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Resection of an adenoma-like mass (ALM) in chronic ulcerative colitis (CUC) complicated by mucosal fibrosis has historically not been technically feasible. Endoscopic submucosal dissection techniques may now provide a therapeutic tool enabling the division of submucosal fibrotic scarring, hence enabling endoluminal resection for the first time in this select patient group. The aim was prospective evaluation of endoscopic submucosal dissection-assisted (ESD) resection of flat, sessile, and lateral spreading tumors in CUC complicated by submucosal desmoplasis. Clinical endpoints were postresection recurrence rates, R0 resection status, and complications.ESD-assisted endoscopic mucosal resection (EMR) using the Olympus KD-630L insulation-tipped knife was performed on selected lesions.Sixty-nine patients met inclusion criteria, of which 2 were excluded due to follow-up default. En bloc resection was performed in 52/67 (78%) cases with 15/67 (7%) requiring a piecemeal approach. R0 resection was achieved in 49/52 (94%) of lesions undergoing en bloc resection (perforation rate 2/67 [3%]). Bleeding complications occurred in 7/67 (10%) of cases. No metachronous circumscribed intraepithelial neoplastic lesions or cancer was detected at follow-up. At a median of 18 months follow-up, overall cure rates for the ESD-assisted EMR cohort was 66/67 (98%).We have shown for the first time that endoscopic resection of ALM even in the presence of complicating mucosal fibrosis is technically achievable using a combined ESD-assisted EMR technique. In an appropriately selected cohort, this technique may provide a technically feasible and clinically acceptable therapy where otherwise colectomy would be required.