Evidence map›Paper›PMID 40513068›Full record

ArticleHepatology (Baltimore, Md.)2026

Refinement of histologic subtypes and identification of biomarkers linked to unfavorable prognosis in cholangiocarcinoma: The ENSCCA registries' framework for digital twin advancement.

Guido Carpino, Diletta Overi, Rocio I R Macias, Vincenzo Cardinale, Laura Izquierdo-Sanchez, Pilar Acedo, Marco Rengo, Michail Doukas, Timothy J Kendall, Julien Calderaro and 29 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Hepatology (Baltimore, Md.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

39 authors.

Guido CarpinoDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.
Diletta OveriDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.
Rocio I R MaciasLaboratory of Experimental Hepatology and Drug Targeting (HEVEPHARM), National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), IBSAL, University of Salamanca, Salamanca, Spain.
Vincenzo CardinaleDepartment of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Laura Izquierdo-SanchezDepartment of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
Pilar AcedoInstitute for Liver and Digestive Health, University College London, London, UK.
Marco RengoDepartment of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
Michail DoukasDepartment of Pathology and Clinical Bioinformatics, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Timothy J KendallUniversity of Edinburgh Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
Julien CalderaroDepartment of Pathology, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
Lara R HeijDepartment of Pathology and Clinical Bioinformatics, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Konrad ReichelDepartment of Surgery and Transplantation, University Hospital Essen, Essen, Germany.
Stefano LeoneDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.
Paolo OnoriDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.
Barbara FranceschiniLaboratory of Hepatobiliary Immunopathology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Cristiana SoldaniLaboratory of Hepatobiliary Immunopathology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Luca Di TommasoDepartment of Biomedical Sciences, Humanitas University, Milan, Italy.
Pedro M RodriguesDepartment of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
Jérémy AugustinDepartment of Pathology, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
Raffaele BrustiaDepartment of Digestive and Hepato-pancreatic-biliary Surgery, Université Paris-Est Créteil, UPEC, Créteil, France.
Guido TorzilliDepartment of Biomedical Sciences, Humanitas University, Milan, Italy.
Manuela Martin-IzquierdoServicio de Radiodiagnostico, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain.
Jose M Hernández-BayoServicio de Radiodiagnostico, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain.
Diego Bueno-SacristanServicio de Patologia, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain.
Ezio LanzaDivision of Interventional Radiology, IRCCS Humanitas Research Hospital, Milan, Italy.
Andres Garcia-SampedroInstitute for Liver and Digestive Health, University College London, London, UK.
Alberto QuagliaDepartment of Cellular Pathology, UCL Cancer Institute, Royal Free Hospital, London, UK.
Francesco ArditoHepatobiliary Surgery Unit, Foundation and Teaching Hospital Sacred Heart IRCCS A. Gemelli, Catholic University of the Sacred Heart, Rome, Italy.
Agostino Maria De RoseHepatobiliary Surgery Unit, Foundation and Teaching Hospital Sacred Heart IRCCS A. Gemelli, Catholic University of the Sacred Heart, Rome, Italy.
Felice GiulianteHepatobiliary Surgery Unit, Foundation and Teaching Hospital Sacred Heart IRCCS A. Gemelli, Catholic University of the Sacred Heart, Rome, Italy.
Elio DamatoDepartment of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy.
Valeria PanebiancoDepartment of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy.
Bas Groot KoerkampDepartment of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Stephen P PereiraInstitute for Liver and Digestive Health, University College London, London, UK.
Gian Luca GraziDepartment of Experimental and Clinical Medicine, HepatoBiliaryPancreatic Surgery, University of Florence, Florence, Italy.
Domenico AlvaroDepartment of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Ana LleoDepartment of Biomedical Sciences, Humanitas University, Milan, Italy.
Jesus M BanalesDepartment of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
Eugenio GaudioDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsCholangiocarcinoma (CCA) displays remarkable anatomical and histological heterogeneity. Besides diagnosis confirmation, histology currently does not have a major role in the management of CCA. We aimed to study the clinical relevance of histological heterogeneity of CCA and putative tissue biomarkers by creating a multicentric digitalized European CCA Histology Registry. APPROACH AND

resultsNine referral centers, participating in the International Cholangiocarcinoma Clinical Registry, shared samples and data from 293 patients. Histological and immunohistochemistry stains (n=10) were performed. Computed tomography (CT) scans (n=112 cases) were analyzed by morphological and radiomics techniques. A selection of cases (n=18) was processed for spatial transcriptomics analysis. No significant differences in 5-year overall survival (OS) were found in perihilar CCA versus intrahepatic (i) CCA, and in small bile duct (SBD) versus large bile duct (LBD) iCCA. When cases were classified by Periodic acid of Schiff (PAS) positivity (mucin content), PAS HIGH LBD iCCA showed a significantly worse 5-year OS compared to PAS LOW iCCA. Multivariate Cox regression identified PAS HIGH LBD iCCA phenotype as an independent predictor of worse OS. PAS HIGH LBD iCCA subtype showed specific molecular characteristics at spatial transcriptomics and immunohistochemistry; CT scans and serology could distinguish PAS HIGH LBD iCCA phenotype with excellent accuracy.

conclusionsOur data underline the importance of identifying morphological subclasses with a significant prevalence in CCA as a tool for risk stratification and prognosis. The European CCA Histology Registry represents a valuable platform for integrating digital pathology with clinical, radiological, and molecular information as a framework for digital twin advancement.

Indexed as

Bile Duct NeoplasmsBiomarkers, TumorCholangiocarcinomaAgedBile Ducts, IntrahepaticEuropeFemaleHumansMaleMiddle AgedPrognosisRegistriesTomography, X-Ray ComputedBiomarkers, Tumorbiliary tract cancercell of origindigital pathologyprimary liver cancerspatial transcriptomics

Identifiers

PMID40513068
PMCPMC12991328

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