Small Bowel Crohn's Disease Research Articles

Local Assessment and Small Bowel Crohn’s Disease Severity Scoring using AI

We present a machine learning and computer vision approach for a localized, automated, and standardized scoring of Crohn's disease (CD) severity in the small bowel, overcoming the current limitations of manual measurements CT enterography (CTE) imaging and qualitative assessments, while also considering the complex anatomy and distribution of the disease. Two radiologists introduced a severity score and evaluated disease severity at 7.5mm intervals along the curved planar reconstruction of the distal and terminal ileum using 236 CTE scans. A hybrid model, combining deep-learning, 3-D CNN, and Random Forest model, was developed to classify disease severity at each mini-segment. Precision, sensitivity, weighted Cohen's score, and accuracy were evaluated on a 20% hold-out test set. The hybrid model achieved precision and sensitivity ranging from 42.4% to 84.1% for various severity categories (normal, mild, moderate, and severe) on the test set. The model's Cohen's score (κ=0.83) and accuracy (70.7%) were comparable to the inter-observer agreement between experienced radiologists (κ=0.87, accuracy = 76.3%). The model accurately predicted disease length, correlated with radiologist-reported disease length (r=0.83), and accurately identified the portion of total ileum containing moderate-to-severe disease with an accuracy of 91.51%. The proposed automated hybrid model offers a standardized, reproducible, and quantitative local assessment of small bowel CD severity and demonstrates its value in CD severity assessment.

Artificial Intelligence for Quantifying Cumulative Small Bowel Disease Severity on CT-Enterography in Crohn's Disease.

Assessing the cumulative degree of bowel injury in ileal Crohn's disease (CD) is difficult. We aimed to develop machine learning (ML) methodologies for automated estimation of cumulative ileal injury on computed tomography-enterography (CTE) to help predict future bowel surgery. Adults with ileal CD using biologic therapy at a tertiary care center underwent ML analysis of CTE scans. Two fellowship-trained radiologists graded bowel injury severity at granular spatial increments along the ileum (1 cm), called mini-segments. ML segmentation methods were trained on radiologist grading with predicted severity and then spatially mapped to the ileum. Cumulative injury was calculated as the sum (S-CIDSS) and mean of severity grades along the ileum. Multivariate models of future small bowel resection were compared with cumulative ileum injury metrics and traditional bowel measures, adjusting for laboratory values, medications, and prior surgery at the time of CTE. In 229 CTE scans, 8,424 mini-segments underwent analysis. Agreement between ML and radiologists injury grading was strong (κ = 0.80, 95% confidence interval 0.79-0.81) and similar to inter-radiologist agreement (κ = 0.87, 95% confidence interval 0.85-0.88). S-CIDSS (46.6 vs 30.4, P = 0.0007) and mean cumulative injury grade scores (1.80 vs 1.42, P < 0.0001) were greater in CD biologic users that went to future surgery. Models using cumulative spatial metrics (area under the curve = 0.76) outperformed models using conventional bowel measures, laboratory values, and medical history (area under the curve = 0.62) for predicting future surgery in biologic users. Automated cumulative ileal injury scores show promise for improving prediction of outcomes in small bowel CD. Beyond replicating expert judgment, spatial enterography analysis can augment the personalization of bowel assessment in CD.

Risk factors for surgery in stricturing small bowel Crohn's disease: A retrospective cohort study from the GETAID pédiatrique.

Previous studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery. Pediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals. Patient characteristics were compared by surgical outcome multivariable Cox regression. Fifty-six patients (61% boys) aged 12.2 ± 2.7 years at diagnosis of CD were included. Median duration of CD before diagnosis of stricture was11.7 months (interquartile range [IQR]: 25-75: 1.2-29.9). Nineteen (34%) patients had stricturing phenotype (B2) at baseline. Treatments received before stricture diagnosis includedMODULEN-IBD (n = 31), corticosteroids (n = 35), antibiotics (n = 10), anti-TNF (n = 27), immunosuppressants (n = 28). Thirty-six patients (64%) required surgery, within 4.8 months (IQR: 25-75: 1.8-17.3) after stricture diagnosis. Parameters associated with surgical resection wereantibiotic exposure before stricture diagnosis (adjusted odds ratio [aOR]: 15.62 [3.35-72.73], p = 0.0005), Crohn's disease obstructive symptoms score (CDOS) > 4 (aOR: 3.04 [1.15-8.03], p = 0.02) and dilation proximal to stricture >28 mm (aOR: 3.62 [1.17-11.20], p = 0.03). In this study, antibiotic treatment before stricture diagnosis, intensity of obstructive symptoms, and diameter of dilation proximal to small bowel stricture on MRE were associated with risk for surgical resection.

Surgical management of duodenal crohn's disease.

Operative options for duodenal Crohn's disease include bypass, stricturoplasty, or resection. What factors are associated with operation selection and whether differences exist in outcomes is unknown. Patients with duodenal Crohn's disease requiring operative intervention across a multi-state health system were identified. Patient and operative characteristics, short-term surgical outcomes, and the need for future endoscopic or surgical management of duodenal Crohn's disease were analyzed. 40 patients underwent bypass (n = 26), stricturoplasty (n = 8), or resection (n = 6). Median age of diagnosis of Crohn's disease was 23.5years, and over half of the patients had undergone prior surgery for CD. Operation type varied by the most proximal extent of duodenal involvement. Patients with proximal duodenal CD underwent bypass operations more commonly than those with mid- or distal duodenal disease (p = 0.03). Patients who underwent duodenal stricturoplasty more often required concomitant operations for other sites of small bowel or colonic CD (63%) compared to those who underwent bypass (39%) or resection (33%). No patients required subsequent surgery for duodenal CD at a median follow-up of 2.8years, but two patients required endoscopic dilation (n = 1 after stricturoplasty, n = 1 after resection). Patients who require surgery for duodenal Crohn's disease appear to have an aggressive Crohn's disease phenotype, represented by a younger age of diagnosis and a high rate of prior resection for Crohn's disease. Choice of operation varied by proximal extent of duodenal Crohn's disease.

Characterization of Th17 tissue-resident memory cells in non-inflamed intestinal tissue of Crohn's disease patients

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.

Fecal calprotectin as an inflammatory biomarker in small bowel Crohn disease.

Small bowel capsule endoscopy (SBCE) is an essential tool for evaluation of small bowel (SB) Crohn disease (CD). Fecal calprotectin (FC) represents an important biomarker of intestinal inflammation, widely used in ulcerative colitis and CD. Our aim was to evaluate the role of FC for diagnosing inflammatory activity in patients with isolated SB CD and how it correlates with SBCE findings. This is a retrospective study conducted in a tertiary inflammatory bowel disease referral center that included patients with SB CD who underwent SBCE between January 2017 and February 2023. FC value was obtained from the closest stool examination to SBCE. One hundred ninety-six patients were included: 123 were women (63%) with a mean age of 44.2 years. In the SBCE, 127 (65%) patients had a Lewis Score ≥135 and, among the 94 patients with FC >200 μg/g, 23 had LS <135, 36 had LS between 135 and 790, and 35 had LS ≥790. FC levels were predictive of endoscopic lesions in SBCE, with significant correlation between FC level and total LS (Pearson correlation coefficient 0.43, P<.001). The sensitivity and specificity were calculated for each cut-off value being respectively 78% and 45% for FC = 100 μg/g, 69% and 59% for FC = 150 μg/g and 67% and 67% for FC = 200 μg/g. FC showed moderate correlation with endoscopic findings in SBCE in SB CD. It is, therefore, a reasonable marker for predicting significant inflammatory lesions in SBCE; however, none of the cut-off had a high sensitivity or specificity.

NON-CASEATING GRANULOMAS ARE ASSOCIATED WITH STRICTURING CROHN’S DISEASE AND THEIR NUMBER AND SIZE ARE INCREASED IN THE MUSCULARIS PROPRIA OF STRICTURED COMPARED TO NON-STRICTURED INTESTINGAL SEGMENTS

Abstract BACKGROUND Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that progressively leads to fibrosis-induced narrowing of the intestinal lumen, bowel obstruction, and need for surgery. CD exhibits transmural inflammation manifested by immune cell infiltrates composed of multiple immune cell types spanning the entire gut wall. Non-caseating granulomas are a typical hallmark of up to 60% of CD patients. Scarce evidence indicates an association of granulomas with post-operative recurrence suggesting a role of granulomas in disease pathogenesis. Strikingly, while evidence exists from other granulomatous diseases, granulomas have not been linked with stricturing CD. METHODS A total of 348 H&amp;E stained sections from segments of small bowel CD surgical resection specimens were evaluated for non-caseating granulomas. Granulomas were defined by a trained inflammatory bowel disease pathologist as a cluster of ≥ 5 epithelioid histiocytes with or without the presence of multinucleated giant cells. CD segments were classified as non-involved (CDni), inflamed non-strictured (CDi), and strictured (CDs) to confirm whether histopathological presence of granulomas correlates with stricturing CD. Paired sets were available in 150 segments of 50 CD patients and analyzed further to determine whether granuloma number, location within the intestinal wall, or size of granulomas correlates with stricturing CD. RESULTS Granulomas were present in 20% of all CD tissue segments. 28% of CDs, 9% of CDi, and 5% of CDni segments were found to have granulomas and the fraction of segments containing granulomas was significantly higher in CDs compared to CDni and CDi (P&amp;lt;0.0001). The paired patient sections resembled the larger dataset with 16% of patients having granulomas in at least one of the three segments (16% of CDs, 8% of CDi, and 0% CDni). Further comparing the CDi and CDs sections in this subset of patients, we found that neither the total number nor the average size of granulomas were significantly different between CDs versus CDi tissue sections. Analysis of the layers of the intestinal wall revealed that the number (P&amp;lt;0.05) and average size (P&amp;lt;0.01) of granulomas were significantly increased in the muscularis propria of CDs versus CDi sections. There were no significant changes in number or average size in the mucosal or submucosal layers of the intestinal wall. CONCLUSION Together these data indicate that non-caseating granulomas are associated with stricturing CD and these granulomas are increased in number and size in the muscularis propria of strictured versus inflamed tissues from the same patient, but not other intestinal layers. This suggests a potential link between granulomas and the pathogenesis of stricturing CD.

P314 Serum levels of Leucin-Rich α2 Glycoprotein predicts endoscopic mucosal healing of Crohn's disease

Abstract Background It has been suggested that serum levels of Leucin-Rich α2 Glycoprotein (LRG) correlate with disease activity of Crohn’s disease (CD). Small bowel capsule endoscopy (SBCE) can be performed together with ileo-colonoscopy (ICS) at the same day to assess mucosal healing in patients with clinically quiescent CD. The aim of this study was to determine the usefulness and a cut off value of LRG that indicate mucosal healing in patients with CD. Methods Clinically quiescent CD (CDAI&amp;lt;150) patients without perianal lesions received SBCE and ICS at the same day between July 2021 and August 2023 were included. Serum levels of CRP and LRG were measured in the time frame of median 23 days before or after the exam (IQR 14, 43). Endoscopic findings were evaluated by modified simple endoscopic score for CD (mSES-CD) composed of 3 variables (size of ulcers, proportion of ulcer surface and disease affected surface) of each 7 segments (jejunum, upper ileum, lower ileum, right colon, transvers colon, left colon and rectum). Mucosal healing was defined by the mSES-CD score of 0. Results Among 51 CD patients enrolled, 88.2% were male with the median age of 20 (IQR 22, 35) and the disease duration of 69 months (IQR 23, 35). History of small or large intestinal resection was found in 15 (29.4%) and 14 (27.4%) cases, respectively. The median CRP and LRG were 0.1 mg/dL (IQR 0.1, 0.4), and 12.3 μg/mL (IQR 8.8, 18.3), respectively. The median mSES-CD was 3 (0,6%), and 20 (39.2%) cases were score 0. There was a high correlation between LRG and CRP levels (p&amp;lt;0.0001, r=0.78), and the cut of value of LRG that indicates negative CRP (&amp;lt; 0.4 mg/dL) was 16.6 μg/mL; area under the curve (AUC) of ROC analysis 0.91, sensitivity 90.0%, specificity 84.8%. In addition, a significant correlation between LRG levels and mSES-CD was found (p&amp;lt; 0.0001, r= 0.65), while no correlation between CRP and mSES-CD (p=0.72, r= 0.27). The cut off value of LRG that indicates mucosal healing was 10.2 μg/mL (AUC 0.915, sensitivity 89.7%, specificity 85.7%) with positive predictive value of 92.9% and negative predictive value of 80.0%. Conclusion LRG can be a reasonable biomarker to monitor disease status of CD especially in clinically quiescent patients with small bowel CD. LRG values less than 10.2 μg/mL indicates endoscopic mucosal healing in patients with CD.

P977 Combined F18-FDG-PET-MRI-imaging can predict clinical remission in small bowel Crohn’s disease

Abstract Background Diagnostics and follow-up of small bowel Crohn’s disease (CD) can be difficult. Combined PET-MRI enterography (MRE) can be used to evaluate intestinal inflammation. Lack of standardized methods and diagnostic thresholds has limited its clinical use in diagnostics and monitoring of small bowel CD. There is no previous data on the use of PET-MRI in follow-up of small bowel CD. Methods 34 patients with suspected CD in small bowel were recruited from Turku University Hospital’s outpatient clinic. A static PET-MRE was obtained with [18F]-FDG (fluorodeoxyglucose) tracer. CD diagnosis was confirmed with small bowel capsule endoscopy. Patients diagnosed with CD were started with appropriate treatment chosen by clinicians. Endoscopic findings including histopathology, laboratory results (Hb, CRP, serum albumin (Alb) and fecal calprotectin (FC)) and medication data were collected. Patients diagnosed with CD (N=16) went through control PET-MRE median 105 days after initial imaging. Highest SUVmax (standardized uptake value) in small intestine was measured and MRE-images with diffusion weighted imaging (DWI) were analyzed by an experienced abdominal radiologist and severity of inflammation was graded from 1-4. Hb, CRP, Alb and FC were measured from the patients at the time of imaging. Results Median SUVmax was significantly lower after three months of medical treatment (3.2 vs. 2.1) (p=0.016). FC was significantly lower at the time of control imaging (p=0.030) (median 725 ug/g vs. 141 ug/g). 10 patients had FC &amp;lt;250 ug/g at the time of control imaging. Using this as a cut- off for clinical response, ROC-curve showed AUC 0.73 for SUVmax and AUC 0.65 for MRE-grading. Sensitivity and specificity were highest at SUVmax 2.4 (83% and 80%). Conclusion Decreased SUVmax measured after starting CD medication seems to predict clinical remission and a cut-off level 2.4 could be used in diagnostics. Diagnostic yield was higher for SUVmax compared to MRE-grading. Here we have shown for the first time that PET-MRE can be used for disease activity monitoring in small bowel CD.

P315 Comparable un-passed patency capsule rates among Crohn’s disease patients during Clinical remission using different preparation protocols

Abstract Background Patency capsule (PC) ingestion has been proven to be a useful tool in assessing small-bowel patency before ingestion of capsule endoscope. However, false positive results of un-passed PC due to colonic hypomotility/constipation, may wrongfully preclude the use of CE in this population. Therefore, we aimed to evaluate the efficacy of intense bowel-preparation protocol before PC ingestion versus standard clear fluid-diet to reduce un-passed PC rates in patients with Crohn’s disease (CD) in clinical remission. Methods This was a bicenter cohort of adult patients (≥18 years-old) with small-bowel CD (L1/L3) in clinical remission, who underwent PC ingestion before CE procedure. Each center regularly follows a different preparation protocol. Patients in the intense-protocol group adhered to a low-residue diet followed by a clear fluid diet for 12 hours and fasting for 12 hours before ingestion. During capsule ingestion they were also given 10mg of Bisacodyl. Drinking and eating were resumed after 2- and 4-hours post-ingestion, respectively. Clear fluids were consumed by the control group. Propensity-score matching (PSM) in a 1:1.75 ratio was performed with adjustment for age, sex, CD-duration&amp;gt;1year and B2/B3 disease-phenotype, with regards to the intense preparation-protocol. The primary outcome was defined as un-passed PC (i.e., the absence of PC excretion in the stool or its presence in the abdomen by abdominal X-ray within 30 hours from ingestion). Results 269 patients were included (intense group-79, control group-190). The cohort following the PSM comprised of 212 patients (intense group-77, control group-135). Current biologic use was less common in the intense-protocol group compared to the controls (37.7% vs. 61.2%, p=0.001). Un-passed PC rates were 13.0% (10/77 patients) vs. 19.3% (26/135 patients) in the intense-protocol and the control groups, respectively (p=0.242). On univariable analysis longer disease-duration (OR 1.042, 95% CI 1.002-1.085, p=0.040) was the only variable to be associated with un-passed PC. Age≥40 was associated with increased risk for un-passed PC as well, however only borderline significance was achieved (OR 1.917, 95% CI 0.927-3.967, p=0.085). Upon multivariate logistic regression analysis, there was no clinico-demographic/disease-related variable that was independently associated with the probability for un-passed PC. Of 269 patients, there was a single subsequent CE retention in the control group, which has resolved spontaneously (0.4%). Conclusion Intense-preparation protocol based on low-residue diet and laxatives was not superior to clear fluid diet alone, for reducing the rates of un-passed PC and for increasing successful patency test of small-bowel, among CD patients in clinical remission.

P515 Exclusive enteral nutrition downstages complicated Crohn’s disease prior to surgical resection: A feasibility study

Abstract Background Exclusive enteral nutrition (EEN, oral or enteral liquid feeds only) is an established first-line therapy to induce remission in Crohn’s disease (CD) in children, but not in adults where low tolerance has been reported. Recently, smaller studies have suggested advantages of EEN in preoperative optimisation in adults. We hypothesise that in this setting, EEN is feasible and is associated with improved inflammatory and nutritional markers. Methods Consecutive patients with small bowel or ileocolic Crohns disease, who started preoperative EEN at two large IBD centres 2020-2023 were retrospectively studied. EEN was part of a 4-6week preoperative optimisation pathway. Outcomes were compliance and serum albumin, c-reactive protein and body weight, respectively. Medians (range) &amp; Wilcoxon tests used. Results Thirty-two patients started EEN for stricturing (n=10) or penetrating disease (n=14). Six patients (19%) did not tolerate EEN and received parenteral nutrition (n=2) or reverted to normal diet (n=4), while 26 patients (81%) completed EEN until surgery. This group received EEN during 38 (17-70) days. C-reactive protein concentrations decreased from 8.5 (1-157) to 3 (1-96) mg/L (p = 0.0051), and albumin levels increased from 33.5 (27-44) to 38 (26-42) g/L (p&amp;lt; 0.001), while body weight did not change, from 67 (48.5-107) to 66.6 (48.5-105.7) kg (p = 0.25). 21 (81%) EEN patients underwent minimally invasive surgery, 22 (85%) had a primary anastomosis and 4 a stoma. Median postoperative length of stay was 4 (2-11) days. One patient with a severe complication, no one with an anastomotic leakage. Conclusion EEN was well tolerated in this cohort of patients undergoing surgery for complicated CD. EEN was associated with improved systemic inflammation, a maintained nutritional status, and favourable postoperative outcomes despite the complexity of disease in this group of patients. These results align with previous studies that have shown the effectiveness of EEN in reducing disease activity and promoting mucosal healing in CD patients.By reducing inflammation and uphold nutritional status, EEN might help to create a more favourable surgical environment, potentially leading to better outcomes and decreased postoperative complications.

P491 Clinical application of ICCE criteria for suspected Crohn’s disease undergoing small bowel capsule endoscopy

Abstract Background Small-bowel capsule endoscopy (SBCE) is the primary diagnostic modality for exploring the small bowel (SB) in patients with suspected Crohn’s disease (CD) and inconclusive ileocolonoscopy findings, provided there are no obstructive symptoms or known bowel strictures. In 2005, the International Conference on Capsule Endoscopy (ICCE) established preselection criteria for these patients (Figure 1). SBCE is indicated if one criterion from group A is met, along with any other from the remaining groups (B/C/D). The aim of this study is to evaluate the diagnostic accuracy of ICCE criteria in unselected cases of suspected small bowel CD (SBCD) explored with SBCE. Methods An observational, single-center, retrospective study was conducted, including all SBCE performed in patients with suspected CD between January 2020 and August 2023. Demographic and clinical data, inflammatory markers, SBCE findings, confirmed CD diagnosis and indication to therapy were analyzed. Results A total of 46 patients were included (67.4% females, median age 43 years, IQR 32-60). SBCE identified lesions suggestive of CD based on Mow's criteria in 23.9% of patients (n=11). These findings led to a CD diagnosis in all cases, with subsequent initiation of immunomodulators or biologic therapy. In the study population, 35 (71.4%) patients had 2 ICCE criteria (A+B/C/D). The percentage of patients with ≥2 criteria did not differ significantly between those with and without CD (90.9% vs. 71.4%, p=0.18). However, overall ungrouped ICCE criteria showed a significant correlation with confirmed CD (OR 1.56, 95%CI 1.03-2.36). The creation of a model using 4 ungrouped ICCE criteria significantly improved CD prediction accuracy (area under the ROC curve 0.77, sensitivity 91%, specificity 51.4%). Patients with 4 ungrouped ICCE criteria had a higher likelihood of having confirmed CD (90 vs 48%, p=0.02). Conclusion In our patient cohort, the existing ICCE criteria seem insufficient for effectively identifying patients with a higher probability of SBCD. Our findings suggest that adopting a cut-off of 4 ungrouped ICCE criteria would increase the diagnostic accuracy of SBCE for SBCD.

P243 Multi-modality intestinal ultrasound is accurate and reproducible to distinguish inflammatory from chronic fibrotic strictures in Crohn’s disease – results from the STRICTURE study

Abstract Background In 30%-50% of patients with Crohn’s disease (CD) stenotic complications occur1. There is currently no imaging modality to identify stricture composition, which would allow early targeted (anti-inflammatory vs surgical) treatment. Intestinal ultrasound (IUS) and advanced modalities (contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE)) have the potential for transmural disease evaluation. The STRICTURE study investigated whether (advanced) IUS techniques could distinguish between inflammatory- (IP) and non-inflammatory phenotypes (non-IP) of stricturing CD. Methods In this prospective, cross-sectional study consecutive patients with small bowel CD undergoing surgery were included. Patients were eligible if they had a non-passable stricture during endoscopy in the small bowel and/or a stricture at cross-sectional imaging (IUS or MRE)2. Prior to surgery, IUS, CEUS and SWE were performed. Two blinded sonographers scored the cine-loops for IUS and CEUS. After surgery, histological slides were retrieved and location matched with IUS. Two blinded pathologists scored for inflammation, adipocytes and fibrosis. Subsequently the predominant phenotype was determined as: [1] inflammatory (IP; Nancy score 4 with no marked fibrosis/adipocytes), [2] fibrotic (FP; structural changes due to marked fibrosis/adipocytes3) or [3] mixed phenotype (MP; inflammatory and fibrotic aspects but no predominant phenotype). FP and MP were both classified as non-IP. Results A total of 36 patients (age: 42±18 years) with a mean BWT of 6.7±1.7 mm were included. Median time between IUS and surgery was 14 [3-50] days. A total of 7 patients had an IP, 18 a FP and 11 a MP. For the conventional IUS parameters, loss of wall layer stratification (WLS) was more frequently found in IP strictures(OR: 7.87 [1.24-50.00], p=0.029). For CEUS, most parameters were significantly higher in IP versus non-IP (Table 1) and at multi-variable logistic regression Wash-in area under the curve remained the only accurate parameter to distinguish IP from non-IP (OR:1.55 [1.03-2.34], p=0.035) [Figure 1]. SWE inversely correlated with CEUS (Table 1, Figure 1) but did not differentiate between IP and non-IP (33.30 kPa vs 43.49 kPa, p=0.48). The agreement for BWT and loss of WLS was good (ICC: 0.77, p&amp;lt;0.001) and moderate (κ: 0.56, p&amp;lt;0.001), respectively. For CEUS, the most accurate parameters had good to excellent agreement [Table 1]. Conclusion Loss of WLS and CEUS are accurate to distinguish an IP from a non-IP stricture in CD and CEUS inversely correlates with SWE. In addition to accuracy, reproducibility was high and multi-modality IUS could be of additional value in this specific population to select patients most suitable for anti-inflammatory treatment. Table 1 Figure 1

P405 Intestinal ultrasound measures are highly correlated with small bowel Lewis score among patients with active Crohn’s disease

Abstract Background Small-bowel assessment is of prime importance among patients with Crohn’s disease (CD). While small-bowel capsule endoscopy (SBCE) evaluates the extent of mucosal inflammation, intestinal ultrasound (IUS) provides a complementary information with regards to transmural disease involvement. We aimed to examine the correlation between SBCE and IUS, among patients with active CD, as well as sensitivity to therapeutic response during follow-up. Methods Patients with active small-bowel CD, who have been started on biologics, were included. Patients were prospectively followed with fecal calprotectin (FC), SBCE and IUS at baseline and after 14 and 52 weeks. Lewis score (LS), Limberg score (LI) and terminal ileum bowel-wall thickness (TIBWT) were documented for each patient. Response to treatment was defined as a 25%-reduction compared to the baseline measure of FC, LS, LI and TIBWT, while FC&amp;lt;150μg/mg, LS&amp;lt;135, LI&amp;lt;2 and TIBWT&amp;lt;3 mm, were defined as biochemical, endoscopic and ultrasonographic remission, respectively (week 0→week 14/ week 14 →week 52). Baseline correlations were obtained using the Spearman's correlation. Comparison between correlations were assessed using the Fisher's Z-transformation. Fisher's exact-test was performed to evaluate the correlation between the examined response/remission outcomes. Results Seventy-one patients were included (median age: 26 (22-43) years, male-49%). The median time between SBCE and IUS procedures was 3 (0-25) days. Baseline LS was well correlated with both TIBWT (r=0.6, p&amp;lt;0.001) and LI (r=0.6, p&amp;lt;0.001). Ultrasonographic remission was significantly correlated with both biochemical remission (FC and TIBWT [p=0.012], FC and LI [p=0.024]) and endoscopic remission (LS and TIBWT [p=0.035], LS and LI [0.013]), [Figure 1]. The baseline correlation between FC and LS (r=0.490, p&amp;lt;0.001) was numerically but not significantly higher than FC and BWT (r=0.386, p=0.002) or FC and LI (r=0.224, p=0.080) [p=0.500 and p=0.110, respectively]. No significant correlation was observed between FC and LS /TIBWT/LI response to treatment (p=0.347 p=0.261, p=0.864, respectively), while there was a trend regarding TIBWT and LS response to treatment correlation (p=0.052). Conclusion IUS measures are highly correlated with SBCE LS among patients with active CD, and provide an accurate and reliable assessment of disease activity during follow-up. Therefore, IUS may serve as a feasible and noninvasive tool in the monitoring and management of patients with CD.

Assessing quality of magnetic resonance enterography and its impact on disease assessment of ileal Crohn's disease.

Assessment of quality of magnetic resonance enterography (MRE) in small bowel Crohn's disease (CD) activity evaluation has received little attention. We assessed the impact of bowel distention and motion artifact on MRE activity indices in ileal CD. A cohort of patients who underwent contemporaneous MRE and colonoscopy for ileal CD assessment between 2014 and 2021 at 2 centers were audited. An abdominal radiologist blinded to clinical data reviewed each MRE, graded bowel distention and motion artifact upon a pre-specified 3-point scale and calculated the original magnetic resonance index of activity (MaRIA) and simplified MaRIA (sMaRIA), London index and CD MRE index (CDMI). Ileal endoscopic activity was graded via the Simplified Endoscopy Score for CD (SES-CD). The performance of MRE indices in discriminating active disease (SES-CD ≥3) stratified by MRE quality was measured by receiver operator characteristic analyses. One hundred and thirty-seven patients had MRE and colonoscopy within a median of 16 days (range, 0-30 days) with 63 (46%) exhibiting active disease (SES-CD ≥3). Forty-four MREs (32%) were deemed low quality due to motion artifact and/or moderate to poor distention. Low-quality MREs demonstrated reduced discriminative performance between ileal SES-CD ≥3 and MRE indices (MaRIA 0.838 vs. 0.634, sMaRIA 0.834 vs. 0.527, CDMI 0.850 vs. 0.595, London 0.748 vs. 0.511, P<0.05 for all). Individually the presence of any motion artifact markedly impacted the discriminative performance (e.g., sMaRIA area under the curve 0.544 vs. 0.814, P<0.05). Image quality parameters can significantly impact MRE disease activity interpretation. Quality metrics should be reported, enabling cautious interpretation in lower-quality studies.

Use of double-balloon endoscopy and an endoscopic scoring system to assess endoscopic remission in isolated small bowel Crohn's disease after treatment with infliximab.

It is unclear how clinical and endoscopic factors affect the attainment of endoscopic remission (ER) in patients with small bowel Crohn's disease (SB-CD) who are infliximab-naïve. We aimed to identify the effect of different factors on attaining ER using double-balloon endoscopy (DBE) evaluation. A single-center retrospective observational study was conducted from 1 January 2018 to 30 November 2022. Among 262 patients who were screened for isolated SB-CD by baseline DBE, 108 patients were assessed for effectiveness during maintenance infliximab therapy by a second DBE evaluation. DBE findings before and after infliximab therapy were compared. ER was defined as a simple endoscopic score for CD (SES-CD) below 3, and segmental ER as SES-CD activity of 0. Multivariate regression with calculations of odds ratios (OR) was used to determine the impact of different factors on attaining ER. In all, 41 patients (38.0%) achieved ER. An elevated C-reactive protein at week 6 was independently associated with a decreased probability of ER [OR: 0.86, 95% confidence interval (CI) = 0.75-0.98, p = 0.03]. Segmental ER of the terminal ileum, rather than the proximal ileum, was associated with a higher rate of ER (60.9% versus 38.2%, p = 0.01). High baseline SES-CD (⩾16) was unrelated to overall ER. For patients with disease in the terminal ileum, those with moderate/severe disease were less likely to attain segmental ER than those with mild disease [adjusted odds ratios (aOR): 0.27, 95% CI: 0.09-0.83, p = 0.02]. A large ulcer in the terminal ileum was associated with a lower rate of segmental ER (aOR: 0.18, 95% CI: 0.06-0.56, p = 0.01). For infliximab-naïve patients with SB-CD, the overall severity of the endoscopic score was unrelated to attainment of ER. Patients were less likely to attain segmental ER if they had greater endoscopic inflammation or larger ulcers in the terminal ileum.

Stricture dilation via balloon-assisted endoscopy in Crohn's disease: approach and intraprocedural outcomes with the single-balloon and double-balloon systems.

Despite recent emerging literature involving the utility of endoscopic balloon dilation (EBD) of strictures via balloon-assisted endoscopy (BAE), specifically regarding the management of Crohn's disease (CD), the optimal clinical approach with balloon systems has been largely neglected in academic literature. This study assesses the intra-procedural success and safety of EBD via BAE for small bowel CD strictures while detailing our clinical approach and technique. Secondarily, we compare the single-balloon endoscope (SBE) and double-balloon endoscope (DBE) systems for EBD-related outcomes. Retrospective consecutive patient cohort analysis. We retrospectively assessed a consecutive small bowel CD patient cohort undergoing BAE at the University of Alberta Hospital endoscopy unit from 2013 to 2020. The primary endpoint discerned the safety and immediate success rate of EBD during endoscopy, and comparisons of the dilation parameters and efficacy of SBE versus DBE were assessed as secondary outcomes. During the study period, 87 patients (44 male) with a mean age of 56 ± 14.7 years underwent 179 endoscopic procedures (92 DBE and 87 SBE). Of 358 strictures encountered, 320 (89.4%) were successfully dilated and traversed. The mean maximum dilation diameter was 15.76 ± 2.10 mm. There were no perforations or major adverse events. EBD via BAE is a safe procedure in small bowel CD with a high intraprocedural success rate. Overall, SBE had a higher success rate in traversing strictures before and after dilation using our technique. This analysis is limited by the retrospective nature of our study and must be balanced against the inherent benefits of the DBE system.

Genetic Variation Between Small Bowel and Colon-Predominant Crohn's Disease

Genetic Variation Between Small Bowel and Colon-Predominant Crohn's Disease

First-in-Human Assessment of Gut Permeability in Crohn’s Disease Patients Using Fluorophore Technology

Background and AimsThe dual sugar absorption test (DSAT) as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (MW=372) compares to lactulose (L) (MW=342) and rhamnose (R) (MW=164)-based DSAT as a measure of gut permeability in people with a spectrum of permeability including those with Crohn’s disease (CD). MethodsWe performed a single center, randomized, open label, crossover study comparing orally administered MB-102 (1.5 or 3.0 mg/kg) to L (1000 mg) and R (200 mg). Adults with active small bowel CD on magnetic resonance enterography (cases) and healthy adults (controls) were randomized to receive either MB-102 or L and R on study day 1, and the other tracer 3-7 days later. Urine was collected at baseline and 1, 2, 4, 6, 8, 10, and 12 hours after tracer ingestion to calculate the cumulative urinary percent excretion of MB-102 and L and R. ResultsNine cases and 10 controls completed the study without serious adverse events. Urinary recovery of administered MB-102 correlated with recovery of lactulose (r-squared = 0.83) for all participants. MB-102 urine recovery also tracked with the L:R ratio urine recovery (r-squared=0.57). In controls, the percentages of L and MB-102 recovered were similar within a narrow range unlike in CD patients. ConclusionsThis first-in-human study of an orally administered fluorophore to quantify gastrointestinal permeability in adults with CD demonstrates that MB-102 is well tolerated, and its recovery in urine mirrors that of percent L and the L:R ratio.

Visceral adipose tissue volume effect in Crohn's disease using reduced exposure CT enterography.

The purpose of this investigation was to assess the effect of visceral adipose tissue volume (VA) on reader efficacy in diagnosing and characterizing small bowel Crohn's disease using lower exposure CT enterography (CTE). Secondarily, we investigated the effect of lower exposure and VA on reader diagnostic confidence. Prospective paired investigation of 256 CTE, 129 with Crohn's disease, were reconstructed at 100% and simulated 50% and 30% exposure. The senior author provided the disease classification for the 129 patients with Crohn's disease. Patient VA was measured, and exams were evaluated by six readers for presence or absence of Crohn's disease and phenotype using a 0-10-point scale. Logistic regression models assessed the effect of VA on sensitivity and specificity. The effect of VA on sensitivity was significantly reduced at 30% exposure (odds radio [OR]: 1.00) compared to 100% exposure (OR: 1.12) (p=0.048). There was no statistically significant difference among the exposures with respect to the effect of visceral fat on specificity (p=0.159). The study readers' probability of agreement with the senior author on disease classification was 60%, 56%, and 53% at 100%, 50%, and 30% exposure, respectively (p=0.004). When detecting low severity Crohn's disease, readers' mean sensitivity was 83%, 75%, and 74% at 100%, 50%, and 30% exposure, respectively (p=0.002). In low severity disease, sensitivity also tended to increase as visceral fat increased (ORs per 1000 cm3 increase in visceral fat: 1.32, 1.31, and 1.18, p=0.010, 0.016, and 0.100, at 100%, 50%, and 30% exposure). While the interaction is complex, VA plays a role in detecting and characterizing small bowel Crohn's disease when exposure is altered, particularly in low severity disease.