Danique Heuvelings

65 International Consensus on Reporting colorectal Anastomotic Leaks (CoReAL) Research questions and search strategy Along the four phases of the AL episode of care, the coordinating team developed a comprehensive list of key questions related to AL (Supplementary S1). Following expert input, the final list was divided among the corresponding WGs for further investigation. A literature search was conducted to assess the evidence related to each question, led by DH and a librarian. The search was performed in PubMed, Embase, and Cochrane electronic libraries on November 3, 2022 (Supplementary S2). Only high-level evidence articles were selected, including randomized controlled trials (RCTs) and systematic reviews with or without metaanalyses, where AL after CRC surgery was a primary or secondary outcome. Eligible articles were required to be published in English after 2000. Articles that did not report on oncological left-sided colorectal resections were excluded. All search results were imported into Rayyan 18 to allocate manuscripts to a given topic and WG, with initial eligibility determined based on title and abstract review. DH and research collaborators performed the screening for each question. In cases of disagreement, the team leads acted as referees. Eligible full-text articles were reviewed and summarized. The search was updated on July 26, 2023. CoReAL definitions As previously demonstrated in our recent systematic review on the quality of AL reporting in CRC trials, significant heterogeneity exists in AL reporting and definitions, a potential source of flawed comparisons 13. In order to overcome this limitation, the team agreed to define AL in the broadest way possible rather than to follow any specific criteria, including the International Study Group of Rectal Cancer (ISREC) definition 8. Thus, for this consensus, AL was defined as any breach or failure in the integrity of the anastomosis, including dehiscence, insufficiency, failure, breakdown, defect, or separation, regardless of the diagnostic modality (radiologic, endoscopic, intraoperative) and irrespective of clinical or biochemical manifestations. Defining the timing of AL diagnosis was considered important due to its different implications on healthcare resource utilization and outcomes. Based on consensus, AL was considered “early” when diagnosed 90 days or less from the index surgery, and “late” or “delayed” when diagnosed after 90 days. Data extraction and Evidence-based statements Data extraction was conducted using RevMan Web (Review Manager Web, Computer program, Version 4.12.0. The Cochrane Collaboration, 2022). General information regarding oncologic colorectal AL, including definitions, severity assessment, diagnostic timeframe, clinical symptoms, biochemical tests, imaging modalities, type of re-interventions, and longterm outcomes, were collected, using standardized forms. Key outcome measures related to AL (e.g. relative risk, odds ratio, hazard ratios) were extracted for every research question. If systematic reviews showed overlapping data, the lowest quality study was excluded, or a new overview was created which only included mutually exclusive studies. If no overlap was found, data was pooled using RevMan Web tools. Methodological quality and risk of bias for included studies were assessed by two research collaborators using the RoB2 tool for RCTs and the 3

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