Introduction

Inflammatory bowel disease (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation of the intestines. This is accompanied by oxidative stress, which plays an important role in the pathophysiology of IBD. Oxidative stress-related biomarkers can serve as potential biomarkers for disease activity monitoring. Systemic free thiols (FT) are found to accurately reflect oxidative stress brought on by inflammation and have shown promise as a biomarker for inflammatory disease activity in IBD. However, the clinical significance of this marker warrants validation. This prospective diagnostic study aimed to compare FT to other validated biomarkers and investigate the link between FT and endoscopic disease activity in patients with IBD.

Aims & Methods

An interim analysis was conducted in 52 patients. FT were measured using a colorimetric detection method. Clinical disease activity was quantified by the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Biochemical disease activity was determined by measuring blood C-reactive protein [CRP] and fecal calprotectin [fCal] levels. Endoscopic disease activity was quantified with the Mayo endoscopic sub score for UC and the Simple Endoscopic Score (SES-CD) for CD. Serum FT levels were assessed for correlations with disease activity parameters using linear and logistic regression analyses. Discriminative capacity of FT as biomarker was assessed by calculating receiver operating characteristics (ROC) statistics.

Results

Serum FT levels demonstrated a significant inverse correlation with clinical parameters, such as the HBI (r=-0.53, p<0.05). Additionally, other inflammatory biomarkers, including CRP, exhibited a negative correlation with serum FT levels (r=-0.43, p<0.05), which were decreased in patients with active IBD . Discrimination between clinically quiescent (HBI<5) and active disease based on serum FT levels was accurate (AUC=0.80, p=0.02) with a value numerically higher than that of fCal (AUC=0.55, p=0.83). Serum FT levels did not significantly differ between biochemically quiescent and active disease based on CRP (AUC=0.69, p=0.20). Both endoscopic scores demonstrated a tendency toward negative associations with serum FT levels. Patients with moderate and severe disease activity had lower FT levels compared to those with mild disease activity (estimated marginal means [EMM] 497.2 vs 529.5 µM, p=0.43) and 447.1 vs 529.5µM , p=0.06, respectively).

Conclusion

The interim analysis of this study indicates that plasma FT levels inversely correlate with IBD activity and may surpass traditional markers like fCal in detecting disease states. Plasma FT demonstrates potential as a sensitive biomarker for both clinical and endoscopic disease activity in IBD. Further patient inclusion and longitudinal data are essential to validate FT's utility fully. Continued research could establish FT as a key tool for personalized treatment strategies, improving patient outcomes in IBD management.

Disclosure

S. Geertsema, A.R. Bourgonje., H. van Goor, G. Dijkstra, and K.N. Faber are supported by a research grant from Janssen Research & Development LLC. A.R. Bourgonje received speaker fees from AbbVie. G. Dijkstra received research grants from Royal DSM, Takeda, and Janssen Pharmaceuticals and speaker fees from AbbVie, Pfizer, Takeda, and Janssen Pharmaceuticals.

Introduction

Upper gastrointestinal bleeding (UGIB) is associated with an unfavorable prognosis in cancer patients. In biliary tract cancers (BTCs), little is known about the occurrence of UGIB and its prognostic relevance for the course of the disease.

Aims & Methods

The aim of this study was to analyze the prevalence of UGIB in BTC patients, compare therapeutic approaches for efficacy, and identify parameters associated with survival and recurrence rates. This retrospective observational study included all patients with BTCs and UGIB, that were treated in our tertiary care hospital between 2010 and 2023.

Results

A total of 1033 patients with BTC were analyzed. 41 (4.0%) of these patients had a total of 60 bleeding events. At the time of the bleeding event, 30.8% of patients displayed symptoms of shock, and 67.5% received red blood cell transfusions. The most common causes of bleeding were tumor infiltration (24.4%), variceal bleeding (19.5%), or ulcer bleeding (14.6%). At the time of presentation, 56.4% of patients had stage IV cancer. Most patients had perihilar (39.0%) or intrahepatic (34.1%) cholangiocarcinoma. At index bleeding, endoscopic treatment was performed in 41,5% of cases, while conservative measures (53,7%) or interventional radiological procedures (4.9%) were used in the remaining cases. In cases of bleeding caused by tumor infiltration, endoscopic hemostasis was usually performed using hemostatic powder (18.8%) or clip application (12.5%). Admission to an intermediate or intensive care unit (odds ratio 6.7; 95% CI 1.5 – 33.9) as well as symptoms of shock at the time of the bleeding event (odds ratio 2.6; 95% CI 0.5 – 15.6) were risk factors of rebleeding within 14 days. In patients with UGIB due to tumor infiltration, bleeding recurred after endoscopic therapy in 33.3% of cases. With conservative therapy, the recurrence rate was 28.6%. Survival of Patients with UGIB due to tumor infiltration was significantly shorter compared with patients having non-tumor-associated UGIB (median survival 0.93 vs. 6.5 months, log-rank test p = 0.018).

Conclusion

UGIB is a rare but serious complication in patients with BTC. Patients with major bleeding episodes should be closely monitored for short-term rebleeding. The occurrence of UGIB due to tumor infiltration is associated with adverse outcomes and significantly shortened survival time.