Introduction

Underwater endoscopic mucosal resection (UEMR) is an alternative to conventional EMR (CEMR) offering consistent negative horizontal margins. However, UEMR does not involve submucosal injection; thus, its ability to achieve a sufficient resection depth comparable to that of CEMR remains uncertain. This randomized controlled trial (RCT) aimed to compare UEMR and CEMR in terms of resection depth.

Aims & Methods

This multicenter, parallel two-arm, open-label, noninferiority RCT was conducted across four Japanese institutions enrolling patients with colorectal tumors measuring 10–20 mm. Participants were randomly assigned in a 1:1 ratio to either to UEMR or CEMR group, using a computerized random-number generator. The primary outcome was the resection depth, which is the distance from the lower edge of the muscularis mucosa to the deep margin of the resected specimen, analyzed based on per-protocol (PP) principles (noninferiority margin of 400 µm).

Results

This study screened 217 patients from September 21, 2022, to December 2, 2024, and randomly assigned them to the UEMR (n =109) or CEMR (n =108) group. The PP analysis revealed that the mean resection depths of the UEMR and CEMR groups were 1688.9 ± 1510.0 µm and 1432.3 ± 1294.2 µm, respectively (mean difference: 256.6 µm, 95% confidence interval: -119.9 µm to 633.1 µm; P = 0.18), indicating the noninferiority of UEMR compared with CEMR in terms of resection depth. Subgroup analyses revealed that the resection depth of lesions by UEMR, especially at the cecum/ascending colon (1822.4 ± 1469.7 µm vs. 1096.5 ± 1007.6 µm; P = 0.01), and those with superficial morphology (1238.7 ± 862.2 µm vs. 731.6 ± 376.1 µm; P < 0.01), was significantly deeper than that achieved by CEMR. Moreover, even for nonexperts, UEMR tended to provide adequate resection depth compared with CEMR, approaching the proficiency level exhibited by experts (1786.6 ± 1471.6 µm vs. 1192.4 ± 1074.7 µm; P = 0.07). There were no significant differences in adverse events between the two groups, including one case of intraoperative perforation (0.9%) in the CEMR group and one case of delayed bleeding (0.9%) in the UEMR group. No EMR-related deaths were reported.

Conclusion

UEMR maintains the equivalent resection depth as CEMR and could become the gold standard endoscopic resection technique for intermediate-size colorectal tumors. UEMR is strongly recommended, especially for lesions at the cecum, ascending colon, and superficial lesions, because it could resect significantly deeper than CEMR. Furthermore, UEMR is recommended for nonexperts as a resection method that provides sufficient resection depth (Clinical trial registration number: UMIN000047432).