Systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials on the impact of indocyanine green fluorescence angiography for anastomotic leakage in colorectal surgery.

Abstract

Fluorescence angiography is increasingly used to reduce anastomotic leakage in colorectal surgery, yet conclusive evidence on its protective effect remains limited. This systematic review with meta-analysis and trial sequential analysis of randomized controlled trials aimed to assess the effectiveness of fluorescence angiography using indocyanine green in reducing anastomotic leakage and determine whether current evidence is sufficient to draw definitive conclusions. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with a comprehensive search of PubMed, Embase, Scopus, and Cochrane databases up to March 1, 2026. All randomized controlled trials evaluating intraoperative indocyanine green use for anastomotic leakage prevention in colorectal surgery were included. The natural logarithm of the risk ratio was calculated using random-effects models. The risk of bias was assessed with the Risk of Bias-2 Tool, and evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation framework. Seven randomized controlled trials involving 4,636 patients (2,318 indocyanine green, 2,318 controls) were included. The anastomotic leakage rate was 7.9% in the indocyanine green group versus 11.6% in the control group (risk ratio, 0.69; 95% confidence interval, 0.58-0.82; P < .001), with negligible heterogeneity (I² = 0%). Trial sequential analysis demonstrated that the cumulative Z-curve crossed the monitoring boundary for benefit, indicating that the required information size had been reached. Subgroup analysis showed a significant reduction in anastomotic leakage in low colorectal or coloanal anastomoses (risk ratio, 0.63; 95% confidence interval, 0.51-0.76; P = .002). Fluorescence angiography significantly reduced both grade A leaks (risk ratio, 0.54; 95% confidence interval, 0.32-0.92; P = .006) and grade B + C leaks (risk ratio, 0.67; 95% confidence interval, 0.48-0.93; P = .006). Postoperative complications were modestly reduced in the indocyanine green group (risk ratio, 0.90; 95% confidence interval, 0.82-0.99; P = .035), whereas no significant differences were observed in operative time, length of hospital stay, or reoperation rate. Fluorescence angiography significantly reduces theanastomotic leakage rate in colorectal surgery. Trial sequential analysis confirms that the required information size has been reached for the overall analysis, supporting the robustness of this finding. However, the subgroup analysis of low anastomoses has not yet reached the required the information size, and further targeted trials are warranted to confirm the benefit in specific subgroups.