Long term follow-up of a simplified and less burdened pancreatic duct ligation model of exocrine pancreatic insufficienc

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RESEARCH ARTICLE

Open Access

Long term follow‑up of a simplified and less burdened pancreatic duct ligation model of exocrine pancreatic insufficiency in Goettingen Minipigs Andreas Minh Luu1*†  , Alexander Brock2†, Sabrina Ritz2, Sandra Junghänel2, Ingo Aldag3, Stella Edskes3, Marcus Hartmann3, Michael Hessler4, Michael Praktiknjo5, Philip Arnemann4, Christian Ertmer4, Waldemar Uhl1, Juergen Schnekenburger2† and Torsten Herzog1†

Abstract  Background:  Pancreatic duct ligation in a minipig model leads to exocrine pancreatic insufficiency (EPI). This allows the study of digestive processes and pancreatic enzyme replacement therapies. However, detailed descriptions of the surgical procedure, perioperative management, a determination of exocrine pancreatic insufficiency are scarce in the literature. Data of the long-term health status of minipigs upon EPI induction are still not available. Therefore, the present study describes in detail an experimental approach to the induction of exocrine pancreatic insufficiency via pancreatic duct ligation in minipigs and the long term follow up of the animal’s health state. Methods:  14 Goettingen minipigs underwent pancreatic duct ligation via midline laparotomy for the induction of exocrine pancreatic insufficiency. Fecal fat content, fat absorption, chymotrypsin levels, body weight and blood vitamin and glucose levels were determined. Results:  Exocrine pancreatic insufficiency was successfully induced in 12 Goettingen minipigs. Two minipigs failed to develop exocrine insufficiency most likely due to undetected accessory pancreatic ducts. All animals tolerated the procedure very well and gained weight within 8 weeks after surgery without requiring pancreatic enzyme replacement therapy. The follow up for approx. 180 weeks showed a stable body weight and health state of the animals with normal blood glucose levels (Table 1). From approx. 130 weeks post pancreatic duct ligation, all animals were supplemented with pancreatic enzymes and vitamins resulting in blood concentrations almost within the reference range. Conclusions:  Pancreatic duct ligation in minipigs is an excellent method of inducing exocrine pancreatic insufficiency. It is important to identify and ligate accessory pancreatic ducts since persistence of accessory ducts will lead to maintenance of exocrine pancreatic function. The EPI model caused no persistent side effects in the animals and has the potential to be used in long-term EPI studies with up to 100 weeks post-OP without supplementation with enzymes and vitamins.

*Correspondence: a.luu@klinikum‑bochum.de † Andreas Minh Luu and Alexander Brock share first authorship † Juergen Schnekenburger and Torsten Herzog share last authorship 1 Department of General Surgery, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany Full list of author information is available at the end of the article © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, s