Structural and molecular features of intestinal strictures in rats with Crohn's-like disease

AIM: To develop a new rat model we wanted to gain a better understanding of stricture formation in Crohn’s disease (CD).METHODS: Chronic colitis was induced locally by the administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS). The relapsing inflammation characteristic to CD was mimicked by repeated TNBS treatments. Animals were randomly divided into control, once, twice and three times TNBS-treated groups. Control animals received an enema of saline. Tissue samples were taken from the strictured colonic segments and also adjacent proximally and distally to its 60, 90 or 120 d after the last TNBS or saline administrations. The frequency and macroscopic extent of the strictures were measured on digital photographs. The structural features of strictured gut wall were studied by light- and electron microscopy. Inflammation related alterations in TGF-beta 2 and 3, matrix metalloproteinases 9 (MMP9) and TIMP1 mRNA and protein expression were determined by quantitative real-time PCR and western blot analysis. The quantitative distribution of caspase 9 was determined by post-embedding immunohistochemistry.RESULTS: Intestinal strictures first appeared 60 d after TNBS treatments and the frequency of them increased up to day 120. From day 90 an intact lamina epithelialis, reversible thickening of lamina muscularis mucosae and irreversible thickening of the muscularis externa were demonstrated in the strictured colonic segments. Nevertheless the morphological signs of apoptosis were frequently seen and excess extracellular matrix deposition was recorded between smooth muscle cells (SMCs). Enhanced caspase 9 expression on day 90 in the SMCs and on day 120 also in myenteric neurons indicated the induction of apoptosis. The mRNA expression profile of TGF-betas after repeated TNBS doses was characteristic to CD, TGF-beta 2, but not TGF-beta 3 was up-regulated. Overexpression of MMP9 and down-regulation of TIMP1 were demonstrated. The progressive increase in the amount of MMP9 protein in the strictures was also obvious between days 90 and 120 but TIMP1 protein was practically undetectable at this time.CONCLUSION: These findings indicate that aligned structural and molecular changes in the gut wall rather than neuronal cell death play the primary role in stricture formation.

Use of small intestinal submucosa graft for repair of anterior urethral strictures

Objective To investigate the feasibility of using small intestinal submucosa ( SIS) graft for repair of anterior urethral strictures. Methods From June 2009 to August 2010,18 men ( mean age,38 yrs) with anterior urethral strictures underwent urethroplasty using a four layer SIS as an onlay patch graft. SIS was used to

Endoscopic balloon dilation for management of stricturing Crohn’s disease in children

BACKGROUND Crohn’s disease(CD)has a multitude of complications including intestinal strictures from fibrostenotic disease.Fibrostenotic disease has been reported in 10%-17%of children at presentation and leads to surgery in 20%-50%of cases within ten years of diagnosis.When symptoms develop from these strictures,the treatment in children has primarily been surgical resection.Endoscopic balloon dilation(EBD)has been shown to be a safe and efficacious alternative to surgery in adults,but evidence is poor in the literature regarding its safety and efficacy in children.AIM To evaluate the outcomes of children with fibrostenosing CD who underwent EBD vs surgery as a treatment.METHODS In a single-center retrospective study,we looked at pediatric patients(ages 0-18)who carry the diagnosis of CD,who were diagnosed after opening a dedicated Inflammatory Bowel Disease clinic on July 1,2012 through May 1,2019.We used diagnostic codes through our electronic medical record to identify patients with CD with a stricturing phenotype.The type of intervention for patients’strictures was then identified through procedural and surgical billing codes.We evaluated their demographics,clinical variables,whether they underwent EBD vs surgery or both,and their clinical outcomes.RESULTS Of the 139 patients with CD,25(18%)developed strictures.The initial intervention for a stricture was surgical resection in 12 patients(48%)and EBD in 13 patients(52%).However,4(33%)patients whom initially had surgical resection required follow up EBD,and thus 17 total patients(68%)underwent EBD at some point in their treatment process.For those 8 patients who underwent successful surgical resection alone,4 of these patients(50%)had a fistula present near the stricture site and 4(50%)had strictures greater than 5 cm in length.All patients who underwent EBD had no procedural complications,such as a perforation.Twenty-two(88%)of the treated strictures were successfully managed by EBD and did not require any further surgical intervention during our follow up period.CONCLUSION EBD is safe and efficacious as an alternative to surgery for palliative management of strictures in selected pediatric patients with CD.