Comparison of endoscopic injection of botulinum toxin and steroids immediately after endoscopic submucosal dissection to prevent esophageal stricture: a prospective cohort study

Background: Widespread endoscopic submucosal dissection (ESD) in early esophageal cancer patients is closely associated with esophageal stricture, which dramatically reduces patients' quality of life and increases huge medical burdens. Endoscopic injection of steroid was proved as a protective method for post-ESD strictures. Other materials such as botulinum toxin type A (BTX-A) may be potential candidates. We conducted this prospective cohort study to compare the efficacy and feasibility of endoscopic injection of BTX-A and triamcinolone acetonide (TA) for the prevention of esophageal stricture. Methods: Seventy-eight patients with esophageal mucosal defects of more than two thirds of the circumference were successively enrolled and divided into 3 groups: BTX-A group (group A, n=26), TA group (group B, n=16) and control group (group C, n=36). Patients in group A were immediately injected with BTX-A after ESD, in group B were immediately injected with TA and in group C received ESD only. Endoscopy was performed when patients reported dysphagia symptoms and at 6 and 12 weeks post-ESD in patients without symptoms. Patients who experienced post-ESD esophageal strictures in all groups received bougie dilation. All patients were followed up for one year. Results: The proportion of patients developing stricture in BTX-A group was 30.00% (intention to treat analysis, 9/30) and 26.92% (per protocol analysis, 7/26), in TA group was 40.90% (intention to treat analysis, 9/22) and 43.75% (per protocol analysis, 7/16), and in control group was 84.21% (intention to treat analysis, 32/38) and 83.33% (per protocol analysis, 30/36) (p<0.001). When further comparing between each of the two groups, the incidence of esophageal stricture was lower in BTX-A group than that in control group (p<0.001), and lower in TA group than that in control group (p=0.004). Furthermore, in entire circumference mucosal defect subgroup, the esophageal stricture was significantly lower in BTX-A group than that in TA group (33.3% vs 100%, p=0.0454). Conclusions: Endoscopic injection of BTX-A and TA were effective in preventing post-ESD esophageal strictures and BTX-A injection was particularly effective in entire circumference mucosal defect patients. Multi-centered, randomized prospective study with larger sample size should be conducted. (Clinical trial registration number: ChiCTR2100042970, registered 1 February 2021, retrospectively registered, http://www.chictr.org.cn/listbycreater.aspx)