Comparison of lymphovenous anastomosis and vascularized lymph node transfer in lymphedema treatment - a literature review.

INTRODUCTION: Primary lymphedema is a devastating and debilitating disease. Much of the current treatment options demonstrate evidence in the treatment of secondary lymphedema. This study was to investigate the outcomes between vascularized lymph node transfers (VLNT) and lymphovenous anastomosis (LVA) in the treatment of primary lymphedema. METHODS: A total of 17 patients with a mean age of 31 (ranged 2- 57) years were recruited to the study with a total of 19 lower limbs with primary lymphedema. All patients reported a non-hereditary, occurrence of lymphedema without surgical and medical history. All patients were treated with either VLNT or LVA. Patients with a grade 1 or early grade 2 lymphedema were treated with LVA whereas late grade 2 to grade 4 patients received VLNT treatment. Quality of life and serial circumferential limb measurements including number of episodes of cellulitis were compared both pre and postoperatively. RESULTS: Fifteen limbs underwent VLNTs and had an average of 3.8 cm circumferential reduction above knee, 3.6 cm below knee and 4 cm above ankle with an average reduction of 3.7 cm. Four limbs received LVA treatment and had an average of 1.3 cm circumferential reduction AK, 3.0 cm BK and 1.5 cm AA, giving an average reduction of 1.9 cm. Follow-up was for an average of 19.7 ± 8.5 months. Patients in the VLNT group had an average cellulitis episode drop from 5.2 preoperatively to 0.1 postoperatively. Patients in the LVA group reported an average reduction in cellulitic episodes from 5 preoperatively to 0.8 postoperatively. In the VLNT group, an average significant improvement in overall quality of life was noted by 2.5 points. In the LVA group, an average improvement in the overall quality of life score was seen by 2 points. CONCLUSION: In conclusion, primary lymphedema can be effectively treated adequately with improvements in both functional and quality of life outcomes with appropriate lymphedema microsurgeries. VLNT when used in severe cases of lymphedema, can provide greater relief with more impactful outcomes in both functional restoration and quality of life outcomes.

Background:Primary lymphedema is a debilitating disease. This study was to investigate the outcomes between vascularized lymph node transfer (VLNT) and lymphovenous anastomosis (LVA) for treating primary lymphedema.Methods:Between January 2010 and December 2016, 17 patients with mean age of 31.5 ± 15.5 (ranged, 2–57) years diagnosed with 19 primary limb lymphedema were recruited. Patients with patent lymphatic ducts on indocyanine green lymphography were indicated for LVA, whereas those without patent lymphatic ducts were indicated for VLNT. Circumferential limb measurements, body weight, episodes of cellulitis and Lymphedema Quality-of-Life (LYMQoL) questionnaire were compared between preoperatively and postoperatively.Results:Fifteen lymphedematous limbs underwent VLNT (79%) and 4 underwent LVA (21%). All VLNT flaps survived. At a mean follow-up of 19.7 ± 8.5 months, mean reduction of limb circumference, body weight, and episodes of cellulitis were 3.7 ± 2.9 cm and 1.9 ± 2.9 cm (P = 0.2); 6.6 ± 5.9 kg and 1.7 ± 0.6 kg (P < 0.05); 5.1 ± 2.8 times/y and 4.2 ± 0.5 times/y in VLNT and LVA groups, respectively (P = 0.7). Improvements in overall score (from 3.9 ± 1.2 to 6.4 ± 1.1, P < 0.05) of the LYMQoL in VLNT group had statistical significant difference than that (from 3.0 ± 1.4 to 5.0 ± 2.4, P = 0.07) in LVA group.Conclusions:Both VLNT and LVA can effectively treat primary lymphedema patients. The reduction of above-knee circumference, body weight, episodes of cellulitis, and the improvement of LYMQoL was significantly greater in LVNT compared with LVA.

Lymphedema surgery including lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT) are effective treatments for lymphedema; however, treating multiple limbs in a single operation using both approaches has not been described. We hypothesize multiple limb lymphedema can be treated effectively in one operation. Retrospective review of seven patients undergoing extreme lymphedema surgery (mean age: 53.2 years; range: 33-66 years) with an average BMI of 34.8kg/m2 (range: 17.6-53.6kg/m2 ). Two patients developed bilateral upper extremity (UE) lymphedema secondary to breast cancer treatment, three had bilateral lower extremity (LE) lymphedema, and two suffered from lymphedema of all four extremities due to breast cancer treatment. One patient with bilateral UE lymphedema was treated with bilateral inguinal node transfers with LVA and the other with combined bilateral DIEP flaps and inguinal node transfers with LVA. Three patients had bilateral LE lymphedema: two were treated with split omental/gastroepiploic nodes, and one underwent simultaneous supraclavicular and submental node transfers. LVAs were performed in one leg in each patient. Two patients with four-limb lymphedema underwent bilateral inguinal node transfers with DIEP flaps and bilateral LE LVA. In total, there were eight UE and 10 LE treated. Average follow-up was 15.8months (range: 12.6-28.4months), all patients reported subjective improvement in symptoms, were able to decrease use of compression garments and pumps, and no patients developed cellulitis. Patients suffering from lymphedema of multiple extremities can be treated safely and effectively combining both LVA and VLNT in a single operation.

Secondary lymphedema is a complex and devastating disease including chronic inflammation and reduced immunofunction, lymphatic fluid and protein accumulation due to misdirected lymphatic transport, and secondary fat deposition followed by fibrosis. While the domain of treatment still is lifelong complex decongestive therapy, it is more and more widespread to treat the disease with a surgical focus on physiologic, reconstructive strategies or debulking surgery. Lymphovenous Anastomosis (LVA) and Vascularized lymph node transplantation (VLNT) are the mostly frequently applied, reconstructive techniques which address restoration or improvement of physiologic lymph clearance. The article summarizes and discusses the recommendations of an expert panel on the diagnostic, indication and therapy of LVA and VLNT in secondary lymphedema during the 40th Meeting of the Germanspeaking Society of Microsurgery in Lugano, Switzerland, 2018. The expert panel addressed the basic diagnostics prior to lymphoreconstructive surgery, including the inevitable application of Indocyanine Green (ICG) based fluorescence lymphangiography and navigation for both techniques including reverse mapping to reduce the rate of donor-site lymphedema for VLNT as well as the use of lymphedema-specific quality of life questionnaires. Both LVA and VLNT are elaborately described, including tips and tricks on identifying functional lymphatic collectors, equipment, types of anastomosis and documentation for LVA and choice of donor and recipient site, number of includable lymph nodes and management of specific donor sites, e. g. jejunal mesenteric for VLNT. The synchronous and sequential application of LVA, VLNT and/or ablative liposuction is discussed against the background of the effectivity and morbidity of both reconstructive, physiologic techniques. Finally, recommendations on post-operative treatment and diagnostics are discussed. The present consensus paper intends to improve the level of standardization for further multicenter studies in the germanspeaking countries in this aspiring field of lymphedema treatment.

Sir: Vascularized lymph node transfer of lymph nodes from donor sites to affected sites can restore lymphatic flow and effectively treat lymphedema. A documented risk of vascularized lymph node transfer is the development of new lymphedema at or around the lymph node harvest donor site or limb. Studies have reported rare instances of donor-site lymphedema following lymph node flap harvest from axillary or groin donor sites.1–3 The supraclavicular area has been described previously as a donor site without risk of secondary lymphedema in the surrounding tissues, with some surgeons favoring this donor site because of the perceived lack of risk.4 We describe a patient who presented with lymphedema of the right arm following vascularized lymph node transfer from the right supraclavicular donor area to the left groin. The development of lymphedema in the right upper extremity following a supraclavicular node harvest challenges this previous notion that the supraclavicular area is without risk of donor-site lymphedema. Careful patient selection, surgical expertise, and methods such as reverse lymph node mapping may reduce this risk.5–8 A 55-year-old woman presented to our office after she developed lymphedema of the right arm approximately 2 years after she had vascularized lymph node transfer performed by another surgeon. She had initially developed left leg lymphedema after an epidural procedure. In the following year, the patient also developed lymphedema in the right leg (Fig. 1). The vascularized lymph node transfer procedure from the right supraclavicular fossa to the left groin was then performed by the other surgeon to treat the swelling (Fig. 2). The patient’s postoperative course was complicated by the accumulation of seroma containing milky fluid at the supraclavicular donor site, which resolved approximately 4 weeks after surgery with conservative treatment. Approximately 6 months after the vascularized lymph node transfer surgery, the patient developed lymphedema in her right arm. A volume excess of 1055 cc was present on follow-up examination (Fig. 3). Lymphoscintigraphic imaging before and after the vascularized lymph node transfer surgery revealed a significant decrease of tracer migration in the right arm and loss of visualization of tracer in the right axillary lymph nodes after the operation, consistent with lymphedema (Fig. 4).Fig. 1: Patient with bilateral lower extremity lymphedema.Fig. 2: Right supraclavicular lymph node transfer donor site.Fig. 3: Right upper extremity lymphedema following vascularized lymph node transfer from the right supraclavicular area.Fig. 4: Lymphoscintigraphic findings before (left) and after (right) supraclavicular lymph node harvest. Note loss of tracer uptake in the right axilla in the postoperative image.Effective treatments for both congenital and secondary lymphedema have been documented extensively in the medical literature. Multiple studies have documented the effectiveness of conservative lymphedema therapy, vascularized lymph node transfer, lymphaticovenous anastomosis, and suction-assisted protein lipectomy for properly selected patients with lymphedema.5–14 Vascularized lymph node transfer involves transfer of lymph nodes and the surrounding soft tissue as a microsurgical free flap from a donor site to the affected area. This technique is most effective for the treatment of fluid-predominant lymphedema, and can reduce the need for compression garment use and lymphedema therapy. Furthermore, vascularized lymph node transfer can improve patient quality of life and dramatically reduce the risk of dangerous lymphedema cellulitis in affected individuals.5–14 This case challenges the previous notion that the supraclavicular donor site is free from postoperative lymphedema risk. Careful patient selection and anatomical dissection, surgeon experience with the vascularized lymph node transfer procedure, and the use of reverse lymphatic mapping may reduce such donor-site risk. DISCLOSURE The authors have no financial interest to declare in relation to the content of this article. Ming Lee, A.B. Emory University School of Medicine Evan McClure, B.A. Emory University School of Medicine, and Goizueta Business School Emory University Erik Reinertsen, B.S. Emory University School of Medicine Wallace H. Coulter Department of Biomedical Engineering at Emory University, and Georgia Institute of Technology Atlanta, Ga. Jay W. Granzow, M.D., M.P.H. Division of Plastic Surgery University of California, Los Angeles Harbor–UCLA Medical Center and UCLA David Geffen School of Medicine Los Angeles, Calif.

Breast Cancer-Related Lymphedema (BCRL) remains a significant burden despite conservative treatments like Complex Decongestive Therapy (CDT). Surgical interventions such as Lymphovenous Anastomosis (LVA) and Vascularized Lymph Node Transfer (VLNT) have emerged as effective alternatives. This study aims to evaluate the effectiveness of LVA and/or VLNT combined with CDT, compared to CDT alone, in reducing upper limb volume in BCRL patients. This prospective controlled study included 92 BCRL patients, divided into four groups: LVA (n=30), VLNT (n=15), LVA + VLNT (n=13), and CDT Control (n=34). Limb volumes were measured preoperatively and one year postoperatively. Volume differential change (RID%) was calculated for each group. The mean volume differential changes were: LVA (-6.21% ± 5.76), VLNT (-9.61% ± 12.03), LVA+VLNT (-7.00% ± 6.56), and CDT control (+3.23% ± 6.83). Statistical analysis revealed significant reductions in limb volume for all surgical groups compared to the CDT control group (p < 0.0001 for LVA, p < 0.0001 for VLNT, and p < 0.0001 for LVA + VLNT). In chronic BCRL patients, surgical interventions (LVA, VLNT, and their grouping) combined with CDT, significantly reduce limb volume compared to CDT alone. These findings highlight the potential of these surgical options, combined with CDT, in the effective management of lymphedema.Level of evidence: Level II (Controlled Trial).

Primary lymphedema is an anomaly of the regional lymphatic system with long symptom duration or severe lymphatic obstruction. Few microsurgical treatments for primary lymphedema have been reported. This aim of this study was to investigate the outcomes of microsurgical treatments in pediatric primary lymphedema patients. Between 2013 and 2017, pediatric primary lymphedema patients who underwent either lymphovenous anastomosis (LVA) or vascularized lymph node transfer (VLNT) were retrospectively reviewed. Cheng's Lymphedema Grading, Taiwan Lymphoscintigraphy Staging and indocyanine green lymphography were used to select the procedures. No compression garments were used postoperatively. Outcome measurements included circumferential difference, episodes of cellulitis, and Lymphedema-specific Quality of life questionnaire (LYMQoL). Nine patients with mean age of 9.2 years (range, 2-19 years) with 11 lower and two upper lymphedematous limbs underwent 11 VLNT and two LVA. All VLNT flaps survived. At a mean 38.4-months (range, 16-63 months) of follow-up, the mean circumferential difference in nine unilateral lymphedematous limbs was improved by 6.7 ± 9.9% (p = .066). Two patients with bilateral lower limb lymphedema had mean limb circumference improvements of 1.3 and 6.5 cm, respectively. In nine limbs with cellulitis preoperatively, episodes of cellulitis decreased by 2.67 times/year (p = .007). At a mean 22.3-months of follow-up (range, 13-24 months), the LYMQoL overall score in 6 patients older than 7 years was improved by 3.2 ± 1.1 points (p = .007). Lymphedema microsurgery significantly improved the episodes of cellulitis and quality of life without utilizing compression garments in pediatric primary lymphedema patients.

To summarize the research progress of combined surgical treatment of lymphedema based on vascularized lymph node transfer (VLNT), and to provide systematic information for combined surgical treatment of lymphedema. Literature on VLNT in recent years was extensively reviewed, and the history, treatment mechanism, and clinical application of VLNT were summarized, with emphasis on the research progress of VLNT combined with other surgical methods. VLNT is a physiological operation to restore lymphatic drainage. Multiple lymph node donor sites have been developed clinically, and two hypotheses have been proposed to explain its mechanism for the treatment of lymphedema. But it has some inadequacies such as slow effect and limb volume reduction rate less than 60%. To address these inadequacies, VLNT combined with other surgical methods for lymphedema has become a trend. VLNT can be used in combination with lymphovenous anastomosis (LVA), liposuction, debulking operation, breast reconstruction, and tissue engineered material, which have been shown to reduce the volume of affected limbs, reduce the incidence of cellulitis, and improve patients' quality of life. Current evidence shows that VLNT is safe and feasible in combination with LVA, liposuction, debulking operation, breast reconstruction, and tissue engineered material. However, many issues need to be solved, including the sequence of two surgeries, the interval between two surgeries, and the effectiveness compared with surgery alone. Rigorous standardized clinical studies need to be designed to confirm the efficacy of VLNT alone or in combination, and to further discuss the subsistent issues in the use of combination therapy.

Secondary lymphedema frequently occurs following surgery, malignancy, trauma, or radiation and is characterized by limb swelling, discomfort, and recurrent infections. Two advanced supermicrosurgical techniques-lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT)-have recently gained popularity as treatment options. However, long-term outcome data for these procedures remain limited. This systematic review and meta-analysis aim to evaluate the long-term efficacy of LVA and VLNT in patients with secondary lymphedema followed for more than 2 years postoperatively, focusing on outcomes such as cellulitis rates and limb circumference. This study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria encompassed studies involving adult patients with secondary lymphedema treated with LVA or VLNT and with at least 24 months of follow-up. The primary outcomes were annual cellulitis incidence and limb circumference change, analyzed separately for upper and lower extremities. Meta-analysis was conducted using R version 4.3.1. Pooled effect sizes were estimated using random-effects models. Subgroup and sensitivity analyses were also performed. A total of 23 studies met the inclusion criteria, covering 648 limbs treated with either LVA (n = 216) or VLNT (n = 432). The weighted average patient age was 56.3 years, and the cohort was predominantly female (99.9%). For LVA, the pooled mean reduction in annual cellulitis events was -1.13 (95% confidence interval [CI], -1.70 to -0.57) for upper extremities and -1.32 (95% CI, -2.08 to -0.55) for lower extremities. VLNT yielded greater reductions in cellulitis, with pooled mean differences of -2.43 (95% CI, -3.36 to -1.50) and -1.38 (95% CI, -2.11 to -0.65) for upper and lower limbs, respectively. Additionally, VLNT reduced limb circumference by 42.7% (95% CI, 36.7-49.7) in upper extremities and 21.98% (95% CI, 19.8-24.4) in lower extremities. LVA and VLNT both result in durable, long-term improvements in cellulitis rates, and VLNT was shown to reduce limb circumference. Given the significant impact on patient quality of life, these interventions should remain integral to the treatment algorithm for secondary lymphedema.

INTRODUCTION: Vascularized lymph node transfer (VLNT) and lymphovenous bypass (LVB) procedures represent physiologic treatment options for symptomatic lymphedema. Secondary causes related to oncologic surgery and/or radiation have been successfully treated using these surgical procedures. Primary lymphedema represents a poorly understood lymphedematous condition with equally poor understanding of the benefits of microsurgical intervention. The purpose of this study was to review our experience with this patient population to better understand the effectiveness of microsurgical procedures. METHODS: A retrospective review of a prospectively maintained database of patients who received microsurgical treatment for primary lymphedema was reviewed. Both LVB and VLNT procedures were used in this patient cohort. Outcomes related to demographics, circumference differences, and symptoms, and quality of life (QoL) changes were evaluated. A validated questionnaire, the LYMQOL, was used to assess QoL outcomes. RESULTS: Thirteen patients were identified and met inclusion criteria. All patients had primary lower extremity lymphedema. Average age and symptom duration was 37.8 years and 162 months, respectively. The average lymphedema stage was classified as Stage II in 66.7% of patients. Average follow-up was 12.2 months. VLNT was used in most cases (69.2%) while LVB was used in the remainder of patients. The average overall circumference reduction was 3.6 cm with more improvement seen in patients who received VLNT as compared to LVB (4.2cm v. 1.9cm). Improvements in body weight and cellulitis occurrence was significantly improved in the VLNT cohort (p<0.05). In addition, patient-reported QoL domains related to function, appearance, symptoms, and mood were significantly improved following VLNT (p<0.05 in all domains) as compared to LVB (p>0.05 in all domains). CONCLUSION: Lymphatic microsurgical procedures are valuable treatment options for patients with primary lymphedema. Vascularized lymph node transfer appears to result in improved overall outcomes as compared to lymphovenous bypass procedures in this specific patient population. Improvements in objective clinical measures (limb circumference, body weight, and cellulitis occurrence) correlate well with improved patient-reported quality of life parameters.

Lymphedema is associated with irreversible changes in the lymphatic system. For this reason, it is difficult to develop a radical treatment due to the dermal sclerosis and the volume increase of fibrous and adipose tissues. Complex decongestive therapy (CDT) is the gold standard in every therapeutic protocol. However, in cases that conventional therapy is inadequate or unsuccessful, new surgical treatments are available nowadays combining microvascular reconstructive techniques: Lympho-Venous Anastomosis (LVA), Vascularized Lymph Node Transfer (VLNT), Lympho-Lymphatic Bypass (LL-Bypass). Finally, for simultaneous breast reconstruction and restoration of lymphedema, chimeric Diep Inferior Epigastric Perforator flap (DIEP flap) can be combined with vascularised lymph node transfer (VLNT) from the inguinal area. Retrospective review of the literature referred to the diagnosis and the treatment of primary or secondary lymphedema. Conventional, as well as microvascular techniques are shown with detailed description of each procedure. Worldwide interest in using microsurgical reconstructive techniques to treat lymphedema is gaining momentum. However, there is no consensus on the indications for which procedure to perform, when to intervene, and/or how to comparatively grade outcomes. Currently there is no cure for lymphedema. For this reason, further research and better understanding of lymphatic anatomy and lymphedema pathophysiology are needed in order to improve further the conventional as well as the surgical methods.

Patient-reported outcomes following lymph reconstructive surgery in lower limb lymphedema: A systematic review of literature

Lymphedema surgery, when integrated into a comprehensive lymphedema treatment program for patients, can provide effective and long-term improvements that non-surgical management alone cannot achieve. Such a treatment program can provide significant improvement for many issues such as recurring cellulitis infections, inability to wear clothing appropriate for the rest of their body size, loss of function of arm or leg, and desire to decrease the amount of lymphedema therapy and compression garment use. The fluid predominant portion of lymphedema may be treated effectively with surgeries that involve transplantation of lymphatic tissue, called vascularized lymph node transfer (VLNT), or involve direct connections from the lymphatic system to the veins, called lymphaticovenous anastomoses (LVA). VLNT and LVA are microsurgical procedures that can improve the patient's own physiologic drainage of the lymphatic fluid, and we have seen the complete elimination for the need of compression garments in some of our patients. These procedures tend to have better results when performed when a patient's lymphatic system has less damage. The stiff, solid-predominant swelling often found in later stages of lymphedema can be treated effectively with a surgery called suction-assisted protein lipectomy (SAPL). SAPL surgeries allow removal of lymphatic solids and fatty deposits that are otherwise poorly treated by conservative lymphedema therapy, VLNT or LVA surgeries. Overall, multiple effective surgical options for lymphedema exist. Surgical treatments should not be seen as a "quick fix", and should be pursued in the framework of continuing lymphedema therapy and treatment to optimize each patient's outcome. When performed by an experienced lymphedema surgeon as part of an integrated system with expert lymphedema therapy, safe, consistent and long-term improvements can be achieved.

Lymphedema surgery was not widely known in Austria before the introduction of lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT) in 2014. This study shares the experience and process of establishing and institutionalizing lymphedema surgery service in Austria. The purpose of introducing reconstructive lymphedema surgery in Austria was to improve lymphedema patients' quality of life and provide them surgical therapy as an adjuvant treatment to complete decongestive therapy. To initialize reconstructive lymphedema surgery in Austria, LVA and VLNT had to be presented and introduced, in the manner of branding and advertizing a new product. Surgeries were performed with quality control by standardized documentation, pre- and postoperatively. Aligned with branding and marketing, presentations were given externally and internally to share knowledge and experience of lymphedema surgery. Lymphedema surgery service was introduced as a new brand in the medical service in Austria. After several communications with the Austrian Health Insurance Fund and with the final application, LVA and VLNT were listed as novel surgical therapies in its 2020 reimbursement catalog. Since 2014, more than 300 lymphedema patients were consulted, and 102 reconstructive lymphedema surgeries were performed. Circumference reduction of extremities after surgery was between 20% and 43%, postoperatively. Acceptance of surgery in lymphedema patients varies among continents, hospitals, and surgeons. Evaluation of the requirement of the surgical setup and insurance conditions for lymphedema surgery is essential to establish lymphedema surgery, providing targeted marketing and branding to spread knowledge of the novel technique and grant patients access to therapeutic treatment of their chronic disease.

Rationale: Despite significant advances in microsurgical techniques, simultaneous vascularized lymph node transfer (VLNT) and lymphovenous anastomosis (LVA) surgeries may be effective for treatment of end-stage lymphedema. This case report describes the successful treatment of end-stage lymphedema with VLNT and LVA.Patient Concerns:A 72-year-old patient with bilateral lower extremity lymphedema was referred to our lymphedema clinic. This patient had a history of lymphoma and treated with radiotherapy on right inguinal area 26 years ago. Interestingly, the patient developed lymphedema on both the right and left lower extremities although she had radiotherapy on her right inguinal area.Diagnosis:According to the indocyanine green lymphography, lymphoscintigraphy, and magnetic resonance lymphangiography, the patient was diagnosed with end-stage lymphedema (International Society of Lymphology stage 3).Intervention:The patient underwent simultaneous VLNT and LVA for treatment of end-stage lymphedema.Outcomes:Significant reduction in circumference and volume of lower extremity was achieved following simultaneous VLNT and LVALessons:Simultaneous VLNT and LVA surgeries may be effective in patients with end-stage lymphedema.