Crohn's Strictures Research Articles

P006 MiR-192 is associated with stricturing phenotype in Crohn’s disease

Abstract Background MicroRNAs (miRNAs) are small, non-coding short (ribonucleic acid) RNAs that have a role in the regulation of genes and protein expression. MiRNAs have altered expression in multiple autoimmune disorders including inflammatory bowel diseases (IBD). This emerging role has led to investigations into miRNA expression profiles in IBD to understand the pathogenesis of these diseases and lead to clinical advances in this area. Due to shared pathways in fibrosis, miRNAs that have a potential role in intestinal fibrosis are worthy of investigation, and miR-192 seems to be associated with fibrosis and strictures in Crohn’s disease (CD). The study aimed to assess the expression levels of tissue and circulating miR-192 in patients with CD. Methods The study included 58 patients with CD and 31 subjects as controls for the validation cohort. Demographic and clinical data (including phenotype of the disease), biomarkers: fecal calprotectin (fCal), endoscopy data: Short Endoscopic Score of Crohn’s disease (SES-CD), the expression levels of miR-192 in tissue and serum were assessed (by RT-PCR). Receiver operating characteristic (ROC) analysis was performed to assess the miR-192 expression level as a potential biomarker for stricturing phenotype of CD. Results The mean fCal was 345+/- 112 μg/g. The mean SES-CD was 3.4 +/- 1.1. Regarding disease phenotype, 26 (44.8%) had inflammatory phenotype, 32 (55.2%) had stricturing phenotype, and no patient had penetrant phenotype. Regarding location, 20 (34.5%) were ileal, 5 (8.7%) were colonic, and 33 (56.8%) were ileocolic. Strictures were all located in the terminal ileum. The expression level of miR-192 was significantly upregulated in CD tissue samples compared to the control tissue samples only in the patients with stricturing phenotype (8.27 ± 2.87 vs. 4.20 ± 1.94; p < 0.01), whereas in inflammatory phenotype miR-192 was downregulated (-3.47 ± 1.02 vs. - 4.30 ± 0.84; p < 0.01). Similarly, serum miR-31 expression level in CD patients was significantly upregulated than in control serum samples only in the patients with stricturing phenotype (4.07 ± 1.00 vs. 1.55 ± 0.91; p < 0.01), whereas in inflammatory phenotype miR-192 was downregulated (- 0.25 ± 0.79 vs. 0.76 ± 0.83; p < 0.01). There was a strong correlation between tissue and circulating miR-192 with stricturing phenotype (r = 0.89, r = 0.85, p < 0.05). ROC analysis revealed that the expression level of miR-192 could help to discriminate stricturing CD patients from other phenotypes with very good specificity and sensitivity. Conclusion MiR-192 is associated with stricturing phenotype in CD and could be a biomarker of intestinal fibrosis. Furthermore, circulating miR-192 could be a non-invasive biomarker of intestinal fibrosis.

Self-expandable metal stents versus endoscopic balloon dilation for the treatment of strictures in Crohn's disease (ProtDilat study): an open-label, multicentre, randomised trial

Endoscopic balloon dilation (EBD) is the established endoscopic treatment for short strictures in Crohn's disease. Fully covered self-expandable metal stents (FCSEMS) have been used for endoscopic treatment of patients for whom EBD was unsuccessful. We aimed to determine the efficacy and safety of the two endoscopic treatments in patients with Crohn's disease with stenosis and compare the mean cost of both treatments. This multicentre, open-label, randomised trial was done in 19 tertiary and secondary hospitals in Spain. Patients with Crohn's disease with obstructive symptoms and predominantly fibrotic strictures of less than 10 cm in length were eligible for inclusion. We excluded patients with stenosis treated with SEMS or EBD in the previous year and stenosis not accessible to a colonoscope. Patients were randomly assigned (1:1) to receive either EBD (EBD group) or FCSEMS (FCSEMS group) using a digital en-block randomisation system (block size of four). In the EBD group, dilation was done with a CRE Boston Scientific (Marlborough, MA, USA) pneumatic balloon with the diameter set at the discretion of the endoscopist; a maximum of two sessions of dilation were allowed with a minimum interval of 15-30 days between them. In the FCSEMS group, a 20 mm diameter Taewoong (Gimpo-si, South Korea) fully covered metal stent was placed; stent length was set at the discretion of the endoscopist. The primary outcome was to assess the efficacy of the endoscopic treatment, defined by the proportion of patients free of a new therapeutic intervention (EBD, FCSEMS, or surgery) due to symptomatic recurrence at 1 year of follow-up. Patients were analysed according to the intention-to-treat principle. Adverse events were recorded for all the patients; events were considered associated to be with the procedure when a causal association was possible, probable, or definite. This trial is registered with ClinicalTrials.gov, NCT02395354. From Aug 28, 2013, to Oct 9, 2017, we assessed the eligibility of 99 patients, of whom 19 (19%) patients were excluded. Thus, 80 (81%) patients were randomly assigned to treatment: 39 (49%) patients to the FCSEMS group and 41 (51%) patients to the EBD group. 33 (80%) of 41 patients in the EBD group and 20 (51%) of 39 patients in the FCSEMS group were free of a new therapeutic intervention at 1 year (odds ratio [OR] 3·9 [95% CI 1·4-10·6]; p=0·0061). Two (3%) of 80 patients had severe adverse events (one [2%] patient in the EBD group and one [3%] patient in the FCSEMS group); both patients had perforations. EBD is more effective than FCSEMS for Crohn's disease strictures, with a good safety profile for both treatments. Spanish National Institute of Health, Foundation of Spanish Society of Digestive Endoscopy, Catalan Society of Gastroenterology, and Taweoong.

Intestinal strictures in Crohn's disease: a 2021 update.

Intestinal strictures remain one of the most intractable and common complications of Crohn’s disease (CD). Approximately 70% of CD patients will develop fibrotic strictures after 10 years of CD diagnosis. Since specific antifibrotic therapies are unavailable, endoscopic balloon dilation and surgery remain the mainstay treatments despite a high recurrence rate. Besides, there are no reliable methods for accurately evaluating intestinal fibrosis. This is largely due to the fact that the mechanisms of initiation and propagation of intestinal fibrosis are poorly understood. There is growing evidence implying that the pathogenesis of stricturing CD involves the intricate interplay of factors including aberrant immune and nonimmune responses, host-microbiome dysbiosis, and genetic susceptibility. Currently, the progress on intestinal strictures has been fueled by the advent of novel techniques, such as single-cell sequencing, multi-omics, and artificial intelligence. Here, we perform a timely and comprehensive review of the substantial advances in intestinal strictures in 2021, aiming to provide prompt information regarding fibrosis and set the stage for the improvement of diagnosis, treatment, and prognosis of intestinal strictures.

Impedance Planimetry for Crohn's Disease Anastomotic Stricture Characterization: A Predictor of Treatment Response?

ABSTRACT Intestinal strictures affect one-third of patients with Crohn's disease (CD) within 10 years of disease onset. Quantification of fibrosis and/or inflammation within the stricture may help in choosing the appropriate treatment. Current endoscopic imaging modalities could benefit from the transmural characterization of tissue modeling from fibrosis. We report the application of EndoFLIP during balloon dilation and stricturotomy of CD-related ileocolonic anastomotic stricture. A low EndoFLIP distensibility was noted which improved after endotherapy. This proof-of-concept application supports the use of EndoFLIP to characterize CD anastomotic stricture and real-time assessment of response to endotherapy.

Intensive drug therapy versus standard drug therapy for symptomatic intestinal Crohn's disease strictures (STRIDENT): an open-label, single-centre, randomised controlled trial

Strictures are the most common structural complication of Crohn's disease. Surgery and endoscopic balloon dilation are the main treatments; drug therapy has been considered contraindicated. Given that most strictures have an inflammatory component, we aimed to find out whether strictures are responsive to drug treatment and whether intensive drug therapy is more effective than standard drug therapy. This open-label, single-centre, randomised controlled trial was performed in one specialist inflammatory bowel disease centre in Australia. Patients aged 18 years or older with Crohn's disease were included. Eligible patients had a de novo or postoperative anastomotic intestinal stricture on MRI or ileocolonoscopy, symptoms consistent with chronic or subacute intestinal obstruction (postprandial abdominal pain in the presence of a confirmed stricture), and evidence of active intestinal inflammation. Patients were randomly assigned (2:1) to receive intensive high-dose adalimumab (160 mg adalimumab once per week for 4 weeks followed by 40 mg every 2 weeks, with escalation of dose at 4 months and 8 months if assessment of disease activity indicated active inflammation) plus thiopurine (initial dose of azathioprine 2·5 mg/kg or mercaptopurine 1·5 mg/kg, with dose adjustment based on thiopurine metabolite testing) or standard adalimumab monotherapy (160 mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks) using stratified fixed block randomisation. Stratification factors were stricture dilation at study baseline colonoscopy and current biologic drug use. The primary endpoint was improvement (decrease) in the 14-day obstructive symptom score at 12 months by one or more points compared with baseline. This trial is registered with ClinicalTrials.gov, NCT03220841, and is completed. Between Sept 10, 2017, and Sept 6, 2019, 123 patients were screened and 77 randomly assigned to intensive adalimumab plus thiopurine treatment (n=52) or standard adalimumab treatment (n=25). At 12 months, improvement in obstructive symptom score was noted in 41 (79%) of 52 patients in the intensive treatment group and 16 (64%) of 25 in the standard treatment group (odds ratio [OR] 2·10 [95% CI 0·73-6·01]; p=0·17). Treatment failure occurred in five (10%) patients in the intensive treatment group versus seven (28%) in the standard treatment group (OR 0·27 [95% CI 0·08-0·97]; p=0·045); four patients in each group required stricture surgery (0·44 [0·10-1·92]; p=0·27). Crohn's Disease Activity Index was less than 150 in 36 (69%) patients in the intensive treatment group versus 15 (60%) in the standard treatment group (1·50 [0·56-4·05]; p=0·42). MRI at 12 months showed improvement using the stricture MaRIA score (≥25%) in 31 (61%) of 51 versus seven (28%) of 25 patients (3·99 [1·41-11·26]; p=0·0091). MRI complete stricture resolution was seen in ten (20%) versus four (16%) patients (1·28 [0·36 to 4·57]; p=0·70). Intestinal ultrasound at 12 months showed improvement (>25%) in bowel wall thickness in 22 (51%) of 43 versus seven (33%) of 21 patients (2·10 [0·71 to 6·21]; p=0·18). Faecal calprotectin normalised in 32 (62%) versus 11 (44%) patients (2·04 [0·77-5·36]; p=0·15). Normalisation of CRP was seen in 32 (62%) versus 11 (44%) patients (2·04 [0·77-5·36]; p=0·15). Eight (15%) patients in the intensive treatment group and four (16%) in the standard treatment group reported serious adverse events. No deaths occurred during the study. Crohn's disease strictures are responsive to drug treatment. Most patients had improved symptoms and stricture morphology. Treat-to-target therapy intensification resulted in less treatment failure, a reduction in stricture-associated inflammation, and greater improvement in stricture morphology, although these differences were not significantly different from standard therapy. Australian National Health and Medical Research Council, Gastroenterological Society of Australia Ferring IBD Clinician Establishment Award, Australasian Gastro Intestinal Research Foundation, AbbVie, and the Spotlight Foundation.

Ultrasound Elastography in the Assessment of the Intestinal Changes in Inflammatory Bowel Disease-Systematic Review.

Inflammatory bowel disease (IBD) is a chronic condition affecting primarily the gastrointestinal tract and characterized by growing incidence worldwide. Complex diagnostic process of IBD as well as evaluation of disease activity and intestinal complications that are crucial for the therapeutic decisions, require repetitive, invasive, expensive, time-consuming and poorly tolerated tests. In contrast to endoscopy and computed tomography, ultrasound elastography (UE) is non-invasive, non-radiating and non-contrasting dependent tool which might be utilized in IBD patients for the assessment of the intestinal changes. Therefore, we performed the systematic review to evaluate the possible application of the ultrasound elastography for assessment of the intestinal changes in IBD. After the search of three databases: PubMed, World of Knowledge and Scopus, we identified 12 papers which were included in the final analysis. The majority of the studies were focused on the evaluation of the symptomatic ileal/ileocolonic strictures in Crohn’s disease patients that required surgical resection. Only one study concerned ulcerative colitis. The authors evaluated different UE techniques: strain elastography (SE), acoustic radiation force impulse (ARFI) and shear wave elastography (SWE). Results were expressed with semi-quantitative color mapping and strain measurement. Histological scores of inflammation and fibrosis in Crohn’s disease were used as a reference test in the majority of studies. Ultrasound elastography seems to be a promising novel imaging technique supporting evaluation of the intestinal strictures in Crohn’s disease patients in respect to fibrosis detection as well as differentiation between fibrosis and inflammation. However, further research is needed to establish the position of ultrasound elastography in IBD management.

Evaluation of the endoscopic treatment with topical prednisolone administration for intestinal strictures in Crohn's disease.

<br><b>Introduction:</b> The prevalence of Crohn's disease amounts to 5.9 cases per 100,000 population. Complications such as intestinal strictures usually occur within a long course of Crohn's disease. Intestinal resection for stricture does not prevent a stricture recurrence and the need for repeated resections, which in turn leads to the formation of short intestine syndrome. The advantage of endoscopic balloon dilatation is organ preservation and a quick clinical therapeutic effiect. However, the frequency of recurrences after conventional endoscopic balloon dilatation of the intestinal stricture in Crohn's disease is still at a relatively high level and amounts to 59%, which justifies the need to improve the endoscopic dilatation technique.</br> <br><b>Aim:</b> The aim of this study to improve the treatment effectiveness for intestinal strictures in Crohn's disease using endoscopic balloon dilatation combined with prednisolone injection in the stricture area.</br> <br><b>Materials and methods:</b> Endoscopic treatment for intestinal strictures in Crohn's disease was performed in 64 patients. Depending on the endoscopic technique, patients were randomized into 2 groups. The first group consisted of 32 (50%) patients who underwent conventional endoscopic balloon dilatation of strictured areas. The second group consisted of 32 (50%) patients in whom an endoscopic balloon dilatation in combination with submucosal injection of prednisolone to the area of stricture after dilatation was performed. Patient groups were comparable in age, sex and length of stricture.</br> <br><b>Results and conclusions:</b> The results showed that endoscopic balloon dilatation with administration of 40 mg of prednisolone in group II patients was more effective compared to conventional balloon dilatation. The recurrence rate was reduced from 34.4% to 9.3%. The risk of recurrence of intestinal stricture in group I during the first year of observation was found to be 4.5 times higher - HR = 4.5 (1.6-12.9); P = 0.010. The effectiveness of advanced endoscopic balloon dilatation for intestinal strictures was confirmed by colonoscopy with patomorphological examination of the intestinal mucosa 6 months after dilation in patients of both groups.</br&gt.

Constrictive and Hypertrophic Strictures in Ileal Crohn’s Disease

Strictures in Crohn's disease (CD) are classically attributed to fibromuscular hypertrophy of the intestinal wall. We have identified and characterized CD-related ileal strictures that result instead from mural constriction (ie, reduced external circumference). Twenty-four strictures and internal controls from 17 adults with obstructive CD were analyzed by cross-sectional morphometry. The stricture-to-control circumference ratios (CRs) ranged from 0.53 to 1.7. Six strictures with CR ≥1.0, designated hypertrophic, had concentrically thickened walls, mean 3-fold increases in cross-sectional area and stainable fibromucular tissue, and high transmural inflammation scores. In contrast, 18 strictures with CR <1.0, designated constrictive, had thin, pliant walls, cross-sectional areas and stainable fibromuscular tissue comparable with control values, and low transmural inflammation scores. Eight mildly constrictive strictures also showed mild fibromuscular mural expansion that fell short of statistical significance. Twelve of 18 constrictive strictures (67%) occurred multiply (2-4 strictures per specimen) in contrast with hypertrophic strictures, all of which occurred singly (P= .01). Constriction correlated quantitatively with circumferential serosal fat wrapping (P= .003) and was associated with myenteric lymphocytic plexitis (P= .02). Disease duration was shortest among subjects with constrictive strictures and correlated with increasing circumference (CR ≤0.8, 6.3 ± 6.2 years; CR >0.8, 8.7 ± 6.4 years; and CR ≥1.00, 13.7 ± 5.0 years, respectively; P= .03). Constrictive ileal strictures in CD differ pathologically and clinically from hypertrophic strictures, featuring little or no fibromuscular mural expansion, frequent multiplicity, and earlier onset. Mesenteric fat wrapping and myenteric plexitis may contribute to their pathogenesis. Pathologic manifestations of constriction and hypertrophy can coexist, suggesting that stricture heterogeneity may be shaped in part by the dynamics of constrictive and hypertrophic processes.

Intestinal stricture in Crohn's disease: A 2020 update

Crohn's disease (CD) is a chronic and relapsing-remitting inflammatory disorder of the gastrointestinal tract. Approximately 70% of patients inevitably develop fibrosis-associated intestinal stricture after 10 years of CD diagnosis, which seriously affects their quality of life. Current therapies play limited role in preventing or reversing the process of fibrosis and no specific anti-fibrotic therapy is yet available. Nearly half of patients thus have no alternative but to receive surgery. The potential mechanisms of intestinal fibrosis remain poorly understood; extracellular matrix remodeling, aberrant immune response, intestinal microbiome imbalance and creeping fat might exert fundamental influences on the multiple physiological and pathophysiological processes. Recently, the emerging new diagnostic techniques have markedly promoted an accurate assessment of intestinal stricture by distinguishing fibrosis from inflammation, which is crucial for guiding treatment and predicting prognosis. In this review, we concisely summarized the key studies published in the year 2020 covering pathogenesis, diagnostic modalities, and therapeutic strategy of intestinal stricture. A comprehensive and timely review of the updated researches in intestinal stricture could provide insight to further elucidate its pathogenesis and identify novel drug targets with anti-fibrotic potentiality.

P413 Characteristics of the stricture, not the ongoing treatment, influence the outcome of endoscopic dilatation in recurrent Crohn’s disease

Abstract Background Endoscopic balloon dilatation (EBD) is a conservative alternative for the treatment of post-surgical anastomotic strictures in Crohn’s disease (CD) that improves obstructive symptoms and could delay or avoid further surgeries. However, the usefulness of this technique and predictors of efficacy have been poorly evaluated in a homogeneous cohort. Aim to evaluate the efficacy of EBD in CD patients with anastomotic strictures as well as to analyze therapeutic success factors and the rate of adverse events. Methods Observational study in a tertiary hospital of a cohort of patients with diagnosis of CD who underwent EBD for anastomotic stricture after previous surgery and with obstructive symptoms. Clinical, demographic and disease characteristics, treatment used, surgery data, inflammatory parameters at time of dilatation, number of dilatations, complications and needed for subsequent surgery were analyzed. Technical success was defined when the endoscope was passed through the stricture after procedure. Therapeutic success per patient was considered when patient did not need surgery at the end of the follow-up. Results 63 EBD were performed in 32 patients. Figure 1 shows the clinical and demographic characteristics of the patients. The diameters of the balloons used were 12-15 mm and 15-18 mm. Of the 63 examinations performed, 63.5% (n=40) showed technical success. The therapeutic success per patient was 62.5% (n=20) at 6 years of mean follow-up. Twelve patients required new surgery. The visualized neoileon after EBD had no significant recurrence (Rutgeerts i0-i2a) in 80% of dilatations. The adverse event rate was 3.1% (n=2) a microperforation and a major bleeding, both patients with Rutgeerts i4. The stricture length was the only predictor of technical and therapeutic success. Strictures with more than 40 mm of length were associated with poor efficacy. Neither the type of surgical anastomosis, current treatment, inflammatory parameters levels or balloon diameter were predictors of therapeutic success. Conclusion EBD appears to be a safe and effective technique that could avoid further surgery in up to two thirds of anastomotic strictures in CD in long-term recurrent CD. Longer stricture length and the presence of severe recurrence were associated with poor response and complications.

ID: 3524317 ENDOSCOPIC STENT PLACEMENT IN THE MANAGEMENT OF STRICTURES IN CROHN’S DISEASE: A META-ANALYSIS OF OBSERVATIONAL STUDIES

Background and Aims: Endoscopic balloon dilation and electroincision have been used for the treatment of Crohn’s disease-associated strictures. Data on the role of stents in the management of stricture in Crohn’s disease remain scarce. We performed this meta-analysis to evaluate efficacy of stent placement for Crohn’s strictures.

International consensus to standardise histopathological scoring for small bowel strictures in Crohn’s disease

ObjectiveEffective medical therapy and validated trial outcomes are lacking for small bowel Crohn’s disease (CD) strictures. Histopathology of surgically resected specimens is the gold standard for correlation with imaging techniques....

Can Conventional and Diffusion-Weighted MR Enterography Biomarkers Differentiate Inflammatory from Fibrotic Strictures in Crohn's Disease?

Background and Objectives: To retrospectively assess the value of magnetic resonance enterography (MRE) parameters derived from conventional and diffusion weighted imaging (DWI) sequences to differentiate fibrotic strictures from inflammatory ones in adult patients with Crohn’s disease (CD), using surgical specimens as the histopathological reference standard. Material and Methods: Twenty-three patients with CD who had undergone surgical resection of ileal strictures with full-thickness histopathologic analysis within 3 months from preoperative MRE were included. Two radiologists blinded to histopathology in consensus evaluated the following biomarkers on MRE images matched to resected pathological specimens: T1 ratio, T2 ratio, enhancement pattern, mural thickness, pre-stenotic luminal diameter, and apparent diffusion coefficient (ADC). A blinded pathologist graded stricture histological specimens with acute inflammation score (AIS) and fibrosis score (FS). MRE measurements were correlated with the reference standard. Results: Inflammation and fibrosis coexisted in 78.3% of patients. T2 ratio was reduced in patients with severe fibrosis (p = 0.01). Pre-stenotic bowel dilatation positively correlated with FS (p = 0.002). The ADC value negatively correlated with FS (p < 0.001) and was different between FS grades (p < 0.05). The area under the receiver operating characteristic curve for discriminating between none and mild/moderate–severe bowel wall fibrosis was 0.75 for pre-stenotic bowel dilatation (sensitivity 100%, specificity 44.4%) and 0.97 for ADC (sensitivity 80%, specificity 100%). Conclusions: Inflammation and fibrosis often coexist in CD bowel strictures needing surgery. The combination of parameters derived from conventional MR sequences (T2 ratio, pre-stenotic dilatation) and from DWI (ADC) may provide a contribution to detect and grade bowel fibrosis in adult CD patients.

A novel postgraduate endoscopic course using a large animal model of secondary Crohn's disease stricture.

The increasing complexity of advanced endoscopic techniques places a high demand on the endoscopist's expertise. Thus, live porcine models have been more frequently used for training. We briefly describe a hands-on postgraduate endoscopic course regarding a novel method of treatment of anastomotic strictures in a porcine model. The porcine model of Crohn's disease anastomotic stricture with two artificial side-to-side ileo-colonic anastomoses was used. Participants performed endoscopic stricturotomy under supervision at one of two equipped endoscopic stations. Available animals were endoscopically re-examined 3months after the course. Twelve anastomoses were prepared for the course. Eleven circumferential stricturotomies together with horizontal cut and clip placement were conducted. All anastomoses were passable for the scope after the procedure, and no case of perforation or bleeding occurred. All anastomoses available for re-examination remained passable for the endoscope after 3months. We successfully organised the first endoscopic hands-on course for the training of endoscopic stricturotomy on a large animal model.

Rapamycin is Effective for Upper but not for Lower Gastrointestinal Crohn's Disease-Related Stricture: A Pilot Study.

Crohn’s disease (CD)-related fibrotic stricture remains a clinical challenge because of no effective treatments. This study aimed to evaluate the potential efficacy of rapamycin in patients with CD-related strictures in different locations in gastrointestinal tract. A pilot prospective study on using rapamycin for CD-related stricture was performed from April 2015 to August 2020 in a single center in China. Fifteen patients were enrolled into the study. The clinical efficacy was evaluated by diet score and gastrointestinal obstruction symptoms score. Clinical responses were defined as the ability to tolerate the regular diet with vegetable fiber combined with a reduction of ≥75% in overall target score and a score of less than two points for each item. Three patients discontinued rapamycin for less than 1-month due to intolerance to adverse events, then, 12 patients received ≥1 dose of the rapamycin and provided ≥1 post-baseline target score after baseline were included for intent-to-treat (ITT) analysis. 100% (5/5) of patients with upper gastrointestinal strictures achieved clinical response after using rapamycin. However, no clinical response was observed in those patients with CD lesions in lower gastrointestinal tract. Adverse events occurred in 40% (6/15) of patients. No death or serious opportunistic infections were observed in the present study. This study firstly reported that rapamycin might be effective for CD-related stricture in the upper, but not in lower gastrointestinal tract.

Efficacy of drug and endoscopic treatment of Crohn's disease strictures: A systematic review.

Strictures are the commonest complication in Crohn's disease. Surgery and endoscopic dilation are the mainstays of treatment, while drug therapy has often been considered contraindicated. The benefit of nonsurgical treatments, particularly drug and endoscopic therapy, need to be defined. Ovid MEDLINE, Embase, Emcare, PsycINFO, CINAHL and the Cochrane Library (inception until August 30, 2019) were searched. Studies with ≥10 patients with Crohn's disease strictures, reporting on outcomes following medication or endoscopic treatment, were included. Of 3480 records, 85 studies met inclusion criteria and formed the basis of this analysis. Twenty-five studies assessed drug therapy; none were randomized trials. Despite study heterogeneity anti-tumor necrosis factor (TNF) therapy appeared effective, with 50% of patients avoiding surgery after 4years of follow up. No other drug therapy was of demonstrable benefit. Sixty studies assessed endoscopic therapy including 56 on endoscopic balloon dilation, two assessed needle knife stricturotomy, and two stent insertion. Dilation was equally effective for de novo and anastomotic strictures ≤5cm in length, with most studies reporting a subsequent surgical rate of 30% to 50%. Repeat dilation was required in approximately half of all patients. Anti-TNF drug therapy and endoscopic balloon dilation are effective strategies for avoiding surgery in patients with stricturing Crohn's disease. Additional endoscopic therapies require further evaluation. Early data suggest that combining these therapies may provide greater benefit than individual therapies. Optimization of current drug and endoscopic therapy, and the incorporation of newer therapies, are needed for stricturing Crohn's disease.

Automated Detection of Crohn's Disease Intestinal Strictures on Capsule Endoscopy Images Using Deep Neural Networks.

Passable intestinal strictures are frequently detected on capsule endoscopy [CE]. Such strictures are a major component of inflammatory scores. Deep neural network technology for CE is emerging. However, the ability of deep neural networks to identify intestinal strictures on CE images of Crohn's disease [CD] patients has not yet been evaluated. We tested a state-of-the-art deep learning network for detecting CE images of strictures. Images of normal mucosa, mucosal ulcers, and strictures of Crohn's disease patients were retrieved from our previously described CE image bank. Ulcers were classified as per degree of severity. We performed 10 cross-validation experiments. A clear patient-level separation was maintained between training and testing sets. Overall, the entire dataset included 27 892 CE images: 1942 stricture images, 14 266 normal mucosa images, and 11 684 ulcer images [mild: 7075, moderate: 2386, severe: 2223]. For classifying strictures versus non-strictures, the network exhibited an average accuracy of 93.5% [±6.7%]. The network achieved excellent differentiation between strictures and normal mucosa (area under the curve [AUC] 0.989), strictures and all ulcers [AUC 0.942], and between strictures and different grades of ulcers [for mild, moderate, and severe ulcers-AUCs 0.992, 0.975, and 0.889, respectively]. Deep neural networks are highly accurate in the detection of strictures on CE images in Crohn's disease. The network can accurately separate strictures from ulcers across the severity range. The current accuracy for the detection of ulcers and strictures by deep neural networks may allow for automated detection and grading of Crohn's disease-related findings on CE.

Management of Isolated Anal Strictures in Crohn's Disease.

Anorectal stricturing is a particularly morbid manifestation of Crohn's disease resulting in a diminished quality of life related to pain, incontinence, and recurrent operative interventions. To determine the role of medical therapy, endoscopic dilation, and surgical intervention for the treatment of isolated anorectal stricturing. An organized search of MEDLINE, PubMed, EMBASE, Scopus, and the Cochrane Database of Collected Reviews was performed from January 1, 1990 through May 1, 2020. Full text papers which included management of isolated anorectal strictures in the setting of Crohn's disease. Medical and surgical management. Symptomatic relief, need for proctocolectomy. Our search identified a total of 553 papers; after exclusion based on title (n = 430) and abstract (n = 47), 76 underwent full text review with 65 relevant to the management of anorectal strictures. A summary of the retrospective reports suggests that medical therapy can help control luminal inflammation, but fibrosis may ultimately set in resulting in a need for endoscopic or surgical intervention. Surgical options are limited in the anal canal due to inflammation and ulceration and concomitant perianal fistulizing disease. While fecal diversion can provide symptomatic relief, successful restoration of intestinal continuity remains uncommon and most patients ultimately undergo a total proctocolectomy with end ileostomy. Limited literature published, all retrospective in nature. Despite significant advances in medical and surgical therapy in Crohn's disease over the last decades, there is clearly an unmet need in the management of anorectal strictures in Crohn's disease.

Fibrotic Strictures in Crohn's Disease: Mechanisms and Predictive Factors.

Fibrotic strictures are one of the most severe complications of Crohn's Disease (CD). They occur in about 50% of patients at five years and in 70% at ten years of the diagnosis. The only treatment available for symptomatic fibrotic strictures is surgical resection and endoscopic dilation. Both strategies are associated with a high rate of recurrence, and with multiple surgical resections, which pose the threat of surgical morbidity and short bowel syndrome. Therefore, it is crucial to identify, early, the patients more prone to develop intestinal fibrosis to intensify follow-ups, switch to more aggressive treatments, and suggest lifestyle modifications. Scarce data are available concerning biomarkers and genetic determinants to predict which patient will develop intestinal fibrosis. Biologic or clinical markers would be useful to determine this subgroup of CD patients and to predict the onset of intestinal fibrosis and, ideally, its severity. Furthermore, the identification of environmental risk factors may suggest lifestyle changes aimed at modifying the natural course, thus decreasing the risk of complicated CD. In this review, we will critically revise clinical, environmental, genetic, and serologic factors that have been associated with a complicated CD course with a particular focus on the fibrostenosing phenotype and their possible implications as predictive factors of intestinal fibrosis.

A novel identification system combining diffusion kurtosis imaging with conventional magnetic resonance imaging to assess intestinal strictures in patients with Crohn's disease.

To determine the utility of diffusion kurtosis imaging (DKI) for assessing bowel fibrosis and to establish a new magnetic resonance imaging (MRI)-based classification based on DKI and conventional MRI parameters for characterizing intestinal strictures in Crohn's disease (CD) using the histological evaluation of resected intestine samples as the reference standard. Thirty-one patients with CD undergoing preoperative conventional MRI and diffusion-weighted imaging (DWI) (b values = 0-2000s/mm2) were consecutively enrolled. We classified the mural T2-weighted signal intensity and arterial-phase enhancement patterns on conventional MRI. We also measured DWI-derived apparent diffusion coefficients (ADCs) and DKI-derived apparent diffusion for non-Gaussian distribution (Dapp) and apparent diffusional kurtosis (Kapp). A new MRI-based classification was established to characterize intestinal strictures in CD. Its performance was validated in nine additional patients with CD. Histological inflammation grades were significantly correlated to T2-weighted signal intensity (r = 0.477; P < 0.001) and ADC (r = -0.226; P = 0.044). Histological fibrosis grades were moderately correlated to Kapp (r = 0.604, P < 0.001); they were also correlated to Dapp (r = -0.491; P < 0.001) and ADC (r = -0.270; P = 0.015). T2-weighted signal intensity could differentiate between no-to-mild and moderate-to-severe bowel inflammation (sensitivity, 0.970; specificity, 0.479). Kapp could differentiate between no-to-mild and moderate-to-severe bowel fibrosis (sensitivity, 0.959; specificity, 0.781). The agreement between the new MRI-based classification and the histological classification was moderate in the test (κ = 0.507; P < 0.001) and validation (κ = 0.530; P < 0.001) sets. DKI can be used to assess bowel fibrosis. The new MRI-based classification can help to distinguish between fibrotic and inflammatory intestinal strictures in patients with CD.