Metformin for preventing esophageal stricture after circumferential endoscopic submucosal dissection in a canine model.

Abstract

Background: Esophageal stricture frequently occur after extensive endoscopic submucosal dissection (ESD). Effective, safe, and straightforward prevention and treatment methods are lacking. This preclinical animal study evaluated the efficacy of metformin in preventing esophageal stricture following ESD using a dog model.

Methods: Ten Beagle dogs were randomly divided into the metformin and control groups. Circumferential esophageal ESD was performed 30-33 cm from the incisors. The metformin group received 100 mg/kg/day metformin from the second postoperative day, while the control group received physiological saline by gavage. After 4 weeks, the Beagles were euthanized, and esophageal tissues were collected for macroscopic and pathological evaluations.

Results: Four weeks post-ESD, the modified dysphagia scores in the metformin group were lower than the control [1 (1, 2) vs 3 (3, 4), P = 0.041, Cliff's D = -0.80 (-0.97 to -0.14)]. Macroscopic examination showed that the stricture rate in the metformin group was lower than the control [38.60% (32.50%, 44.30%) vs 53.90% (52.30%, 62.00%), P = 0.056, Cliff's D = -0.76 (-0.97 to 0.09)]. Hematoxylin and eosin staining revealed that the re-epithelialization rate in the metformin group was higher than the control [88.30% (85.60%, 90.10%) vs 20.60% (11.20%, 27.40%), P = 0.008, Cliff's D = 1.00 (0.82-1.00)]. Masson's trichrome staining indicated that the submucosal fibrosis in the metformin group was thin and orderly, with a maximum thickness of 863.00 (786.00, 932.00) μm, whereas the control group exhibited disordered fibrosis with a maximum thickness of 1,275.00 (1,266.00, 1,340.00) μm [P = 0.008, Cliff's D = -1.00 (-1.00 to -0.82)].

Conclusion: Metformin effectively promoted esophageal wound re-epithelialization after ESD, reduced submucosal fibrosis, and showed a trend toward alleviating esophageal stricture.