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 Global data demonstrate an inverse relationship between hospital ileoanal pouch volume and adverse outcomes, highlighting the need for quality metrics for this technically demanding procedure.1-4 Currently, there are no standardised quality indicators to define high-quality pouch surgery. This study aimed to establish international consensus on key performance indicators (KPIs) in pouch surgery. Methods A modified Delphi process was conducted among an international, multidisciplinary panel of experts. Participants were identified through professional networks, literature review, and direct email invitation; additional participants recruited via a snowball sampling approach over one month. Candidate KPIs were generated from literature review and expert input across 5 domains. Each item was rated on a 9-point Likert scale (1 = not important, 9 = critically important); consensus was predefined as ≥ 80% of respondents rating an item 7–9. Items not reaching consensus were re-rated in a second round following anonymized group feedback. Results Round 1 included 312 participants from 37 countries. Demographics (Table 1): 53% were age 45 years, 35.2% were female, and included surgeons (68.6%) and gastroenterologists (31.1%). Most (76.6%) practice at academic or university hospitals, with a median of 11 (5–17) years in practise; 78.9% perform >1 pouchoscopy per month, and 39.5% of surgeons perform 5 pouches/year. Respondents’ regions included North America (51%), Europe (26%), Oceania (9%), Asia (6%), Latin America (4%), and the Middle East/Africa (4%). Seven (18%) countries (Denmark, Lithuania, Malaysia, Norway, United Arab Emirates, Sweden, and Switzerland) reported pouch surgery is already centralised, while 70.6% agreed pouch centralisation should be implemented. Cost/logistics and professional autonomy were the most important barriers to centralisation, whereas capacity and training exposure were least important. Overall, 37/59 (62.7%) candidate KPIs reached consensus after Round 1. The Round 2 response rate was 61%, and 2 additional KPIs reached consensus (preop ileitis and long-term risk of pouchitis). Additionally, 14 of 25 (56%) informed consent items reached consensus, and 64% of respondents felt informed consent for pouch surgery requires 2 or more office visits. Consensus items were used to populate a KPIPS Checklist (Figure 1). Conclusion Through an international Delphi process, the KPIPS study identified a consensus-derived set of key performance indicators to measure quality in pouch surgery. These quality metrics provide a foundation for benchmarking outcomes and represent a critical step towards centralization and the development of designated pouch centres of excellence to improve global standards of care for pouch patients. References: 1. Worley GHT, Fearnhead NS, Brown SR, et al. Review of current practice and outcomes following ileoanal pouch surgery: Lessons learned from the ileoanal pouch registry and the 2017 ileoanal pouch report. Colorectal Dis 2018;20:913–22. 2. Giddings HL, Yang PF, Steffens D, Solomon MJ, Ng KS. Influence of hospital-level and surgeon factors on the outcomes after ileo-anal pouch surgery for inflammatory bowel disease: Systematic review. Br J Surg 2024;111. 3. Hoang CM, Maykel JA, Davids JS, et al. Distribution of elective ileal pouch-anal anastomosis cases for ulcerative colitis: A study utilizing the university health system consortium database. J Gastrointest Surg 2020;24:2613–9. 4. Moojen TB, Visser E, Reijntjes MA, et al. One-year stoma-free survival of ileoanal pouches for uc in european centers: The miracle project. Ann Surg Open 2025;6:e596. Conflict of interest: Prof. Holubar, Stefan: No conflict of interest Soop, Mattias: No conflict of interest Poskus, Tomas: No conflict of interest Neary, Peter: No conflict of interest Uchino, Tairin: No conflict of interest Yang, Song-soo: No conflict of interest Adamina, Michel: No conflict of interest Avellaneda, Nicolas Luis: No conflict of interest Barnes, Edward: No conflict of interest Brouquet, Antoine: No conflict of interest Brown, Steven Ross: No conflict of interest De Buck Van Overstraeten, Anthony: No conflict of interest Buskens, Christianne J.: No conflict of interest Chiorean, Michael: No conflict of interest Clark, David: No conflict of interest Cohen, Benjamin: No conflict of interest El Ouali, Sara: No conflict of interest Faiz, Omar Darius: No conflict of interest Fichera, Alessandro: No conflict of interest Hahnloser, Dieter: No conflict of interest Hancock, Laura: No conflict of interest Herfarth, Hans: No conflict of interest Johnston, Michael: No conflict of interest Kayal, Maia: No conflict of interest Laharie, David: No conflict of interest Liberman, Sender: No conflict of interest Loftus, Jr, Edward: No conflict of interest Moeslein, Gabriela: No conflict of interest Myrelid, Pär: No conflict of interest Poylin, Vitaliy: No conflict of interest Qazi, Taha: No conflict of interest Raffals, Laura: No conflict of interest Rubin, David T.: No conflict of interest Spinelli, Antonino: No conflict of interest Steinhagen, Emily: No conflict of interest Tozer, Philip: No conflict of interest Verstockt, Bram: No conflict of interest Warusavitarne, Janindra: No conflict of interest Wexner, Steven: No conflict of interest Winter, Desmond: No conflict of interest

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 Since 2009, inflammatory bowel disease (IBD) specialists have utilized “IBD LIVE,” a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified “IBD-mimics” with consequent clinical management implications. Methods Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018–February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup. Results Confirmed IBD cases made up 82.5% (306/371; 193 Crohn’s disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced (n = 8) or vasculitis (n = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies (n = 13, 21%), surgical exploration/pathology (n = 10, 16.5%), biopsies from outside the GI tract (n = 10, 16.5%), genetic/laboratory testing (n = 8, 13%), extensive review of patient history (n = 8, 13%), imaging (n = 5, 8%), balloon enteroscopy (n = 5, 8%), and capsule endoscopy (n = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib. Conclusions The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care.

Abstract Background Recent evidence challenges the current standard of offering surgery to patients with ileocecal Crohn’s disease only when they present complications of the disease. Methods A retrospective, multicenter comparative analysis was performed including patients operated for primary ileocecal CD at 12 referral centers. Patients were divided in 2 groups, according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short-term results were compared. Patients operated on for primary isolated ileocaecal CD (last 50 cm of the terminal ileum and cecum), either for predominantly inflammatory phenotype or for complications of the disease (stricturing or fistulizing pattern), between January 2012 - December 2021 were considered eligible to participate in this study. Patients with previous abdominal procedures for CD, and patients who had activity of the disease in other intestinal segments other than the ileocaecal region at the time of surgery, were excluded from the study. Results 2013 patients were included, 291 (14.5%) in the ICD group. No differences were found between groups in time from diagnosis to surgery or in the levels of exposure to biologic drugs before indication of surgery. CCD patients had higher rates of low BMI, anemia (40.9 vs. 27%, p: &lt; 0.001), and low albumin (11.3 vs. 2.6%, p: &lt; 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: &lt; 0.001). CCD had 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 surgeries (OR: 3.44, p: 0.001) and requirements of multiple intraoperative procedures (OR: 8.39, p: 0.030). Conclusion Indication of surgery in patients who present an inflammatory phenotype of CD was associated with better outcomes when compared to patients operated on for complications of the disease, without a difference between groups in time from diagnosis to surgery.

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.