Diagnosis of cholangiocarcinoma: the new biological and technological horizons

The diagnosis of cholangiocarcinoma (CCA) remains challenging. Although new technologies have been developed and validated, their routine use in clinical practice is needed. Conventional cytology obtained during endoscopic retrograde cholangiopancreatography-guided brushings is the first-line technique for the diagnosis of CCA, but it has shown limited sensitivity when combined with endoscopic ultrasound-guided biopsy. Other diagnostic tools have been proposed for the diagnosis of CCA, with their respective advantages and limitations. Cholangioscopy with biopsy or cytology combined with FISH analysis, intraductal biliary ultrasound and confocal laser microscopy have made significant advances in the last decade. More recently, developments in the analytical "omics" sciences have allowed the mapping of the microbiota of patients with CCA, and liquid biopsy with proteomic and extracellular vesicle analysis has allowed the identification of new biomarkers that can be incorporated into the predictive diagnostics. Furthermore, in the preoperative setting, radiomics, radiogenomics and the integrated use of artificial intelligence may provide new useful foundations for integrated diagnosis and personalized therapy for hepatobiliary diseases. This review aims to evaluate the current diagnostic approaches and innovative translational research that can be integrated for the diagnosis of CCA.