The Effect of Botulinum Toxin Type A Injections on Stricture Formation, Leakage Rates, Esophageal Elongation, and Anastomotic Healing Following Primary Anastomosis in a Long- and Short-Gap Esophageal Atresia Model – A Protocol for a Randomized, Controlled, Blinded Trial in Pigs

Abstract

Background: Esophageal atresia (EA) is a congenital malformation affecting 1:3000-4500 newborns. Approximately 15% have a long-gap EA (LGEA), in which case a primary anastomosis is often impossible to achieve. To create continuity of the esophagus patients instead have to undergo lengthening procedures or organ interpositions; methods associated with high morbidity and poor functional outcomes. Esophageal injections of Botulinum Toxin Type A (BTX-A) could enable primary anastomosis and mitigate stricture formation through decreased tissue tension. Methods and Analysis: In this randomized controlled blinded animal trial, 24 pigs are divided into a long- or short-gap EA group (LGEA and SGEA, respectively) and randomized to receive BTX-A or isotonic saline injections. In the LGEA group, injections are given endoscopically in the esophageal musculature. After seven days, a 3 cm esophageal resection and primary anastomosis is performed. In the SGEA group, a 1 cm esophageal resection and primary anastomosis is performed, followed by intraoperative injections of BTX-A or isotonic saline. After 14 days, stricture formation, presence of leakage, and esophageal compliance is assessed using endoscopic and manometric techniques, and in vivo and ex vivo contrast radiography. Tissue elongation is evaluated in a stretch-tension test, and the esophagus is assessed histologically to evaluate anastomotic healing. Ethics and Dissemination: The study complies with the ARRIVE guidelines for animal studies and has been approved by the Danish Animal Experimentation Council. Results will be published in peer-reviewed journals and presented at national and international conferences. Highlights: The optimal management of long-gap esophageal atresia remains controversial Primary anastomosis could improve functional outcomes and reduce complications Botulinum Toxin Type A decreases tissue tension and could facilitate anastomosis Reduced tension could further abate the risk for anastomotic stricture and leakage We present a model to evaluate the method in long- and short-gap esophageal atresia

Botulinum Toxin Treatment for Cancer-Related Disorders: A Systematic Review

“…The authors found that the effect of statins and BoNT injections in preventing the development of strictures were comparable with each other, and the stricture occurrence rates in the statins and BoNT group were significantly lower than both the steroid treatment and the non-intervention approach (Table 3). The positive results of the abovementioned studies in humans are supported by several animal studies that show injection of BoNTs close to the site of esophagectomy can reduce the development of esophageal strictures [50,51].…”

“…The positive results of the abovementioned studies in humans are supported by several animal studies that show injection of BoNTs close to the site of esophagectomy can reduce the development of esophageal strictures [ 50 , 51 ].…”

Endoscopic Injections of Botulinum Toxin Type A in the Piglet Esophagus Is Safe and Feasible but Did Not Result in any Significant Structural Changes 3 Days after Injection

“…A planned randomized controlled trial (RCT) study will include a 7-day waiting period from endoscopic BTX-A injections to surgery where a resection of a 3-cm segment of the esophagus will be performed, followed by an esophageal anastomosis, and a 14-day follow-up. 13…”