Holubar, Stefan D

Abstract Background & Aims Stricturing Crohn’s disease (CD) is a significant problem, and no selective anti-fibrotic therapies are available. Anti-inflammatory approaches are the mainstay of medical treatment. However, data on the efficacy of ustekinumab (USTE) in ileal stricturing CD are lacking. Our aim was to assess its efficacy in this setting. Methods We performed an international multicenter observational cohort study evaluating adult CD patients who received USTE within 6 months of imaging-confirmed symptomatic stricturing small bowel disease. Outcomes were rates of endoscopic balloon dilation (EBD), surgery, intervention (defined as the composite need for EBD or surgery), recurrent obstructive symptoms, and USTE persistence. Results Fifty-seven patients were included (51% female, median age 43 years). Median follow-up was 17 months. Intervention rates were 35%, 45%, and 69% of patients, at 12, 24, and 48 months, respectively. USTE persistence was 78%, 76%, and 52% at 12, 24, and 48 months. Estimated obstructive symptoms rates were 31% and 49% at 12 and 24 months, respectively. EBD within 6 months prior to starting USTE was associated with an increased risk of intervention. Increased bowel wall thickness on imaging, prior biologic use, and obstructive symptom duration were associated with USTE discontinuation. Occurrence of obstructive symptoms during treatment was associated with prior biologic use, EBD within 6 months of starting USTE, and a lower BMI. Conclusions USTE appears to be an appropriate medical option in biologic-experienced CD patients with ileal strictures. Further prospective data are needed to better define outcomes and predictors of response in this setting.

Abstract Background Patients with Crohn disease (CD) face an elevated risk of developing small bowel adenocarcinoma (SBA), a malignancy characterized by late-stage diagnosis and poor prognosis. In this study we aimed to characterize surgical management and oncologic outcomes for CD-associated SBA. Methods A retrospective review was conducted across 3 tertiary IBD centers, analyzing 99 patients with CD who underwent surgery for SBA between 1992 and 2025. Data included patient demographics, CD history, surgical details, and oncologic outcomes. Results The median time from CD diagnosis to SBA was 25 years. The SBA diagnosis was incidental in 74.8% of cases, discovered during surgery for other complications. Tumors were predominantly located in the ileum (80.8%) and showed aggressive features: 56.6% were poorly differentiated (grade 3), and 85.9% were pathologically advanced (T3/T4 on TNM staging). Nodal involvement was present in 45.5% of patients, and 18.2% had distant metastases at diagnosis. A complete (R0) resection was achieved in 90.9% of surgeries, with a 30-day morbidity rate of 26.3%. After a median follow-up of 36 months, the distant recurrence rate was 28.3%, and overall mortality was 27.3% (18.2% cancer related). Conclusion In patients with long-standing CD, SBA is typically an incidental diagnosis made at an advanced stage. While high rates of complete surgical resection are possible, the prognosis remains guarded due to aggressive tumor biology and high recurrence rates. These findings highlight a critical need for improved risk stratification to guide surveillance and for the development of evidence-based adjuvant treatment strategies.

Abstract Background and Aims Over 10% of patients with Crohn’s disease require permanent ileostomy. We aimed to summarize the existing data on diagnosis, definitions of recurrence, and management of Crohn’s disease patients with permanent ileostomy. Methods MEDLINE, Embase, and CENTRAL databases were searched from inception to February 6, 2024. Randomized controlled trials, cohort and cross-sectional studies, and case series of more than 5 patients reporting on postoperative recurrence or the need for surgery in patients with Crohn’s disease and permanent ileostomy were included. Search results were independently screened, and full text of all titles meeting eligibility criteria was obtained. Outcomes of interest included diagnostic techniques, recurrence definitions, and management approaches. We estimated pooled rates (with 95% confidence interval [CI]) of recurrence. Results Thirty cohort studies including 2055 Crohn’s patients with permanent ileostomy were included (53% female, median age at the time of ileostomy creation 32 years, the most common reason for ileostomy was refractory disease). The postoperative recurrence rate was 27% (95% CI, 21.3–33.3, 26 studies, 451/1805 patients). Modalities for diagnosis of Crohn’s disease recurrence were symptoms (15 studies), endoscopy (4 studies), histology from endoscopic biopsies (2 studies), imaging (5 studies), and surgery (22 studies). The reported definitions of recurrence for each modality were heterogeneous. Conclusions There is a lack of standardized monitoring tools and criteria for diagnosing recurrence in patients with Crohn’s disease and permanent ileostomy. The results of this systematic review will form the basis of a global expert recommendation exercise focused on developing management standards and trial endpoints for this condition.

AbstractBackgroundInflammatory bowel disease (IBD) affects more than 10 million people worldwide. Men and women are equally affected by Crohn's disease (CD). It has been shown that patients with CD are at an increased risk of a colorectal cancer (CRC) diagnosis and CRC‐related mortality. During the last two decades, biological therapies have revolutionized the treatment of CD. There are no current studies investigating the prevalence of CRC in patients with CD in the era of biological therapy and the possible features of patients with CD who are at high risk of developing CRC.AimWe aim to assess the prevalence of CRC, risk factors and profile of CRC in patients with CD receiving biological treatment compared with those who are not under biological therapy and the impact of CD‐associated colorectal strictures on CRC development. The study hypothesis is that the use of biological therapy in the control of CD activity may decrease the risk of developing CRC.Study design and settingAn international, retrospective, snapshot of the prevalence of CRC in patients with CD, reported according to the SPIRIT guidelines. The study will involve centres that hold regular IBD multidisciplinary team meetings and have both IBD colorectal surgeons and gastroenterologists. Each participating centre will provide a local consultant lead and a local trainee lead. Data will be collected within a 2‐year recruitment period (January 2017–January 2019).Study populationAdult patients who presented with CD during the study period. Patients with an incidental diagnosis of CD during evaluation for CRC will be excluded.Statistical planBaseline patient characteristics will be summarized using the appropriate descriptive statistics. Univariable, multivariable and Cox regression models will be used to identify factors significantly associated with CRC. For noncontinuous variables a comparison between the subgroups will be carried out using the chi‐square test corrected by Fisher's exact test if appropriate. A p‐value of <0.05 will be considered statistically significant.Data storageData will be stored on a secured server, pin‐code protected according to the local data management agreement.

Abstract Aim Recent evidence challenges the current standard of offering surgery to patients with ileocaecal Crohn's disease (CD) only when they present complications of the disease. The aim of this study was to compare short‐term results of patients who underwent primary ileocaecal resection for either inflammatory (luminal disease, earlier in the disease course) or complicated phenotypes, hypothesizing that the latter would be associated with worse postoperative outcomes. Method A retrospective, multicentre comparative analysis was performed including patients operated on for primary ileocaecal CD at 12 referral centres. Patients were divided into two groups according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short‐term results were compared. Results A total of 2013 patients were included, with 291 (14.5%) in the ICD group. No differences were found between the groups in time from diagnosis to surgery. CCD patients had higher rates of low body mass index, anaemia (40.9% vs. 27%, p < 0.001) and low albumin (11.3% vs. 2.6%, p < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3% vs. 93.1%, p = 0.001) and higher conversion rates (9.3% vs. 1.9%, p < 0.001). CCD patients had a longer hospital stay and higher postoperative complication rates (26.1% vs. 21.3%, p = 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1% vs. 8.3%, p : 0.017). In multivariate analysis, CCD was associated with prolonged surgery (OR 3.44, p = 0.001) and the requirement for multiple intraoperative procedures (OR 8.39, p = 0.030). Conclusion Indication for surgery in patients who present with an inflammatory phenotype of CD was associated with better outcomes compared with patients operated on for complications of the disease. There was no difference between groups in time from diagnosis to surgery.

Abstract Background The level of inflammatory bowel disease (IBD) training in general gastroenterology fellowship is often insufficient to prepare trainees to deliver advanced IBD care in practice. Advanced IBD fellowships have been developed to fill this training gap, but there is no established curriculum, and significant variability exists across programs. Entrustable professional activities (EPAs) are practical and realistic objectives that define essential tasks of a specialty that physicians should master to be competent during independent practice. The American College of Gastroenterology (ACG) and Crohn’s & Colitis Foundation (Foundation) established a task force to develop and appraise EPAs for advanced IBD fellowship. Methods Entrustable professional activities were developed using a multistep approach in a similar manner to other specialties. Initial EPAs identified via focus groups were evaluated, critiqued, and changed using an iterative model of feedback. The final EPAs were selected after the task force conducted a 3-phase modified Delphi method consisting of 2 sequential rounds of web-based voting and an in-person consensus meeting. Results Ten EPAs for advanced IBD fellowship were established including detailed descriptions with the associated knowledge, skills, and attitudes for each that can serve as curricular milestones. Conclusion Ten EPAs describing the core work of an advanced IBD fellowship–trained physician have been established by a multisociety task force. Creating EPAs for an advanced curriculum comes with unique challenges, particularly the need to prevent duplication of prior training competencies while demonstrating the potential for unique milestones.

BACKGROUND: Risk factors for pouch survival may or may not have a linear relationship with pouch loss over time. Conditional survival is a method to describe these nonlinear time-to-event relationships by reporting the expected survival at various time points. OBJECTIVE: The aim of this study was to calculate conditional pouch survival based on occurrence of risk factors for pouch loss. DESIGN: This was a retrospective study from an institutional database. SETTINGS: The study was conducted at the Cleveland Clinic Foundation. PATIENTS: Patients with ulcerative or indeterminate colitis who underwent index IPAA construction between 1986 and 2016 were included. MAIN OUTCOME MEASURES: Patients were stratified based on postoperative anastomotic leak, abscess, or fistula occurrence. The Kaplan–Meier method with conditional survival was used to estimate overall and cause-specific survival at 10 years. RESULTS: A total of 3468 patients underwent IPAA during the study period. The overall 10-year pouch survival rate was 0.94 (95% CI, 0.93–0.95), and after 1 year the conditional pouch survival increased to 0.95 (95% CI, 0.94–0.96), after 3 years to 0.97 (95% CI, 0.96–0.98), and after 5 years to 0.98 (95% CI, 0.98–0.99). A total of 122 patients (3.5%) developed anastomotic leak, and the 10-year IPAA survival in patients with leak was 0.85 (95% CI, 0.77–0.93). In this group, after 1 year of pouch survival, the conditional pouch survival increased to 0.89 (95% CI, 0.82–0.96) and after 3 years to 0.98 (95% CI, 0.94–1.00). A similar pattern was seen for IPAA with postoperative abscess. The conditional survival curve was stable over time for patients with a fistula. LIMITATIONS: This was a retrospective, single-institution study. CONCLUSIONS: Overall conditional pouch survival improved over time for patients with postoperative anastomotic leak and abscess. These novel findings can be useful to counsel patients regarding expectations for long-term pouch survival even if they develop leaks and abscesses. See Video Abstract at http://links.lww.com/DCR/B217. SUPERVIVENCIA CONDICIONAL DESPUÉS DE ANASTOMOSIS CON BOLSA ÍLEO ANAL, PARA COLITIS ULCERATIVA E INDETERMINADA: ¿LA SOBREVIDA DE LA BOLSA A LARGO PLAZO, MEJORA O EMPEORA CON EL TIEMPO? ANTECEDENTES: Los factores de riesgo para la sobrevida de la bolsa, pueden o no tener una relación lineal con la pérdida de la bolsa y con el tiempo. La supervivencia condicional es un método para describir estas relaciones no lineales de tiempo, hasta el evento informando la supervivencia esperada en varios puntos de tiempo. OBJETIVO: El objetivo de este estudio fue calcular la supervivencia condicional de la bolsa, en función de aparición de factores de riesgo para la pérdida de bolsa. DISEÑO: Estudio retrospectivo de una base de datos institucional. AJUSTES: Cleveland Clinic Foundation. PACIENTES: Pacientes con colitis ulcerativa o indeterminada, sometidos a una anastomosis de bolsa íleo anal, de 1986 a 2016. PRINCIPALES MEDIDAS DE RESULTADO: Los pacientes fueron estratificados en función de la fuga anastomótica postoperatoria, absceso o aparición de fístula. El método de Kaplan Meier con supervivencia condicional, se utilizó para estimar la supervivencia general y la causa específica a los 10 años. RESULTADOS: Un total de 3.468 pacientes fueron sometidos a anastomosis ileal con bolsa anal durante el período de estudio. La tasa de supervivencia global de la bolsa a 10 años, fue de 0,94 (0,93 a 0,95), y después de 1 año, la supervivencia condicional de la bolsa aumentó a 0,95 (0,94 a 0,96), después de 3 años a 0,97 (0,96 a 0,98) y después de 5 años a 0.98 (0.98 - 0.99). Un total de 122 (3,5%) pacientes desarrollaron fuga anastomótica, y la supervivencia de la anastomosis de bolsa íleo anal a 10 años en pacientes con fuga fue de 0,85 (IC del 95%: 0,77 a 0,93). En este grupo, después de 1 año de supervivencia de la bolsa, la supervivencia condicional de la bolsa aumentó a 0,89 (IC del 95%: 0,82 a 0,96), y después de 3 años a 0,98 (IC del 95%: 0,94 a 1). Se observó un patrón similar para la anastomosis de bolsa íleo anal con absceso postoperatorio. La curva de supervivencia condicional fue estable en el tiempo para los pacientes con una fístula. LIMITACIONES: Estudio retrospectivo, de una sola institución. CONCLUSIONES: La supervivencia condicional global de la bolsa, mejoró con el tiempo para pacientes con fuga anastomótica postoperatoria y absceso. Estos nuevos hallazgos pueden ser útiles para aconsejar a los pacientes con respecto a las expectativas de supervivencia de la bolsa a largo plazo, incluso si desarrollan fugas y abscesos. Consulte Video Resumen http://links.lww.com/DCR/B217. (Traducción—Dr Fidel Ruiz Healy)