Introduction and objectives: Cholangiocarcinomas (CCAs) are classified into intrahepatic (iCCA), perihilar (pCCA) or distal (dCCA). Their etiologies are mostly unknown and their pathogenesis are poorly understood. Large international registries of CCA patients with demographic, biochemical, clinical and histopathological information are missing and necessary to better understand this disease and improve its management.

Methods: The European CCA Registry is an international multicenter initiative supported by the European Network for the Study of CCA (ENS-CCA) and the European Association for the Study of the Liver (EASL Registry Award 2016) that includes patients with CCA from 8 institutions and 4 countries in the secure online platform REDCap. Clinical data was retrospectively (2010) and prospectively (2016) collected by experts in the field (inclusion criteria: diagnosis by imaging and/or histology). The project protocol was approved by the Ethical Committees for Clinical Research of the participant Institutions, and patients signed written consents.

Results: A total of 1,011 records are entered, including 48% iCCAs, 23% pCCAs, 28% dCCAs and 1% CCA-HCC mixed tumors. Mean age at diagnosis was 65,6, and the male/female ratio 1:0.76. The most common known risk factors were cirrhosis (6.4%), viral hepatitis (3.1% HCV; 1.8% HBV), diabetes (20.5%), obesity (15.2%), alcohol (17.2%) and presence of primary sclerosing cholangitis (PSC: 1.3%). Serum levels (mean; IU/L) of biochemical markers of cholestasis (GGT: 417; ALP: 313) and liver injury (ALT: 74.1; AST: 60.8), as well as non-specific tumor markers (CA19.9: 5.138 UI/mL; CEA: 163 ng/mL) were altered. These biomarkers were considered for diagnosis together with imaging (53.1%: MRI, CT, USG, ERPC) and pathological (34.5%: biopsy/cytology) approaches. Tumor staging (TNM; AJCC 7^th Edition) at diagnosis revealed that 39.7% of cases had stages I-III, 39.9% stage IV, and 20.4% unknown. Moreover, 38.9% of patients underwent surgical resection (R0- R1) (81.0% I-III; 12.2% IV; 6.8% unknown) with an overall survival (OS) of 18 months (IC95: 16-22). On the other hand, 61.1% of the tumors were unresectable: 70% (16.8% I-III; 59.7% IV; 23.5% unknown) received chemo- or locoregional therapies, and 30% did not receive treatment (10.2% I-III; 57.2% IV; 32.5% unknown). Chemo- or locoregional therapies provided an OS of 10 months (IC95: 9-11), whereas non-treated patients exhibited an OS of 4 months (IC95: 3-6).

Conclusions: This international initiative shows the current management of patients with CCA, and demonstrates the need of international collaborations to improve diagnosis, staging and treatment. The European CCA Registry, which also includes biological samples, emerges as a unique and extraordinary platform for future collaborative studies.