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

Abstract

Introduction Treatment for long-gap esophageal atresia (LGEA) aims at achieving primary anastomosis with minimal tension. Previous studies have shown that intramural injections with botulinum toxin type-A (BTX-A) from the adventitial side can increase the elongation of the piglet and rat esophagus before bursting, and that this effect is dose and time dependent. Our aim was to determine if endoscopic injections would be feasible, safe, and with an effect on the mechanical properties of the esophagus.

Methods Twenty-two male piglets (5.15 kg) were randomized into two groups, one receiving 2 units/kg BTX-A, the other equal volume 0.9% NaCl. On day 3, the esophagus was harvested and tested in a stretch-tension machine to evaluate elongation and maximum load, followed by histological examination.

Results No adverse effects to the procedure were observed. No statistically significant difference in elongation or maximum load before bursting between the treatment and placebo group was found. In histopathological analysis, inflammation and abscess formation were observed with no statistically significant difference between the two groups.

Conclusion Endoscopic placement of BTX-A injections in the piglet esophagus was safe and feasible but did not result in any difference in the mechanical properties or histology of the esophagus.

Keywords

esophageal atresia - long gap esophageal atresia - botulinum toxin type-A - pigs

Publikationsverlauf

Eingereicht: 15. September 2021

Angenommen: 11. Februar 2022

Artikel online veröffentlicht:
10. Juni 2022

• References

• 1 Nassar N, Leoncini E, Amar E. et al. Prevalence of esophageal atresia among 18 international birth defects surveillance programs. Birth Defects Res A Clin Mol Teratol 2012; 94 (11) 893-899 (Part A)
• 2 Pedersen RN, Calzolari E, Husby S, Garne E. EUROCAT Working group. Oesophageal atresia: prevalence, prenatal diagnosis and associated anomalies in 23 European regions. Arch Dis Child 2012; 97 (03) 227-232
• 3 Sroka M, Wachowiak R, Losin M. et al. The Foker technique (FT) and Kimura advancement (KA) for the treatment of children with long-gap esophageal atresia (LGEA): lessons learned at two European centers. Eur J Pediatr Surg 2013; 23 (01) 3-7
• 4 Pinheiro PFM, Simões e Silva AC, Pereira RM. Current knowledge on esophageal atresia. World J Gastroenterol 2012; 18 (28) 3662-3672
• 5 Gallo G, Zwaveling S, Groen H, Van der Zee D, Hulscher J. Long-gap esophageal atresia: a meta-analysis of jejunal interposition, colon interposition, and gastric pull-up. Eur J Pediatr Surg 2012; 22 (06) 420-425
• 6 Larsen HF, Jensen TSR, Rasmussen L, Ellebæk M, Qvist N. Intramural injection with botulinum toxin significantly elongates the pig esophagus. J Pediatr Surg 2013; 48 (10) 2032-2035
• 7 Ellebæk MB, Qvist N, Schrøder HD, Rasmussen L. Intramural injection with botulinum toxin type A in piglet esophagus. The influencer on maximum load and elongation: a dose response study. Eur J Pediatr Surg 2016; 26 (03) 282-286
• 8 Dibbern CB, Rose M, Ellebæk MB, Qvist N. The effect of intramural botulinum toxin injections on the elongation of the piglet oesophagus is time dependent. Eur J Pediatr Surg 2017; 27 (01) 56-60
• 9 Pike AH, Zvara P, Antulov MR. et al. Intramural injection of botulinum toxin A in surgical treatment of a long gap esophageal atresia-rat model. Eur J Pediatr Surg 2020; 30 (06) 517-523
• 10 Hallett M. Explanation of timing of botulinum neurotoxin effects, onset and duration, and clinical ways of influencing them. Toxicon 2015; 107 (pt. A): 64-67
• 11 Frevert J. Xeomin: an innovative new botulinum toxin type A. Eur J Neurol 2009; 16 (Suppl. 02) 11-13
• 12 Oetzmann von Sochaczewski C, Heimann A, Linder A, Kempski O, Muensterer OJ. Esophageal blood flow may not be directly influenced by anastomotic tension: an exploratory laser Doppler study in swine. Eur J Pediatr Surg 2019; 29 (06) 516-520
• 13 Svensson E, Zvara P, Qvist N. et al. 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; 25 (01) 171-177