Early versus delayed defunctioning ileostomy closure after low anterior resection for rectal cancer: a meta-analysis and trial sequential analysis of safety and functional outcomes

Purpose We performed a systematic review and meta-analysis with trial sequential analysis (TSA) to answer whether early closure of defunctioning ileostomy may be suitable after low anterior resection. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched, up to October 2021, for RCTs comparing early closure (EC <= 30 days) and delayed closure (DC >= 60 days) of defunctioning ileostomy. The risk ratio (RR) with 95% CI was calculated for dichotomous variables and the mean difference (MD) with 95% CI for continuous variables. The GRADE methodology was implemented for assessing Quality of Evidence (QoE). TSA was implemented to address the risk of random error associated with sparse data and/or multiple testing. Results Seven RCTs were included for quantitative synthesis. 599 patients were allocated to either EC (n = 306) or DC (n = 293). EC was associated with a higher rate of wound complications compared to DC (RR 2.56; 95% CI 1.33 to 4.93; P = 0.005; I-2 = 0%, QoE High), a lower incidence of postoperative small bowel obstruction (RR 0.46; 95% CI 0.24 to 0.89; P = 0.02; I-2 = 0%, QoE moderate), and a lower rate of stoma-related complications (RR 0.26; 95% CI 0.16 to 0.42; P < 0.00001; I-2 = 0%, QoE moderate). The rate of minor low anterior resection syndrome (LARS) (RR 1.13; 95% CI 0.55 to 2.33; P = 0.74; I-2 = 0%, QoE low) and major LARS (RR 0.80; 95% CI 0.59 to 1.09; P = 0.16; I-2 = 0%, QoE low) did not differ between the two groups. TSA demonstrated inconclusive evidence with insufficient sample sizes to detect the observed effects. Conclusion EC may confer some advantages compared with a DC. However, TSA advocated a cautious interpretation of the results. Prospero Register ID CRD42021276557