BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection may result in complications or may be unsuitable for tumors that are difficult to treat endoscopically. We investigated the usefulness of a newly developed endoscopic resection technique-EMR with an over-the-scope clip (EMR-O)-for difficult-to-treat lesions. METHOD: We retrospectively examined patients who underwent EMR-O for colorectal tumors between September 2017 and January 2024. Patient and lesion characteristics, technical success rates, en bloc resection rates, R0 resection rates, procedure time, histopathology, and the clinical course were evaluated. RESULTS: EMR-O was performed for 18 patients. Indications for EMR-O included residual or recurrent lesions (seven patients
38.9%), diverticulum lesions (five patients
27.8%), appendiceal orifice lesions (three patients
16.7%), T1 cancers (two patients
11.1%), and subepithelial tumors (one patient
5.5%). The median lesion size was 11 mm. The rates of technical success, en bloc resection, and R0 resection were 100%, 86.7%, and 86.7%. The median procedure time was 10 min. The only adverse event was diverticulitis (one patient
5.5%). Intraoperative and delayed perforation and bleeding were not observed. The pathological resection depths were full-thickness for three patients (16.7%), muscularis resection for four patients (22.2%), and deep submucosal resection for 11 patients (61.1%). CONCLUSION: Although EMR-O is limited by the target lesion size, it shortens the procedure time, prevents perforation, and avoids the need for surgery. EMR-O may be a minimally invasive treatment option for small lesions that are difficult to treat endoscopically.