Betulin gel alleviates esophageal stricture following endoscopic submucosal dissection: an animal study.

Abstract

Esophageal stenosis is a troublesome complication after circumferential ESD. This study examined the efficacy of betulin gel in preventing esophageal stenosis after ESD in a porcine model. Twelve pigs were randomized to betulin group and control group evenly. At the distal esophagus, circumferential ESD was performed in all animals. In the betulin group, betulin gel was applied at days 1, 3, and 7. Endoscopy examination was performed at day 3, 1week, 2weeks, and 4weeks post-ESD. Then pigs were killed for macroscopic and histologic esophageal evaluation. The rate of esophageal stricture was lower in the betulin group (53.3 ± 12.5% vs 88.3% ± 2.9, p = 0.02). Betulin-treated pigs had lower dysphagia score (2.0 ± 0 vs 3.3 ± 0.5, p < 0.001), less weight loss (11.78% ± 2.16 vs 15.85% ± 3.63, p = 0.04), and better passability of the open and closed biopsies forceps (83.33% vs. 0%, p = 0.015, and 100% vs. 0%, p = 0.002) 4weeks post-ESD. Histologically, better re-epithelization (63.2 ± 10.7mm vs 22.8 ± 10.1mm, p < 0.001), slighter submucosal fibrosis (0.95 ± 0.17mm vs 2.32 ± 0.48mm, p = 0.002), lower muscularis propria damage score (1 vs 3, p < 0.001), and less inflammatory cells (307 vs 675 per high-power field, p = 0.002) were noted in the betulin group. The expression levels of TGF-β1, collagen i, collagen III, and α-SMA were significantly lower in the betulin group compared to the control group (p < 0.05). Betulin gel shows promise in reducing fibrosis, enhancing repair, and preventing esophageal stricture after ESD, suggesting a potential new strategy for prevention.