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 $\leq$ 30 days) and delayed closure (DC $\geq$ 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; I2 = 0\%, QoE High), a lower incidence of postoperative small bowel obstruction (RR 0.46; 95\% CI 0.24 to 0.89; P = 0.02; I2 = 0\%, QoE moderate), and a lower rate of stoma-related complications (RR 0.26; 95\% CI 0.16 to 0.42; P < 0.00001; I2 = 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; I2 = 0\%, QoE low) and major LARS (RR 0.80; 95\% CI 0.59 to 1.09; P = 0.16; I2 = 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.