Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence.

Introduction and objectives: The incidence of cholangiocarcinoma (CCA) has been increasing globally. Although a concomitant increase in the incidence of metabolic disorders might suggest a causal relationship, the data are scarce. We aimed to describe the prevalence of metabolic disorders in patients with CCA and report the clinical features and outcomes. Patients and Methods: Retrospective study including patients with CCA. Patients were divided into: (1) past history of diabetes or/and overweight/obesity (“metabolic disorder group”) and (2) without any of these features (“non-metabolic-disorder group”). A Cox regression model was used to determine the prognostic factors. Results: 122 patients were included. In total, 36 (29.5%) had overweight/obesity, 24 (19.7%) had diabetes, and 8 (6.6%) had both. A total of 29 (23.8%) patients had resectable disease and received upfront surgery. A total of 104 (85.2%) received chemotherapy for advanced/recurrent disease. The overall survival of the cohort was 14.3 months (95% CI: 10.1−17.3). ECOG-PS 0 (p < 0.0001), resectable disease (p = 0.018) and absence of vascular invasion (p = 0.048) were independently associated with better prognosis. The “metabolic disorder group” (n = 52) had a median survival of 15.5 months (95% CI 10.9−33.9) vs. 11.5 months (95% CI 8.4−16.5) in the “non-metabolic-disorder group” (n = 70) (HR: 1.10; 95% CI 0.62−1.94). Patients with resectable disease in the “metabolic group” had longer survival than patients in the “non-metabolic group” (43.4 months (95% CI 33.9-NR) vs. 21.8 months (95% CI 8.6−26.9); HR = 0.12, 95% CI 0.03−0.59). Conclusion: Metabolic disorders are frequent among CCA patients. Underlying metabolic comorbidities may be associated with prognosis in resectable CCA. There is a need to explore the mechanism that drives CCA carcinogenesis in a metabolic background.