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SummaryBackgroundEvidence for endoscopic balloon dilation of small intestinal strictures in Crohn's disease (CD) using balloon‐assisted enteroscopy is scarce.AimTo evaluate endoscopic balloon dilation for the treatment of small intestinal CD strictures using balloon‐assisted enteroscopy.MethodsCitations in Embase, MEDLINE, and Cochrane were systematically reviewed. In a meta‐analysis of 18 studies with 463 patients and 1189 endoscopic balloon dilations, technical success was defined as the ability to dilate a stricture. Individual data were also obtained on 218 patients to identify outcome‐relevant risk factors.ResultsIn the pooled per‐study analysis, technical success rate of endoscopic balloon dilation was 94.9%, resulting in short‐term clinical efficacy in 82.3% of patients. Major complications occurred in 5.3% of patients. During follow‐up, 48.3% of patients reported symptom recurrence, 38.8% were re‐dilated and 27.4% proceeded to surgery. On the per‐patient‐based multivariable analysis, that patients with disease activity in the small intestine had lower short‐term clinical efficacy (odds ratio 0.32; 95% confidence interval 0.14‐0.73, P = 0.007). Patients with concomitant active disease in the small and/or large intestine had an increased risk to proceed toward surgery (hazard ratio 1.85; 95% confidence interval 1.09‐3.13, P = 0.02 and hazard ratio 1.77; 95% confidence interval 1.34‐2.34, P < 0.001).ConclusionsBalloon‐assisted enteroscopy for dilatation of CD‐associated small intestinal strictures has high short‐term technical and clinical efficacy and low complication rates. However, up to two‐thirds of patients need re‐dilation or surgery.

Background: Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). Aim: To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. Methods: A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported.Results: Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%-41.3%) and 18.5% (95% CI: 8.3%-36.2%), respectively over a median follow-up of 23 months (range 5.5-105.8), and 21.8 months (range 5-47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%-77.3%) over a median follow-up of 21.8 months (range 5-47). Conclusions:There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery.

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Background: Intestinal fibrosis leading to strictures remains a significant clinical problem in inflammatory bowel diseases (IBD). The role of bacterial components in activating intestinal mesenchymal cells and driving fibrogenesis is largely unexplored. Methods: Tamoxifen inducible α-SMA promoter Cre mice crossed with floxed MyD88 mice were subjected to chronic dextran sodium sulfate colitis. MyD88 was deleted prior to or after induction of colitis. Human intestinal myofibroblasts (HIMF) were exposed to various bacterial components and assessed for fibronectin (FN) and collagen I (Col1) production. RNA sequencing was performed. Post-transcriptional regulation was assessed by polysome profiling assay. Results: Selective deletion of MyD88 in α-SMA positive cells prior to, but not after induction of experimental colitis decreased the degree of intestinal fibrosis. HIMF selectively responded to flagellin with enhanced FN or Col1 protein production in a MyD88 dependent manner. RNA sequencing suggested minimal transcriptional changes induced by flagellin in HIMF. Polysome profiling revealed higher proportions of FN and Col1 mRNA in the actively translated fractions of flagellin exposed HIMF, which was mediated by eIF2 alpha and 4EBP1. Conclusions: Selectivity of flagellin-induced ECM secretion in HIMF is post-transcriptionally regulated. The results may represent a novel and targetable link between the gut microbiota and intestinal fibrogenesis.