Introduction: Cold snare polypectomy (CSP) and underwater endoscopic mucosal resection (UEMR) are used for small superficial nonampullary duodenal epithelial tumors (SNADETs). This study aimed to compare the resection depth of SNADETs removed by CSP versus UEMR. Methods: Data from SNADETs resected with CSP or UEMR between April 2018 and July 2023 at Nagoya City University Hospital were collected retrospectively. An independent pathologist, blinded to clinical information, evaluated the resected specimens and categorized resection depth into four groups: mucosa only (M), incomplete muscularis mucosae with defects (iMM), complete muscularis mucosae without submucosa (cMM), and complete muscularis mucosae with submucosa (SM). Results: Among 109 SNADETs, 78 were resected with CSP and 31 with UEMR. The percentages of M, iMM, cMM, and SM for CSP were 23.1%, 50.0%, 5.1%, and 21.8%, respectively, while for UEMR they were 0%, 6.5%, 6.5%, and 87.1%. The UEMR group had a higher SM resection rate and significantly greater median submucosal depth than the CSP group (783 μm [range, 0–2,220] vs. 0 μm [range, 0–1,226]; p < 0.001). In the multivariate analysis, UEMR was an independent and significant factor for achieving SM resection. Conclusion: UEMR achieved a significantly higher SM resection rate than CSP for all types of SNADETs. Clinically diagnosed duodenal high-grade dysplasia and adenocarcinoma should be treated with UEMR rather than CSP.

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