Conventional Versus Underwater Endoscopic Mucosal Resection for Superficial Non-Ampullary Duodenal Epithelial Tumors ≤ 20 mm: Study Protocol for a Multicenter Randomized Controlled Trial (D-CURE Trial)

Background: Underwater endoscopic mucosal resection (UEMR) is a relatively new treatment method for sporadic non-ampullary duodenal epithelial tumors (SNADETs), and its usefulness has been reported for SNADETs ≤ 20 mm. However, its effectiveness and safety compared with conventional endoscopic mucosal resection (CEMR) remain controversial. This study aims to assess the treatment outcomes and evaluate the beneficial effects and safety of UEMR for SNADETs ≤ 20 mm. Methods: This is an open-label, multicenter collaborative, non-inferiority randomized controlled trial with two parallel groups conducted across 40 institutions in Japan. The study subjects will be patients with SNADETs ≤ 20 mm. A total of 320 patients will be randomized to either the CEMR or UEMR group in a 1:1 allocation ratio. The primary endpoint is the 1-year recurrence-free survival rate, defined as the number of cases with no recurrence of SNADET or death from any cause within one year of EMR. The secondary endpoints include the en bloc resection rate, histological complete resection rate, adverse events, technical success rate, total procedure time, resection time, mucosal closure time, complete mucosal closure rate, complete mucosal closure rate with standard clips, 1-year duodenum preservation survival rate, and device cost. Discussion: This multicenter, open-label, randomized controlled trial (RCT) with 320 subjects aims to determine whether the 1-year recurrence-free survival rate of underwater endoscopic resection is not inferior to that of conventional endoscopic mucosal resection for SNADETs ≤ 20 mm. If the efficacy and safety of UEMR are proven in this RCT, it is expected to be recognized as the standard treatment for SNADETs ≤ 20 mm. Owing to the absence of submucosal injection, UEMR is a simpler and more cost-effective technique compared to CEMR and is anticipated to become the primary method of EMR.