Introduction

Surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). Present risk stratification strategies do not discriminate sufficiently between risk groups. We aimed to develop and validate a dynamic multivariable prediction model for advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD.

Aims & Methods

We pooled data from six existing surveillance cohort studies (two unpublished).^1-3 Patients with IBD and an indication for CRC surveillance were included if they underwent at least one follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictors were selected based on the results of a recent meta-analysis,⁴ frequency, and data availability: extensive disease, prior dysplasia (indefinite for dysplasia or low-grade dysplasia), primary sclerosing cholangitis, male sex, IBD type, post-inflammatory polyps, age, and maximal endoscopic inflammation. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modelling.⁵ Model performance was assessed with Harrell’s c-statistic and by calibration curves, adjusted for optimism by internal cross-validation. In a sensitivity analysis model performance was assessed in data ≥2010 only (internal validation). Generalizability across the surveillance cohorts was evaluated by internal-external cross-validation.

Results

The surveillance cohorts encompassed time periods 1973-2021 and comprised 3,731 patients (54% male sex; 75% ulcerative colitis or IBD-unclassified and 25% Crohn’s disease) with a median follow-up of 5.7 years (interquartile interval 3.3-9.6; 26,336 patient-years of follow-up); 146 individuals were diagnosed with aCRN (see table 1 for patient characteristics). The final model contained eight predictors, with a cross-validation median c-statistic of 0.74 and 0.75 and calibration slope of 0.77 and 0.83 for, respectively, a 5- and 10-year prediction window in overall analyses. Calibration plots showed good calibration. Ninety percent of 10-year predicted aCRN risks were between 0.9 and 18.7%. Model discrimination improved in data ≥2010 and calibration results remained unchanged (48% of all procedures ≥2010). Internal-external cross-validation results showed medium discrimination and reasonable to good calibration.

Conclusion

We generated a model based on clinical factors that predicts future aCRN risk, with moderate to good model discrimination and good calibration. However, generalizability results vary and are impacted by varying cohort sizes and should be interpreted with caution. Future research should focus on formal external validation, relate predicted aCRN risks to surveillance intervals, and investigate the impact of this new model in daily clinic prior to clinical application.

References

1. Choi CR, Al Bakir I, Ding NJ, et al. Cumulative burden of inflammation predicts colorectal neoplasia risk in ulcerative colitis: a large single-centre study. Gut 2019;68:414-422.
2. Mahmoud R, Shah SC, Ten Hove JR, et al. No Association Between Pseudopolyps and Colorectal Neoplasia in Patients With Inflammatory Bowel Diseases. Gastroenterology 2019;156:1333-1344 e3.
3. Ten Hove JR, Shah SC, Shaffer SR, et al. Consecutive negative findings on colonoscopy during surveillance predict a low risk of advanced neoplasia in patients with inflammatory bowel disease with long-standing colitis: results of a 15-year multicentre, multinational cohort study. Gut 2019;68:615-622.
4. Wijnands AM, de Jong ME, Lutgens M, et al. Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis. Gastroenterology 2021;160:1584-1598.
5. van Houwelingen, H., & Putter, H. (2012). Dynamic Prediction in Clinical Survival Analysis (1st ed.). CRC Press. https://doi.org/10.1201/b11311:

Disclosure

Laurent Beaugerie: Research grants: Biogen, Celltrion, Takeda, Ferring, Celltrion, Viatris; Personal fees: Takeda, Nordic Pharma, Janssen, BMS, and Viatris.
Charles N. Bernstein: Dr Bernstein is supported by the Bingham Chair in Gastroenterology. Dr. Bernstein has served on advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, Eli Lilly Canada, Roche Canada, Janssen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada; Educational grants from Abbvie Canada, Amgen Canada, Bristol Myers Squibb Canada, Ferring Canada, Organon Canada, Pfizer Canada, Takeda Canada, and Janssen Canada. Speaker’s panel for Abbvie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from Abbvie Canada, Amgen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada.
Steven H. Itzkowitz: Dr Itzkowitz has served on Advisory Board for Exact Sciences Corporation and a consultant for Geneoscopy. He has received research support from Exact Sciences Corporation and Freenome.
Julien Kirchgesner: Lecture fees from Janssen and Lilly, and consulting fees from Roche, Gilead, Pfizer, Janssen, Celltrion, Lilly, Takeda, and Abbvie.
Cyriel Y. Ponsioen: Received grant support from Gilead and Perspectum and speaker’s fees from Tillotts

Introduction

Eosinophilic esophagitis (EoE) is a chronic, type-2 inflammation-driven esophageal disease causing dysphagia and esophageal dysfunction. Patients with inflammatory bowel disease (IBD) or other type-2 inflammatory disorders may have an increased risk of EoE, but prevalence data are limited. This study examines the prevalence of dysphagia and EoE in patients with type-2 inflammatory diseases or IBD.

Aims & Methods

In this prospective, multicentric, questionnaire-based screening study, patients from the departments of gastroenterology, pulmonology, dermatology, and otolaryngology at the Medical University of Vienna, as well as from the Allergy Center Floridsdorf, were screened for dysphagia using the validated brief esophageal dysphagia questionnaire (BEDQ). The primary endpoint was the prevalence of clinically relevant dysphagia, defined as a BEDQ score ≥10 or a history of bolus impaction in the past year. Endoscopy was offered to symptomatic patients without recent biopsies. Patient characteristics and differences in absolute eosinophil count, eosinophilic cationic protein (ECP), and IgE levels were analyzed using independent-samples T-tests.

Results

A total of 690 patients (45.7% female, mean age 54.5 years) were screened; 54.4% had IBD, 20.2% allergic rhinitis, 16.4% asthma, 8.7% atopic dermatitis, 6.4% chronic rhinosinusitis with nasal polyps (CRSwNP), and 5.2% IgE-mediated food allergy with multiple diagnoses possible. Overall, 5.1% (n=35) exhibited clinically relevant dysphagia. EoE was previously diagnosed in 2.0% (n=14), including four patients with clinically relevant dysphagia. Among the remaining 31 patients, eight had prior endoscopies ruling out EoE, seven underwent endoscopy revealing two new EoE cases, and 16 are still awaiting gastroscopy. No significant differences in IgE, eosinophilic count, or ECP were found between patients with EoE, those with dysphagia, and asymptomatic individuals.

Conclusion

Patients with IBD and type-2 inflammatory diseases exhibit a high prevalence of dysphagia. While EoE is more common than in the general population, most dysphagia remains unexplained. Systematic dysphagia screening in this high-risk population may reduce diagnostic delay.

Clinical Case Summary

Introduction: The most common complications of ERCP include acute pancreatitis, post-sphincterotomy bleeding, and intestinal perforation. Traumatic arterio-biliary fistulas, although rare, have been reported following manipulation. This case presents severe haemorrhage secondary to an arterio-biliary fistula.
Case Report: A 61-year-old male, chronic alcoholic with chronic liver disease (BCLC-B) and distal bile duct stricture of filarial aetiology, was admitted for biliary stent replacement. Post-procedure, the patient developed worsening clinical parameters, including abdominal pain, leucocytosis, and elevated cholestasis markers. Imaging revealed the proximal end of the stent was in the cystic duct, requiring a second ERCP for repositioning.
The patient's condition deteriorated with severe acute cholangitis, haemorrhagic rectal bleeding, and haemodynamic instability. CT showed further biliary dilatation and haematic content within the bile ducts. A third ERCP was performed to remove clots and place a covered metallic stent to control the bleeding. Despite this, haemorrhage persisted. CT-angiography revealed a 9 mm pseudoaneurysm from the pancreaticoduodenal arcade and pancreatic artery (Figure 1). Selective embolisation was successful (Figure 2), with follow-up confirming no further aneurysm filling (Figures 3 and 4).
Discussion: Arterio-biliary fistulas are typically iatrogenic or traumatic, often following biliary or hepatic procedures like liver biopsy or cholecystectomy. Post-ERCP incidence is rare, with only three reported cases. Diagnosis requires high clinical suspicion and angiography. Fistulas can cause pseudoaneurysms, which may lead to haemobilia, presenting as gastrointestinal bleeding. Management is multidisciplinary; conservative treatment is suitable for small, non-bleeding fistulas, while endoscopic or radiological interventions are used for severe cases. Early intervention is key to favourable outcomes.

References

1. Rai R. Potentially fatal haemobilia due to inappropriate use of an expanding biliary stent. World Journal of Gastroenterology. 2003;9(10):2377.
2. Berry R, Han J, Mohit Girotra, Tabibian JH. Hemobilia: Perspective and Role of the Advanced Endoscopist. 2018 Jul 12;2018:1–12.
3. Delayed Massive Hemobilia After Biliary Stenting. Endoscopy. 2003 Nov;35(11):976–7.
4. Siu, W. T., Chau, C. H., Ka Bo Law, B., Yau, K. K., Luk, Y. W., & KaWah Li, M. Non-operative management of endoscopic iatrogenic haemobilia: case report and review of literature. Acta gastro-enterologica Belgica. 2005;68(4): 428–431.
5. Panno, C., Gutiérrez, S. C., Echeverría, R., Garbe, C., Milocco, M., Ianniccillo, H., Valenzuela, M., Cubilla, A., Alvarez, F., & Alvarez, E. Hemobilia secundaria a pseudoaneurisma de la arteria hepática [Hemobilia secondary to hepatic artery pseudoaneurysm]. Acta gastroenterologica Latinoamericana. 2015;45(2):133–136.