RCT of Gastric ESD With or Without Epineprhine Added Solution

Endoscopic submucosal dissection (ESD) is an endoscopic technique aiming to achieve en-bloc resection of mucosal neoplastic lesion in the gastrointestinal tract. It is now considered as the standard of treatment for early gastric cancer confined to the mucosa, achieving an excellent overall survival comparable to that of surgical resection.

Important adverse events associated with gastric ESD include hemorrhage (intraoperative or delayed) and perforation. The reported incidence of intraprocedural and delayed hemorrhage of gastric ESD is generally higher than that of esophageal or colorectal ESD5. This is likely due to the rich blood supply of the stomach penetrating from the muscularis to the submucosal layer. Bleeding during ESD would result in difficulty in visualizing the correct plane of dissection from blood clots obscuring view of the endoscope. As a result, prolonged procedural time may be required to achieve hemostasis and obtain adequate view for dissection.

There are currently different options of the solution for submucosal injection during gastric ESD. Epineprhine has often been added into these solutions with the aim of causing vasoconstrictive effect and potentially reduce bleeding during the procedure. The use of epinephrine has been recommended when removing larger pedunculated polyps with endoscopic mucosal resection (EMR)6. However the exact clinical benefit of adding epinephrine during gastric ESD has not been proven in the literature. On the other hand, when larger dose of epinephrine is absorbed systemically it may rarely cause significant tachycardia and generalized vasoconstriction, putting patients at risk of myocardial infarction or cerebrovascular accident.

A retrospective propensity score analysis was previously performed in one of our Japanese center (Presented at JGCA 2019, Shizuoka). After adjustment of important confounding factors including age, sex, tumor location, specimen size, depth of tumor invasion, presence of histological ulcer or scar and operators' experience, the addition of epinephrine into submucosal solution was associated with a significantly shorter procedural time upon multivariate analysis. The mean procedural time was 72±54 minutes versus 93±62 minutes with and without epinephrine respectively. (p<0.001) With the encouraging result from a single center retrospective study, we plan to conduct a prospective multicenter randomized controlled study to confirm the benefit of adding epinephrine into the submucosal solution during gastric ESD.