Dataset Information

Optimal use of biologics with endoscopic balloon dilatation for repeated intestinal strictures in Crohn's disease.

ABSTRACT:

Background and aim

Intestinal strictures in Crohn's disease (CD) have a high rate of repeated surgery. As alternatives to surgery, endoscopic balloon dilatation (EBD), immunomodulators (IMs), and antitumor necrosis factor alpha (anti-TNF?) have been proposed. We aimed to assess the effectiveness of the combined therapy with anti-TNF? and EBD in preventing intestinal stricture recurrence and surgery in patients with CD.

Methods

This retrospective cohort study included patients from the nationwide administrative database in Japan who were hospitalized and underwent at least one EBD between 1 April 2010 and 31 March 2017. The effectiveness of anti-TNF? was evaluated by performing survival analysis for the primary outcome. We selected the inverse probability of treatment weighting method for adjustment of covariates. As an exploratory analysis, we evaluated the association of anti-TNF? initiation timing with intestinal stricture recurrence.

Results

The anti-TNF? exposed group had a significantly lower risk of intestinal stricture recurrence than that of the anti-TNF? nonexposed group (hazard ratio = 0.38, 95% confidence interval 0.31-0.48, P?ConclusionThe combined therapy with anti-TNF? and EBD could have preventive effects for intestinal stricture recurrence and surgery in hospitalized patients with CD. In particular, anti-TNF? initiation may be recommended before or after EBD, not immediately after EBD. With respect to EBD, it is important to clarify the effectiveness of combination therapy with several new medication treatments, such as biologics.

SUBMITTER: Uda A

PROVIDER: S-EPMC7273704 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Optimal use of biologics with endoscopic balloon dilatation for repeated intestinal strictures in Crohn's disease.

Uda Akihito A Kuwabara Hiroyo H Shimizu Sayuri S Iwakiri Ryuichi R Fushimi Kiyohide K

JGH open : an open access journal of gastroenterology and hepatology 20200328 3

<h4>Background and aim</h4>Intestinal strictures in Crohn's disease (CD) have a high rate of repeated surgery. As alternatives to surgery, endoscopic balloon dilatation (EBD), immunomodulators (IMs), and antitumor necrosis factor alpha (anti-TNFα) have been proposed. We aimed to assess the effectiveness of the combined therapy with anti-TNFα and EBD in preventing intestinal stricture recurrence and surgery in patients with CD.<h4>Methods</h4>This retrospective cohort study included patients from ...[more]

PMID: 32514466

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Project description:AimTo develop a new rat model we wanted to gain a better understanding of stricture formation in Crohn's disease (CD).MethodsChronic 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.ResultsIntestinal 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.ConclusionThese findings indicate that aligned structural and molecular changes in the gut wall rather than neuronal cell death play the primary role in stricture formation.

Dataset Information

Optimal use of biologics with endoscopic balloon dilatation for repeated intestinal strictures in Crohn's disease.

Background and aim

Methods

Results

Publications

Optimal use of biologics with endoscopic balloon dilatation for repeated intestinal strictures in Crohn's disease.

Similar Datasets

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