New methods
Experimental endoscopy
Novel porcine model of Crohn's disease anastomotic stricture suitable for evaluation and training of advanced endoscopic techniques

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Background and Aims

Currently, treatment options in postsurgical recurrence of stricturing Crohn's disease (CD) are limited. However, development of new invasive endoscopic techniques in clinical practice has safety constraints. The aim of this study was to create a large animal model of anastomotic stricture with CD properties to enable development of new techniques and training.

Methods

A side-to-side ileocolonic anastomosis was created in a modified Roux-en-Y manner with bowel continuity preserved. Two weeks after surgery, we began endoscopic submucosal injections of phenol/trinitrobenzenesulfonic acid solution. This solution was injected every 2 weeks in each quadrant of the anastomosis until development of a stricture. The anastomosis site was assessed endoscopically 2 weeks after the last application (baseline) and then every 2 months until month 6. Endoscopically nonpassable strictures were treated with balloon dilation, endoscopic stricturotomy, and stent placement to confirm the feasibility of such interventions.

Results

Nineteen minipigs were included with no postoperative adverse events. After a mean of 4.4 ± .7 injection sessions with 10.5 ± 3.0 mL of the solution, anastomotic strictures were created in 16 pigs (84.2%). Mean diameter of the strictures at baseline was 11.6 ± 2.2 mm. The strictures were inflamed, and the endoscope could not pass. Follow-up was successfully completed in 15 animals (79.0%) with the mean deviation from the initial diameter in every measurement of –.02 ± 2.26 mm (P = .963) and a mean final diameter of 11.7 ± 3.4 mm. The histopathologic evaluation revealed the presence of submucosal fibrosis, chronic inflammation, and microgranulomas. All strictures were amenable to endoscopic therapeutic interventions.

Conclusions

We developed a novel, reproducible porcine model of anastomotic stricture with histologically verified changes mimicking CD and stable diameter for more than 6 months. It is suitable for further endoscopic interventions.

Section snippets

Experimental animals

Miniature pigs from the Institute of Animal Physiology and Genetics (Libechov, Czech Republic) were used. This porcine breed was imported in 1967 from the Hormel Institute, University of Minnesota, and from the Institute for Animal Breeding and Genetics of the University of Göttingen in Germany. The animals are bred beginning at 5 months of age, when they reach sexual maturity. At this stage, their weight is approximately 12 to 15 kg. Survival of parental minipig breeds (Hormel and Göttingen)

Model success rate

Nineteen minipigs (weighing 48.8 ± 8.1 kg) underwent surgery with no adverse postoperative events. After a median of 4 injection sessions (range, 4-6) of 10.5 ± 3.0 mL of the solution, an anastomotic stricture was created in 16 pigs (84.2%). We were unable to create a stricture in 3 pigs. In 1 pig the anastomosis remained wide open even after 6 injection sessions, and in 2 pigs the anastomosis occluded completely during the induction (Fig. 5).

Fifteen animals (79.0%) completed the 6-month

Discussion

In this work, we were able to create a reproducible model of CD anastomotic stricture in a porcine model that was proven to remain stable for at least 6 months. Moreover, we confirmed that the induced stricture is eligible for various endoscopic interventions, including balloon dilation, stricturotomy, and stent placement, using standard endoscopic tools for human use. Thus, the model is suitable for evaluation and training of new endoscopic methods to treat CD strictures.

Several animal models

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    DISCLOSURE: All authors disclosed no financial relationships. Research support for this study was provided by the Czech Health Research Council (grant NV19-08-00449, Czech Republic (Czechia), New minimally invasive techniques for treatment of postoperative Crohn’s disease recurrence on experimental model); National Sustainability Program I, project number LO1609, Czech Ministry of Education, Youth and Sports; institutional support (RVO: 67985904); the Ministry of Defense (MO1012), Czech Republic; and IBD-Comfort Foundation.

    If you would like to chat with an author of this article, you may contact Dr Lukas at [email protected].

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