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

M. Lukas, M. Kolar, O. Ryska, S. Juhas, J. Juhasova, J. Kalvach, J. Pazin, T. Kocisova, O. Foltan, H. Kristianova, J. Ptacnik, I. Vitkova, M. Bortlik, M. Lukas

. 2021 ; 93 (1) : 250-256. [pub] 20200612

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc21019538

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.

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$a 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.
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$a Kolar, Martin $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; IBD Clinical and Research Center, ISCARE a.s., Prague, Czech Republic
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$a Ryska, Ondrej $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; Royal Lancaster Infirmary, University Hospitals of Morecambe Bay NHS Foundation Trust, Lancaster, UK
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$a Juhas, Stefan $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic
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$a Juhasova, Jana $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic
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$a Kalvach, Jaroslav $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; Department of Surgery, Military University Hospital and 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Pazin, Jaroslav $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; Department of Surgery, Military University Hospital and 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Kocisova, Tereza $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; Department of Surgery, Military University Hospital and 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Foltán, Ondřej $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; First Surgical Clinic of Thoracic, Abdominal and Injury Surgery, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic $7 xx0321133
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$a Kristianova, Hana $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; First Surgical Clinic of Thoracic, Abdominal and Injury Surgery, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Ptacnik, Jan $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; First Surgical Clinic of Thoracic, Abdominal and Injury Surgery, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Vitkova, Ivana $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; Institute of Pathology, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Bortlik, Martin $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; IBD Clinical and Research Center, ISCARE a.s., Prague, Czech Republic; Department of Internal Medicine, Military University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic; Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Lukas, Milan $u PIGMOD Center, Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; IBD Clinical and Research Center, ISCARE a.s., Prague, Czech Republic; Institute of Medical Biochemistry and Laboratory Medicine, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
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