Safe and Efficient Colonic Endoscopic Submucosal Dissection Using an Injectable Hydrogel

Endoscopic submucosal dissection (ESD) has not yet been widely adopted in the treatment of early colonic cancers due to the greater technical difficulty involved, longer procedure time, and the increased risk of perforation. Adequate mucosal elevation by submucosal injection is crucial for en bloc resection and prevention of perforation during colonic ESD. This study is aimed to evaluate the efficacy of an injectable thermoreversible hydrogel as the colonic submucosal agent for the first time. Triblock copolymer poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) was synthesized, and its concentrated aqueous solution was injected into the colonic submucosa of living minipig and spontaneously transformed into an in situ hydrogel with adequate mucosal elevation at body temperature. Such a mucosal lifting lasted for a longer time than that created by the control group, glycerol fructose. Colonic ESD was then performed with the administration of hydrogels at various polymer concentrations or glycerol fructose. All colonic lesions were successfully resected en bloc after one single injection of the hydrogel, and repeated injections were not needed. No evidence of major hemorrhage, perforation and tissue damage were observed. Considering the injection pressure, duration of mucosal elevation and efficacy of "autodissection", the hydrogel containing 15 wt % polymer was the optimized system for colonic ESD. Consequently, the thermoreversible hydrogel is an ideal submucosal fluid that provides a durable mucosal lifting and makes colonic ESD accessible to a large extent. In particular, the efficacy of "autodissection" after one single injection of the hydrogel simplifies significantly the procedures while minimizing the complications.