Baker, Mark E.

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.

AbstractBackgroundRisk factors for intervention in terminal ileal (TI) stricturing Crohn's disease (CD) are poorly defined. Novel and rigorous definitions for TI strictures recently became available.ObjectiveWe aimed to describe the rates of symptoms or need for endoscopic balloon dilation (EBD) or surgery as well as risk factors of progression in a well‐defined stricturing CD cohort.MethodsConsecutive adult patients with non‐penetrating stricturing TI CD, as defined by centrally‐read magnetic resonance enterography CONSTRICT criteria, were separated into a derivation and validation cohort. Clinical and imaging characteristics were collected following prespecified scoring conventions. Primary outcome was a composite endpoint of EBD or surgery (“intervention”). Multivariable analysis was performed.ResultsEighty‐six patients (48.8% female, median age 36 years) met selection criteria, 17.4% had prior EBD, 59.3% previously received biologics and 58.1% of strictures were anastomotic. Median follow‐up was 63.4 [95% CI: 57, 68.9] months. In the derivation cohort, at 12 and 48 months, 26% and 45% of patients had intervention, respectively. Multivariable analysis showed obstructive symptoms (Hazard ratio [HR] 1.444; 95% CI 1.126–1.852), stricture duration (HR 0.974; 95% CI, 0.954–0.995) and length (HR 1.039; 95% CI, 1.011–1.069) predicted intervention. The concordance index for split‐sample validation was 0.74 and 0.67, respectively. Biologics were not associated with intervention. An online risk calculator was constructed.ConclusionIn patients with TI stricturing CD, 26% and 45% required intervention at 1 and 4 years. Obstructive symptoms, stricture duration and length were independent and validated predictors of the need for intervention. These findings are important for clinical practice and aid in the design of future trials for CD strictures.

Abstract Background We aimed to determine if patient symptoms and computed tomography enterography (CTE) and magnetic resonance enterography (MRE) imaging findings can be used to predict near-term risk of surgery in patients with small bowel Crohn’s disease (CD). Methods CD patients with small bowel strictures undergoing serial CTE or MRE were retrospectively identified. Strictures were defined by luminal narrowing, bowel wall thickening, and unequivocal proximal small bowel dilation. Harvey-Bradshaw index (HBI) was recorded. Stricture observations and measurements were performed on baseline CTE or MRE and compared to with prior and subsequent scans. Patients were divided into those who underwent surgery within 2 years and those who did not. LASSO (least absolute shrinkage and selection operator) regression models were trained and validated using 5-fold cross-validation. Results Eighty-five patients (43.7 ± 15.3 years of age at baseline scan, majority male [57.6%]) had 137 small bowel strictures. Surgery was performed in 26 patients within 2 years from baseline CTE or MRE. In univariate analysis of patients with prior exams, development of stricture on the baseline exam was associated with near-term surgery (P = .006). A mathematical model using baseline features predicting surgery within 2 years included an HBI of 5 to 7 (odds ratio [OR], 1.7 × 105; P = .057), an HBI of 8 to 16 (OR, 3.1 × 105; P = .054), anastomotic stricture (OR, 0.002; P = .091), bowel wall thickness (OR, 4.7; P = .064), penetrating behavior (OR, 3.1 × 103; P = .096), and newly developed stricture (OR: 7.2 × 107; P = .062). This model demonstrated sensitivity of 67% and specificity of 73% (area under the curve, 0.62). Conclusions CTE or MRE imaging findings in combination with HBI can potentially predict which patients will require surgery within 2 years.

Objective Effective medical therapy and validated trial outcomes are lacking for small bowel Crohn’s disease (CD) strictures. Histopathology of surgically resected specimens is the gold standard for correlation with imaging techniques. However, no validated histopathological scoring systems are currently available for small bowel stricturing disease. We convened an expert panel to evaluate the appropriateness of histopathology scoring systems and items generated based on panel opinion. Design Modified RAND/University of California Los Angeles methodology was used to determine the appropriateness of 313 candidate items related to assessment of CD small bowel strictures. Results In this exercise, diagnosis of naïve and anastomotic strictures required increased bowel wall thickness, decreased luminal diameter or internal circumference, and fibrosis of the submucosa. Specific definitions for stricture features and technical sampling parameters were also identified. Histopathologically, a stricture was defined as increased thickness of all layers of the bowel wall, fibrosis of the submucosa and bowel wall, and muscularisation of the submucosa. Active mucosal inflammatory disease was defined as neutrophilic inflammation in the lamina propria and any crypt or intact surface epithelium, erosion, ulcer and fistula. Chronic mucosal inflammatory disease was defined as crypt architectural distortion and loss, pyloric gland metaplasia, Paneth cell hyperplasia, basal lymphoplasmacytosis, plasmacytosis and fibrosis, or prominent lymphoid aggregates at the mucosa/submucosa interface. None of the scoring systems used to assess CD strictures were considered appropriate for clinical trials. Conclusion Standardised assessment of gross pathology and histopathology of CD small bowel strictures will improve clinical trial efficiency and aid drug development.

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.