Small Bowel Crohn's Disease Research Articles

P195 Is fecal calprotectin truly valuable in the management of isolated small bowel Crohn’s disease?

Abstract Background Crohn’s disease (CD) is a complex inflammatory bowel disease (IBD) with different locations and behaviors. Although fecal calprotectin (FC) is recommended [1, 2] and has been used to monitor IBD, clinical practice has raised doubts about its utility in small bowel (SB) CD. Even though initial studies did not find a role for FC in SB CD, recent literature confirmed its acuity in SB active inflammation [2]. In fact, recent studies have confirmed a correlation between FC values and the degree in inflammatory activity in magnetic resonance enterography (MRE) [3, 4, 5, 6]. However, all these studies included patients with simultaneous colonic disease. Therefore, we evaluated the role of FC in predicting active inflammation in patients with isolated SB CD. Methods 40 patients with L1 CD according to Montreal classification [7] who underwent MRE, FC and C-reactive protein (CRP) assessment [maximum time between all exams was 60 days] were included. MRE data included disease location and extension, SB wall thickness and contrast enhancement, presence of SB dilation, fistulous tracts, inflammatory masses or abscesses, mesenteric findings. FC was both evaluated as a continuous variable and divided into 3 categorical variables: < 50 mg/g (“negative”), 50-150 mg/g (“low”) and > 150 mg/g (“high”). CRP was also divided in < 0.5 mg/dl (“negative”), 0.5-1 mg/dl (“low”) and > 1 mg/dl (“high”). Non parametric tests were used to correlate MRE findings with continuous FC and CRP values and Pearson’s chi-squared test was used to correlate categorical FC and CRP values. Results FC values ranged from 0 to 2872 mg/g, with an average of 301 mg/g. 31.7% had “negative”, 24.4% “low” and 43.9% “high” FC values. Table 1 represents MRE findings. We found a significant statistical correlation between both continuous and categorical FC values with positive mesenteric findings (p=0.0283 and p=0.037), increased bowel wall thickness (p=0.0455 and p=0.039) and presence of stenotic segments (p=0.0193 and p=0.05). All stenosis had signs of active inflammation. We did not find any correlation between FC and disease location or extension, bowel wall contrast enhancement or presence of penetrating disease. CRP values did not correlate with any of MRE findings. Conclusion Although imaging exams are essential for initial evaluation and treatment response in ileal disease, FC is a useful tool to evaluate active disease in isolated SB CD with both inflammatory (B1) and stenotic (B2) disease, in predominantly inflammatory stenosis. Our results do not support FC use to monitor penetrating (B3) disease.

P260 Care pathway modelling and economic analysis of a single NHS IBD Service following introduction of Small bowel ultrasound.

Abstract Background Small bowel ultrasound (SBUS) is an accurate, inexpensive and non-invasive method of diagnosing and monitoring IBD. The service delivery and economic implications of SBUS implementation on NHS IBD services have not previously been explored. Methods This study took the form of a service evaluation. Analysis of patient care episodes and flow through the established imaging (MRE and SBUS) and IBD care pathways was undertaken, data relating to patient flow, waiting times, resource use and healthcare engagement of patients were collected from care episodes between 01/01/2021 – 30/03/2022. Costs were calculated per care episode. Results Data from a service evaluation relating to 192 imaging referrals from IBD clinics for patients with Small bowel Crohn's disease (SBCD), and patient flow through the pathway were collected. Per scan, MRE was almost 5 times more costly than SBUS examinations (£305 versus £51 respectively). Patients from the SBUS pathway had fewer healthcare interactions across all three categories (Helpline, IBD Nurse or IBD Consultant appointments). Patients from the MRE pathway. Estimated costs per patient in the SBUS pathway were £81.72, and £379.58 per patient in the MRE pathway. Further to this the waiting times for MRE were significantly longer than those for SBUS. Conclusion The use of SBUS is a potential cost saving option when compared to MRE for adult patients with SBCD. There was a difference between the SBUS and MRE pathways in the waiting times for both the medical imaging scans, the reports of the scans and the initiation of an appropriate treatment plan. SBUS waiting times were shorter in all aspects except for the time between scanning report and the treatment initiation, indicating that it is the waiting times for the scans and the respective reporting that cause delays in treatment initiation. Future research in this area should attempt to consider the wider impact on cost effectiveness of the use of SBUS through investigation of costs including treatment costs, including the timing and use of biologic and immunomodulator treatments, impact of delays on service use and healthcare interactions of patients, work productivity and quality adjusted life years.

P192 Comparison of Endoscopic Scoring System and Simplified Magnetic Resonance Index of Activity in Patients with Small Bowel Crohn’s Disease: Basis for Therapeutic Plan?

Abstract Background The newly derived simplified magnetic resonance index of activity (MARIAs) has not been verified in comparison with balloon-assisted enteroscopy (BAE) for patients with small-bowel Crohn’s disease (CD). We studied the correlation of MARIAs with simple endoscopic score for Crohn's disease (SES-CD) of ileum based on magnetic resonance enterography (MRE) and BAE, respectively, in patients with small-bowel CD. In addition, we determined the impact of these tools on clinical decision-making. Methods Fifty patients with small-bowel CD who underwent BAE and MRE concurrently within three months from September 2020 to June 2021, followed by the reference date of December 2021, were enrolled. The primary outcome was correlation between the active score of ileal SES-CD (ileal SES-CDa)/ileal SES-CD and MARIAs based on BAE and MRE in segmented ileum. The active/severe disease index was set as ileal SES-CDa/ileal SES-CD of 5/7 and MARIAs of 1/2. The secondary outcome was the basis for step-up treatment. Results The ileal SES-CDa/ileal SES-CD and MARIAs showed strong associations (R=0.76, p<0.001/R=0.78, p<0.001). The AUROC of MARIAs for ileal SES-CDa ≥ 5 was 0.92 (95% CI: 0.88-0.97). The AUROC of the MARIAs for ileal SES-CD ≥ 7 was 0.92 (95% CI: 0.87-0.97). Among the 26 patients who experienced step-up treatment after BAE and MRE, 23 patients showed active disease on both BAE and MRE. Conclusion We validated the applicability of MARIAs compared to the BAE-based ileal SES-CDa/SES-CD. Assessment of disease activity based on both BAE and MRE could optimize the management of small-bowel CD patients.

P286 Combined F18-FDG-PET-MRI-imaging: A promising tool for diagnostics of small bowel Crohn’s disease

Abstract Background Diagnostics of small bowel Crohn’s disease (CD) may be difficult. Combined PET-MRI has been documented to be a reliable tool for evaluating intestinal metabolism, but clinical use has been limited due to accessibility, costs and lack of standardized methods to quantify inflammation. Our study aims to prove that combined PET-MRI can be used to detect active CD inflammation in small bowel. Methods 25 patients with suspected ileal CD in ileocolonoscopy were recruited from Turku University Hospital’s outpatient clinic. The patients’ endoscopic findings in ileum were graded according to SES-CD- score (Simple Endoscopic Score for Crohn’s disease). A static PET-MRI was obtained with [18F]-FDG (fluorodeoxyglucose) tracer and gadolinium contrast agent (Dotarem®). Hemoglobin (Hb), C-reactive protein (CRP), serum albumin (Alb) and fecal calprotectin (FC) were measured. After PET-MRI, a small bowel capsule endoscopy was done and the findings graded along the CECDAI-system (Capsule Endoscopy Crohn’s disease Activity Index). The patient’s symptoms were scored with a validated questionnaire. Medication data was also collected. The MR images with a small bowel protocol and diffusion weighted imaging (DWI) were analyzed and the degree of inflammation graded on a visual scale of 1-4, from none to severe by an experienced abdominal radiologist. SUVmax (standardized uptake value) was measured from PET-sequences for each patient from terminal ileum. Results Twenty (80%) of the patients diagnosed with small bowel CD had mean SUVmax 3.40 (±1.54), while the 20% without CD diagnosis had lower SUVmax 2.15 (± 0.93) (p=0.047). Patients who were later treated with immunomodulators or biologics had higher SUVmax than patients who didn’t need medication or were treated with oral budesonide only (3.71 (±1.49) vs 2.07 (±0.82), p=0.0093). There was a correlation with SUVmax and visual MRI grading, CECDAI-score, ileal SES-CD-score and FC (r=0.406, p=0.049; r=0.504, p=0.056; r=0.419, p=0.042 and r=0.49, p=0.014 respectively). SUVmax correlated negatively with Alb (r=0.599, p=0.0025) but not with Hb, CRP or the symptom score of the patients. Conclusion In this study we have shown that SUVmax measured from terminal ileum in combined PET-MRI could be used for prediction of patients CD progression. SUVmax also correlated with SES-CD-score, fecal calprotectin and serum albumin. These findings suggest that combined PET-MRI can be used in the future in diagnostics of small bowel CD. Further analyses are needed to define threshold values for small intestine CD.

P128 The role of small bowel capsule endoscopy as a diagnostic tool in isolated complex perianal disease

Abstract Background Isolated complicated perianal disease (cPD) might be the sole representation of Crohn’s disease (CD). We aimed to evaluate the impact of small bowel capsule endoscopy (SBCE) as a diagnostic tool for CD in this population. Methods A multicenter, retrospective cohort study from three tertiary centers. Patients with cPD who had a negative workup for CD (Ileocolonoscopy and cross-sectional imaging) and underwent evaluation with SBCE were included. Demographics, biomarkers, and the Lewis inflammatory score (LS) were recorded and analyzed. A LS≥135 was considered a positive SBCE. Results Ninety-one patients were included: 65 males (71.4%), mean age 40 (14) years, median duration of cPD 25.13 months (12.53-66.1). SBCE was positive in 24 patients (26.37%). Median LS was 675 (222-1518). Fecal calprotectin (FC) positively correlated with LS (r=0.81; p<0.0001): patients with a positive vs. negative SBCE had a significantly higher mean FC level (255 [389] vs 97[180], p=0.02), Figure 1. Correspondingly, a FC level ≥ 300 mg/kg had a specificity of 90% for a positive SBCE, while a cutoff of FC level <100 mg/kg or <50 mg/kg had a sensitivity of only 40% or 50% to rule out small bowel CD, respectively. Conclusion SBCE was positive in over a quarter of patients with cPD and a negative workup for CD. FC levels correlated with the degree of inflammation defined by the LS. However, the sensitivity of low FC to rule out CD was low. These results suggest that SBCE is an essential diagnostic tool for patients with cPD even after negative workup.

P188 Middle small-bowel segment Lewis score may predict long-term outcomes among patients with quiescent Crohn’s disease

Abstract Background Video capsule endoscopy (VCE) has been proven to accurately diagnose small-bowel inflammation and predict flares among patients with quiescent Crohn’s disease (CD). In this study we aimed to predict worse clinical outcomes over an extended follow-up. Methods This was a post-hoc analysis of adult patients with quiescent small-bowel CD who were followed with VCE, inflammatory biomarkers and magnetic resonance enterography (MRE) in a prospective study (between 2013-2018). We extracted extended clinical data from our hospital electronic health records to include the most recent follow-up (until Apr 2022). The primary composite outcome was clinical exacerbation defined as either intestinal-surgery, endoscopic dilation, CD-related admission, need for corticosteroids or biological/immunomodulator treatment change during the follow-up. Results Out of the 61 patients who were included in the study (median age of 29 [24-37] years, male–57.4%, current biologic treatment–46.7%), 18 patients met the composite outcome during an extended long-term follow-up (median of 58 [interquartile range 35-93] months). On univariable analysis, complicated (Hazard ratio [HR] 7.348, p=0.002) and stricturing disease-phenotype (HR 5.305, p=0.001) were associated with higher risk for clinical exacerbation during follow-up. A baseline VCE middle small-bowel segment Lewis score (midLS) of≥135 identified patients with future exacerbation (AUC of 0.767, 95% CI 0.633-0.902, p=0.001, HR 6.317, negative predictive value [NPV] of 93%), while the conventional Lewis score had an AUC of 0.734 (CI 0.589-0.879, p=0.004). Performing sensitivity analysis restricted to patients with either complicated (n=34) or stricturing disease-phenotype (n=26), we revealed that midLS still predicted disease exacerbation during the extended follow-up (AUC of 0.747 and 0.753, respectively) in these patients. Conclusion MidLS predicts treatment failure in quiescent Crohn's disease patients (median follow-up 5 years) independently of disease-phenotype.

P173 Patency capsule: A novel independent predictor for long-term outcomes among patients with quiescent Crohn’s disease

Abstract Background Patency capsule (PC) is a recommended procedure to rule-out small-bowel stenosis before video capsule endoscopy (VCE).We examined future clinical outcomes among patients with failed-PC versus patients in whom PC had passed (passed-PC). Methods A Post-hoc analysis of two prospective cohort studies of adult patients with quiescent small-bowel CD that underwent PC between 2013-2020. The primary composite-outcome was the need for intestinal-surgery or endoscopic-dilation during follow-up in patients with or without failed-PC. Results A total of 191 patients were included (47-failed PC, 144-passed PC, median follow-up 34.12 months). Patients with a failed-PC had higher rates of the primary composite-outcome (21.3% vs. 1.4%, Hazard ratio [HR] 20.4, 95% confidence interval [CI] 4.4-94.1, p<0.001) and also secondary outcomes including intestinal-surgery (14.9% vs. 0.70%, p<0.001), endoscopic-dilation (14.9% vs. 0.70%, p<0.001), admissions (23.3% vs. 5.7%, p<0.001) and clinical-flares (43.9% vs. 27.5%, p=0.005) during follow-up compared with controls. Failed-PC was the only statistically significant factor for surgery and/or endoscopic-dilation, regardless of a B2/B3 phenotype at baseline. In sensitivity-analyses restricted only to patients with stricturing phenotype (n=74), failed-PC still predicted worse long-term composite-outcome (HR 23.1 95% CI 2.3-228.0, p=0.007). Of the 191 patients ingesting a PC, only one patient with a failed-PC had 48 hours of self-limiting mild symptoms Conclusion Clinically-stable CD patients with failed-PC have worse long-term clinical outcomes than those without, independently of CD phenotype. Standalone PC may serve as a novel, safe and affordable prognostic examination to stratify patients with CD for future risk of poor outcomes and potentially guide pre-emptive management decisions.

Motility Mapping Quantification Using the Classical Optical Flow Algorithm for Small Bowel Crohn's Disease: Comparison with Balloon-assisted Enteroscopy Findings.

To quantify bowel motility shown on cine MRI using the classical optical flow algorithm and compare it with balloon-assisted enteroscopy (BAE) findings in patients with Crohn's disease (CD). This retrospective study included 29 consecutive patients with CD who had undergone MR enterocolonography (MREC) and BAE between March and May 2017. We developed computer software to present motion vector magnitudes between consecutive cine MR images as bowel motility maps via a classical optical flow algorithm using the Horn-Schunck method. Cine MR images were acquired with a balanced steady-state free precession sequence in the coronal direction to capture small bowel motility. The small bowels were divided into three segments. In total, 63 bowel segments were assessed via BAE and MREC. Motility scores on the maps, simplified MR index of activity (sMaRIA), and MREC score derived from a 5-point MR classification were assessed independently by two radiologists and compared with the CD endoscopic index of severity (CDEIS). Correlations were assessed using Spearman's rank coefficient. The areas under the receiver-operating characteristic curve (AUCs) of motility score for differentiating CDEIS was calculated; a P value < 0.05 was considered statistically significant. Motility score was negatively correlated with CDEIS (r = -0.59 [P < 0.001] and -0.54 [P < 0.001]), and the AUCs of motility scores for detecting CDEIS ≥ 3 were 88.2% and 78.6% for observers 1 and 2, respectively. There were no significant differences in the AUC for detecting CDEIS ≥ 3 and CDEIS ≥ 12 between motility and sMaRIA or MREC score. The motility map was feasible for locally quantifying the bowel motility. In addition, the motility score on the map reflected the endoscopic inflammatory activity of each small bowel segment in patients with CD; hence, it could be used as a tool in objectively interpreting cine MREC to predict inflammatory activity in CD.

Middle small-bowel segment Lewis score may predict long-term outcomes among patients with quiescent Crohn's disease.

Video capsule endoscopy (VCE) has been proven to accurately diagnose small-bowel inflammation and predict flares among patients with quiescent Crohn's disease (CD). However, data regarding its predictive role in this population over an extended follow-up are scarce. To predict clinical exacerbation and to assess the yield of Lewis score in identifying CD patients with future clinical exacerbation during an extended follow-up (>24 months). A post hoc analysis study. Adult patients with quiescent small-bowel CD who were followed with VCE, inflammatory biomarkers and magnetic resonance enterography in a prospective study (between 2013 and 2018). We extracted extended clinical data (up to April 2022). The primary composite outcome (i.e. clinical exacerbation) was defined as intestinal surgery, endoscopic dilation, CD-related admission, corticosteroid administration, or biological/immunomodulator treatment change during follow-up. Of the 61 patients in the study [median age 29 (24-37) years, male 57.4%, biologic treatment 46.7%], 18 patients met the primary outcome during an extended follow-up [median 58.0 (34.5-93.0) months]. On univariable analysis, complicated [hazard ratio (HR) 7.348, p = 0.002] and stricturing disease phenotype (HR 5.305, p = 0.001) were associated with higher risk for clinical exacerbation during follow-up. A baseline VCE middle small-bowel segment Lewis score (midLS) ⩾ 135 identified patients with future exacerbation [AUC (area under the curve) 0.767, 95% confidence interval (CI) 0.633-0.902, p = 0.001, HR 6.317, 93% negative predictive value], whereas the AUC of the conventional Lewis score was 0.734 (95% CI: 0.589-0.879, p = 0.004). Sensitivity analysis restricted to patients with either complicated (n = 34) or stricturing (n = 26) disease phenotype revealed that midLS still predicted clinical exacerbation during follow-up (AUC 0.747/0.753, respectively), in these patients. MidLS predicts treatment failure in quiescent CD patients (median follow-up of 5 years) independently of disease phenotype.

Patency Capsule: A Novel Independent Predictor for Long-Term Outcomes Among Patients With Quiescent Crohn's Disease.

Patency capsule (PC) is a recommended procedure to rule out small bowel stenosis before video capsule endoscopy (VCE). We examined future clinical outcomes among patients with a failed PC vs patients in whom the PC had passed (passed PC). A post hoc analysis of 2 prospective cohort studies of adult patients with quiescent small bowel Crohn's disease (CD) who underwent PC between 2013 and 2020. The primary composite outcome was the need for intestinal surgery or endoscopic dilation during follow-up in patients with or without a failed PC. A total of 190 patients were included (47: failed PC and 143: passed PC, median follow-up 34.12 months). Patients with a failed PC had higher rates of the primary composite outcome (21.3% vs 1.4%, hazard ratio [HR] 20.3, 95% confidence interval [CI] 4.4-93.7, P < 0.001) and also secondary outcomes including intestinal surgery (14.9% vs 0.70%, P < 0.001), endoscopic dilation (14.9% vs 0.70%, P < 0.001), admissions (23.3% vs 5.7%, P < 0.001), and clinical flares (43.9% vs 27.7%, P = 0.005) during follow-up compared with controls. Failed PC was the only statistically significant factor for surgery and/or endoscopic dilation, regardless of a B2/B3 phenotype at baseline. In sensitivity analyses restricted only to patients with a stricturing phenotype (n = 73), a failed PC still predicted the long-term composite outcome (HR 8.68, 95% CI 1.72-43.68, P = 0.002). Of the 190 patients ingesting a PC, only 1 patient with a failed PC had 48 hours of self-limiting mild symptoms. Patients with clinically stable CD with a failed PC have worse long-term clinical outcomes than those without, independently of the CD phenotype. Standalone PC may serve as a novel, safe, and affordable prognostic examination to identify patients with quiescent CD who have a higher risk for future worse clinical outcomes.

Diagnostic accuracy of different cross-sectional imaging techniques for disease location and activity in Crohn's disease and external validation and comparison of MARIAs and IBUS-SAS.

The comparative accuracy of cross-sectional imaging techniques for evaluating Crohn's disease (CD) remains uncertain. This study aimed to assess diagnostic accuracy of disease location and activity in different cross-sectional images and validate and compare International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) and Simplified Magnetic Resonance Index of Activity (MARIAs). CD patients were retrospectively included from August 2018 to May 2021. We compared accuracy of B-mode intestinal ultrasound (B-IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) for the identification of disease location. Meanwhile, disease activity was compared on B-IUS, color Doppler imaging, CTE, and MRE. ROC analyses were used to validate MARIAs and IBUS-SAS. Spearman rank correlation was performed to evaluate the relationships between MARIAs/IBUS-SAS and CDAI, SES-CD, and inflammatory indicators. A total of 115 CD patients were evaluated. The diagnostic accuracy of MRE in detecting small bowel disease was superior to that of B-IUS/CTE, showing sensitivity (89.3%), specificity (71.4%), and AUC (0.820). B-IUS had the highest sensitivity (81.2%), specificity (84.8%), and AUC (0.830) for detecting terminal ileal lesions. The diagnostic accuracy for colonic disease and disease activity was not significantly different among these techniques. In the validation of IBUS-SAS, the AUC was 0.860, with an optimal cutoff value to predict active disease of 46.7. MARIAs and IBUS-SAS showed no significant differences in the correlations of CDAI, SES-CD, and inflammatory indicators. MRE and B-IUS are more sensitive for detecting small bowel CD and terminal ileal CD, respectively. IBUS-SAS has potential for precisely defining CD activity.

Single-balloon Enteroscopy for Evaluation of Small Bowel Crohn Disease Strictures: Peripheral Blood Lymphocytes As a Risk Factor for Strictures.

Few reports have focused on single-balloon enteroscopy (SBE) for evaluation of small bowel Crohn disease (CD) strictures. The aim of this study was to analyze the relationships between peripheral blood inflammatory markers and small bowel CD strictures observed by SBE. CD patients who underwent SBE between January 2016 and December 2020 were enrolled. The clinical characteristics and peripheral blood inflammatory markers were collected and analyzed to screen for predictive factors significantly associated with small bowel CD strictures. A total of 221 CD patients underwent SBE. The lymphocyte (LC) counts in peripheral blood were significantly lower in the active group (n=178) than in the inactive group (n=43) according to the simple endoscopic score for CD (SES-CD), P =0.011, and was correlated with the SES-CD ( r =-0.134, P =0.047). The LC levels were significantly lower in the stricture group (n=116) than in the nonstricture group (n=105) based on whether small bowel strictures developed, P =0.000, and LC was a risk factor for strictures in the multivariate analysis [hazard ratio (HR), 2.332; 95% CI, 1.102-4.937; P =0.027]. In the subgroup analysis, LC levels notably decreased after stricture aggravation ( P =0.000). Forty-seven patients who underwent small bowel resection underwent SBE at 6 to 12 months after surgery. The LC level was significantly lower in the postoperative patients with strictures ( P =0.025), and LC (HR, 4.444; 95% CI, 1.265-15.617; P =0.020) was a risk of postoperative strictures by univariate analysis, but the age at diagnosis (HR, 6.462; 95% CI, 1.272-22.560; P =0.022) was an independent risk factor by multivariate analysis. Peripheral blood LC levels were correlated with SES-CD and gradually decreased as the intestinal stricture increased in small bowel CD patients. The LC level was also significantly lower in the postoperative CD patients with strictures. The level of LC was a risk factor for small bowel strictures. These results suggest that peripheral blood LC could be a novel marker of small bowel CD strictures to guide CD diagnosis and therapy.

CROHN’S DISEASE: A REVIEW ON EPIDEMIOLOGY, DIAGNOSIS AND THERAPEUTIC MANAGEMENT

Crohn’s disease (CD) is a kind of inflammatory bowel disease (IBD) characterized by the chronic transmural inflammatory state of gastrointestinal tract that typically affects ileum, colon, and perineum. Although the precise etiology is unknown, the major risk aspects concerned with CD consist of several environmental factors, altered microbiota, unhealthy low fiber- high carbohydrate diet, and certain medicines like non-steroidal anti-inflammatory drugs. The disease has wide distribution and inflammation may affect the different areas of the alimentary tract in diverse people. In about 80 % of patients, only small bowel involvement is typically present, affecting distal ileum resulting in ileitis. In about 50 % patients, both ileum and colon are affected resulting in ileocolitis and in approximately 20 % patients, disease is limited to colonic portion. Perianal disease affects almost one-third of patients. As per the various genetic researches in the CD patients, various genetic mutations affect the body’s immunological system that results in severe inflammatory state. The two major gene mutations which result in the pathological state of CD are autophagy-related 16-like 1 (ATG16L1) and nucleotidebinding oligomerization domain-containing protein 2 (NOD2/ Card15). The main techniques used for diagnosis of CD include the combination of pathological findings, endoscopic and radiographic findings demonstrating the disease features. The utmost preferred radiologic study for assessing the small bowel CD is abdominal computerized tomography (CT). The goal of current treatment strategies is to address symptomatic relief. Sequence of treatment includes induction therapy, followed by maintenance of remission. The currently used drugs that effectively can cause induction as well as maintain remission include 5-aminosalicylic acid, Tumor Necrosis Factor (TNF) inhibitors, immunomodulators and steroids. Treatment and management should be integrated with lifestyle and dietary amendments to prevent therapeutic failure and consideration of surgical intervention.

Challenges and Strategies to Optimising the Quality of Small Bowel Magnetic Resonance Imaging in Crohn's Disease.

Magnetic resonance enterography (MRE) is one of the most highly utilised tools in the assessment of patients with small bowel Crohn’s disease (CD). As a non-invasive modality, it has both patient and procedure-related advantages over ileocolonoscopy which is the current gold standard for Crohn’s disease activity assessment. MRE relies upon high-quality images to ensure accurate disease activity assessment; however, few studies have explored the impact of image quality on the accuracy of small bowel CD activity assessment. Bowel distension and motion artifacts are two key imaging parameters that impact the quality of images obtained through MRE. Multiple strategies have been employed to both minimise the effects of motion artifacts and improve bowel distension. This review discusses the definitions of bowel distension and motion artifacts within the literature with a particular focus on current strategies to improve bowel distension and limit motion artifacts in MRE.

The Simplified MR Index of Activity Score in Pediatric Small-Bowel Crohn Disease: An Interreader Agreement and Responsiveness Study.

BACKGROUND. The simplified MR index of activity (MaRIA) score is used to assess the severity of small-bowel inflammation without use of IV contrast material. OBJECTIVE. The purposes of this study were to assess interreader agreement on the use of simplified MaRIA scores for evaluation of the inflammatory activity of terminal ileal Crohn disease in children and young adults and to assess whether simplified MaRIA scores change after biologic medical therapy. METHODS. This analysis was ancillary to a previously reported primary prospective research investigation. The study included 20 children and young adults with newly diagnosed ileal Crohn disease and 15 healthy control participants who underwent research small-bowel MRI examinations between December 2018 and October 2021. The participants with Crohn disease underwent baseline MRI and MRI 6 weeks and 6 months after beginning anti-tumor necrosis factor α-treatment as well as weighted pediatric Crohn disease activity index (wPCDAI) and C-reactive protein (CRP) assessment on the day of each examination. Control participants underwent one MRI examination. Four pediatric radiologists independently assigned simplified MaRIA scores using axial and coronal T2-weighted SSFSE images. Median simplified MaRIA score among readers was computed. Interreader agreement was assessed with Fleiss kappa coefficients and intra-class correlation coefficient (ICC). Analysis included the Mann-Whitney U test, Friedman test, and Spearman rank correlation. RESULTS. Simplified MaRIA scores (across time points and study groups) had substantial interreader agreement (κ = 0.65 [95% CI, 0.56-0.74]; ICC, 0.71 [95% CI, 0.63-0.78]). Median scores were higher in participants with Crohn disease at baseline than in healthy control participants (3.5 [IQR, 2.5-4.9] vs 0.5 [IQR, 0-2.0]; p < .001). Scores decreased after medical treatment in participants with Crohn disease (p = .005). The median score was 3.5 (IQR, 2.5-4.9) at baseline, 2.3 (IQR, 1.6-3.9) at 6 weeks, and 2.0 (IQR, 0.5-2.5) at 6 months. In participants with Crohn disease, median scores had significant correlations with wPCDAI (ρ = 0.46 [95% CI, 0.18-0.64]; p < .001) and CRP level (ρ = 0.48 [95% CI, 0.27-0.65]; p < .001). CONCLUSION. Radiologists had substantial agreement in use of simplified MaRIA scores to assess intestinal inflammation in ileal Crohn disease. Scores changed over time after medical therapy. CLINICAL IMPACT. The results support the simplified MaRIA score as an objective MRI-based clinical measure of intestinal inflammation in children and young adults with Crohn disease.

Predictive Markers of Crohn's Disease in Small Bowel Capsule Endoscopy: A Retrospective Study of Small Bowel Capsule Endoscopy.

To distinguish between functional gastrointestinal disorders like irritable bowel syndrome (IBS) and mild small bowel Crohn′s disease (CD) can be a burden. The diagnosis of CD often requires small bowel capsule endoscopy (SBCE). The main goal of this research was to find predictive markers to rule out clinically significant small bowel CD without SBCE. A retrospective study of 374 patients who underwent SBCE for suspected small bowel CD in Turku University Hospital in 2012–2020 was conducted. We gathered the patient′s laboratory, imaging and endoscopic findings at the time of SBCE. SBCE findings were graded along CECDAI (Capsule Endoscopy Crohn’s Disease Activity Index)-scoring system. Fecal calprotectin (FC), serum albumin and ESR were significantly different with patients diagnosed with CD and those with not. Hb and CRP had no significant differences between the two groups. Sensitivity, specificity, PPV and NPV for FC < 50 ug/g were 96.4%, 19.6%, 34.6% and 92.5% and for CECDAI (cut-off value 3) 98.2%, 90.3%, 81.1% and 99.1%, respectively. A CECDAI-score of 3 would be a reasonable cut-off value for small bowel CD. Small bowel CD is possible with FC < 100 ug/g. Our results suggest a follow-up with FC before SBCE for patients with no endoscopic ileitis, negative imaging results and FC < 50 ug/g before SBCE.

Fecal calprotectin predicts endoscopic activity and mucosal healing of small bowel Crohn's disease evaluated by double-balloon endoscopy.

Fecal calprotectin (FC) levels can reflect the level of intestinal inflammation. Crohn's disease (CD), which affects the small bowel, has not been linked to FC levels. We determined if FC levels and endoscopic activity were related by performing double-balloon endoscopy (DBE). Herein, patients with small bowel CD diagnosed by DBE between January 2020 and January 2022 were prospectively observed. Feces and blood samples of patients were collected before performing DBE and checked for the levels of FC and serological biomarkers. The endoscopic activity and mucosal healing (MH) were evaluated using the partial simple endoscopic score (pSES-CD). In all 254 CD patients, FC levels were correlated with pSES-CD (r = 0.775, P < 0.001). Even in patients with isolated small bowel CD, FC levels were strongly correlated with pSES-CD (r = 0.753, P < 0.001). In all patients, FC as an endoscopic remission indicator was found to have an area under the curve (AUC) of 0.872, with a cut-off value of 156.09 µg/g. In patients with isolated small bowel CD, FC yielded a high AUC of 0.865 for predicting endoscopic remission, with a cut-off value of 211.48 µg/g, sensitivity of 73.95%, and specificity of 91.30%. FC was optimally cut-off at 76.99 µg/g to predict MH in accordance with the AUC of 0.877. Using DBE findings, FC was found to be significantly correlated with pSES-CD. Even in isolated small bowel CD, FC may be a more reliable marker of accurately predicting endoscopic remission and MH.

MRI-Based Characterization of Intestinal Motility in Children and Young Adults With Newly Diagnosed Ileal Crohn Disease Treated by Biologic Therapy: A Controlled Prospective Study.

BACKGROUND. Changes in intestinal motility in patients with newly diagnosed Crohn disease have historically been evaluated primarily in a subjective manner. OBJECTIVE. The purpose of this study was to assess longitudinal changes in objective intestinal motility scores in children and young adults with newly diagnosed ileal Crohn disease treated with biologic (anti-tumor necrosis factor-α) medical therapy compared with those in control participants. METHODS. This prospective study included 20 children and young adults (eight female and 12 male patients; mean age, 14.6 ± 2.1 [SD] years) with newly diagnosed ileal Crohn disease who were recruited between December 2018 and October 2021 as well as 15 control participants without any known gastrointestinal conditions (eight female and seven male patients; mean age, 18.1 ± 4.4 years). All participants underwent research MRI examinations of the small bowel, including dynamic cine 2D SSFP sequences. Patients with Crohn disease underwent additional research MRI examinations performed at both 6 weeks and 6 months after initiation of biologic therapy. Two operators independently derived terminal ileal intestinal motility scores from the dynamic cine sequences by use of FDA-approved software (with higher scores indicating greater intestinal motility). Intestinal motility scores were compared between patient and control groups by use of t tests, whereas changes in intestinal motility scores after treatment were assessed using linear mixed models. Interoperator absolute agreement was assessed using the intra-class correlation coefficient (ICC). RESULTS. Mean terminal ileal intestinal motility scores were not significantly different between patients with newly diagnosed ileal Crohn disease and control participants (for operator 1, 180.9 ± 63.3 vs 229.7 ± 115.2, respectively [p = .12]; for operator 2, 175.0 ± 62.2 vs 236.4 ± 117.4, respectively [p = .05]). Mean intestinal motility scores changed over time compared with baseline in response to biologic therapy, for operator 1 (180.9 ± 63.3 at baseline, 248.1 ± 104.9 at 6 weeks after treatment initiation, and 249.1 ± 73.2 at 6 months after treatment initiation [p = .04]) and operator 2 (175.0 ± 62.2 at baseline, 247.8 ± 112.7 at 6 weeks after treatment initiation, and 239.6 ± 72.7 at 6 months after treatment initiation [p = .03]). Absolute agreement in intestinal motility scores was excellent between operators (ICC = 0.89). CONCLUSION. MRI measurements of intestinal motility are dynamic in children and adults with newly diagnosed small-bowel Crohn disease, showing early increases in response to biologic therapy. CLINICAL IMPACT. MRI-based intestinal motility scores may aid individualized assessment of disease activity and treatment response in patients with small-bowel Crohn disease.

Ultrasound shear wave elastography in pediatric stricturing small bowel Crohn disease: correlation with histology and second harmonic imaging microscopy.

Preclinical animal as well as small exploratory ex vivo and in vivo human studies have suggested that bowel wall shear wave speed (SWS) measurements may be a noninvasive biomarker of intestinal damage. To evaluate the relationships between bowel wall stiffness, measured using ultrasound shear wave elastography (SWE), and intestinal fibrosis and smooth muscle hypertrophy as determined by (1) histology and (2) second harmonic imaging microscopy (SHIM) in surgically resected ileal strictures from pediatric Crohn disease patients. Nineteen pediatric Crohn disease patients with symptomatic ileal strictures underwent research ultrasound examinations before surgical resection between December 2017 and September 2020. Two-dimensional SWE was performed through the area of the most severe stenosis, with measurements obtained from the bowel wall at the 9:00, 12:00 and 3:00 o'clock locations with 0%, 10% and 20% abdominal strain. Overall right lower quadrant stiffness also was documented. Median bowel wall and overall right lower quadrant SWS measurements were correlated with bowel wall histological scores of inflammation, fibrosis and smooth muscle proliferation as well as SHIM collagen signal. Diagnostic ultrasound SWE imaging was obtained from 18 participants. The median age was 16.8 years. There were negative correlations between histological mucosal active inflammation and both bowel wall SWS with 10% abdominal strain (r=-0.50, P = 0.04) and overall right lower quadrant SWS with 20% abdominal strain (r=-0.69, P = 0.002). There were positive correlations between histological muscularis propria inner layer smooth muscle hypertrophy and both median bowel wall SWS with 10% abdominal strain (r = 0.72, P = 0.002) and overall right lower quadrant SWS with 20% abdominal strain (r = 0.71, P = 0.002). There were no associations between ultrasound stiffness metrics and bowel wall SHIM collagen measurements. Bowel wall and overall right lower quadrant ultrasound stiffness measurements correlate with mucosal active inflammation and muscularis propria smooth muscle hypertrophy in pediatric stricturing ileal Crohn disease, but not with intestinal fibrosis.

Therapeutic Drug Monitoring of Biologics in Crohn's Disease.

Reactive therapeutic drug monitoring (TDM) is considered the standard of care for optimizing biologics in inflammatory bowel disease (IBD) including Crohn's disease (CD). Preliminary data show that proactive TDM is associated with positive outcomes in IBD and can be also used to efficiently guide therapeutic decisions in specific clinical scenarios. Higher biological drug concentrations are associated with favorable therapeutic outcomes in specific IBD populations or phenotypes including pediatric CD, perianal fistulizing CD, small bowel CD, and following an ileocolonic resection for CD. Future perspectives of TDM include the use of rapid testing, pharmacogenomics, and pharmacokinetic dashboards toward individualized therapy.