A global consensus on the definitions, diagnosis and management of fibrostenosing small bowel Crohn's disease in clinical practice.

Fibrostenosis of the small bowel is common in patients with Crohn's disease. No consensus recommendations on definition, diagnosis and management in clinical practice are currently available. In this Consensus Statement, we present a clinical practice RAND/UCLA appropriateness study on the definition, diagnosis and clinical management of fibrostenosing Crohn's disease. It was conducted by a panel of 28 global experts and one patient representative. Following a systematic literature review, 526 candidate items grouped into 136 questions were generated and subsequently evaluated for appropriateness. Strictures are best defined as wall thickening, luminal narrowing and prestenotic dilation. Cross-sectional imaging is required for accurate diagnosis of fibrostenosing Crohn's disease, and it is recommended before making treatment decisions. It should also assess the degree of inflammation in the bowel wall. Multiple options for medical anti-inflammatory, endoscopic and surgical therapies were suggested, including follow-up strategies following therapy. This Consensus Statement supports clinical practice through providing guidance on definitions, diagnosis and therapeutic management of patients with fibrostenosing small bowel Crohn's disease.

Systematic review: Defining, diagnosing and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound.

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.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A case series of image-guided percutaneous drainage of abdominal aortic graft infection as bridge therapy.

INTRODUCTION: Aortic graft infection (AGI) is a rare complication following endovascular aneurysm repair and is associated with substantial morbidity and mortality. The traditional management of AGI is intravenous antibiotic therapy and surgical explantation. In this case series, percutaneous drainage was used as a bridge therapy in the treatment of AGI. METHODS: We report two cases, 78-year-old male and 57-year-old female, in whom image-guided percutaneous drainage was used to treat AGI in two contrasting contexts. Informed consent was obtained from both cases/relatives for publication. RESULTS: Both cases underwent successful percutaneous drainage of AGI utilized as a bridge therapy before definitive surgical reconstruction and graft explantation. Each patient had a different outcome. In the first case, the patient's comorbidities and severe disease state could not be overcome, resulting in his death. The second patient benefitted from the percutaneous drainage by allowing her more time ameliorate her malnutrition before definitive surgery. CONCLUSION: Data on the outcomes of percutaneous drainage of AGI is limited. The successful procedure described in this case series emphasizes the need to conduct more research to evaluate the safety and efficacy of this treatment approach before the surgical explantation.

Future directions in imaging pouches.

The sections of this special issue on the ileal pouch demonstrate that in the nearly 45 years since the ileal pouch has been utilized to treat patients with colitis and familial adenomatous polyposis, a substantial number of patients experience both short- and long-term morbidity and that imaging plays an important role in their management. Further, referral centers are encountering an increasing number of patients with pouch and peri-pouch complications and dysfunction. Many of these patients have had their pouches for years, and many have experienced a reduced quality of life as a result of their symptoms.As we look to the future, what are the specific questions that arise from this compilation of experience from institutions that see large numbers of patients with an ileal pouch? In what areas are we deficient? In what areas are we using the wrong methods? What should we be doing differently?

Dynamic ileal pouch emptying studies.

Although much radiologic literature has focused on the short-term post-operative complications associated with ileal pouches, as the number of patients with long-term pouches has grown, there is increasing realization of the functional deficits that may occur long after pouch creation. Dynamic pouch imaging using fluoroscopy and MRI can provide assessment of the underlying causes of symptomatic pouch dysfunction and can provide critical insight to the management of this complex patient population. In this paper, we provide an overview of the unique problems encountered in patients with long-term ileal pouches, and provide an overview of the techniques, interpretation, and reporting for fluoroscopic and MR pouch defecography.

Clinical issues facing pouch patients: an introduction to a special issue on the ileal pouch.

For over 40 years, restorative proctocolectomy has been used in patients with ulcerative colitis or familial adenomatous polyposis undergoing proctocolectomy. Radiologists are now encountering an increasing number of patients with an ileal pouch and therefore need to understand the clinical issues and concerns in these patients. This review is the introduction of a special issue on the ileal pouch and was written with both surgeon and gastroenterology input. The intent is to assist the radiologist in understanding the clinical questions posed by both the patients and their physicians. Subsequent sessions will address specific imaging modalities and techniques, how the gastroenterologists and surgeons address issues with these patients, and a final session summarizing the sessions and speculating on future investigations and approaches.

Validation of stricture length, duration and obstructive symptoms as predictors for intervention in ileal stricturing Crohn's disease.

BACKGROUND: Risk 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. OBJECTIVE: We 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. METHODS: Consecutive 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. RESULTS: Eighty-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. CONCLUSION: In 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.

Crohn's disease related strictures in cross-sectional imaging: More than meets the eye?

Strictures in Crohn's disease (CD) are a hallmark of long-standing intestinal damage, brought about by inflammatory and non-inflammatory pathways. Understanding the complex pathophysiology related to inflammatory infiltrates, extracellular matrix deposition, as well as muscular hyperplasia is crucial to produce high-quality scoring indices for assessing CD strictures. In addition, cross-sectional imaging modalities are the primary tool for diagnosis and follow-up of strictures, especially with the initiation of anti-fibrotic therapy clinical trials. This in turn requires such modalities to both diagnose strictures with high accuracy, as well as be able to delineate the impact of each histomorphologic component on the individual stricture. We discuss the current knowledge on cross-sectional imaging modalities used for stricturing CD, with an emphasis on histomorphologic correlates, novel imaging parameters which may improve segregation between inflammatory, muscular, and fibrotic stricture components, as well as a future outlook on the role of artificial intelligence in this field of gastroenterology.

Predicting Risk of Surgery in Patients With Small Bowel Crohn's Disease Strictures Using Computed Tomography and Magnetic Resonance Enterography.

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.

Computed tomography and magnetic resonance enterography imaging measurements and observations, in combination with patient symptoms, can potentially predict which patients will require surgery within 2 years with modest degree of accuracy.

Test Characteristics of Cross-sectional Imaging and Concordance With Endoscopy in Postoperative Crohn's Disease.

BACKGROUND & AIMS: Postoperative Crohn's disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging is less clear. We evaluated the concordance of cross-sectional enterography with endoscopic recurrence and the predictive ability of radiography for future CD postoperative recurrence. METHODS: We performed a multi-institution retrospective cohort study of postoperative adult patients with CD who underwent ileocolonoscopy and cross-sectional enterography within 90 days of each other following ileocecal resection. Imaging studies were interpreted by blinded, expert CD radiologists. Patients were categorized by presence of endoscopic postoperative recurrence (E+) (modified Rutgeerts' score ≥i2b) or radiographic disease activity (R+) and grouped by concordance status. RESULTS: A total of 216 patients with CD with paired ileocolonoscopy and imaging were included. A majority (54.2%) exhibited concordance (34.7% E+/R+; 19.4% E-/R-) between studies. The plurality (41.7%; n = 90) were E-/R+ discordant. Imaging was highly sensitive (89.3%), with low specificity (31.8%), in detecting endoscopic postoperative recurrence. Intestinal wall thickening, luminal narrowing, mural hyper-enhancement, and length of disease on imaging were associated with endoscopic recurrence (all P < .01). Radiographic disease severity was associated with increasing Rutgeerts' score (P < .001). E-/R+ patients experienced more rapid subsequent endoscopic recurrence (hazard ratio, 4.16; P = .033) and increased rates of subsequent endoscopic (43.8% vs 22.7%) and surgical recurrence (20% vs 9.5%) than E-/R- patients (median follow-up, 4.5 years). CONCLUSIONS: Cross-sectional imaging is highly sensitive, but poorly specific, in detecting endoscopic disease activity and postoperative recurrence. Advanced radiographic disease correlates with endoscopic severity. Patients with radiographic activity in the absence of endoscopic recurrence may be at increased risk for future recurrence, and closer monitoring should be considered.

Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease: A Systematic Review.

BACKGROUND AND AIMS: Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures. METHODS: We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal). RESULTS: Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties. CONCLUSIONS: There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.

Development and Validation of a Novel Computed-Tomography Enterography Radiomic Approach for Characterization of Intestinal Fibrosis in Crohn's Disease.

BACKGROUND & AIMS: No reliable method for evaluating intestinal fibrosis in Crohn's disease (CD) exists; therefore, we developed a computed-tomography enterography (CTE)-based radiomic model (RM) for characterizing intestinal fibrosis in CD. METHODS: This retrospective multicenter study included 167 CD patients with 212 bowel lesions (training, 98 lesions; test, 114 lesions) who underwent preoperative CTE and bowel resection at 1 of the 3 tertiary referral centers from January 2014 through June 2020. Bowel fibrosis was histologically classified as none-mild or moderate-severe. In the training cohort, 1454 radiomic features were extracted from venous-phase CTE and a machine learning-based RM was developed based on the reproducible features using logistic regression. The RM was validated in an independent external test cohort recruited from 3 centers. The diagnostic performance of RM was compared with 2 radiologists' visual interpretation of CTE using receiver operating characteristic (ROC) curve analysis. RESULTS: In the training cohort, the area under the ROC curve (AUC) of RM for distinguishing moderate-severe from none-mild intestinal fibrosis was 0.888 (95% confidence interval [CI], 0.818-0.957). In the test cohort, the RM showed robust performance across 3 centers with an AUC of 0.816 (95% CI, 0.706-0.926), 0.724 (95% CI, 0.526-0.923), and 0.750 (95% CI, 0.560-0.940), respectively. Moreover, the RM was more accurate than visual interpretations by either radiologist (radiologist 1, AUC = 0.554; radiologist 2, AUC = 0.598; both, P < .001) in the test cohort. Decision curve analysis showed that the RM provided a better net benefit to predicting intestinal fibrosis than the radiologists. CONCLUSIONS: A CTE-based RM allows for accurate characterization of intestinal fibrosis in CD.

MR Enterography of Complicated Crohn Disease: Stricturing and Penetrating Disease.

ABSTRACT: Stricturing and penetrating disease are complications of Crohn disease (CD) that significantly affect patient outcomes. Careful evaluation for such complications is critical to the interpretation of magnetic resonance enterography. This manuscript outlines the key findings related to stricturing and penetrating CD and discusses current understanding of the pathophysiology and prognosis of complicated CD based on the literature.

Degree of Creeping Fat Assessed by Computed Tomography Enterography is Associated with Intestinal Fibrotic Stricture in Patients with Crohn's Disease: A Potentially Novel Mesenteric Creeping Fat Index.

BACKGROUND AND AIMS: Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn's disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. METHODS: MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30]. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. RESULTS: In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate-severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC] = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000]. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. CONCLUSIONS: MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.

Effect of obesity on ability to lower exposure for detection of low-attenuation liver lesions.

PURPOSE: The purpose of this study was to assess the effect of obesity and iterative reconstruction on the ability to reduce exposure by studying the accuracy for detection of low-contrast low-attenuation (LCLA) liver lesions on computed tomography (CT) using a phantom model. METHODS: A phantom with four unique LCLA liver lesions (5- to 15-mm spheres, -24 to -6 HU relative to 90-HU background) was scanned without ("thin" phantom) and with ("obese" phantom) a 5-cm thick fat-attenuation ring at 150 mAs (thin phantom) and 450 mAs (obese phantom) standard exposures and at 33% and 67% exposure reductions. Images were reconstructed using standard filtered back projection (FBP) and with iterative reconstruction (Adaptive Model-Based Iterative Reconstruction strength 3, ADMIRE). A noninferiority analysis of lesion detection was performed. RESULTS: Mean area under the curve (AUC) values for lesion detection were significantly higher for the thin phantom than for the obese phantom regardless of exposure level (P < 0.05) for both FBP and ADMIRE. At 33% exposure reduction, AUC was noninferior for both FBP and ADMIRE strength 3 (P < 0.0001). At 67% exposure reduction, AUC remained noninferior for the thin phantom (P < 0.0035), but was no longer noninferior for the obese phantom (P ≥ 0.7353). There were no statistically significant differences in AUC between FBP and ADMIRE at any exposure level for either phantom. CONCLUSIONS: Accuracy for lesion detection was not only significantly lower in the obese phantom at all relative exposures, but detection accuracy decreased sooner while reducing the exposure in the obese phantom. There was no significant difference in lesion detection between FBP and ADMIRE at equivalent exposure levels for either phantom.

Prevention and Treatment of Stricturing Crohn's Disease - Perspectives and Challenges.

Introduction: Fibrostenosis is a hallmark of Crohn's disease (CD), remains a challenge in today's clinical management of inflammatory bowel disease patients and represents a key event in the disease course necessitating improved preventative strategies and a multidisciplinary approach to diagnosis and management. With the advent of anti-fibrotic therapies and well-defined clinical endpoints for stricturing CD, there is promise to impact the natural history of disease.Areas covered: This review summarizes current evidence in the natural history of stricturing Crohn's disease, discusses management approaches as well as future perspectives on intestinal fibrosis.Expert opinion: Currently, there are no specific therapies to prevent progression to fibrosis or to treat it after it becomes clinically apparent. In addition to the international effort by the Stenosis Therapy and Anti-Fibrotic Research (STAR) consortium to standardize definitions and propose endpoints in the management of stricturing CD, further research to improve our understanding of mechanisms of intestinal fibrosis will help pave the way for the development of future anti-fibrotic therapies.