Preventing Secondary Lymphedema: A Systematic Review and Meta-Analysis on the Efficacy of Immediate Lymphovenous Anastomosis

Abstract

Background: Secondary lymphedema is a debilitating condition following oncologic lymphadenectomy. Despite advancements in rehabilitation and microsurgical interventions, there is no cure for lymphedema. Performing a lymphovenous anastomosis (LVA) at the time of a regional node dissection has been purported to reduce the risks of secondary lymphedema; however, there are conflicting studies and no clear consensus about the routine use of LVA for preventing lymphedema after lymphadenectomy. The present study aims to perform a comprehensive review and meta-analysis on immediate LVA for the prevention of secondary lymphedema.

Methods: A systematic review and literature search were performed using PubMed, Embase, Web of Science, and Cochrane databases. Studies evaluating primary or immediate LVA in oncologic surgery were included. Studies with a control group were included in the meta-analysis.

Results: Overall, 39 studies, including 3697 patients (1,722 LVA; 1975 control), met inclusion criteria. Seventeen of the studies were included in the meta-analysis. Pooled analysis across all studies revealed a secondary lymphedema incidence of 7.1% in the LVA cohort versus 35.0% in controls. Meta-analysis demonstrated a significant reduction in lymphedema risk with immediate LVA (RR: 0.31). Subgroup analysis confirmed strong protective effects in breast cancer patients (RR: 0.28) and a significant but lesser benefit in dermatologic malignancies (RR: 0.35).

Conclusion: Based on the current literature, immediate LVA at time of lymphadenectomy significantly reduces the risk of secondary lymphedema in patients undergoing oncologic treatment. Given these findings, patients undergoing multimodal oncologic treatment including radiation and surgical lymphadenectomy should be considered candidates for immediate LVA.

Keywords: immediate lymphovenous anastomosis; lymph node surgery; lymphatic bypass; lymphedema; microsurgery; oncologic reconstruction; supermicrosurgery.

Figure 1

Figure 1 illustrates the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram for the study selection process. The initial search identified 1024 records from three databases: PubMed (n = 748), Web of Science (n = 148), and Embase (n = 128). No additional references were obtained through other sources such as citation searching or gray literature. After removing 298 duplicates, 726 studies remained for screening. Of these, 648 studies were excluded based on title and abstract screening, leaving 78 studies for full‐text assessment. No studies were unavailable for retrieval. Following eligibility assessment, 39 studies were excluded due to reasons such as lack of full text (n = 7), reporting of irrelevant outcomes (n = 11), use of the wrong intervention (n = 10), incorrect study design (n = 9), or an inapplicable patient population (n = 2). Ultimately, 39 studies were included in the final systematic review.

Figure 2

This forest plot illustrates the pooled risk ratio (RR) with 95% confidence intervals (CI) for the incidence of secondary lymphedema in patients undergoing immediate LVA compared to controls. Each included study is represented as a data point, with the horizontal lines indicating the confidence interval and the size of the square reflecting the study weight. The diamond at the bottom represents the overall effect estimate. The meta‐analysis demonstrates a significant reduction in secondary lymphedema risk in the LVA cohort (RR: 0.31, 95% CI: 0.23–0.42, p < 0.00001), indicating that immediate LVA is associated with a 69% lower risk of developing lymphedema compared to standard oncologic surgery alone. Heterogeneity analysis (I ² = 22%, p = 0.20) suggests low variability among included studies.

Figure 3

This forest plot presents the pooled risk ratio (RR) with 95% confidence intervals (CI) for the development of secondary lymphedema after mastectomies with immediate lymphovenous anastomosis (LVA) compared to those who did not receive LVA. Each study is represented as a square, with the horizontal lines denoting the confidence interval, while the size of the square reflects the study's weight in the analysis. The diamond at the bottom represents the overall effect estimate. The meta‐analysis indicates a significant reduction in lymphedema risk for the LVA cohort (RR: 0.28, 95% CI: 0.20–0.39, p < 0.00001), demonstrating a 72% lower risk of developing secondary lymphedema compared to controls. Heterogeneity analysis (I ² = 22%, p = 0.23) suggests a low degree of variability across included studies.

Figure 4

This forest plot displays the pooled risk ratio (RR) with 95% confidence intervals (CI) for the incidence of secondary lymphedema in patients undergoing immediate lymphovenous anastomosis (LVA) following lymphadenectomy for dermatologic malignancies, including melanoma and squamous cell carcinoma. Each included study is represented by a square, with horizontal lines indicating the confidence interval, while the size of the square reflects the study's weight in the analysis. The diamond at the bottom represents the overall effect estimate. The meta‐analysis demonstrates a significant reduction in lymphedema risk for the LVA cohort (RR: 0.35, 95% CI: 0.13–0.98, p = 0.05), indicating a 65% lower risk of developing secondary lymphedema compared to controls. Heterogeneity analysis (I ² = 46%, p = 0.14) suggests moderate variability among included studies.