Comparative effectiveness of dye-assisted lymphatic mapping during varicocelectomy for preventing postoperative hydrocele: a design-stratified systematic review and network meta-analysis

BACKGROUND: Postoperative hydrocele is a clinically relevant complication of varicocelectomy and is largely attributed to disruption of testicular lymphatic drainage. Several vital dyes and fluorescence-based tracers have been used to improve intraoperative identification and preservation of lymphatic vessels, but their comparative effectiveness remains uncertain. METHODS: We conducted a systematic review and network metaanalysis in accordance with PRISMA 2020 and the PRISMA extension for network meta-analyses. Comparative randomized controlled trials (RCTs) and non-randomized studies evaluating isosulfan blue, methylene blue, Patent Blue V, indocyanine green, or no dye during varicocelectomy were eligible. RCTs and non-RCTs were synthesized in separate frequentist randomeffects networks using CINeMA version 2.0.0. Ranking analyses were performed in R version 4.4.3 using meta version 8.3-0 and netmeta version 3.4-0. Odds ratios (ORs) were used for dichotomous outcomes and mean differences (MDs) for operative time. No dye was selected as the common reference. Treatment ranking was summarized using the surface under the cumulative ranking curve (SUCRA). RESULTS: The evidence set comprised 12 eligible reports: four RCTs and eight observational reports. Eleven reports contributed arm-level data to at least one outcome-specific quantitative synthesis. Because some Italian cohorts may overlap across reports, a single unduplicated participant total was not calculated. In the RCT network, isosulfan blue reduced postoperative hydrocele compared with no dye (OR 0.083, 95% CI 0.010- 0.673), whereas estimates for methylene blue (OR 0.100, 95% CI 0.005-1.924) and Patent Blue V (OR 0.094, 95% CI 0.005- 1.849) were imprecise. In the non-RCT postoperative-hydrocele network, isosulfan blue was associated with lower odds of hydrocele (OR 0.028, 95% CI 0.004-0.201); indocyanine green (OR 0.084, 95% CI 0.004-1.683) and methylene blue (OR 0.573, 95% CI 0.242-1.355) numerically favoured hydrocele prevention but remained inconclusive. In the non-RCT hydrocele-requiringintervention network, all active estimates were highly imprecise. In the non-RCT recurrence network, no tracer showed a statistically clear difference from no dye. CONCLUSIONS: Randomized evidence suggests that isosulfan blue provides the most consistent signal toward reducing postoperative hydrocele after varicocelectomy. Observational evidence also favoured isosulfan blue for postoperative hydrocele, although possible cohort overlap, confounding, sparse events, and star-shaped networks limit certainty. Recurrence and hydrocele-requiring-intervention estimates did not establish reliable benefit or harm for any tracer.