Page 216 - Read Online

Page 10 of 16 Cardinale et al. Hepatoma Res 2018;4:20 I http://dx.doi.org/10.20517/2394-5079.2018.46

liver diseases and related molecular carcinogenesis . Being somatic mutagenesis and epigenome features
[12]
highly cell/lineage type-specific , and largely driven by the pre-neoplastic tissue pathologic milieu (see
[149]
inflammation), finally, the multiple lineages of origin plus the related diseases may explain the intertumoral
heterogeneity observed at any level in iCCA, comprising molecular profiling, with clear implication into
preventive strategies in patient with clinical or subclinical underlining hepatic or biliary diseases, therapy
and in near future approaches of personalized medicine in iCCA patients.

DECLARATIONS
Authors’ contributions
Concept, design, definition of intellectual content, literature search, data acquisition and analysis, statistical
analysis, manuscript preparation, editing and review: Cardinale V, Bragazzi MC, Carpino G
Data acquisition and analysis: Di Matteo S, Overi D, Nevi L
Manuscript editing and review: Gaudio E
Definition of intellectual content, literature search, manuscript preparation, editing and review: Alvaro D

Availability of data and materials
Not applicable.

Financial support and sponsorship
The study was supported by Consorzio Interuniversitario Trapianti d'Organo, Rome, Italy and by a sponsored
research agreement from Vesta Therapeutics (Bethesda, MD).

Conflicts of interest
None.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2018.

REFERENCES
1. Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, Pawlik TM, Gores GJ. Guidelines for the diagnosis and management
of intrahepatic cholangiocarcinoma. J Hepatol 2014;60:1268-89.
2. Blechacz B, Komuta M, Roskams T, Gores GJ. Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol
2011;8:512-22.
3. Banales JM, Cardinale V, Carpino G, Marzioni M, Andersen JB, Invernizzi P, Lind GE, Folseraas T, Forbes SJ, Fouassier L, Geier A,
Calvisi DF, Mertens JC, Trauner M, Benedetti A, Maroni L, Vaquero J, Macias RI, Raggi C, Perugorria MJ, Gaudio E, Boberg KM,
Marin JJ, Alvaro D. Expert consensus document: cholangiocarcinoma: current knowledge and future perspectives consensus statement
from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol 2016;13:261-80.
4. Komuta M, Govaere O, Vandecaveye V, Akiba J, Van Steenbergen W, Verslype C, Laleman W, Pirenne J, Aerts R, Yano H, Nevens F,
Topal B, Roskams T. Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes. Hepatology
2012;55:1876-88.
5. Aishima S, Oda Y. Pathogenesis and classification of intrahepatic cholangiocarcinoma: different characters of perihilar large duct type
versus peripheral small duct type. J Hepatobiliary Pancreat Sci 2015;22:94-100.
6. Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 2013;145:1215-29.
7. Andersen JB, Spee B, Blechacz BR, Avital I, Komuta M, Barbour A, Conner EA, Gillen MC, Roskams T, Roberts LR, Factor VM,
Thorgeirsson SS. Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase