Ileal Stricture Research Articles

P0693 The Chicago Mesenteric Fat Index: A Novel Biomarker for Assessing Inflammation in Pediatric Crohn’s Disease with Point of Care Intestinal Ultrasound

Abstract Background Pediatric Crohn’s disease (CD) is a chronic, progressive disorder that may result in lifelong disability. There is a need for tools that facilitate early detection and accurate assessment of disease. Point-of-care intestinal ultrasound (IUS) is an accurate and non-invasive tool that provides an alternative to magnetic resonance and/or computed tomographic enterography. In addition to bowel wall thickness (BWT) and hyperemia, mesenteric fat (MF) is one of the measures of CD severity visualized with IUS. Current guidance for grading MF is subjective and binary. We have previously proposed the Chicago Mesenteric Fat Index (CMFI) to standardize grading MF in adults, and demonstrated moderate to substantial inter-rater reliability (IRR). The aim of this study was to determine the IRR of MF assessment and validate the CMFI in pediatric CD. Methods IUS images of children with ileal CD were captured from November 2023 to May 2024. Those with prior surgery were excluded. CMFI differentiates severity based on the degree of wrapping: "none" (none or minimal MF wrapping), "incomplete" (incomplete circumferential MF wrapping with skipped areas along the terminal ileum), and "complete" (circumferential MF wrapping, continuous along the terminal ileum) (Figure 1). MF grading was performed by experienced pediatric intestinal sonographers, blinded to clinical data. IRR was analyzed using Cohen’s kappa statistic. We used population and clinical data and assessed the correlation of MF using chi-square for categorical data and Kruskal-Wallis for continuous variables. Results 48 IUS examinations in 36 patients were included [50% female, 69% ileocolonic disease, predominately non-stricturing, non-penetrating in 67%]. Median BWT on IUS was 3.55 mm [1.9-5.25] (Table 1). Of the 48 scans, 32 (67%) had presence of MF wrapping,16 had incomplete MF wrapping and 16 had complete MF wrapping. The IRR for the binary assessment of MF was substantial (k = 0.6936), and grading according to the CMFI also showed substantial agreement (k = 0.6038). MF was associated with other IUS parameters, including BWT (p<0.001 for both binary and graded index and binary), loss of bowel wall stratification (p = 0.001 for binary assessment and p = 0.002 for graded index) and the presence of hyperemia (p = 0.002 for binary assessment and p = 0.011 for graded index). MF was not associated with ileal strictures (p = 0.224 for graded index, p = 0.132 for binary assessment) (Table 1). Conclusion We demonstrate that IUS is a reliable tool for the assessment of MF in pediatric CD. MF assessment with the CMFI could be used as a potential objective non-invasive biomarker of CD severity in children, allowing for enhanced clinical decision-making and improved outcomes.

Discordance between MR enterography and endoscopic detection of Crohn's disease ileal strictures: evidence to inform recommendations.

To evaluate correlation between terminal ileal (TI) stricture diagnosis at MR enterography (MRE) and ileocolonoscopy (IC) in patients with Crohn's disease (CD). One hundred and four patients with CD (51% females; 41 ± 15 years) underwent IC and MRE within 3 months in this retrospective case-control study. Positive cases had TI strictures diagnosed by endoscopy (n = 35); or MRE (threshold small bowel dilation ≥ 3cm; n = 34). Negative controls did not have stricture by either modality (n = 35). Three radiologists examined MRE exams, with per-patient stricture diagnosis based on majority agreement. Sensitivity for stricture diagnosis using threshold dilation of 2.5 cm at MRE was also evaluated. There were 69 CD TI strictures (57 by endoscopy; 43 by MRE). Sensitivity by endoscopy and MRE criteria were 82.6% (57/69) and 62.3% (43/69), respectively, with additional 20.3% (14/69) of MRE exams classified as "probable stricture" by SAR/AGA/SPR criteria. Lowering MRE small bowel dilation threshold to 2.5 cm increased MRE sensitivity for endoscopically-diagnosed strictures to 71.9% (41/57; up from 56.1% [32/57]), without sacrificing interobserver agreement (κ = 0.684 vs. κ = 0.587). Of 25 new patients diagnosed with a TIstricture using a 2.5 cm threshold by 2 or more readers, 96% (24/25) had hospitalization, small bowel obstruction, endoscopic dilation, and/or surgical resection during clinicalfollow-up. Nine false negative MRE exams had short strictures with bowel dilation ≥ 2.5 cm. Either IC or MRE alone is insufficient to diagnose Crohn's small bowel strictures. Diagnostic criteria should incorporate endoscopic and MRE findings. Lowering threshold dilation to 2.5 cm increases sensitivity in stricture diagnosis and identifies clinically significant strictures.

A case of nasal endoscopy contributing to the diagnosis of terminal ileal stenosis

A case of nasal endoscopy contributing to the diagnosis of terminal ileal stenosis

VS 01 - BN Chronic loop gastrojejunostomy volvulus masquerading as a Crohn’s stricture

Abstract Background A video presentation of a case of chronic loop gastrojejunostomy volvulus masquerading as a Crohn's stricture. Method 61 year old female with a previous loop gastrojejunostomy and subsequent ileocaecal resection for Crohn's related pyloric stenosis and terminal ileal stricture. Acute worsening of post-prandial pain and vomiting 5 years later, re-investigation revealed a stenosed gastrojejunostomy thought to be Crohn's related. Results Intraoperative volvulus of the gastrojejunostomy was demonstrated related to traction forces resulting in the migration of the duodeno-jejunal flexure to the right of midline. The gastrojejunostomy was revised to a Roux-en-Y configuration with relief of mechanical obstruction. Conclusion An ileocaecal resection may create unexpected traction forces

Retrograde endoscopic ultrasound-guided entero-enterostomy for the management of a high-output enterocutaneous fistula and ileal stricture in a complex surgical abdomen.

Retrograde endoscopic ultrasound-guided entero-enterostomy for the management of a high-output enterocutaneous fistula and ileal stricture in a complex surgical abdomen.

S4926 Successful Multidisciplinary Treatment of Small Bowel Obstruction with Ileal Stricture Resulting in Bowel Perforation in the Setting of Multidrug-Resistant Gastrointestinal Tuberculosis: A Case Report

S4926 Successful Multidisciplinary Treatment of Small Bowel Obstruction with Ileal Stricture Resulting in Bowel Perforation in the Setting of Multidrug-Resistant Gastrointestinal Tuberculosis: A Case Report

Neonatal intestinal obstruction secondary to Meckel's diverticulum with associated band and ileal stricture: A case report

Background: Symptomatic Meckel’s diverticulum is exceptionally rare in neonates, often presenting as intestinal obstruction or perforation. The differential diagnosis may encompass more prevalent conditions like intestinal atresia, malrotation, or Hirschsprung's disease. Case Presentation: We present a case of a 21-day-old female who presented with intestinal obstruction. Exploratory laparotomy revealed Meckel's diverticulum with a mesodiverticular band causing closed-loop obstruction along with three passable strictures in the ileum. Surgical resection of the affected bowel and the creation of an ileostomy were performed due to bowel ischemia and hemodynamic instability. Conclusion: Early diagnosis and prompt surgical intervention are pivotal in managing neonatal Meckel's diverticulum, reducing risks of bowel necrosis and complications.

Reliability of CT Enterography for Describing Fibrostenosing Crohn Disease.

Background Standardized methods to measure and describe Crohn disease strictures at CT enterography are needed to guide clinical decision making and for use in therapeutic studies. Purpose To assess the reliability of CT enterography features to describe Crohn disease strictures and their correlation with stricture severity. Materials and Methods A retrospective study was conducted in 43 adult patients with symptomatic terminal ileal Crohn disease strictures who underwent standard-of-care CT enterography at a tertiary care center at the Cleveland Clinic between January 2008 and August 2016. After training on standardized definitions, four abdominal radiologists blinded to all patient information assessed imaging features (seven continuous measurements and nine observations) of the most distal ileal stricture in two separate sessions (separated by ≥2 weeks) in random order. Features with an interrater intraclass correlation coefficient (ICC) of 0.41 or greater (ie, moderate reliability or better) were considered reliable. Univariable and multivariable linear regression analysis identified reliable features associated with a visual analog scale of overall stricture severity. Significant reliable features were assessed as components of a CT enterography-based model to quantitate stricture severity. Results Examinations in 43 patients (mean age, 52 years ± 16 [SD]; 23 female) were evaluated. Five continuous measurements and six observations demonstrated at least moderate interrater reliability (interrater ICC range, 0.42 [95% CI: 0.25, 0.57] to 0.80 [95% CI: 0.67, 0.88]). Of these, 10 were univariably associated with stricture severity, and three continuous measurements-stricture length (interrater ICC, 0.64 [95% CI: 0.42, 0.81]), maximal associated small bowel dilation (interrater ICC, 0.80 [95% CI: 0.67, 0.88]), and maximal stricture wall thickness (interrater ICC, 0.50 [95% CI: 0.34, 0.62])-were independently associated (P value range, <.001 to .003) with stricture severity in a multivariable model. These three measurements were used to derive a well-calibrated (optimism-adjusted calibration slope = 1.00) quantitative model of stricture severity. Conclusion Standardized CT enterography measurements and observations can reliably describe terminal ileal Crohn disease strictures. Stricture length, maximal associated small bowel dilation, and maximal stricture wall thickness are correlated with stricture severity. © RSNA, 2024 Supplemental material is available for this article. See also the article by Rieder et al in this issue. See also the editorial by Galgano and Summerlin in this issue.

Reliability of MR Enterography Features for Describing Fibrostenosing Crohn Disease.

Background Clinical decision making and drug development for fibrostenosing Crohn disease is constrained by a lack of imaging definitions, scoring conventions, and validated end points. Purpose To assess the reliability of MR enterography features to describe Crohn disease strictures and determine correlation with stricture severity. Materials and Methods A retrospective study of patients with symptomatic terminal ileal Crohn disease strictures who underwent MR enterography at tertiary care centers (Cleveland Clinic: September 2013 to November 2020; Mayo Clinic: February 2008 to March 2019) was conducted by using convenience sampling. In the development phase, blinded and trained radiologists independently evaluated 26 MR enterography features from baseline and follow-up examinations performed more than 6 months apart, with no bowel resection performed between examinations. Follow-up examinations closest to 12 months after baseline were selected. Reliability was assessed using the intraclass correlation coefficient (ICC). In the validation phase, after five features were redefined, reliability was re-estimated in an independent convenience sample using baseline examinations. Multivariable linear regression analysis identified features with at least moderate interrater reliability (ICC ≥0.41) that were independently associated with stricture severity. Results Ninety-nine (mean age, 40 years ± 14 [SD]; 50 male) patients were included in the development group and 51 (mean age, 45 years ± 16 [SD]; 35 female) patients were included in the validation group. In the development group, nine features had at least moderate interrater reliability. One additional feature demonstrated moderate reliability in the validation group. Stricture length (ICC = 0.85 [95% CI: 0.75, 0.91] and 0.91 [95% CI: 0.75, 0.96] in development and validation phase, respectively) and maximal associated small bowel dilation (ICC = 0.74 [95% CI: 0.63, 0.80] and 0.73 [95% CI: 0.58, 0.87] in development and validation group, respectively) had the highest interrater reliability. Stricture length, maximal stricture wall thickness, and maximal associated small bowel dilation were independently (regression coefficients, 0.09-3.97; P < .001) associated with stricture severity. Conclusion MR enterography definitions and scoring conventions for reliably assessing features of Crohn disease strictures were developed and validated, and feature correlation with stricture severity was determined. © RSNA, 2024 Supplemental material is available for this article. See also the article by Rieder and Ma et al in this issue. See also the editorial by Galgano and Summerlin in this issue.

A Novel Method to Localize Patency Capsule by Ileocolonoscopy Facilitates Endoscopic Assessment of the Small and Large Intestine in Patients with Crohn’s Disease

Introduction: Patients with Crohn’s disease (CD) require an assessment of small bowel lesions, while difficulties exist in performing small intestinal examinations, especially in small-sized medical offices. Small bowel capsule endoscopy (SBCE) is handy and can be performed in most clinical settings. The only drawback of SBCE is a requirement of patency testing prior to the exam because it sometimes requires CT scanning to localize the ingested patency capsule (PC), which may be a substantial burden for the patient. We have developed a novel PC detection system named PICS (patency capsule, ileocolonoscopy, and small bowel capsule endoscopy) method by which we can avoid CT scanning. In the PICS method, ileocolonoscopy (ICS) is performed after 30–33 h of PC ingestion and the PC can be localized by ICS in patients who have not excreted the PC, and the entire intestine can be examined in combination with subsequent SBCE without additional bowel preparation. The aim of this study was to assess the usefulness and safety of the PICS method for CD patients. Methods: CD patients who underwent PICS method from April 2021 to March 2023 were reviewed for clinical data, outcome of PICS method including the rates of PC detection by ICS, the number of patients underwent SBCE, and adverse events. Lewis score was used to assess SBCE results. Results: The PICS method was performed in 54 patients. The median age of patients was 28.5 years old, and 64.8% of them were ileocolic type. The median disease duration was 10.5 months and 24.1% had history of small bowel resection. Five cases (9.3%) confirmed gastrointestinal patency by ICS, and none of the cases required CT scanning. One patient who could not be confirmed patency by ICS, and the other patient who excreted PC but was found ileal stenosis by ICS did not undergo SBCE. Remaining 52 patients received SBCE, and the median Lewis score of them was 0 (IQR 0, 450). There were no adverse events including small bowel obstruction by PC and SBCE retention in this series. Conclusion: The PICS method is not only feasible and safe but also convenient to assess disease extent in patients with CD. By localizing PC with ICS, additional CT scanning could be unnecessary for SBCE, which benefits both physicians and CD patients.

Clinico-Epidemiological Analysis of Small Bowel Obstruction in Adults at a Tertiary Care Center in India.

Acute small bowel obstruction (SBO) is a common surgical emergency.The study aims to provide a comprehensive clinical-epidemiological description of SBO in adults at a tertiary care center in western India. Thishospital-based cross-sectionalstudy was conducted from July 2020 to June 2022 and enrolled88SBO patients requiring surgical intervention. After adequately resuscitating the patients, various surgical procedures were performed based on the intraoperative conditions of the bowel. Patients were assessedpostoperativelyfor the duration of their hospital stay, postoperative complications, and surgical recovery. There was amalepreponderance (n=55), with a median age of 50 (18-90) years. Abdominal discomfort was the most frequent symptom, necessitating a hospital visit (97.9%, n= 86), followed by nausea (85.2%, n= 75), constipation (78.1%, n=69), and abdominal distension (51.1%, n=45). Ileal strictures (18.2%, n=16) were the most common etiology,followed by postoperative adhesions (14.8%, n=13) and bands (13.6%, n=12), of which 76.4% (n=9) had past surgical history. Resection and anastomosis were the most frequently performed surgical interventions in this study (36.4%, n=32), followed by stoma creation (27.3%, n=24) and adhesiolysis (17%, n=15). The postoperative 30-day mortality of 11.36% (n=10) was noted, which could be ascribed to the elderly population with comorbidity, postoperative complications, and who required extended stay in the critical care unit. Benign ileal stricture was the most common cause of acute SBO in the emergency. Prompt and timely diagnosis combined with a multidisciplinary approach and effective management can improve outcomes and reduce morbidity and mortality in adult patients with SBO.

Radiomics to Detect Inflammation and Fibrosis on Magnetic Resonance Enterography in Stricturing Crohn's Disease.

Non-invasive cross-sectional imaging via magnetic resonance enterography [MRE] offers excellent accuracy for the diagnosis of stricturing complications in Crohn's disease [CD] but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathological inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE. This single-centre, cross-sectional study included 51 CD patients [n = 34 for discovery; n = 17 for validation] with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both were evaluated against histopathology. Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both the discovery (area under the curve [AUC = 0.69, 0.83] and validation [AUC = 0.67, 0.78] cohorts. Radiologist visual scoring had an AUC = 0.67 for identifying severe inflammation and AUC = 0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation [AUC = 0.79] and modestly improved assessment of severe fibrosis [AUC = 0.79 for severe fibrosis] over individual approaches. Radiomic features of CD strictures on MRE can accurately identify severe histopathological inflammation and severe histopathological fibrosis, as well as augment performance of the radiologist visual scoring in stricture characterization.

Differential expression of small bowel TGFβ1 and TGFβ3 characterizes intestinal strictures in patients with fibrostenotic Crohn's disease.

Small bowel strictures remain a debilitating consequence of Crohn's disease and contribute to poor outcomes for patients. Recently, TGFβ has been identified as an important driver of intestinal fibrosis. We studied the localization of TGFβ isoforms in ileal strictures of patients with Crohn's disease using in situ hybridization to understand TGFβ's role in stricture formation. The mucosa of strictures was characterized by higher TGFβ1 while the stricture submucosa showed higher TGFβ3 compared to normal ileum from patients without Crohn's disease (p = 0.02 and p = 0.044, respectively). We correlated these findings with single-cell transcriptomics which demonstrated that TGFβ3 transcripts overall are very rare, which may partially explain why its role in intestinal fibrosis has remained unclear to date. There were no significant differences in fibroblast or B cell TGFβ1 and/or TGFβ3 expression in inflamed vs. noninflamed ileum. We discuss the implications of these findings for therapeutic development strategies to treat patients with fibrostenotic Crohn's disease.

Imaging and clinical predictors of surgery in stricturing ileal Crohn's disease: a retrospective study from a large pediatric hospital.

(1) To determine the frequency of surgical management in children with Crohn's Disease (CD) and a new radiologic ileal stricture, and (2) to identify imaging and clinical features that predict the need for surgery. This retrospective study included pediatric patients (< 21 years old) with CD and a new ileal stricture diagnosed by MRE, CTE, or CT between July 2018 and June 2023. Three board-certified radiologists recorded stricture length, maximum mural thickness, minimum lumen diameter, maximum upstream diameter, and simplified magnetic resonance index of activity (sMaRIA) score. Anthropometrics, laboratory data, and surgical interventions performed after stricture diagnosis were also recorded. Multivariable logistic regression was used to identify imaging and clinical variables associated with the need for surgery. 44 pediatric CD patients (median age 16.5years) presented with a new ileal stricture during the study period. 30 (68.2%) patients required surgery, with a median time of 87.5days between stricture diagnosis and surgery. Median stricture measurements were length: 7.0cm, maximum mural thickness: 7.3mm, minimum lumen diameter: 0.2cm, and maximum upstream diameter: 3.3cm. Median sMaRIA score was 3.0, and 14 (31.8%) strictures had associated internal penetrating disease. Stricture ratio (ratio of maximum upstream lumen diameter to minimum lumen diameter) (OR = 1.15 [95% CI 1.02-1.30]; p = 0.02) and sMaRIA (OR = 2.12 [95% CI 0.87-5.17; p = 0.10) were associated with need for surgery. Surgery remains common in stricturing pediatric CD, with increasing stricture ratio and sMaRIA score associated with need for surgical management.

A234 DOES FECAL CALPROTECTIN CORRELATE WITH INFLAMMATION ON ULTRASOUND IN CROHN’S DISEASE STRICTURES?

Abstract Background Fibrostenotic Crohn’s Disease (CD) is a challenging phenotype particularly due to the absence of intestinal anti-fibrotic therapies. Differentiating between strictures that are predominantly fibrotic as opposed to inflammatory remains a diagnostic dilemma. The ability to make this differentiation is critical to inform decisions for therapeutic approach. Fecal calprotectin (FC) is a stool marker reflective of intestinal inflammation. Very few studies have evaluated the relationship of FC concentration in ileal CD strictures and parameters of inflammation on intestinal ultrasound (IUS). Strictures on imaging are defined as 1) increased bowel wall thickness (BWT), 2) narrowed luminal apposition, and 3) pre-stenotic dilation (PSD). BWT and hyperemia (color Doppler signal (CDS)) are the most sensitive markers for CD inflammation on IUS. It is predicted that FC will match CDS in ileal strictures, similar to non-stricture phenotypes. Aims We aim to correlate FC levels with IUS inflammation of ileal CD strictures. Methods We performed a retrospective cohort pilot study exploring the relationship between FC levels and IUS inflammatory parameters in ileal strictures. FC levels were obtained ≤ 60 days of index IUS in fibrostenotic ileal CD patients. Individuals who underwent medication changes or experienced a clinical flare during this period were excluded. Inflammation was measured as BWT and CDS using a modified Limberg (ML) score. Pearson correlation for continuous variables, Spearman rank correlation and a Kruskal-Wallis test for FC and Limberg scale were completed. Results A total of 25 fecal samples were obtained from 17 patients with ileal strictures (47% male, median age 59 years (range 18-76)) were assessed. Median FC concentrations was 204.9 ug/g, IQR: 250.4. Median ileal stricture BWT was 7.0 mm (range 3.0–10.0). 40% (10/25) had ML1 (short chains in bowel), 32% (8/25) ML2 (long chains in bowel), and 28% (7/25) ML3 (long chains and perienteric fat). There was no correlation between FC and BWT (r= .02, p = 0.92), nor FC with ML scores (r=0.20, p= 0.25). In those with ML1, median FC was 232.4, while those with ML2 or 3, had a FC of 155.6 and 469.7, respectively. FC values were significantly different between the ML scores, pampersand:003C0.0001. Conclusions FC levels were not correlated with inflammatory parameters as seen on IUS in ileal CD. This unexpected finding may be due to ML2 scores having lower FC than anticipated, and small sample size. Other imaging factors such as loss of wall stratification need to be taken into account, and are perhaps more reflective of inflammation than BWT and CDS. This study provides the initial data to assess accuracy of FC and hyperemia of ileal CD strictures on IUS compared to histologic measures of inflammation on resected specimens. Funding Agencies None

A243 BONE MINERAL DENSITY AND DIETARY BONE NUTRIENTS DIFFER IN PATIENTS WITH CROHN'S DISEASE STRICTURES

Abstract Background Crohn’s disease (CD) phenotypes include inflammatory (non-stricture) and stricture behaviours. Strictures are bowel narrowing’s that may lead to obstructions and subsequent dietary restrictions to prevent blockages. Bone mineral density (BMD) in CD is affected by many factors including corticosteroid use, CD itself, but also dietary changes. Clinical gold standard for measuring BMD is by dual x-ray absorptiometry (DXA) scans. High-resolution peripheral quantitative computed tomography (HR-pQCT), a more precise imaging modality assesses volumetric BMD, bone geometry and bone microarchitecture. We aim to compare dietary intake, and bone quality in both stricture and non-stricture CD. Aims To identify nutritional patterns, bone quality differences and deficiencies between two subtypes of CD; including energy intake, dietary components and/or micronutrients Methods Individuals (≥55 years old) with ileal CD strictures (fixed, angulated bowel or thickened bowel with pre-stenotic dilation on diagnostic imaging), or inflammatory CD were prospectively recruited. Patients with short gut, celiac disease, dysphagia history were excluded. All patients completed DXA hip and spine scans and HR-pQCT radius and tibia scans. Dietary assessment questionnaires (Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24), and Diet History Questionnaire III for food frequency over the past year were completed. Results 56 (27 inflammatory (48% female, mean age 64.2, BMI 28.7, 16 years CD duration) and 29 strictures (45% female, mean age 65.9, BMI 27.3, 25 years CD duration, 15 (51.7%) prior bowel resection) were included. 31/56 (55.4%) patients were on biologics and 11 (19.5%) had past corticosteroid exposure. DXA-based BMD for stricture versus non-stricture CD patients was not significantly different at the hip or spine. However, HR-pQCT-based radial total BMD (p=0.03), cortical thickness (p=0.01) and cortical area (p=0.04) were lower in stricture than non-stricture patients.11 (7 stricture, 4 inflammatory) patients with past steroids consumed more dairy (p=0.01), vitamin D (p = 0.04), and calcium (p=0.03) than other CD patients. Stricture patients had significantly less consumption of vitamin K (p=0.001), vegetables (p=0.02), calcium (p=0.03), and dairy (p=0.03). Conclusions Patients with CD strictures have lower BMD and cortical bone quality at the radius than those without strictures. Patients with CD strictures also consume significantly less vitamin K, calcium, and dairy, all vital dietary components to prevent OP, compared to non-stricture patients. Overall, the skeletal fracture risk is likely much greater in CD patients with strictures than without, due to greater inherent bone fragility, and less consumption of key nutrition building blocks of bones. Funding Agencies Koopmans Memorial Research Fund

A130 RETROGRADE ENDOSCOPIC ULTRASOUND-GUIDED ENTERO-ENTEROSTOMY USING A LUMEN-APPOSING METAL STENT FOR THE MANAGEMENT OF A HIGH-OUTPUT ENTEROCUTANEOUS FISTULA AND ILEAL STRICTURE IN A COMPLEX SURGICAL ABDOMEN

Abstract Background A 26-year-old male sustained significant traumatic thoracoabdominal injuries following a gunshot. He underwent several laparotomies, small bowel resections, an extended left hemicolectomy with end-colostomy formation, and a flap to close the abdomen. He subsequently developed a high-output enterocutaneous fistula (ECF) and loss of colostomy output. CT imaging confirmed an ECF from the ileum to the anterior abdominal wall and a severe ileal stricture distal to the fistula. Aims In the context of his complex surgical abdomen and proximity of the ECF to the abdominal flap, surgical re-intervention was deemed high-risk. He was placed on total parenteral nutrition and referred for endoscopic management. Methods Under fluoroscopic guidance, we injected methylene blue &amp; contrast dye from the skin side of the ECF. A dilated segment of small bowel was filled, with no downstream passage of contrast (Fig 1A). Retrograde ileoscopy was performed with an Olympus pediatric colonoscope via the patient’s colostomy. 90 cm from the ileocecal valve (ICV), we encountered a benign enteric stenosis that could not be traversed. Contrast was injected, with fluoroscopy revealing a 10 cm long tortuous stenosis (Fig 1B), extending to the previously filled loop of small bowel. Given the length and characterof the stricture, endoscopic balloon dilation and enteral stenting were technically infeasible. Results We proceeded to retrograde endoscopic ultrasound (EUS)-guided entero-enterostomy creation. With the aid of a guidewire, and under endoscopic, fluoroscopic and endosonographic guidance, a linear echoendoscope was advanced into the ileum via the colostomy, cecum and ICV. 50 cm from the ICV, we identified an adjacent dilated loop of small bowel (Fig. 1C). Water was instilled through the ECF, with the endosonographic view demonstrating filling, thus indicating this location to be upstream from the ECF. A 19-gauge needle was punctured through, with subsequent aspiration of methylene blue (Fig. 1D). We then created an EUS-guided entero-enterostomy using a 15mm lumen-apposing metal stent (Hot-AXIOS; Boston Scientific, Massachusetts, USA; Fig. 1E). Passage of methylene blue &amp; contrast through the stent confirmed accurate deployment (Fig. 1F&amp;G). With both the ECF &amp; stricture bypassed, the patient’s colostomy output returned and ECF output diminished. Conclusions Electrocautery-enhanced lumen apposition with metal stenting is well established. It can facilitate the formation of an anchored anastomosis across non-adherent luminal structures in a single-step fashion. Herein, we have reported a novel application of this technique in the management of a complex post-surgical trauma patient with a high-output ECF and deep enteric stenosis. Figure 1: Retrograde EUS-guided entero-enterostomy Funding Agencies None

P476 Correlation between fecal calprotectin and inflammation on ultrasound in fibrostenotic Crohn’s Disease

Abstract Background Fibrostenotic Crohn’s Disease (CD) is a challenging phenotype particularly due to the absence of intestinal anti-fibrotic therapies. Differentiating between strictures that are predominantly fibrotic versus inflammatory remains a diagnostic dilemma. The ability to make this differentiation is critical to inform therapeutic decisions. Fecal calprotectin (FC) is a stool marker reflective of intestinal inflammation. Very few studies have evaluated the relationship of FC concentration in ileal CD strictures and parameters of inflammation on intestinal ultrasound (IUS). Strictures on imaging are defined as 1) increased bowel wall thickness (BWT), 2) narrowed luminal apposition, and 3) pre-stenotic dilation (PSD). BWT and hyperemia (color Doppler signal (CDS)) are the most sensitive markers for CD inflammation on IUS. It is predicted that FC will match CDS in ileal strictures, similar to non-stricture phenotypes. We aim to correlate FC levels with IUS inflammation of ileal CD strictures. Methods We performed a retrospective cohort pilot study exploring the relationship between FC levels and IUS inflammatory parameters in ileal strictures. FC levels were obtained ≤ 60 days of index IUS in fibrostenotic ileal CD patients. Individuals who underwent medication changes or experienced a clinical flare during this period were excluded. Inflammation was measured as BWT and CDS using a modified Limberg (ML) score. Pearson correlation for continuous variables, Spearman rank correlation and a Kruskal-Wallis test for FC and Limberg scale were completed. Results A total of 25 fecal samples were obtained from 17 patients with ileal strictures (47% male, median age 59 years (range 18-76)) were assessed. Median FC concentrations was 204.9 ug/g, IQR: 250.4. Median ileal stricture BWT was 7.0 mm (range 3.0–10.0). 40% (10/25) had ML1 (short chains in bowel), 32% (8/25) ML2 (long chains in bowel), and 28% (7/25) ML3 (long chains and perienteric fat). There was no correlation between FC and BWT (r=0.02, p=0.92), nor FC with ML scores (r=0.20, p=0.25). In those with ML1, median FC was 232.4, while those with ML2 or 3, had a FC of 155.6 and 469.7, respectively. FC values were significantly different between the ML scores, p&amp;lt;0.0001. Conclusion FC levels were not correlated with inflammatory parameters as seen on IUS in ileal CD. This unexpected finding may be due to ML2 scores having lower FC than anticipated, and small sample size. Other imaging factors such as loss of wall stratification need to be taken into account, and are perhaps more reflective of inflammation than BWT and CDS. This study provides the initial data to assess accuracy of FC and hyperemia of ileal CD strictures on IUS compared to histologic measures of inflammation on resected specimens.

DOP61 Up-regulated Gremlin 1 in fibroblasts from Crohn’s Disease fibrotic strictures: A potential therapeutic target

Abstract Background Fibrosis is a common complication in Crohn’s disease (CD), often leading to intestinal strictures that are refractory to available biologic drugs and require surgery. Addressing this complication remains a significant unmet need. This study aims to explore the transcriptomic signature of fibrostenotic ileal CD to identify novel therapeutic targets. Methods 9 CD patients undergoing surgery for fibrotic strictures were prospectively recruited. All patients underwent magnetic resonance enterography, ileoscopy, and assessment of C-reactive protein and faecal calprotectin. A multidisciplinary team adjudicated the presence of fibrotic strictures, warranting surgical resection. Resected specimens were harvested directly from the operating theatre and delivered fresh to pathologists, who dissected samples from the strictured area, and the proximal and distal non-strictured regions. RNA was extracted from all samples for bulk-transcriptomic and single-cell RNA sequencing (scRNAseq) analysis, using the 10x Chromium Controller® platform. Differentially expressed genes (adj. p-value &amp;lt;0.05) were identified. Machine learning analyses, including PCA and PLS-DA, were employed to compare gene expression patterns among different tissue segments. Pathway enrichment analysis pinpointed relevant pathways. Further, the random forest model was constructed to evaluate the predictive significance of genes in relation to strictures, and the resulting ranked list of genes was subsequently validated through qPCR, confirming the significance of selected genes. Results Bulk-transcriptomic analysis revealed 64 significantly up-regulated genes in strictures, associated with inflammation, matrix remodeling, adipogenesis and cellular stress. Furthermore, 17 down-regulated genes were linked to epithelial barrier integrity. Normalised gene expression of GREM1, SERPINE1, FGF2, HDAC1 AND LY96 showed high predictive value for strictures compared to distal and proximal segments. Notably, qPCR confirmed the significant up-regulation of GREM1 expression exclusively in the ileal stricture samples (non-stricture vs. stricture: AUC 0.88, 95% CI 0.77-0.95). scRNAseq linked up-regulated GREM1 exclusively to the fibroblast cell population (THY1+, COL1A1+,ACTA2+). Conclusion Bulk and single-cell transcriptomics, along with qPCR validation of resected CD ileal strictures, showed the up-regulation of GREM1 in fibroblasts within stricture compared to adjacent proximal and distal intestinal samples. These findings confirmed in ileal CD previous reports from animal models, highlighting the role of GREM1 in promoting intestinal fibrosis. Therefore, GREM1 emerges an attractive target for the treatment of fibrotic strictures in CD.

P750 Endoscopic balloon dilation associated with biological therapy in Crohn's Disease strictures: a single center experience

Abstract Background Symptomatic luminal stricture in Crohn’s Disease (CD) occurs in up to 20% of patients at the diagnosis and in more than 50% during their lifetime. A considerable percentage of patients often require further surgery for post-operative CD recurrence, with a consequent increased burden of short bowel syndrome. In this scenario, combining biological therapy with endoscopic balloon dilation (EBD) could potentially reduce this risk. Our study aimed to evaluate the efficacy of EBD combined with biologic therapy in symptomatic gastrointestinal strictures in CD patients. Methods We conducted a retrospective study including consecutive CD patients who underwent EBD for low gastrointestinal strictures from December 2015 until November 2022 at our tertiary IBD Center. Subsequent subocclusive/occlusive episodes, the need for steroids, and surgery due to CD stenosis were evaluated during a follow-up period of 6 and 12 months. Results A total of 52 patients treated with EBD with an overall number of 55 strictures were included. The mean age was 46,8 (18-77) years. The median of disease duration was 9 (0-42) years. Among the total of 55 studied strictures: 14 (25%) in patients with active smoking, 21 (38%) with increased CRP values at the time of dilation, 43 (78%) had evidence of moderate or severe endoscopic disease activity with ulcerative lesions at stricture site. Anastomotic strictures accounted for 26 (47%) of all 55 strictures. The remaining 29 (53%) were de novo stricture: 8 (15%) ileal, 11 (20%) at ileocecal valve, 4 (7%) colonic, and 6 (11%) anal . Forty-two patients (76%) were under biologic therapy at the time of EBD and 2 (4%) started after EBD. EBD technical success was reported in 60% of the procedures, and no adverse events were recorded. After 6 months from EBD, at univariate analysis, increased CRP at the time of dilation resulted in a risk factor for the need for steroids (OR 14,63, IC 2,690 to 71,50; p-value = 0,0006, Table 2). Concomitant biological therapy, active smoke, and the presence of ulcerative lesions did not show a significant correlation with considered outcomes. After 12 months from EBD, concomitant biological therapy resulted in being a protective factor for surgery (OR 0,06; IC 0,005 to 0,502; p-value=0,0047), while subocclusive and occlusive events were less frequent in anastomotic strictures than ileal stenosis (OR 0,07; IC 0,005 to 0,651; p-value=0,0152). Conclusion In patients with CD undergoing EBD for intestinal CD stricture, concomitant biological therapy reduces the risk of surgery for CD stenosis recurrence. Further prospective and controlled studies are underway to confirm these observations.