Rimola, Jordi

In participants with Crohn disease (CD), an abbreviated MR enterography (MRE) protocol demonstrated similar interreader agreement to contrast-enhanced MRE and high intrareader concordance for detecting active CD and related complications.

Abstract Background and Aims Intestinal ultrasound (IUS) is increasingly used to monitor treatment efficacy in inflammatory bowel disease (IBD) trials. However, standardized definitions for response, remission, and optimal assessment timing remain undefined. An international expert consensus meeting was held to establish IUS endpoints for clinical trials. Methods A panel of 35 international gastroenterologists and radiologists participated in a modified Delphi process, reviewing the literature and developing consensus statements. Agreement was defined as at least 75% consensus. Results Consensus was reached on 150 statements across four domains: general IBD (30 statements), luminal Crohn’s disease (CD) (43), perianal CD (51), and ulcerative colitis (UC) (26). For luminal CD and UC, ultrasound response was defined by: (1) a ≥25% reduction in bowel wall thickness (BWT) from baseline, or (2) multifactorial improvement, combining BWT reduction with ≥1 grade decrease in color Doppler signal (CDS) or another IUS parameter. Assessments were set at weeks 4-8 for the colon and week 12 for the terminal ileum. Ultrasound remission in luminal CD was defined as: (1) BWT normalization (≤3 mm) or (2) normalization of multiple parameters, including BWT, CDS, and all other IUS parameters. Similar remission criteria were proposed for UC, but the sigmoid BWT normal range (3-4 mm) remained uncertain. The bowel ultrasound score (BUSS) for CD and the Milan ultrasound criteria (MUC) for UC were supported as standardized scoring systems for trials. Conclusion This consensus provides standardized IUS definitions to enhance consistency in IBD trials, supporting the integration of IUS in future research.

This consensus by the Society of Abdominal Radiology Inflammatory Bowel Disease Disease Focused Panel provides an updated imaging-based definition of small bowel Crohn disease stricture for CT and MR enterography.

Abstract Background Progress in clinical trials and drug development for paediatric perianal fistulising CD (pfCD) depends upon accurate, reproducible imaging to assess disease activity and measure treatment response. We evaluated the inter- and intra-rater reliability of existing radiologic disease activity indices and anatomical classification systems previously identified as appropriate for assessment of paediatric pfCD.1 Methods A retrospective cohort (N=50) of magnetic resonance imaging (MRI) exams representing a full spectrum of paediatric (<18 years) perianal CD severity was selected by a single expert paediatric radiologist. Methods described by Zou2 were used to estimate sample size. Three separate radiologists (2 paediatric) blinded to clinical information assessed pfCD in the exams using the Magnetic Resonance Novel Index for Fistula Imaging in CD (MAGNIFI-CD), Van Assche Index (VAI), modified VAI (mVAI), Paediatric MRI based Perianal Crohn’s disease (PEMPAC) index, a visual analogue scale (VAS) of overall pfCD disease severity (range, 0-100 mm), as well as with the Park’s and St. James University Hospital anatomic classification systems. Two radiologists read all exams twice, separated by 2 weeks, and 1 radiologist read the exams once (250 total reads). Intra- and inter-rater reliability was evaluated using intraclass correlation coefficients (ICC; equivalent to weighted kappa). Precision of the ICC estimates was quantified with 95% confidence intervals (CIs) obtained using clustered bootstrapping. Degree of reliability was interpreted with benchmarks proposed by Landis and Koch3. Results Median age of children was 13.5 years (IQR 11.4-16.1), and 64% were male. Median Paediatric Crohn’s Disease Activity Index score at time of imaging was 17.5 (IQR 10-32.5). Substantial (ICC>0.61) inter-rater reliability was observed for MAGNIFI-CD, VAI, and mVAI (Table 1), with the highest ICCs observed for the mVAI (0.72 [0.6 to 0.79]). Moderate (ICC>0.41) inter-rater reliability was observed for PEMPAC, St. James University Hospital classification, and the VAS, and fair (ICC>0.21) inter-rater reliability was observed for Parks classification. Intra-rater reliability was nearly perfect (ICC>0.81) for the VAS, and substantial for all indices except for Parks classification, which had moderate (0.60 [0.44 to 0.75]) intra-rater reliability (Table 1). Conclusion Most existing multi-item MRI-based disease activity indices and the St. James Hospital classification were reliable for the assessment of paediatric pfCD in our cohort. Our preliminary results suggest that the disease activity indices may have utility to measure treatment effect in paediatric pfCD clinical trials. References 1.Crowley E, Ma C, Guizzetti L, Zou G, Lewindon PJ, Gee MS, et al. Recommendations for Standardizing MRI-based Evaluation of Perianal Fistulizing Disease Activity in Pediatric Crohn's Disease Clinical Trials. Inflamm Bowel Dis. 2024;30(3):357-69. 2.Zou GY. Sample size formulas for estimating intraclass correlation coefficients with precision and assurance. Statistics in Medicine. 2012;31(29):3972-398 3.Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159-74.

Summary Background Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross‐sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri‐enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed. Aims To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition. Methods We searched four databases up to 6 January 2024. Two‐stage screening was done in duplicate. We assessed risk of bias using QUADAS‐2. Results There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation. Conclusions This systematic review is the first step for a structured program to develop a stricture IUS index for CD.

Abstract Background Perianal fistulas and abscesses occur commonly as complications of pediatric Crohn’s disease (CD). A validated imaging assessment tool for quantification of perianal disease severity and activity is needed to evaluate treatment response. We aimed to identify magnetic resonance imaging (MRI)-based measures of perianal fistulizing disease activity and study design features appropriate for pediatric patients. Methods Seventy-nine statements relevant to MRI-based assessment of pediatric perianal fistulizing CD activity and clinical trial design were generated from literature review and expert opinion. Statement appropriateness was rated by a panel (N = 15) of gastroenterologists, radiologists, and surgeons using modified RAND/University of California Los Angeles appropriateness methodology. Results The modified Van Assche Index (mVAI) and the Magnetic Resonance Novel Index for Fistula Imaging in CD (MAGNIFI-CD) were considered appropriate instruments for use in pediatric perianal fistulizing disease clinical trials. Although there was concern regarding the use of intravascular contrast material in pediatric patients, its use in clinical trials was considered appropriate. A clinically evident fistula tract and radiologic disease defined as at least 1 fistula or abscess on pelvic MRI were considered appropriate trial inclusion criteria. A coprimary clinical and radiologic end point and inclusion of a patient-reported outcome were also considered appropriate. Conclusion Outcomes of treatment of perianal fistulizing disease in children must include MRI. Existing multi-item measures, specifically the mVAI and MAGNIFI-CD, can be adapted and used for children. Further research to assess the operating properties of the indices when used in a pediatric patient population is ongoing.

Abstract Background Computed tomography enterography (CTE) is frequently used to assess stricturing Crohn’s disease (CD). However, the reliability of CTE items used for assessment has not been established and there is no validated radiologic stricture severity index. Methods We conducted a retrospective study of 43 patients with symptomatic, terminal ileal stricturing CD. Four radiologists assessed a comprehensive list of pre-defined radiologic items potentially associated with stricture severity in 48 CTE scans in two separate rounds in random order. Reliability was quantified using the intraclass correlation coefficient (ICC). Items with at least moderate (ICC≥0.41) inter-rater reliability that were correlated with a visual analogue scale of overall stricture severity were candidate items for the development of a CTE stricture index. Results Inter-rater reliability was almost perfect for assessment of luminal diameter of pre-stenotic dilation (ICC 0.817 [95% confidence interval 0.703, 0.878]), substantial for stricture length (ICC 0.628 [0.419, 0.797]), and moderate for stricture wall thickness (0.482 [0.330, 0.601]). Intra-rater reliability was almost perfect (ICC ≥ 0.850) for all three items. A stricture severity index was derived and was well calibrated (optimism-adjusted calibration slope = 1.009), with scores calculated as the sum of stricture length (cm) + luminal diameter of pre-stenotic dilation (mm) + 5 x stricture wall thickness (mm). Conclusion Stricture length, prestenotic dilation, and stricture wall thickness can be reliably assessed, and are component items for a novel CTE stricture index (CTE-SI) of stricture severity for CD-related terminal ileal strictures. Additional external index validation for clinical and research contexts is required.

Abstract Background Small bowel fibrostenotic strictures are common in patients with Crohn’s disease (CD). No global consensus recommendations on definitions, diagnosis and clinical management are available. Methods Several systematic reviews followed by a RAND/University of California Los Angeles appropriateness study on the definitions, diagnosis and clinical management of fibrostenosing CD in clinical practice were performed. A panel of 28 global experts and a patient representative were convened. They assessed a total of 152 candidate items. The items were subsequently evaluated for appropriateness. Results No accurate predictive biomarkers are available for naïve or anastomotic fibrostenosing strictures. Accurate diagnosis of fibrostenosing CD requires cross-sectional imaging which should evaluate bowel wall thickness, luminal narrowing and prestenotic dilatation. A potential inflammatory component should be assessed. Abdominal cross-sectional imaging was considered necessary prior to any treatment decision. The panel proposed an approach to medical, endoscopic, and surgical therapies (Figure 1 and Table 1). Technical characteristics for endoscopic balloon dilation and follow up strategies after successful dilation therapy were identified. Appropriateness, types and performance of different surgical approaches in various settings were evaluated. Conclusion This global consensus provides clinical guidance for the diagnostic and therapeutic management of patients with fibrostenotic CD.

Patients with Crohn’s disease commonly develop ileal and less commonly colonic strictures, containing various degrees of inflammation and fibrosis. While predominantly inflammatory strictures may benefit from a medical anti-inflammatory treatment, predominantly fibrotic strictures currently require endoscopic balloon dilation or surgery. Therefore, differentiation of the main components of a stricturing lesion is key for defining the therapeutic management. The role of endoscopy to diagnose the nature of strictures is limited by the superficial inspection of the intestinal mucosa, the lack of depth of mucosal biopsies and by the risk of sampling error due to a heterogeneous distribution of inflammation and fibrosis within a stricturing lesion. These limitations may be in part overcome by cross-sectional imaging techniques such as ultrasound, CT and MRI, allowing for a full thickness evaluation of the bowel wall and associated abnormalities. This systematic literature review provides a comprehensive summary of currently used radiologic definitions of strictures. It discusses, by assessing only manuscripts with histopathology as a gold standard, the accuracy for diagnosis of the respective modalities as well as their capability to characterise strictures in terms of inflammation and fibrosis. Definitions for strictures on cross-sectional imaging are heterogeneous; however, accuracy for stricture diagnosis is very high. Although conventional cross-sectional imaging techniques have been reported to distinguish inflammation from fibrosis and grade their severity, they are not sufficiently accurate for use in routine clinical practice. Finally, we present recent consensus recommendations and highlight experimental techniques that may overcome the limitations of current technologies.