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Review
. 2025 Apr 16;15(8):1011.
doi: 10.3390/diagnostics15081011.

Diagnosis of Cholangiocarcinoma: The New Biological and Technological Horizons

Federico Selvaggi  1   2 , Loris Riccardo Lopetuso  3   4 , Andrea Delli Pizzi  5   6 , Eugenia Melchiorre  7 , Marco Murgiano  3   8 , Alessio Lino Taraschi  9 , Roberto Cotellese  2 , Michele Diana  10 , Marco Vivarelli  11 , Federico Mocchegiani  11 , Teresa Catalano  12 , Gitana Maria Aceto  2   13
Affiliations
Review

Diagnosis of Cholangiocarcinoma: The New Biological and Technological Horizons

Federico Selvaggi et al. Diagnostics (Basel). .

Abstract

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.

Keywords: artificial intelligence; biomarkers; cholangiocarcinoma; diagnosis; endoscopy; liquid biopsy; microbiota; prognosis; radiogenomics; radiomics.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Risk factors for CCA influenced by gut microbiota.
Figure 2
Figure 2
A schematic overview of the prevalence of CCAs and the best diagnostic methods. CCA is classified as intrahepatic CCA (iCCA) and extrahepatic CCA, which is divided into perihilar CCA (pCCA) and distal CCA (dCCA). iCCA is located proximally to second-order bile ducts and the insertion of the cystic duct into the common bile duct. dCCA is confined to the common bile duct below the cystic duct insertion.
Figure 3
Figure 3
The multistep process of medical imaging analysis is based on image acquisition and reprocessing, segmentation, feature extraction, data analysis and model building.
Figure 4
Figure 4
Intraoperative images of hepatectomy for Klatskin’s tumor with biliary resection over the 2nd confluence (a). Bilio-enteric reconstruction (b). Intraoperative radiological imaging of bilio-enteric anastomosis (c). Courtesy of Professor Paolo Innocenti, from his personal archive.
See this image and copyright information in PMC

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