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P044 A novel porcine model of Crohn’s disease anastomotic stricture

M. Lukas*1, M. Kolar1, O. Ryska2,3, S. Juhas3, J. Juhasova3, J. Kalvach3,4, J. Pazin3,4, J. Hadac3,4, I. Vitkova5, M. Bortlik1,6,7, M. Lukas1,8

1ISCARE I.V.F. a.s., IBD Clinical and Research Centre, Prague, Czech Republic, 2University Hospitals of Morecambe Bay NHS Foundation Trust, Royal Lancaster Infirmary, Lancaster, UK, 3Institute of Animal Physiology and Genetics, Czech Academy of Sciences, PIGMOD Centre, Laboratory of Cell Regeneration and Plasticity, Libechov, Czech Republic, 4Military University Hospital and 2nd Faculty of Medicine, Charles University, Department of Surgery, Prague, Czech Republic, 5Institute of Pathology of the First Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic, 6Military University Hospital and First Faculty of Medicine, Charles University, Department of Internal Medicine, Prague, Czech Republic, 7Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic, 8Institute of Medical Biochemistry and Laboratory Medicine, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic

Background

Ileocolonic resection is the most common surgical procedure performed in patients with Crohn’s disease (CD). Up to 70% of patients experience recurrence of the disease within 1 year at the site of anastomosis. Frequently, these patients have to be re-operated due to reoccurrence of fibrostenotic stricture which can hardly be managed medically. In order to develop and test advanced endoscopic methods of treatment of these strictures a suitable model of anastomotic stricture in large animal would be of benefit.

Methods

A side-to-side ileo-colic anastomosis 20 cm from anus was created in a modified Y-roux manner in 13 pigs with the bowel continuity preserved. Two weeks after surgery we started endoscopic submucosal injection of a 5% Phenol and 0.2% Trinitrobenzensulfonic acid solution. This solution was injected every 2 weeks in each quadrant at the site of anastomosis until the development of stricture, but at least 4 times. The site of anastomosis was assessed and measured endoscopically in 2 weeks after the last application and then resected and sent for histology. This project was approved by the respective ethics committee.

Results

Thirteen female pigs (47.1 ± 8.2 kg) were included with no postoperative complications. After a mean of 4.6 ± 0.7 injections of 10.6 ± 3.2 ml of the solution the anastomotic stricture was created in 12 pigs. Mean diameter of the stricture was 11.4 ± 2.2 mm. The strictures were macroscopically inflamed and ulcerated, not passable for the endoscope.

Anastomotic stricture in a porcine model

The histopathologic evaluation revealed the presence of an intense chronic inflammation with lymphoplasmacytic infiltrate and numerous eosinophils. Multiple histiocytic granulomas with multi-nuclear foreign-body giant cells occasionally with an abscess in the centre were present as well as epithelioid microgranulomas similar to those in CD.

Epithelioid microgranulomas

In one pig we were unable to induce stricture even after 6 applications.

Conclusion

We developed a novel reproducible porcine model of anastomotic stricture with histologically verified changes mimicking Crohn’s disease which is suitable for further applications.

Acknowledgements: This study was supported by the National Sustainability Program I, project number LO1609 (Czech Ministry of Education), RVO: 67985904, MO1012 (Ministry of Defense), and IBD-Comfort Foundation