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

Emma Svensson; Peter Zvara; Niels Qvist; Lars Hagander; Sören Möller; Lars Rasmussen; Henrik Daa Schrøder; Eva Kildall Hejbøl; Niels Bjørn; Súsanna Petersen; Kristine Cederstrøm Larsen; Jan Krhut; Oliver J Muensterer; Mark Bremholm Ellebæk

doi:10.29337/ijsp.156

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

Int J Surg Protoc. 2021 Aug 11;25(1):171-177. doi: 10.29337/ijsp.156. eCollection 2021.

Authors

Affiliations

¹ Pediatric surgery, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University. Skane University Hospital Lund, 221 84 Lund, Sweden.
² Research Unit for Urology, Department of Clinical Research, University of Southern Denmark, J. B. Winsløws Vej 4, 5000 Odense C, Denmark.
³ Research Unit for Surgery, Odense University Hospital, University of Southern Denmark, J. B. Winsløws Vej 4, 5000 Odense C, Denmark.
⁴ OPEN - Open Patient data Explorative Network, Odense University Hospital; Department of Clinical Research, University of Southern Denmark, J. B. Winsløws Vej 9A, 5000 Odense C, Denmark.
⁵ Department of Pathology, Odense University Hospital, University of Southern Denmark, J.B. Winsløws Vej 15, 5000 Odense, Denmark.
⁶ Department of Surgical Studies, Medical Faculty, Ostrava University, Syllabova 19, 703 00, Ostrava, Czech Republic.
⁷ Department of Urology, University Hospital, 17.listopadu 1790, 708 52 Ostrava, Czech Republic.
⁸ Department of Pediatric Surgery, Dr. von Hauner Children's Hospital of the Ludwig-Maximilians-University Munich, Lindwurmstraße 4, 80337 Munich, Germany.

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 controversialPrimary anastomosis could improve functional outcomes and reduce complicationsBotulinum Toxin Type A decreases tissue tension and could facilitate anastomosisReduced tension could further abate the risk for anastomotic stricture and leakageWe present a model to evaluate the method in long- and short-gap esophageal atresia.

Keywords: anastomotic stricture; botulinum toxin; oesophageal atresia.