Prevention Effect Of Endoscopic Rapamycin Injection On Esophageal Stricture After Endoscopic Submucosal Dissection

Background: Endoscopic submucosal dissection(ESD) have gained widespread acceptance as minimally invasive therapie for early esophageal cancer and high-grade intraepithelial neoplasia of esophagus. However, postoperative stricture frequently occurs after esophageal endoscopic submucosal dissection, especially a large area of esophageal mucosal defect. The therapeutic effect of esophageal stricture is unsatisfactory, thus prevention of esophageal post-ESD stricture is especially important. There are many methods to prevent esophageal post-ESD stricture.We devised a trial to evaluate the efficacy of rapamycin to prevent post-ESD stricture through animal experiments.Objective: To evaluate the efficacy and feasibility of endoscopic injection of rapamycin to prevent esophageal post-ESD stricture.Methods: A total of eight adult male experimental dogs were randomly divided into a control group(n=4) and an experimental group(n=4). They were subjected to circumferential esophageal ESD from 36 cm to 40 cm as measured from the dental arch. Doses of 0.5 ml rapamycin were endoscopically injected 12 times into the exposed submucosal tissue in the experimental group immediately after ESD, as well as the 7th day,the 14 th day and the 21 th day after ESD. While the control group was injected the same dose of saline at the same time and position.The diet and general condition of the experimental animals were observed after operation. Follow-up endoscopy was performed at 1, 2, 3, and 4 week after ESD. All dogs were euthanized for histological examination the 28 th day after ESD. After observing and measuring the breadth of esophageal strictures, percentage of contraction was calculated. Hematoxylin and eosin staining were performed by using conventional methods, to observe the epithelium coverage condition of surface, inflammatory response and fibrosis degree of nidus.Results:Circumferential ESD was performed successfully in all dogs. The time of establishing the experimental animal model of post-ESD between the two groups showed no significant difference(P=0.881). All dogs survived for the designated 4-week followup period. All dogs in the control group could not eat or eat only a small amount of liquid food 4 weeks after the operation, While the dogs in the experimental group could eat solid food or semi-liquid food. In the control and the experimental groups, the mean±standard deviation(SD) weight gains were-2.13±0.22 Kg and-1.60±0.18Kg(P=0.011)respectively.The difference between the two groups has statistical significance. All control dogs showed severe esophageal stricture 7 days after ESD, and more serious in the 28 th day,similar to a pinhole. While all experimental dogs showed mild esophageal stricture 14 days after ESD, and endoscopy available through 28 days after surgery. The mea ± SD rates of mucosal constriction for the control and experimental group were 84.50±2.08% and 64.25±7.41%(P=0.020), respectively.The lesions of two groups were fully covered with the regenerated epithelial layer 28 days after ESD. Inflammatory cell infiltration at the submucosal layer was observed in both groups at this time. At the muscle layer, fibrotic tissue invaded through the inner muscularis in the control group, whereas fibrosis in the muscularis was mild in the transplanted group.Conclusion: Endoscopic injection of rapamycin can decrease the level of esophageal stricture and play an role in the prevention of the esophageal stricture.