A novel piglet model of esophageal stricture following variable segmental esophageal resection and re-anastomosis

Christina Oetzmann von Sochaczewski , Ann-Kristin Riedesel , Andreas Lindner , Axel Heimann , Arne Schröder , Oliver J. Muensterer

Animal Models and Experimental Medicine ›› 2024, Vol. 7 ›› Issue (6) : 936 -943.

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Animal Models and Experimental Medicine ›› 2024, Vol. 7 ›› Issue (6) : 936 -943. DOI: 10.1002/ame2.12498
ORIGINAL ARTICLE

A novel piglet model of esophageal stricture following variable segmental esophageal resection and re-anastomosis

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Abstract

Background: Esophageal strictures following esophageal atresia repair are a source of significant morbidity. To test new therapeutic approaches, we designed a piglet model of esophageal stricture by resecting variable lengths of esophagus with subsequent re-anastomosis. This study describes the model and validates its physiologic impact by blinded analysis of the weight gains of the piglets.

Methods: A total of 24 two-week old Pietrain piglets had esophageal resections performed, ranging from 0 to 5 cm, with the goal of inducing postoperative esophageal strictures. Postoperative body-weights were evaluated by repeated analysis of variance followed by pairwise group-comparisons based on estimated marginal means. In addition, body weight was modeled by linear-mixed model regression. Different resection lengths were compared. The esophagi were evaluated postmortem for stricture.

Results: Of 24 operated piglets, 23 reached the endpoint, and 90% developed an esophageal stricture that was radiologically visible in a contrast study, as well as appreciable macroscopically in the necropsy. We found differences in pre-and postoperative body weights for all piglets (F (1, 18) = 298.54, p < 0.001), but no differences between resection lengths (F (4, 18) = 0.36, p = 0.837).

Conclusion: Our model of postoperative esophageal stricture offers the opportunity to investigate potential treatments for strictures associated with esophageal atresia, since it reliably induces strictures and results in minimal loss of animals. The similar body weight gain in all groups indicates that stricture is mainly the result of esophageal resection and re-anastomosis, regardless of the length of the resected segment.

Keywords

esophageal atresia / esophageal surgery / postoperative complication / stricture / swine model

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Christina Oetzmann von Sochaczewski, Ann-Kristin Riedesel, Andreas Lindner, Axel Heimann, Arne Schröder, Oliver J. Muensterer. A novel piglet model of esophageal stricture following variable segmental esophageal resection and re-anastomosis. Animal Models and Experimental Medicine, 2024, 7(6): 936-943 DOI:10.1002/ame2.12498

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References

[1]

Haight C, Towsley HA. Congenital atresia of the esophagus with tracheoesophageal fistula: extrapleural ligation of fistula and end-to-end anastomosis of esophageal segments. Surg Gynecol Obstet. 1943;76:672-688.

[2]

Schneider A, Blanc S, Bonnard A, et al. Results from the French National Esophageal Atresia register: one-year outcome. Orphanet J Rare Dis. 2014;9(1):206.

[3]

Sistonen SJ, Koivusalo A, Nieminen U, et al. Esophageal morbidity and function in adults with repaired esophageal atresia with tracheoesophageal fistula: a population-based long-term follow-up. Ann Surg. 2010;251(6):1167-1173.

[4]

Takada Y, Kent G, Filler RM. Circular myotomy and esophageal length and safe esophageal anastomosis: an experimental study. J Pediatr Surg. 1981;16(3):343-348.

[5]

Oetzmann von Sochaczewski C, Tagkalos E, Lindner A, et al. Esophageal biomechanics revisited: a tale of tenacity, anastomoses, and suture bite lengths in swine. Ann Thorac Surg. 2019;107(6):1670-1677.

[6]

Glauser EM. Advantages of piglets as experimental animals in pediatric research. Exp Med Surg. 1966;24(2):181-190.

[7]

Conrad MS, Johnson RW. The domestic piglet: an important model for investigating the neurodevelopmental consequences of early life insults. Annu Rev Anim Biosci. 2015;3(1):245-264.

[8]

Livaditis A, Jönsson L. The piglet in experimental pediatric surgery. Z Versuchstierkd. 1979;21(2):78-82.

[9]

Livaditis A, Okmian L, Björck G, Ivemark B. Esophageal suture anastomosis: an experimental study in piglets. Scand J Thorac Cardiovasc Surg. 1969;3(2–3):163-173.

[10]

Livaditis A, Rådberg L, Odensjö G. Esophageal end-to-end anastomosis:reduction of anastomotic tension by circular myotomy. Scand J Thorac Cardiovasc Surg. 1972;6(2):206-214.

[11]

Nelson Ö, Okmian L. Healing of esophageal end-to-end anastomoses one, two and three weeks postoperatively. Z Kinderchir. 1976;19:25-37.

[12]

Schaarschmidt K, Paschertz KW, Stratmann U, Ruprecht L, Willital GH, Unsüld E. Tracheoesophageal anastomosis, continent gastrostomy and oesophagostomy-a new experimental model in minipiglets. Lab Anim. 1995;29(4):411-419.

[13]

Lorincz A, Langenburg SE, Knight CG, Gidell K, Rabah R, Klein MD. Robotically assisted esophago-esophagostomy in newborn pigs. J Pediatr Surg. 2004;39(9):1386-1389.

[14]

Sullins VF, Traum PK, French SW, Wu BM, Dunn JCY, Lee SL. A novel method of esophageal lengthening in a large animal model of long gap esophageal atresia. J Pediatr Surg. 2015;50(6):928-932.

[15]

Oetzmann von Sochaczewski C, Lindner A, Heimann A, et al. Beyond Magnamosis: a method to test Sutureless esophageal anastomotic devices in living swine by creating an esophageal bypass loop for natural Oral nutrition. J Laparoendosc Adv Surg Tech A. 2019;29(6):852-855.

[16]

Li L, Itani MI, Salimian KJ, et al. A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics. Sci Rep. 2021;11(1):13344.

[17]

Pauli EM, Schomisch SJ, Furlan JP, et al. Biodegradable esophageal stent placement does not prevent high-grade stricture formation after circumferential mucosal resection in a porcine model. Surg Endosc. 2012;26(12):3500-3508.

[18]

Nonaka K, Miyazawa M, Ban S, et al. Different healing process of esophageal large mucosal defects by endoscopic mucosal dissection between with and without steroid injection in an animal model. BMC Gastroenterol. 2013;13(1):72.

[19]

Ellebæk M, Qvist N, Schrøder H, 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. 2015;26(3):282-286.

[20]

Dibbern C, Rose M, Ellebæk M, 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(1):56-60.

[21]

Muensterer OJ, Sterlin A, Oetzmann von Sochaczewski C, et al. An experimental study on magnetic esophageal compression anastomosis in piglets. J Pediatr Surg. 2020;55(3):425-432.

[22]

Baumgart J, Deigendesch N, Lindner A, et al. Using multidimensional scaling in model choice for congenital oesophageal atresia: similarity analysis of human autopsy organ weights with those from a comparative assessment of Aachen Minipig and Pietrain piglets. Lab Anim. 2020;54(6):576-587.

[23]

Festing MFW, Altman DG. Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR J. 2002;43(4):244-258.

[24]

von Kortzfleisch VT, Karp NA, Palme R, Kaiser S, Sachser N, Richter SH. Improving reproducibility in animal research by splitting the study population into several ’mini-experiments’. Sci Rep. 2020;10(1):16579.

[25]

Festing MF. On determining sample size in experiments involving laboratory animals. Lab Anim. 2018;52(4):341-350.

[26]

Parker EF, Brockington WS. Esophageal resection with end-to-end anastomosis: experimental and clinical observations. Ann Surg. 1949;129(5):588-603.

[27]

Jönsson L, Friberg LG, Gatzinsky V, Jennische E, Sandin A, Abrahamsson K. Early regenerative response in the intrathoracic porcine esophagus—the impact of the inflammation. Artif Organs. 2014;38(6):439-446.

[28]

Obernier JA, Baldwin RL. Establishing an appropriate period of acclimatization following transportation of laboratory animals. ILAR J. 2006;47(4):364-369.

[29]

Livaditis A, Ivemark B. Esophageal anastomosis in piglets: histologic and microangiographic aspects of the early phases of healing. Scand J Thorac Cardiovasc Surg. 1969;3(2–3):174-180.

[30]

R Core Team. R: A Language and Environment for Statistical Computing. Published online 2019. Accessed February 25, 2019. https://www.R-project.org

[31]

Singmann H, Bolker B, Westfall J, et al. afex: Analysis of Factorial Experiments. Published online July 22, 2021. Accessed December 19, 2021. https://CRAN.R-project.org/package=afex

[32]

Lenth RV, Buerkner P, Herve M, et al. emmeans: Estimated Marginal Means, aka Least-Squares Means. Published online November 29, 2021. Accessed December 19, 2021. https://CRAN.R-project.org/package=emmeans

[33]

Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B. 1995;57(1):289-300.

[34]

Nieuwenhuis R, Pelzer B, Grotenhuis M. influence.ME: Tools for Detecting Influential Data in Mixed Effects Models. Published online June 7, 2017. Accessed December 20, 2021. https://CRAN.R-project.org/package=influence.ME

[35]

Bates D, Maechler M, Bolker B, et al. lme4: Linear Mixed-Effects Models using “Eigen” and S4. Published online June 22, 2021. Accessed December 19, 2021. https://CRAN.R-project.org/package=lme4

[36]

Oetzmann von Sochaczewski C, Riedesel AK, Lindner A, Heimann A, Schröder A, Muensterer OJ. Raw data for bodyweights of piglets used to establish the Mainz piglet model of oesophageal strictures. Published online December 28, 2021. doi:10.5281/ZENODO.5807805

[37]

Vergouwe FWT, Spoel M, van Beelen NWG, et al. Longitudinal evaluation of growth in oesophageal atresia patients up to 12 years. Arch Dis Child Fetal Neonatal Ed. 2017;102(5):F417-F422.

[38]

Angelino G, Tambucci R, Torroni F, De Angelis P, Dall’Oglio L. New therapies for esophageal strictures in children. Curr Opin Pediatr. 2021;33(5):503-508.

[39]

McKinnon LJ, Kosloske AM. Prediction and prevention of anastomotic complications of esophageal atresia and tracheoesophageal fistula. J Pediatr Surg. 1990;25(7):778-781.

[40]

Upadhyaya VD, Gangopadhyaya AN, Gupta DK, et al. Prognosis of congenital tracheoesophageal fistula with esophageal atresia on the basis of gap length. Pediatr Surg Int. 2007;23(8):767-771.

[41]

Boyle EM, Irwin ED, Foker JE. Primary repair of ultra-long-gap esophageal atresia: results without a lengthening procedure. Ann Thorac Surg. 1994;57(3):576-579.

[42]

Michaud L, Guimber D, Sfeir R, et al. Sténose anastomotique après traitement chirurgical de lˈatrésie de lˈoesophage : fréquence, facteurs de risque et efficacité des dilatations oesophagiennes. Arch Pediatr. 2001;8(3):268-274.

[43]

Serhal L, Gottrand F, Sfeir R, et al. Anastomotic stricture after surgical repair of esophageal atresia: frequency, risk factors, and efficacy of esophageal bougie dilatations. J Pediatr Surg. 2010;45(7):1459-1462.

[44]

Sillén U, Hagberg S, Rubenson A, Werkmäster K. Management of esophageal atresia: review of 16 years’ experience. J Pediatr Surg. 1988;23(9):805-809.

[45]

Saxena AK, Biro E, Sommer G, Holzapfel GA. Esophagus stretch tests: biomechanics for tissue engineering and possible implications on the outcome of esophageal atresia repairs performed under excessive tension. Esophagus. 2021;18(2):346-352.

[46]

Oetzmann von Sochaczewski C, Deigendesch N, Lindner A, et al. Comparing Aachen Minipigs and Pietrain piglets as models of experimental pediatric urology to human reference data. Eur Surg Res. 2020;61(2–3):95-100.

[47]

Koffeman GI, Hulscher JBF, Schoots IG, van Gulik TM, Heij HA, van Gemert WG. Intestinal lengthening and reversed segment in a piglet short bowel syndrome model. J Surg Res. 2015;195(2):433-443.

[48]

Kaska M, Blazej S, Turek Z, et al. The effect of three different surgical techniques for colon anastomosis on regional postoperative microperfusion: laser Doppler Flowmetry study in pigs. Clin Hemorheol Microcirc. 2018;68(1):61-70.

[49]

Strobel CT, Byrne WJ, Ament ME, Euler AR. Correlation of esophageal lengths in children with height: application to the Tuttle test without prior esophageal manometry. J Pediatr. 1979;94(1):81-84.

[50]

Putnam PE, Orenstein SR. Determining esophageal length from crown-rump length. J Pediatr Gastroenterol Nutr. 1991;13(4):354-359.

[51]

Moreau B, Kambites S, Lévesque D. Esophageal length: esophageal Manometry remains superior to mathematical equations. J Pediatr Gastroenterol Nutr. 2013;57(2):236-239.

[52]

Oetzmann von Sochaczewski C, Tagkalos E, Lindner A, et al. Bodyweight, not age, determines oesophageal length and breaking strength in rats. J Pediatr Surg. 2019;54(2):297-302.

[53]

Pawlowsky K, Ernst L, Steitz J, et al. The Aachen Minipig: phenotype, genotype, hematological and biochemical characterization, and comparison to the Göttingen Minipig. Eur Surg Res. 2017;58(5–6):193-203.

[54]

Plotzki E, Heinrichs G, Kubícková B, Ulrich RG, Denner J. Microbiological characterization of a newly established pig breed, Aachen Minipigs. Xenotransplantation. 2016;23(2):159-167.

[55]

Bailoo JD, Reichlin TS, Wurbel H. Refinement of experimental design and conduct in laboratory animal research. ILAR J. 2014;55(3):383-391.

[56]

Percie du Sert N, Hurst V, Ahluwalia A, et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol. 2020;18(7):e3000410.

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2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

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