Introduction: Endoscopic full-thickness resection (EFTR) is used to resect difficult superficial mucosal lesions and sub-epithelial lesions (SELs). We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of EFTR for upper gastrointestinal tract (GIT) lesions. Methods: We conducted a comprehensive literature search of MEDLINE, EMBASE, Cochrane, ClinicalTrials.gov, and Scopus databases for studies published in the English language that addressed outcomes of EFTR for upper GIT lesions through November 2021. The weighted pooled rates with the 95% confidence interval (CI) were calculated. Cochran Q test and I statistics were used to calculate heterogeneity. Results: We identify 740 articles on the initial search and six studies met the inclusion criteria. 140 patients (45.7% females) with 142 lesions were analyzed. Four studies used the full-thickness resection device (FTRD®). EFTR was performed for 26 adenomas, 97 SELs, six adenocarcinomas, and ten full-thickness biopsies. The overall technical success rate was 86.9% (CI 79.8–94%, I 2 = 38.9%), R0 resection was 80% (CI 67.6–92.3%, I 2 = 75.6%), and the overall adverse events rate was 18.6% (9.8–27.2%, I 2 = 49.4%). Major adverse events included six episodes of major bleeding, three micro-perforations, one large duodenal perforation, and one case of mucosal damage from FTRD®. At 3–6 months follow-up, there were only two cases of recurrence (R0 was not achieved in both). Conclusion: EFTR has a high technical and clinical success rate in managing upper GIT lesions with an acceptable safety profile. Large prospective studies comparing EFTR with conventional endoscopic resection techniques are needed.
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