Journal of Crohn's & colitis最新文献

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of unknown cause for which no curative treatments have been developed. Cytokines play an important role in the pathogenesis of UC, and therapies targeting specific cytokines have been successful in treating refractory UC. The purpose of this study was to measure mucosal cytokines in UC and identify those that contribute to non-relapsing mucosal healing diagnosed by endoscopy.

Methods: This prospective, observational study included 163 patients with UC. The mucosa was evaluated by Mayo Endoscopic Subscore (MES) and linked color imaging (LCI) at the time of endoscopy, and cytokine mRNA expression in biopsy tissue taken from the same site was quantified by real-time PCR and compared with endoscopic findings. The relationship between cytokine mRNA expression and endoscopic findings was investigated.

Results: Cytokines such as IFNγ, IL-1β, IL-8, IL-17A, and IL-23 were significantly elevated in proportion to endoscopic severity of MES and LCI classification.Interestingly, we found differences in the expression of cytokines (e.g., IL-22 and IL-33) between MES and LCI classification according to disease severity. Additionally, pathway analysis based on RNA sequencing compared between LCI-A and LCI-B in the patients diagnosed as MES 0 revealed that IL-5 and IL-6 are involved in the finer differences in endoscopic mucosal redness.

Conclusions: This study is the first to report the correlation between mucosal cytokine expression and the pathogenesis of mucosal healing (MH) in UC and supports the contribution of specific cytokines as molecular markers of MH or in the pathogenesis of MH in UC.

Background and aims: Non-invasive cross-sectional imaging via magnetic resonance enterography [MRE] offers excellent accuracy for the diagnosis of stricturing complications in Crohn's disease [CD] but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathological inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE.

Methods: This single-centre, cross-sectional study included 51 CD patients [n = 34 for discovery; n = 17 for validation] with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both were evaluated against histopathology.

Results: Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both the discovery (area under the curve [AUC = 0.69, 0.83] and validation [AUC = 0.67, 0.78] cohorts. Radiologist visual scoring had an AUC = 0.67 for identifying severe inflammation and AUC = 0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation [AUC = 0.79] and modestly improved assessment of severe fibrosis [AUC = 0.79 for severe fibrosis] over individual approaches.

Conclusions: Radiomic features of CD strictures on MRE can accurately identify severe histopathological inflammation and severe histopathological fibrosis, as well as augment performance of the radiologist visual scoring in stricture characterization.

Background and aims: Despite advances in the medical treatment of Crohn's disease [CD], many patients will still need bowel resections and face the subsequent risk of recurrence and re-resection. We describe contemporary re-resection rates and identify disease-modifying factors and risk factors for re-resection.

Methods: We conducted a retrospective, population-based, individual patient-level data cohort study covering 47.4% of the Danish population, including all CD patients who underwent a primary resection between 2010 and 2020.

Results: Among 631 primary resected patients, 24.5% underwent a second resection, and 5.3% a third. Re-resection rates after 1, 5, and 10 years were 12.6%, 22.4%, and 32.2%, respectively. Reasons for additional resections were mainly disease activity [57%] and stoma reversal [40%]. Disease activity-driven re-resection rates after 1, 5, and 10 years were 3.6%, 10.1%, and 14.1%, respectively. Most stoma reversals occurred within 1 year [80%]. The median time to recurrence was 11.0 months. Biologics started within 1 year of the first resection revealed protective effect against re-resection for stenotic and penetrating phenotypes. Prophylactic biologic therapy at primary ileocaecal resection reduced disease recurrence and re-resection risk (hazard ratio [HR] 0.58, 95% confidence interval [CI] [0.34-0.99], p = 0.047). Risk factors for re-resection were location of resected bowel segments at the primary resection, disease location, disease behaviour, smoking, and perianal disease.

Conclusion: Re-resection rates, categorised by disease activity, are lower than those reported in other studies and are closely associated with disease phenotype and localisation. Biologic therapy may be disease-modifying for certain subgroups when initiated within 1 year of resection.

Inflammatory bowel disease [IBD] patients are at increased risk of developing colorectal neoplasia [CRN]. In this review, we aim to provide an up-to-date overview and future perspectives on CRN management in IBD. Advances in endoscopic surveillance and resection techniques have resulted in a shift towards endoscopic management of neoplastic lesions in place of surgery. Endoscopic treatment is recommended for all CRN if complete resection is feasible. Standard [cold snare] polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection should be performed depending on lesion complexity [size, delineation, morphology, surface architecture, submucosal fibrosis/invasion] to maximise the likelihood of complete resection. If complete resection is not feasible, surgical treatment options should be discussed by a multidisciplinary team. Whereas [sub]total and proctocolectomy play an important role in management of endoscopically unresectable CRN, partial colectomy may be considered in a subgroup of patients in endoscopic remission with limited disease extent without other CRN risk factors. High synchronous and metachronous CRN rates warrant careful mucosal visualisation with shortened intervals for at least 5 years after treatment of CRN.

This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines.

Background and aims: It is uncertain whether ulcerative colitis leads to accumulated bowel damage on cross-sectional image. We aimed to characterise bowel damage in patients with ulcerative colitis using magnetic resonance imaging [MRI], and to determine its relation with duration of disease and the impact on patients' quality of life.

Methods: In this prospective study, patients with ulcerative colitis [UC] in endoscopic remission underwent MRI without bowel cleansing, and completed quality-of-life questionnaires. Participants' magnetic resonance findings were analysed considering normal values and thresholds determined in controls with no history of inflammatory bowel disease [n=40], and in patients with Crohn's disease with no history of colonic involvement [n = 12]. Subjects with UC were stratified according to disease duration [< 7 years vs 7‒14 years vs > 14 years].

Results: We analysed 41 subjects with ulcerative colitis [20 women; Mayo endoscopic subscore 0 in 38 [92.7%] and 1 in three [7.3%]]. Paired segment-by-segment comparison of magnetic resonance findings in colonic segments documented as being affected by ulcerative colitis versus controls showed that patients with ulcerative colitis had decreased cross-sectional area [p ≤ 0.0034] and perimeter [p ≤ 0.0005] and increased wall thickness [p = 0.026] in all segments. Colon damage, defined as wall thickness ≥ 3 mm, was seen in 22 [53.7%] patients. Colon damage was not associated with disease duration or quality of life.

Conclusions: Morphological abnormalities in the colon were highly prevalent in patients with ulcerative colitis in the absence of inflammation. Structural bowel damage was not associated with disease duration or quality of life.

Background and aims: Pan-enteric capsule endoscopy (PillCam Crohn's capsule [PCC]) is a useful tool in diagnosing and monitoring Crohn's disease [CD]. Eliakim score [ES] reliability and its strong correlation to Lewis score [LS] and to inflammatory biomarkers have been previously demonstrated using PCC in quiescent CD. We aimed to examine ES performance in active CD and its responsiveness to clinical/biochemical change over time.

Methods: Patients with CD who have started biologics were included, and were prospectively followed based on clinical visits, biomarkers, and PCC at baseline, after 14 and 52 weeks. Crohn's disease activity index [CDAI], C-reactive protein [CRP], and faecal calprotectin [FC] levels were determined, and LS and ES were calculated [independently reviewed by two experienced readers]. Inter-class classification [ICC], Spearman's baseline correlation, and repeated-measures correlation [RMC] analyses were performed.

Results: Seventy-four patients were included (age: 30.5 [range 23.3-45.0] years old, male 50%). In total, 142 PCCs were read [baseline, 62; week 14, 58; week 52, 22]. Inter-rater agreement was high for both LS and ES (ICC: 0.872 [p < 0.001] and 0.925 [<0.001], respectively). Baseline correlations between FC&ES [r = 0.509 [p < 0.001]) and FC&LS (r = 0.467 [p < 0.001]) were comparable [p = 0.56]. RMCs between the inflammatory biomarkers and ES were higher than between the former and LS (Reader 1: CRP r = 0.306 vs r = 0.138 [p = 0.057], FC r = 0.479 vs r = 0.297 [p = 0.034]; Reader 2 CRP r = 0.376 vs r = 0.204 [p = 0.035], FC r = 0.549 vs r = 0.412 [p = 0.075]). Moreover, ES was better correlated to CDAI than LS [p = 0.036].

Conclusions: ES is a reliable scoring system in assessing pan-enteric mucosal inflammation in active CD, and might have a better responsiveness to clinical/biochemical change over time compared to LS.

Background and aims: Crohn's disease [CD] is characterised by the expansion of mesenteric adipose tissue [MAT], named creeping fat [CF], which seems to be directly related to disease activity. Adipose-stem cells [ASCs] isolated from the CF of patients with CD are extremely pro-inflammatory, which persists during disease remission. We hypothesised that the dysfunctional ASCs in CD accumulate epigenetic modifications triggered by the inflammatory environment, that could serve as molecular markers.

Methods: Genome-wide DNA methylome and transcriptome profiling were performed in ASCs isolated from MAT biopsies of patients with active and inactive disease and from non-Crohn's disease patients [non-CD]. A validation cohort was used to test the main candidate genes via quantitative polymerase chain reaction in other fat depots and immune cells.

Results: We found differences in DNA methylation and gene expression between ASCs isolated from patients with CD and from non-CD subjects, but we found no differences related to disease activity. Pathway enrichment analysis revealed that oxidative stress and immune response were significantly enriched in active CD, and integration analysis identified MAB21L2, a cell fate-determining gene, as the most affected gene in CD. Validation analysis confirmed the elevated gene expression of MAB21L2 in MAT and in adipose tissue macrophages in active CD. We also found a strong association between expression of the calcium channel subunit gene CACNA1H and disease remission, as CACNA1H expression was higher in ASCs and MAT from patients with inactive CD, and correlates negatively with C-reactive protein in peripheral blood mononuclear cells.

Conclusion: We identified a potential gene signature of CD in ASCs obtained from MAT. Integration analysis highlighted two novel genes demonstrating a negative correlation between promoter DNA methylation and transcription: one linked to ASCs in CD [MAB21L2] and the other [CACNA1H] related to disease remission.