Large nonpedunculated colorectal lesions are increasingly detected thanks to screening programs worldwide. ESD is the technique which provides a high-quality resection of these large polyps.

Nevertheless, colorectal ESD is burdened by technical difficulties and several adverse events affecting its outcomes. The adverse events could be life-threatening, call for or prolong the hospitalization, require blood transfusion, additional endoscopic or surgical procedures and increase costs. Failure of endoscopic resection requiring surgery for benign lesions could affect patients' quality of life and increase healthcare systems' costs.

Thus, improving colorectal ESD outcomes is an important clinical and medico-economic objective. The underwater setting with saline has been already established as a better option than conventional CO2 insufflation for EMR of large colonic polyps. Moreover, use of the underwater approach for colorectal ESD has been increasingly reported with good results in the last few years. However, a randomized comparative trial between conventional and underwater colorectal ESD clarifying which should be the preferred approach is lacking.

Expected benefits are a decrease of adverse events and an increase of successful R0 resection rate of colorectal ESD.

The procedure in this study involves the application of underwater ESD for the resection of large nonpedunculated colorectal polyps.

Underwater ESD is a technique wherein the polyp is removed in an en bloc fashion. The procedure initiates with the identification and delineation of the polyp borders through careful endoscopic examination. Subsequently, after filling the lumen with saline and sucking all the air, initial submucosal injection of saline and methylene blue is performed to lift the lesion. After that, subsequent mucosal incision with ESD knife all around the lesion and submucosal dissection deep in the submucosal layer leading to an en bloc resection will be performed.

The clinical practice and technique of underwater ESD and conventional ESD performed during the course of the trial, will not be modified from standard clinical practice.

Inclusion Criteria:

• all patients ≥ 18 years of age with indication of ESD for large (>20mm) nonpedunculated colorectal polyps
• patients who were able to give informed written consent

Exclusion Criteria:

• Suspicion of deep submucosal cancer by analysis of pit pattern (KUDO Vn)
• Suspicion of serrated/hyperplastic polyps by analysis of pit pattern (Kudo IIo)
• Polyp involving the appendix deeply (type 2 or 3 according to Toyonaga classification)
• Polyp involving the anal verge
• Polyp inside the ileo-cecal valvula