Introduction

Among immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs), gastrointestinal irAEs (GI-irAEs) are relatively rare, and their risk factors and prognostic implications remain unclear.

Aims & Methods

We retrospectively analyzed 1,104 patients who initiated ICI therapy at our institution between January 2016 and December 2022 and for whom survival data were available. GI-irAEs were defined as colitis with an increase of ≥3 bowel movements/day from baseline in the absence of other causes, or symptomatic gastritis confirmed histologically. Risk factors and prognostic impact of GI-irAEs were evaluated.

Results

The median duration of ICI therapy was 107 days. The cohort included 754 males (68%) with a median age of 69 years. The primary tumor types were lung cancer (32%), gastrointestinal cancers (19%), urothelial carcinoma (13%), head and neck cancer (13%), and melanoma (11%). The overall response rate was 27.8%, and the disease control rate was 49.0%. irAEs of any grade occurred in 310 patients (28%), and GI-irAEs were observed in 30 patients (2.7%). In univariate logistic regression analysis, use of anti-CTLA-4 antibody, combination ICI therapy, a prognostic nutritional index (PNI) ≥ 40, and platelet-to-lymphocyte ratio (PLR) ≥ 1.8 were associated with an increased risk of GI-irAEs. In multivariate analysis, only anti-CTLA-4 antibody use remained a significant risk factor (odds ratio: 9.2; 95% CI: 1.9–45). Kaplan–Meier analysis revealed that patients with GI-irAEs had significantly longer overall survival (OS) compared to those without irAEs in the overall cohort (median OS: 22.9 vs. 12.6 months, P < 0.0001). However, this difference was not observed in landmark analyses at 4 and 8 weeks post-treatment. Subgroup analysis based on PNI showed that in patients with PNI ≥ 40, those with GI-irAEs had significantly longer OS than those without irAEs (median not reached vs. 19.3 months, P = 0.0003). In contrast, in patients with PNI < 40, GI-irAE cases tended to have shorter OS than non-irAE cases (8.2 vs. 9.3 months). This trend was consistent in landmark analyses at 4 and 8 weeks.

Conclusion

The impact of GI-irAEs on prognosis appears to differ depending on the patient’s nutritional status. Particular caution is warranted for patients in poor general condition receiving ICIs, especially those involving anti-CTLA-4 antibodies, as GI-irAEs may serve as a poor prognostic factor in this population.

Clinical Case Summary

Background: Crohn’s disease (CD) is a chronic inflammatory condition frequently managed with biologic therapies. While venous thromboembolism (VTE) is a recognized complication in inflammatory bowel disease (IBD), certain biologics, including JAK2 inhibitors, have been linked to increased thrombotic events. This case report describes a rare instance of recurrent, unprovoked pulmonary embolism (PE) in a CD patient receiving Vedolizumab (VDZ).
Case presentation: A 45-year-old male with a long-standing history of CD experienced recurrent disease flares. His medical history included an ileo-colonic resection and anastomotic revision, after which he developed a provoked PE requiring long-term anticoagulation. Previous treatments, including infliximab, Adalimumab, Ustekinumab, Methotrexate, and 6-MP, had failed before he was started on VDZ monotherapy, which effectively controlled his colitis. Despite intensified anticoagulation, he had four hospitalizations for unprovoked PE within a year. A comprehensive hematologic evaluation, reviewed by a consultant haematologist, ruled out any underlying thrombophilic disorders. Given concerns about a potential association between VDZ and recurrent VTE, the medication was discontinued, and the patient was transitioned to Risankizumab. After four months, no further VTE episodes were reported.
Discussion & conclusion: Emerging evidence, including a study by Cross et al. (2017), suggests that patients treated with VDZ have a higher risk of thrombotic complications. This case highlights a potential, yet rare, association between Vedolizumab and recurrent PE in CD patients. Clinicians should remain vigilant when prescribing VDZ, particularly in patients with a history of thromboembolic events. Further research is needed to explore this association and guide clinical decision-making.

References

https://www.researchgate.net/publication/316370555_The_Incidence_of_Cardiovascular_Events_in_Patients_with_Crohn's_Disease_Treated_with_Vedolizumab_and_Anti-TNF_Therapies

Disclosure

No Conflict of Interest

Introduction

Women have been historically underrepresented in gastrointestinal endoscopy research. Understanding the current patterns of female authorship is essential to assess progress and identify persistent gaps within this field.

Aims & Methods

This study aimed to evaluate the representation of women as first and senior (last) authors the three highest-impact journals in gastrointestinal endoscopy (Endoscopy, Gastrointestinal Endoscopy and Digestive Endoscopy) from 2015 to 2024. For each publication, we extracted bibliometric data of original articles, review articles and editorials, including the names of the first and senior authors, their primary country of affiliation, and the year of publication. Countries and territories were categorized by geographic region. Author gender was predicted using Genderize.io software (https://genderize.io), and only authors with ≥80% gender prediction accuracy were included.

Results

We analyzed 4,414 publications. Among first authors, 885 (20.15%) were women from 36 countries and 3,507 (79.85%) were men from 49 countries. Most female first authors were affiliated with institutions in North America (36.61%), while most male first authors were based in Asia (40.82%). The greatest gender disparity among first authors was observed in Asia (male-to-female ratio = 6.8), and the lowest in Europe (male-to-female ratio = 2.5). Among senior authors, 433 (11.51%) were women from 32 countries and 3,328 (88.49%) were men from 47 countries. Female senior authors were most frequently from Europe (38.57%), whereas male senior authors were again predominantly from Asia (41.12%). The largest disparity in senior authorship was in Oceania (male-to-female ratio = 44), and the lowest in Latin America (male-to-female ratio = 4.1). Notably, the odds of a woman being the first author nearly doubled when the senior author was also a woman. Overall, over the 10-year period, the male-to-female ratio among first authors improved from 4.46 (2015–2016) to 3.25 (2023–2024), and among senior authors from 9.10 to 6.43.

Conclusion

Women remain underrepresented in first and senior authorship positions in gastrointestinal endoscopy research. These disparities may be influenced by limited female representation and mentorship in the field. Although gender gaps have narrowed over the past decade, sustained and coordinated efforts are needed to promote equity in academic publishing.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a widely utilized procedure for managing biliary and pancreatic disorders (1). ERCP is associated with complications, and potential factors influencing the ERCP outcomes is a critical area of research (2). Among these factors, obesity has emerged as a variable of interest due to its increasing prevalence globally and its known associations with a range of health conditions (3). Previous studies have yielded conflicting results on the influence of obesity on ERCP outcomes, with some reporting higher complication rates, while others found no significant associations (4, 5). The interplay between weight and procedural outcomes across a spectrum of BMI categories remains underexplored. This study aimed to assess the impact of body mass index (BMI) on clinical aspects and procedural outcomes of ERCP.

Aims & Methods

A total of 2143 patients who underwent ERCP at Hitit University Hospital between January 2020 and February 2024 were initially included. Of these, 1315 patients were excluded due to incomplete clinical information, previous ERCP history, altered anatomy and pregnancy, resulting in a final cohort of 828 patients for analysis.
The included patients were stratified into BMI categories: ≤30 kg/m² and >30 kg/m². Additionally, subgroup analyses were performed across finer BMI classifications: ≤20, 20 to ≤25, 25 to ≤30, 30 to ≤35, and >35 kg/m². Clinical and procedural parameters evaluated included admission diagnoses of acute pancreatitis and acute cholangitis (according to Tokyo cholangitis grade), American Society of Anesthesiologists (ASA) scores, gender, history of cholecystectomy, cannulation success, cannulation time, post-ERCP complications including post-ERCP pancreatitis and other complications according to modified Cotton criteria and 30-day readmission rates. The relationships between BMI and the clinical aspects as well as procedural outcomes of ERCP were investigated.

Results

The study cohort consisted of 828 patients, with 75.8% (n=628) having a BMI ≤30 kg/m² and 24.2% (n=200) having a BMI >30 kg/m². Within the finer BMI categories, 3.7% (n=31) of patients had a BMI ≤20 kg/m², 24.2% (n=200) were in the 20 to ≤25 kg/m² range, 47.9% (n=397) were in the 25 to ≤30 kg/m² range, 19.7% (n=163) were in the 30 to ≤35 kg/m² range, and 4.5% (n=37) had a BMI >35 kg/m². The majority of patients (47.9%) were within the BMI range of 25–30 kg/m², reflecting a significant proportion of overweight individuals in the cohort. Patients with a BMI >35 kg/m² constituted the smallest group, accounting for only 4.5% of the total population.
The study found no statistically significant differences between the groups concerning admission rates for acute pancreatitis and acute cholangitis, ASA scores, cannulation success, post-ERCP complications, and readmission within 30 days after the procedure (p>0.05). Notably, women were found to be significantly more obese (p<0.001), and a higher weight was associated with an increased history of cholecystectomy (p=0.013).
Additionally, there were no significant differences in average age, Charlson comorbidity index, cannulation time, length of hospital stay, or white blood cell count at admission between the BMI groups (p>0.05). However, CRP and total bilirubin levels were significantly higher in the non-obese group compared to the obese group (p=0.01 and p=0.011, respectively).

Conclusion

BMI did not influence the incidence of acute pancreatitis or acute cholangitis on admission, ASA scores, cannulation success or time, post-ERCP complications, length of hospital stays, or 30-day readmission rates. Interestingly, higher CRP and total bilirubin levels were observed in patients without obesity at admission, warranting further investigation into their clinical implications.

References

1. Tokmak S TS. History of ERCP. The Turkish Journal of Academic Gastroenterology 2021;20: 1-2.
2. Duzenli T, Koseoglu H. Endoscopic Retrograde Cholangiopancreatography During the COVID-19 Pandemic: Effects of Enhanced Personal Protective Equipment. Dig Dis Sci 2021;66: 1845-1851.
3. Alfaris N, Alqahtani AM, Alamuddin N, Rigas G. Global Impact of Obesity. Gastroenterol Clin North Am2023;52: 277-293.
4. Deenadayalu VP, Blaut U, Watkins JL, Barnett J, Freeman M, Geenen J, et al. Does obesity confer an increased risk and/or more severe course of post-ERCP pancreatitis?: a retrospective, multicenter study. J Clin Gastroenterol2008;42: 1103-1109.
5. Fujisawa T, Kagawa K, Hisatomi K, Kubota K, Sato H, Nakajima A, et al. Obesity with abundant subcutaneous adipose tissue increases the risk of post-ERCP pancreatitis. J Gastroenterol 2016;51: 931-938.