compare the effectiveness of vascularized supraclavicular lymph node transfer (VSLNT) versus
Received December 10, 2014, and accepted for publication, after revision, February 2, 2015. From the *Department of Plastic and Reconstructive Surgery, Chiba Cancer Center; †Department of Plastic, Reconstructive and Aesthetic Surgery, Chiba University, Faculty of Medicine, Chiba; ‡Department of Plastic and Reconstructive Surgery in Kochi Medical School Hospital, Nankoku; and §Division of Nuclear Medicine, Chiba Cancer Center, Chiba, Japan. Conflicts of interest and sources of funding: none declared. Reprints: Shinsuke Akita, Department of Plastic and Reconstructive Surgery, Chiba Cancer Center 666-2, Nitona-cho, Chuo-ku, Chiba City, Chiba, Japan. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/15/0000–0000 DOI: 10.1097/SAP.0000000000000513
Annals of Plastic Surgery • Volume 00, Number 00, Month 2015
LVA for the treatment of severe LEL. This is the first report to compare the results of different reconstructive surgical procedures for the treatment of lymphedema based on both lymphedematous volume and lymphatic function.
METHODS This study was carried out at the Chiba University Hospital (Chiba, Japan) and Chiba Cancer Center (Chiba, Japan) with approval of the institutional review board and permission from the ethics committee. Written permission for publication of photographs was obtained from all patients. Patients with severe LEL who underwent surgical treatment at the Chiba University and Chiba Cancer Center between January 2012 and February 2014 were included in this study. The clinical stages of lymphedema and lymphatic function were evaluated in all patients. The severity of lymphedema in all patients, except those with an allergy to iodine, was assessed via indocyanine green (ICG) lymphography. For those patients with secondary lymphedema, lymphatic function was categorized as stage I to V in accordance with the guidelines reported by Yamamoto et al23 (Table 1). For patients who were obese or diagnosed with advanced stage lymphedema, ICG lymphography may not be an ideal modality because it is insufficient for detecting lymphatic function greater than 15 mm from the skin surface. For this group of patients, lymphoscintigraphy proved more useful in assessing lymphatic function in the deeper layers.24 Cases of secondary lymphedema assessed by lymphoscintigraphy were categorized as type 0-V, as described by Maegawa et al25 (Table 2). Lymphatic function in all patients with primary lymphedema was assessed via ICG lymphography and lymphoscintigraphy. Vascularized lymph node transfer was not selected as a surgical option for patients with early-stage lymphedema. Lymphaticovenular anastomosis was recommended as the treatment of choice for all patients categorized as Internal Society of Lymphology (ISL) clinical stage I or early II with confirmed adequate lymphatic function.26 For patients with stage I or II secondary lymphedema, ICG lymphography was used to establish preserved lymphatic function, whereas lymphoscintigraphy was the diagnostic modality for patients with type I or II disease. A diagnosis of mild primary lymphedema was made by the visualization of functional lymphatics. For these individuals, LVA was recommended as the optimal treatment.27 Patients with secondary lymphedema graded as late ISL clinical stage II or worse and those with lymphatic function categorized as type III-V by lymphoscintigraphy or stage III-V by ICG lymphography were considered to have advanced stage lymphedema. Patients with ISL clinical stage II primary lymphedema or worse and those with undetectable functional linear lymphatics were deemed to have advanced stage primary lymphedema. All patients with advanced stage lymphedema received supervised compression therapy for at least 3 months. After the completion of compression therapy, the patients received counseling on the respective benefits of VLNT and LVA, both orally and in writing, www.annalsplasticsurgery.com
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TABLE 1. Indocyanine Green Lymphography Stage Stage
0 I II III IV V
Description
No dermal back flow pattern A splash pattern around the groin/axillary region A stardust pattern extending proximally to the superior border of the patella/elbow A stardust pattern extending distally to the superior border of the patella/elbow A stardust pattern extending to the entire limb The existence of a diffuse pattern with a stardust pattern in the background
by a single plastic surgeon. Based on this knowledge, each patient selected LVA or VLNT depending on the appropriateness of the procedure. No patient underwent simultaneous LVA and VLNT or the wedge resection of fibrotic subcutaneous adipose tissue. Although our LVA surgical technique includes some intricate procedures designed to prevent reflux within small subcutaneous veins, our method was essentially the same as that reported elsewhere.3–5,9,13,28 Multiple side-to-end anastomoses between the collecting lymphatics and small veins were preferable to end-to-end anastomosis. Most LVA procedures were performed under local anesthesia, unless the patient preferred general anesthesia. The average postoperative hospitalization period was approximately 7 days. The donor site for VLNT was selected from the thoracic (vascularized thoracic lymph node transfer [VTLNT]), groin (vascularized groin lymph node transfer [VGLNT]), or supraclavicular regions (VSLNT).17,18,21,22,29 Vascularized groin lymph node transfer was not selected if the patient exhibited any sign of secondary lymphedema after pelvic lymph node dissection. In the remaining cases, the normal lymphatic function of the contralateral leg was confirmed by lymphoscintigraphy and ICG lymphography before performing VGLNT. In our institution, the submental region was generally not recommended to the patient as a donor site.20 The VLNT recipient site was selected from the distal region of the thigh or the ankle, depending on the area most affected. If symptoms were most severe at the thigh, the distal thigh was selected. If symptoms at the lower leg were severe, the ankle was selected. If adequately sized collecting lymphatics were evident in both the recipient lesion and afferent lymphatics to the transferring lymph nodes, they were anastomosed to each other. In the VLNT group, all surgeries were performed under general anesthesia. For these patients, hospitalization was extended to 2 weeks postoperatively. All patients performed simple lymph drainage procedures by themselves after discharge. TABLE 2. Lymphoscintigraphy Type Type
0 I II III IV V
2
Description
Inguinal/axillary lymph nodes stained normally; no dermal back flow pattern is seen The number of visible inguinal/axillary lymph nodes is reduced Few or no inguinal/axillary lymph nodes are seen; dermal back flow is seen in the thigh/upper arm No inguinal/axillary lymph nodes are detected; dermal back flow is seen in the thigh and leg/upper arm and forearm Dermal back flow and lymph stasis are seen in the leg/forearm No dermal back flow is seen; no tracer migration is seen
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All patients with advanced stage lymphedema received supervised compression therapy for at least 3 months before surgery, and the preoperative lymphedematous volume of the limb was measured afterward. Changes in the postoperative volume were compared using the LEL index, which was calculated from the circumferences of 5 points on the limb (the superior edge of the patella, 10 cm above and below the patella, the lateral malleolus, and the dorsum of the foot) and the body mass index, which yielded an accurate quantitative assessment of the severity of lymphedema.30 Improvement achieved by surgical treatment was defined as the difference between the preoperative and postoperative LEL indices. The postoperative LEL index was measured for at least 3 months after surgery. Postoperative lymphatic function, assessed by ICG lymphography or lymphoscintigraphy, was compared with the preoperative findings. When an improvement in the ICG lymphography stage or lymphoscintigraphy type was confirmed, lymphatic function was regarded as improved. Even if the stage remained unchanged, dermal backflow was reduced by more than 25%, and lymphatic function was determined to have improved. The results of all patients treated for advanced stage lymphedema during the study period were collected. Improvements in the LEL index and the proportion of patients with improved lymphatic function after surgery were compared against the surgical methods. Hospital stay, operation time, anesthesia type (local or general), and postoperative complications were also compared between the surgical methods. Statistical analyses were performed using IBM SPSS Statistics 22 (IBM-SPSS, Inc., Chicago, IL). An unpaired t test was used to compare the level of improvement according to the LEL index, hospital stay, and operation time. A standard χ2 test and the Yates corrected χ2 test were used to compare the proportion of patients with improved lymphatic function after surgery, anesthesia type, and the incidence of postoperative complications. A probability (P) value less than 0.05 was considered statistically significant.
RESULTS During the study period, surgical treatment for LEL was performed in 127 limbs. In 63 limbs, lymphatic function was sufficiently preserved to meet our criteria of early-stage lymphedema. These patients were treated by LVA. The other 64 limbs exhibited advanced stage lymphedema. Of these patients, 43, 13, 4, and 4 underwent multiple LVA, VSLNT, VTLNT, and VGLNT procedures, respectively. For the cases that underwent VLNT, anastomoses between lymphatics could not be performed in 1 case that received VGLNT and in 2 cases that received VTLNT. These 3 cases were young patients with primary lymphedema and sizable collecting lymphatics that could not be detected at the recipient site. For cases that underwent VSLNT, anastomoses between lymphatics were performed in all cases. Because relatively few patients underwent VTLNT and VGLNT, the statistical comparisons were only performed for LVA and VSLNT. The characteristics of patients according to surgical treatment are listed in Table 3. Among the baseline characteristics, the patients' age was significantly lower in the LVA group (P = 0.03). A history of phlegmon was noted in 39 of 43 limbs (90.7%) in the LVA group and all 13 limbs (100%) in the VSLNT group. In the LVA group, the anastomoses were 5.1 ± 1.8 (mean ± standard deviation). The mean operation time was shorter in the LVA group than in the VSLNT group with significant difference (213 ± 68 vs. 414 ± 65 minutes, respectively; P < 0.01). In the LVA group, the operation was performed under general anesthesia in 8 of 43 limbs in accordance with the patients' wishes. The other 35 limbs underwent LVA under local anesthesia. All 13 patients in the VSLNT group underwent the operation under general anesthesia. There was a significant difference between the 2 groups regarding anesthesia type (P < 0.01). The mean hospital stay was shorter for the LVA group than the VSLNT © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Annals of Plastic Surgery • Volume 00, Number 00, Month 2015
TABLE 3. Surgical Treatments for Patients With Advanced Stage Lymphedema and Patients' Characteristics
Total no. limbs Female Secondary Age, y Postoperative follow-up period, mo Preoperative BMI
LVA
VSLNT
P
43 40 34 54.1 ± 14.8 18.3 ± 8.8 24.8 ± 5.8
13 13 11 63.7 ± 7.0 15.1 ± 1.9 23.0 ± 2.8
1.00 1.00 0.03 0.06 0.30
BMI indicates body mass index.
group with significant difference (8.9 ± 2.9 vs 15.2 ± 1.6 days, respectively; P < 0.01). The LVA group showed lower incidence of complications than the VSLNT group with significant difference (0 vs 3 cases, respectively; P < 0.01). No significant complications occurred in the LVA group, whereas congestion to the skin paddle was observed in three patients in the VSLNT group on the day of surgery. The patency of the anastomosed vessels and adequate blood circulation to the transferred lymph nodes at the deep layer were confirmed by re-exploration in 2 cases. In these cases, because the problem was believed to involve the venous drainage from the skin flap skin paddle via the perforators, the congested skin flaps were removed and the blood circulation to the transferred lymph nodes was monitored by color Doppler sonography. In both cases, the patency of the anastomosed vessels was monitored until the final examination 2 weeks after surgery. Venous thrombosis at the anastomosis site was observed in a third case, for which the vein was re-anastomosed and the flap salvaged. In these 3 complicated cases, hospitalization was extended for a few days beyond the preoperative plan. In all cases, the transferred lymph nodes survived. Perioperative improvement, as indicated by the mean value of the LEL index, was significantly better in the VSLNT group than in the LVA group (21.2 ± 2.0 vs 26.5 ± 4.4, respectively; P = 0.032). Lymphatic function improved in 10 cases (23.3%) in the LVA group and in 7 cases (53.8%) in the VSLNT group. A significant difference was observed between the LVA and VSLNT groups (P = 0.046) (Table 4). None of the 64 patients with advanced stage lymphedema regained normal lymphatic function or were completely free from compression therapy. Most of them wore elastic garments occasionally until the final follow-up.
CASE REPORTS
Comparison of VSLNT and LVA
Cases 8 (right), 9 (left) A 34-year-old woman presented with bilateral primary LEL with an onset at 17 years of age. After 6 months of follow-up with conservative treatment, she received multiple LVAs in both legs. One year after surgery, her legs were thinner, and she had managed to lose a total of 3 kg. After surgery, her LEL index improved from 258.8 to 245.2 for the right leg and from 292.5 to 265.5 for the left leg (Fig. 2, above). Preoperatively, the migration of the tracer was poor in both legs. Postoperatively, linear collecting lymphatics and lymph nodes were detected in her right leg, and lymphatic function on this side was determined to be improved. However, no significant improvement was observed in her left leg (Fig. 2, below).
Case 30 A 49-year-old woman presented with left LEL after pelvic lymph node dissection 2 years ago. After 6 months of follow-up with conservative treatment, she received VSLNT to the left thigh. One year after surgery, her legs were thinner, and she had managed to lose a total of 5 kg. The LEL index of her left limb improved from 317.6 to 292.0 perioperatively (Fig. 3, above). Lymphoscintigraphy findings improved from type IV to III after surgery (Fig. 3, below).
Case 56 A 64-year-old woman presented with left LEL after pelvic lymph node dissection 10 years ago. After 5 months of follow-up with conservative treatment, she received VSLNT to the left thigh. One year after surgery, her legs were thinner without losing any body weight. The LEL index of her left limb improved from 262.5 to 236.9 (Fig. 4, above). Lymphoscintigraphy findings improved from type V to III (Fig. 4, below).
DISCUSSION Both LVA and VLNT are recognized as effective reconstructive surgical treatments for extremity lymphedema. Marten et al31 performed a meta-analysis to compare the effectiveness of lymphovenous shunt procedures and VLNT from the results of 22 studies of lymphovenous shunt procedures and 5 studies of VLNT.31 They ultimately concluded that VLNT may provide better outcomes than lymphovenous shunting, although most of the studies about VLNTwere associated with upper extremity lymphedema. In contrast, the studies that involved lymphovenous shunting included both the upper and lower extremities. However, there are important differences in venous pressure and fat volume between the upper and lower extremities. To properly assess the effectiveness of surgical treatment, the upper and lower extremities should be separately evaluated because lymphedema is much more refractory in the lower extremities. In addition, because assessment modalities for lymphedema have not yet been standardized, the comparisons of the volume reduction among different studies appear unsound. Furthermore, the severity of the disease and
Cases 31 (right), 32 (left) A 50-year-old woman presented with bilateral LEL after pelvic lymph node dissection 10 years ago. Although she had received conservative therapy, the limb volume did not decrease. After a 12-month follow-up period with conservative treatments by specialists, she received multiple LVA in both legs. One year after surgery, her legs were thinner, and she had managed to lose a total of 8 kg (Fig. 1, above). After surgery, her LEL index improved from 285.9 to 257.7 for the right leg and from 258.9 to 233.0 for the left leg. Although the lymphoscintigraphy of the left leg showed improvement from type III to type II, the right leg remained as type V. The straight staining lines on the bilateral thighs in the postoperative lymphoscintigraphy image were the veins (Fig. 1, below). © 2015 Wolters Kluwer Health, Inc. All rights reserved.
TABLE 4. Results of Each Type of Treatment for the Patients With Advanced Stage Lymphedema
No. patients Days of hospitalization Preoperative LEL index Postoperative LEL index Improvement value of LEL index Improvement of lymphatic function
LVA
VSLNT
43 8.9 ± 2.9 292.2 ± 35.1 271.0 ± 33.1 21.2 ± 2.0 10
13 15.2 ± 1.6 288.2 ± 23.4 261.7 ± 26.3 26.5 ± 4.4 7
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FIGURE 1. A 50-year-old woman with bilateral lower extremity lymphedema. (above, left) After 12 months of follow-up with conservative treatments. (above, right) One year after multiple LVA in both legs. (below, left) Preoperative lymphoscintigraphy revealed type V lymphatic function in the right leg and type III in the left leg. (below, right) Postoperative lymphoscintigraphy findings for the right leg did not show any improvement. Dermal back flow at the left thigh was reduced significantly, and lymphatic function in the left leg was redesignated as type II. The straight staining lines on the bilateral thighs in the postoperative lymphoscintigraphy image were the veins. 4
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FIGURE 2. A 34-year-old woman with bilateral primary lower extremity lymphedema. (above, left) After 6 months of follow-up with conservative treatments. (above, right) One year after multiple LVA in both legs. (below, left) Preoperative lymphoscintigraphy showed minor migration of the tracer in both legs. (below, right) Postoperatively, linear collecting lymphatics and lymph nodes were detectable in the right leg, but no significant improvement was observed in the left leg.
effectiveness of conservative treatment may have influenced the surgical outcomes. When comparing one surgery for lymphedema against another, targeting of the limb to precisely assess disease severity and matching conservative therapy protocols are essential. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Annals of Plastic Surgery • Volume 00, Number 00, Month 2015
FIGURE 3. A 49-year-old woman with left lower extremity lymphedema. (above, left) After 6 months of follow-up with conservative treatments. (above, right) 12 months after VSLNT to the left thigh. (below, left) Lymphoscintigraphy findings demonstrated type IV lymphatic function before surgery. (below, right) Dermal back flow was seen in both the thigh and lower leg after surgery; lymphatic function improved to type III. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Comparison of VSLNT and LVA
FIGURE 4. A 64-year-old woman with left lower extremity lymphedema. (above, left) After 12 months of follow-up with conservative treatments. (above, right) 12 months after VSLNT to the left thigh. (below, left) Lymphoscintigraphy findings demonstrated type V lymphatic function before surgery. (below, right) Dermal back flow was observed in the thigh and lower leg. Lymphatic function improved to type III after surgery. Note that the transferred lymph nodes were also stained (red arrow). www.annalsplasticsurgery.com
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Annals of Plastic Surgery • Volume 00, Number 00, Month 2015
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In the present study, we adopted the LEL index to evaluate changes in limb volume because body mass index was factored into the formula.30 To compare the effectiveness of surgical treatments during a long-term follow-up, changes in body weight should be taken into consideration. Some patients successfully lose body weight whereas others do not. The LEL index appears to be a reasonable formula for case comparisons. In addition, this formula facilitates the evaluation of patients with bilateral lymphedema because it is not necessary to compare the circumferences of the affected and unaffected legs. For patients with upper extremity lymphedema, an upper extremity lymphedema index has also been described.32,33 We have previously reported the results of LVA in patients with early-stage lymphedema, who only had dermal backflow at the thigh and preserved lymphatic function of the lower leg.27 In this study, the LEL index improved from 255.7 ± 22.7 to 245.2 ± 19.0 and lymphatic function improved in 53.8% of the patients. Thus, we concluded that LVA can be recommended as the first surgical approach for patients with early-stage lymphedema because it is a minimally invasive surgical treatment that requires no donor sites, only a small skin incision, and a short hospital stay, and achieves good results. We have never performed VLNT for patients with early-stage lymphedema because it is too invasive. In this study, among patients with advanced stage lymphedema who received LVA, the improvement in the LEL index was greater than that among patients with early-stage lymphedema at our institution, which was similar to that reported in previous articles.34–36 However, improved lymphatic function was achieved in only 23.3% of cases. The supraclavicular area is a favorable donor site for VLNT because it is not likely to induce extremity lymphedema after donor site dissection.22 In the present study, the improvement in lymphedematous volume was greater among VSLNT cases than among LVA cases. In addition, improved lymphatic function was achieved more frequently in the VSLNT group than in the LVA group. However, in this study, none of the 64 patients with advanced stage lymphedema regained normal lymphatic function or were completely free from compression therapy. This was far different from our results regarding early-stage lymphedema, where 44.8% of our patients who received LVA no longer required daily compression therapy.27 Despite the encouraging outcomes of lymphedema treatment in clinical cases, the interactions between VLNT and the lymphatic system at the recipient site remain poorly understood.37 However, spontaneous reconnection between the recipient site and afferent lymphatic vessels of the transferred lymph node has been described.29,38 The results of experimental studies have shown that lymphangiogenesis can be enhanced by combining VLNT with the cytokine administration of vascular endothelial growth factor C or hepatocyte growth factor.39–44 In clinical settings, lymphangiogenesis among the lymphatics cannot be assured with current treatment modalities. Therefore, we anastomosed the collecting lymphatics to assist the affluence of lymph into the transferred lymph nodes. Lin et al and Cheng et al hypothesized that transferred lymph nodes act as “lymph pumps,” absorbing lymph fluid from the surrounding interstitial tissue and ejecting it into the venous circulation by means of lymphovenous communication within the nodes.18,20,21 In advanced stage lymphedema, the walls of the collecting lymphatics in the affected limb become thickened, resulting in functional decline because of increased concentrations in smooth muscle cells and collagen fibers.45 The effectiveness of LVA can be significantly reduced by the dysregulated pumping of the lymphatic vessels in patients with advanced stage lymphedema. Therefore, in advanced stage lymphedema, the pumping ability of the transferred lymph nodes may be more beneficial in VLNT than LVA. Vascularized supraclavicular lymph node transfer has some disadvantages compared with LVA, including longer hospital stay, longer operation time, necessity of general anesthesia, the risk of flap loss from 6
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thrombosis of anastomosed vessels, donor site morbidity (eg, abnormality of sensation at the subclavian region), and a visible donor site scar. In this study, younger patients tended to select LVA because they did not want the long hospital stay. We selected donor sites for VLNT after consideration about the possibility of donor site morbidity. Patients should be informed of the disadvantages of each donor site in advance and the relative efficacy of available treatments vis-à-vis potential donor sites should also be discussed. It remains unclear whether LVA or VLNT is the better treatment strategy for patients with advanced stage lymphedema. Besides discussing the advantages and disadvantages of each treatment modality, the patient should also be advised of the limited efficacy of each (a distinct possibility depending on preoperative lymphatic function) and given other choices for surgical intervention, such as liposuction or the wedge resection of the fibrotic and subcutaneous adipose tissue.46,47 In addition, combining treatments may achieve better results.48,49 Further studies to explore treatment strategies for advanced stage LEL may yield practicable results.
CONCLUSIONS Reconstructive surgery can improve both the lymphedematous volume and lymphatic function. The extent of volume decrease and degree of improvement in lymphatic function achievable by surgery may be greater in VSLNT than in LVA. However, none of the patients diagnosed with advanced stage LEL in this study were completely diseasefree after treatment. Depending on the individual case, both VSLNT and LVA can be recommended. However, LVA is less invasive and usually requires a shorter hospital stay. REFERENCES 1. O'Brien BM, Sykes P, Threlfall GN, et al. Microlymphaticovenous anastomoses for obstructive lymphedema. Plast Reconstr Surg. 1977;60:197–211. 2. O'Brien BM, Mellow CG, Khazanchi RK, et al. Long-term results after microlymphaticovenous anastomoses for the treatment of obstructive lymphedema. Plast Reconstr Surg. 1990;85:562–572. 3. Koshima I, Nanba Y, Tsutsui T, et al. Long-term follow-up after lymphaticovenular anastomosis for lymphedema in the leg. J Reconstr Microsurg. 2003;19:209–215. 4. Koshima I, Inagawa K, Urushibara K, et al. Supermicrosurgical lymphaticovenular anastomosis for the treatment of lymphedema in the upper extremities. J Reconstr Microsurg. 2000;16:437–442. 5. Koshima I, Nanba Y, Tsutsui T, et al. 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. 6. 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. 7. Nagase T, Gonda K, Inoue K, et al. Treatment of lymphedema with lymphaticovenular anastomoses. Int J Clin Oncol. 2005;10:304–310. 8. Damstra RJ, Voesten HG, van Schelven WD, et al. 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. 9. Chang DW. Lymphaticovenular bypass for lymphedema management in breast cancer patients: a prospective study. Plast Reconstr Surg. 2010;126:752–758. 10. Demirtas Y, Ozturk N, Yapici O, et al. Comparison of primary and secondary lower-extremity lymphedema treated with supermicrosurgical lymphaticovenous anastomosis and lymphaticovenous implantation. J Reconstr Microsurg. 2010; 26:137–143. 11. Auba C, Marre D, Rodríguez-Losada G, et al. Lymphaticovenular anastomoses for lymphedema treatment: 18 months postoperative outcomes. Microsurgery. 2012;32:261–268. 12. Maegawa J, Mikami T, Yamamoto Y, et al. Types of lymphoscintigraphy and indications for lymphaticovenous anastomosis. Microsurgery. 2010;30:437–442. 13. Maegawa J, Yabuki Y, Tomoeda H, et al. Outcomes of lymphaticovenous sideto-end anastomosis in peripheral lymphedema. J Vasc Surg. 2012;55:753–760.
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Annals of Plastic Surgery • Volume 00, Number 00, Month 2015
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Comparison of VSLNT and LVA
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