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.

中文翻译：

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克罗恩病吻合狭窄的新型猪模型，适用于评估和培训先进的内窥镜技术。

背景和目标

当前，狭窄克罗恩病（CD）的术后复发中的治疗选择是有限的。然而，在临床实践中新的侵入性内窥镜技术的发展具有安全性约束。这项研究的目的是创建具有CD特性的吻合口狭窄的大型动物模型，以开发新技术和训练。

方法

以改良的Roux-en-Y方式创建了一个侧对侧回肠结肠吻合术，并保留了肠的连续性。手术后两周，我们开始内镜下黏膜下注射苯酚/三硝基苯磺酸溶液。每2周在吻合术的每个象限中注射该溶液，直到形成狭窄。在最后一次应用后（基线）在两周内镜检查吻合部位，然后每2个月检查一次，直到第6个月。对内镜无法通过的狭窄进行球囊扩张，内窥镜切开术和支架置入术，以证实此类干预的可行性。

结果

包括19只小型猪，无术后不良事件。用10.5±3.0 mL溶液平均注射4.4±.7次后，在16头猪中产生吻合口狭窄（84.2％）。基线处的狭窄平均直径为11.6±2.2毫米。狭窄处发炎，内窥镜无法通过。对15只动物（79.0％）的随访成功完成，每次测量的初始直径平均偏差为–.02±2.26 mm（P  = .963），平均最终直径为11.7±3.4 mm。组织病理学评估显示存在粘膜下纤维化，慢性炎症和微肉芽肿。所有狭窄均适合内窥镜治疗干预。

结论

我们开发了一种新颖的，可复制的猪吻合口狭窄模型，并通过组织学验证的模仿CD和直径稳定超过6个月的变化。它适用于进一步的内窥镜干预。