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 inhibitors. Gastroenterology 2012;142:1021-31.

8. Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, Hama N, Hosoda F, Urushidate T, Ohashi S, Hiraoka N, Ojima H, Shimada K, Okusaka T, Kosuge T, Miyagawa S, Shibata T. Genomic spectra of biliary tract cancer. Nat Genet 2015;47:1003-10.

9. Nakanuma Y, Sato Y, Harada K, Sasaki M, Xu J, Ikeda H. Pathological classification of intrahepatic cholangiocarcinoma based on a new concept. World J Hepatol 2010;2:419-27.

10. Cardinale V, Carpino G, Reid L, Gaudio E, Alvaro D. Multiple cells of origin in cholangiocarcinoma underlie biological, epidemiological and clinical heterogeneity. World J Gastrointest Oncol 2012;4:94-102.

11. England Rare and less common cancers: Incidence and Mortality in, 2010-2013. A Report from Pubblic Health England, National Cancer Registration and Analysis Service. Available from: http://www.ncin.org.uk/publications/rare_and_less_common_cancers. [Last accessed on 8 Jun].

12. Bertuccio P, Bosetti C, Levi F, Decarli A, Negri E, La Vecchia C. A comparison of trends in mortality from primary liver cancer and intrahepatic cholangiocarcinoma in Europe. Ann Oncol 2013;24:1667-74.

13. Lepage C, Capocaccia R, Hackl M, Lemmens V, Molina E, Pierannunzio D, Sant M, Trama A, Faivre J, EUROCARE-5 Working Group. Survival in patients with primary liver cancer, gallbladder and extrahepatic biliary tract cancer and pancreatic cancer in Europe 1999-2007: results of EUROCARE-5. Eur J Cancer 2015;51:2169-78.

14. Smittenaar CR, Petersen KA, Stewart K, Moitt N. Cancer incidence and mortality projections in the UK until 2035. Br J Cancer 2016;115:1147-55.

15. Llovet JM, Villanueva A, Lachenmayer A, Finn RS. Advances in targeted therapies for hepatocellular carcinoma in the genomic era. Nat Rev Clin Oncol 2015;12:408-24.

16. Varadhachary GR, Raber MN. Cancer of unknown primary site. N Engl J Med 2014;371:757-65.

17. Alvaro D, Bragazzi MC, Benedetti A, Fabris L, Fava G, Invernizzi P, Marzioni M, Nuzzo G, Strazzabosco M, Stroffolini T, " AISF, Cholangiocarcinoma", committee. Cholangiocarcinoma in Italy: a national survey on clinical characteristics, diagnostic modalities and treatment. Results from the "Cholangiocarcinoma" committee of the Italian Association for the Study of Liver disease. Dig Liver Dis 2011;43:60-5.

18. Farges O, Fuks D, Le Treut YP, Azoulay D, Laurent A, Bachellier P, Nuzzo G, Belghiti J, Pruvot FR, Regimbeau JM. AJCC 7th edition of TNM staging accurately discriminates outcomes of patients with resectableintrahepatic cholangiocarcinoma: by the AFC-IHCC-2009 study group. Cancer 2011;117:2170-7.

19. Liau JY, Tsai JH, Yuan RH, Chang CN, Lee HJ, Jeng YM. Morphological subclassification of intrahepatic cholangiocarcinoma: etiological, clinicopathological, and molecular features. Mod Pathol 2014;27:1163-73.

20. Nakanuma Y, Xu J, Harada K, Sato Y, Sasaki M, Ikeda H, Kim J, Yu E. Pathological spectrum of intrahepatic cholangiocarcinoma arising in non biliary chronic advanced liver diseases. Pathol Int 2011;61:298-305.

21. Komuta M, Spee B, Vander Borght S, De Vos R, Verslype C, Aerts R, Yano H, Suzuki T, Matsuda M, Fujii H, Desmet VJ, Kojiro M, Roskams T. Clinicopathological study on cholangiolocellular carcinomasuggesting hepatic progenitor cellorigin. Hepatology 2008;47:1544-56.

22. Carpino G, Cardinale V, Onori P, Franchitto A, Berloco PB, Rossi M, Wang Y, Semeraro R, Anceschi M, Brunelli R, Alvaro D, Reid LM, Gaudio E. Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages. J Anat 2012;220:186-99.

23. Theise ND, Saxena R, Portmann BC, Thung SN, Yee H, Chiriboga L, Kumar A, Crawford JM. The canals of Hering and hepatic stem cells in humans. Hepatology 1999;30:1425-33.

24. Kuwahara R, Kofman AV, Landis CS, Swenson ES, Barendswaard E, Theise ND. The hepatic stem cell niche: identification by label-retaining cell assay. Hepatology 2008;47:1994-2002.

25. Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao HL, Moss N, Melhem A, McClelland R, Turner W, Kulik M, Sherwood S, Tallheden T, Cheng N, Furth ME, Reid LM. Human hepatic stem cells from fetal and postnatal donors. J Exp Med 2007;204:1973-87.

26. Cardinale V, Wang Y, Carpino G, Cui CB, Gatto M, Rossi M, Berloco PB, Cantafora A, Wauthier E, Furth ME, Inverardi L, Dominguez-Bendala J, Ricordi C, Gerber D, Gaudio E, Alvaro D, Reid L. Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets. Hepatology 2011;54:2159-72.

27. Turner R, Lozoya O, Wang Y, Cardinale V, Gaudio E, Alpini G, Mendel G, Wauthier E, Barbier C, Alvaro D, Reid LM. Human hepatic stem cell and maturational liver lineage biology. Hepatology 2011;53:1035-45.

28. Farshidfar F, Zheng S, Gingras MC, Newton Y, Shih J, Robertson AG, Hinoue T, Hoadley KA, Gibb EA, Roszik J, Covington KR, Wu CC, Shinbrot E, Stransky N, Hegde A, Yang JD, Reznik E, Sadeghi S, Pedamallu CS, Ojesina AI, Hess JM, Auman JT, Rhie SK, Bowlby R, Borad MJ, Cancer Genome Atlas Network, Zhu AX, Stuart JM, Sander C, Akbani R, Cherniack AD, Deshpande V, Mounajjed T, Foo WC, Torbenson MS, Kleiner DE, Laird PW, Wheeler DA, McRee AJ, Bathe OF, Andersen JB, Bardeesy N, Roberts LR, Kwong LN. Integrative genomic analysis of cholangiocarcinoma identifies distinct IDH-mutant molecular profiles. Cell Rep 2017;18:2780-94.

29. Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, Allen C, Hansen G, Woodbrook R, Wolfe C, Hamadeh RR, Moore A, Werdecker A, Gessner BD, Te Ao B, McMahon B, Karimkhani C, Yu C, Cooke GS, Schwebel DC, Carpenter DO, Pereira DM, Nash D, Kazi DS, De Leo D, Plass D, Ukwaja KN, Thurston GD, Yun Jin K, Simard EP, Mills E, Park EK, Catalá-López F, deVeber G, Gotay C, Khan G, Hosgood HD 3rd, Santos IS, Leasher JL, Singh J, Leigh J, Jonas JB, Sanabria J, Beardsley J, Jacobsen KH, Takahashi K, Franklin RC, Ronfani L, Montico M, Naldi L, Tonelli M, Geleijnse J, Petzold M, Shrime MG, Younis M, Yonemoto N, Breitborde N, Yip P, Pourmalek F, Lotufo PA, Esteghamati A, Hankey GJ, Ali R, Lunevicius R, Malekzadeh R, Dellavalle R, Weintraub R, Lucas R, Hay R, Rojas-Rueda D, Westerman R, Sepanlou SG, Nolte S, Patten S, Weichenthal S, Abera SF, Fereshtehnejad SM, Shiue I, Driscoll T, Vasankari T, Alsharif U, Rahimi-Movaghar V, Vlassov VV, Marcenes WS, Mekonnen W, Melaku YA, Yano Y, Artaman A, Campos I, MacLachlan J, Mueller U, Kim D, Trillini M, Eshrati B, Williams HC, Shibuya K, Dandona R, Murthy K, Cowie B, Amare AT, Antonio CA, Casta-eda-Orjuela C, van Gool CH, Violante F, Oh IH, Deribe K, Soreide K, Knibbs L, Kereselidze M, Green M, Cardenas R, Roy N, Tillmann T, Li Y, Krueger H, Monasta L, Dey S, Sheikhbahaei S, Hafezi-Nejad N, Kumar GA, Sreeramareddy CT, Dandona L, Wang H, Vollset SE, Mokdad A, Salomon JA, Lozano R, Vos T, Forouzanfar M, Lopez A, Murray C, Naghavi M; Global Burden of Disease Cancer Collaboration. The global burden of cancer 2013. JAMA Oncol 2015;1:505-27.

30. Poomphakwaen K, Promthet S, Kamsa-Ard S, Vatanasapt P, Chaveepojnkamjorn W, Klaewkla J, Sujirarat D, Pichainarong N. Risk factors for cholangiocarcinoma in Khon Kaen, Thailand: a nested case-control study. Asian Pac Cancer Prev 2009;10:251-8.

31. Shin HR, Oh JK, Masuyer E, Curado MP, Bouvard V, Fang Y, Wiangnon S, Sripa B, Hong ST. Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma--focus on East and South-Eastern Asia. Asian Pac J Cancer Prev 2010;11:1159-66.

32. Sripa B, Kaewkes S, Sithithaworn P, Mairiang E, Laha T, Smout M, Pairojkul C, Bhudhisawasdi V, Tesana S, Thinkamrop B, Bethony JM, Loukas A, Brindley PJ. Liver fluke induces cholangiocarcinoma. PLoS Med 2007;4:e201.

33. Lepage C, Capocaccia R, Hackl M, Lemmens V, Molina E, Pierannunzio D, Sant M, Trama A, Faivre J; EUROCARE-5 Working Group. Survival in patients with primary liver cancer, gallbladder and extrahepatic biliary tract cancer and pancreatic cancer in Europe 1999-2007: results of EUROCARE-5. Eur J Cancer 2015;51:2169-78.

34. Donato F, Gelatti U, Tagger A, Favret M, Ribero ML, Callea F, Martelli C, Savio A, Trevisi P, Nardi G. Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy. Cancer Causes Control 2001;12:959-64.

35. Tao LY, He XD, Qu Q, Cai L, Liu W, Zhou L, Zhang SM. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a case-control study in China. Liver Int 2010;30:215-21.

36. Welzel TM, Graubard BI, El-Serag HB, Shaib YH, Hsing AW, Davila JA, McGlynn KA. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based case-control study. Clin Gastroenterol Hepatol 2007;5:1221-8.

37. Yamamoto S, Kubo S, Hai S, Uenishi T, Yamamoto T, Shuto T, Takemura S, Tanaka H, Yamazaki O, Hirohashi K, Tanaka T. Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma. Cancer Sci 2004;95:592-5.

38. Lee TY, Lee SS, Jung SW, Jeon SH, Yun SC, Oh HC, Kwon S, Lee SK, Seo DW, Kim MH, Suh DJ. Hepatitis B virus infection and intrahepatic cholangiocarcinoma in Korea: a case-control study. Am J Gastroenterol 2008;103:1716-20.

39. Shaib YH, El-Serag HB, Nooka AK, Thomas M, Brown TD, Patt YZ, Hassan MM. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a hospital-based case-control study. Am J Gastroenterol 2007;102:1016-21.

40. Zhou YM, Yin ZF, Yang JM, Li B, Shao WY, Xu F, Wang YL, Li DQ. Risk factors for intrahepatic cholangiocarcinoma: a case-control study in China. World J Gastroenterol 2008;14:632-5.

41. Lee CH, Chang CJ, Lin YJ, Yeh CN, Chen MF, Hsieh SY. Viral hepatitis-associated intrahepatic cholangiocarcinoma shares common disease processes with hepatocellular carcinoma. Br J Cancer 2009;100:1765-70.

42. Choi D, Lim JH, Lee KT, Choi SH, Heo JS, Jang KT, Lee NY, Kim S, Hong ST. Cholangiocarcinoma and Clonorchis sinensis infection: a case-control study in Korea. J Hepatol 2006;44:1066-73.

43. Zhou H, Wang H, Zhou D, Wang H, Wang Q, Zou S, Tu Q, Wu M, Hu H. Hepatitis B virus-associated intrahepatic cholangiocarcinoma and hepatocellular carcinoma may hold common disease process for carcinogenesis. Eur J Cancer 2010;46:1056-61.

44. Welzel TM, Graubard BI, Zeuzem S, El-Serag HB, Davila JA, McGlynn KA. Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in SEER-Medicare database. Hepatology 2011;54:463-71.

45. Zhou Y, Zhou Q, Lin Q, Chen R, Gong Y, Liu Y, Yu M, Zeng B, Li K, Chen R, Li Z. Evaluation of risk factors for extrahepatic cholangiocarcinoma: ABO blood group, hepatitis B virus and their synergism. Int J Cancer 2013;15:1867-75.

46. Brandi G, Di Girolamo S, Farioli A, de Rosa F, Curti S, Pinna AD, Ercolani G, Violante FS, Biasco G, Mattioli S. Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis. Cancer Causes Control 2013;24:911-8.

47. Patel T. Cholangiocarcinoma—controversieses and challenges. Nat Rev Gastroenterol 2011:8189-200.

48. Broomé U, Olsson R, Lööf L, Bodemar G, Hultcrantz R, Danielsson A, Prytz H, Sandberg-Gertzén H, Wallerstedt S, Lindberg G. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996;38:610-5.

49. Farrant JM, Hayllar KM, Wilkinson ML, Karani J, Portmann BC, Westaby D, Williams R. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 1991;100:1710-7.

50. Rosen CB, Nagorney DM, Wiesner RH, Coffey RJ Jr, LaRusso NF. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg 1991;213:21-5.

51. Erichsen R, Jepsen P, Vilstrup H, Ekbom A, Sørensen HT. Incidence and prognosis of cholangiocarcinoma in Danish patients with and without inflammatory bowel disease: a national cohort study, 1978-2003. Eur J Epidemiol 2009;24:513-20.

52. Chapman MH, Webster GJ, Bannoo S, Johnson GJ, Wittmann J, Pereira SP. Cholangiocarcinoma and dominant strictures in patients with primary sclerosing cholangitis: a 25-year single-centre experience. Eur J Gastroenterol Hepatol 2012;24:1051-8.

53. Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Lööf L, Danielsson A, Hultcrantz R, Lindgren S, Prytz H, Sandberg-Gertzén H, Almer S, Granath F, Broomé U. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol 2002;36:321-7.

54. Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, Gores GJ, American Association for the Study of Liver Diseases. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2010;51:660-78.

55. Claessen MM, Vleggaar FP, Tytgat KM, Siersema PD, van Buuren HR. High lifetime risk of cancer in primary sclerosing cholangitis. J Hepatol 2009;50:158-64.

56. Carpino G, Cardinale V, Renzi A, Hov JR, Berloco PB, Rossi M, Karlsen TH, Alvaro D, Gaudio E. Activation of biliary tree stem cells within peribiliary glands in primary sclerosing cholangitis. J Hepatol 2015;63:1220-8.

57. Huai JP, Ding J, Ye XH, Chen YP. Inflammatory bowel disease and risk of cholangiocarcinoma: evidence from a meta-analysis of population-based studies. Asian Pac J Cancer Prev 2014;15:3477-82.

58. Weismüller TJ, Trivedi PJ, Bergquist A, Imam M, Lenzen H, Ponsioen CY, Holm K, Gotthardt D, Färkkilä MA, Marschall HU, Thorburn D, Weersma RK, Fevery J, Mueller T, Chazouillères O, Schulze K, Lazaridis KN, Almer S, Pereira SP, Levy C, Mason A, Naess S, Bowlus CL, Floreani A, Halilbasic E, Yimam KK, Milkiewicz P, Beuers U, Huynh DK, Pares A, Manser CN, Dalekos Eksteen B GN, Invernizzi P, Berg CP, Kirchner GI, Sarrazin C, Zimmer V, Fabris L, Braun F, Marzioni M, Juran BD, Said K, Rupp C, Jokelainen K, Benito de Valle M, Saffioti F, Cheung A, Trauner M, Schramm C, Chapman RW, Karlsen TH, Schrumpf E, Strassburg CP, Manns M, K4 Lindor, G5 Hirschfield, Hansen BE, Boberg KM, International PSC Study Group. Patient age, sex, and inflammatory bowel disease phenotype associate with course of primary sclerosing cholangitis. Gastroenterology 2017;152:1975-84.

59. Tyson GL, El-Serag HB. Risk factors for cholangiocarcinoma. Hepatology 2011;54:173-84.

60. Tiwari SK, Khan AA, Ibrahim M, Habeeb MA, Habibullah CM. Helicobacter pylori and other Helicobacter species DNA in human bile samples from patients with various hepatobiliary diseases. World J Gastroenterol 2006;12:2181-6.

61. Bulajic M, Maisonneuve P, Schneider-Brachert W, Müller P, Reischl U, Stimec B, Lehn N, Lowenfels AB, Löhr M. Helicobacter pylori and the risk of benign and malignant biliary tract disease. Cancer 2002;95:1946-53.

62. Chang JS, Tsai CR, Chen LT. Medical risk factors associated with cholangiocarcinoma in Taiwan: a population-based case-control study. PLoS One 2013;8:e69981.

63. Pandey M, Shukla M. Helicobacter species are associated with possible increase in risk of hepatobiliary tract cancers. Surg Oncol 2009;18:51-6.

64. Murphy G, Michel A, Taylor PR, Albanes D, Weinstein SJ, Virtamo J, Parisi D, Snyder K, Butt J, McGlynn KA, Koshiol J, Pawlita M, Lai GY, Abnet CC, Dawsey SM, Freedman ND. Association of seropositivity to Helicobacter species and biliary tract cancer in the ATBC study. Hepatology 2014;60:1963-71.

65. Kaewpitoon SJ, Loyd RA, Rujirakul R, Panpimanmas S, Matrakool L, Tongtawee T, Kootanavanichpong N, Pengsaa P, Kompor P, Chavengkun W, Kujapun J, Norkaew J, Ponphimai S, Padchasuwan N, Polsripradist P, Eksanti T, Phatisena T, Kaewpitoon N. Helicobacter species are possible risk factors of cholangiocarcinoma. Asian Pac J Cancer Prev 2016;17:37-44.

66. Leelawat K, Suksumek N, Leelawat S, Lek-Uthai U. Detection of VacA gene specific for Helicobactor pylori in hepatocellular carcinoma and cholangiocarcinoma specimens of Thai patients. Southeast Asian J Trop Med Public Health 2007;38:881-5.

67. Sithithaworn P, Yongvanit P, Duenngai K, Kiatsopit N, Pairojkul C. Roles of liver fluke infection as risk factor for cholangiocarcinoma. J Hepatobiliary Pancreat Sci 2014;21:301-8.

68. Xia J, Jiang SC, Peng HJ. Association between liver fluke infection and hepatobiliary pathological changes: a systematic review and meta-analysis. PLoS One 2015;10:1-19.

69. Li J, Han T, Xu L, Luan X. Diabetes mellitus and the risk of cholangiocarcinoma: an updated meta-analysis. Prz Gastroenterol 2015;10:108-17.

70. Shaib YH, El Serag HB, Davila JA, Morgan R, McGlynn KA. Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study. Gastroenterology 2005;128:620-6.

71. Huang YJ, Wu AT, Chiou YH, Chuang MT, Meng TC, Chien LN, Yen Y. Interactive role of diabetes mellitus and female sex in the risk of cholangiocarcinoma: a population-based nested case–control study. Oncotarget 2017;8:6642-51.

72. Carpino G, Puca R, Cardinale Renzi A V, Scafetta G, Nevi L, Rossi M, Berloco PB, Ginanni Corradini S, Reid LM, Maroder M, Gaudio E, Alvaro D. Peribiliary glands as a niche of extrapancreatic precursors yielding insulin-producing cells in experimental and human diabetes. Stem Cells 2016;34:1332-42.

73. Chaiterakij R, Yang JD, Harmsen WS, Slettedahl SW, Mettler TA, Fredericksen ZS, Kim WR, Gores GJ, Roberts RO, Olson JE, Therneau TM, Roberts LR. Risk factor for intrahepatic cholangiocarcinoma association between metformin use and reduced cancer risk. Hepatology 2013;57:648-55.

74. Ling S, Feng T, Ke Q, Fan N, Li L, Li Z, Dong C, Wang C, Xu F, Li Y, Wang L. Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines. Oncol Rep 2014;31:2611-8.

75. Palmer WC, Patel T. Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma. J Hepatol 2012;57:69-76.

76. Reddy SK, Hyder O, Marsh JW, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, Pulitano C, Barroso E, Aldrighetti L, Geller DA, Sempoux C, Herlea V, Popescu I, Anders R, Rubbia-Brandt L, Gigot JF, Mentha G, Pawlik TM. Prevalence of nonalcoholic steatohepatitis among patients with resectable intrahepatic cholangiocarcinoma. J Gastrointest Surg 2013;17:748-55.

77. Shin HR, Lee CU, Park HJ, Seol SY, Chung JM, Choi HC, Ahn YO, Shigemastu T. Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea. Int J Epidemiol 1996;25:933-40.

78. Li H, Hu B, Zhou ZQ, Guan J, Zhang ZY, Zhou GW. Hepatitis C virus infection and the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma: evidence from a systematic review and meta-analysis of 16 case-control studies. World J Surg Oncol 2015;13:161-8.

79. Plentz RR, Malek NP. Clinical presentation, risk factors and staging systems of cholangiocarcinoma. Best Pract Res Clin Gastroenterol 2015;29:245-52.

80. Zhou HB, Hu JY, Hu HP. Hepatitis B virus infection and intrahepatic cholangiocarcinoma. World J Gastroenterol 2014;20:5721-9.

81. Zhang H, Biqing Z, He Z, Jianxin L, Wenting Z. HBV infection status and the risk of cholangiocacinoma in Asia: a meta-analysis. Bio Med Research International 2016;2016:3417976.

82. Cardinale V, Bragazzi MC, Alvaro D. New Insights into Epidemiology of Cholangiocarcinoma. In: Brandi G, Ercolani G, editors. Cholangiocarcinoma. Nova Science Pub; 2015. pp. 19-38.

83. Cardinale V, Alvaro D. Molecular Profiling. In: Herman J, Pawlik T, Thomas CR Jr, editors. Biliary Tract and Gallbladder Cancer: A Multidisciplinary Approach, 2nd Edition. Springer Science Pub; 2013. pp. 99-115.

84. Jiao Y, Pawlik TM, Anders RA, Selaru FM, Streppel MM, Lucas DJ, Niknafs N, Guthrie VB, Maitra A, Argani P, Offerhaus GJA, Roa JC, Roberts LR, Gores GJ, Popescu I, Alexandrescu ST, Dima S, Fassan M, Simbolo M, Mafficini A, Capelli P, Lawlor RT, Ruzzenente A, Guglielmi A, Tortora G, de Braud F, Scarpa A, Jarnagin W, Klimstra D, Karchin R, Velculescu VE, Hruban RH, Vogelstein B, Kinzler KW, Papadopoulos N, Wood LD. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet 2013;45:1470-3.

85. Ong CK, Subimerb C, Pairojkul C, Wongkham S, Cutcutache I, Yu W, McPherson JR, Allen GE, Ng CC, Wong BH, Myint SS, Rajasegaran V, Heng HL, Gan A, Zang ZJ, Wu Y, Wu J, Lee MH, Huang D, Ong P, Chan-on W, Cao Y, Qian CN, Lim KH, Ooi A, Dykema K, Furge K, Kukongviriyapan V, Sripa B, Wongkham C, Yongvanit P, Futreal PA, Bhudhisawasdi V, Rozen S, Tan P, Teh BT. Exome sequencing of liver fluke-associated cholangiocarcinoma. Nat Genet 2012;44:690-3.

86. Zou S, Li J, Zhou H, Frech C, Frech C, Jiang X, Chu JS, Zhao X, Li Y, Li Q, Wang H, Hu J, Kong G, Wu M, Ding C, Chen N, Hu H. Mutational landscape of intrahepatic cholangiocarcinoma. Nat Commun 2014;5:5696.

87. Borad MJ, Champion MD, Egan JB, Liang WS, Fonseca R, Bryce AH, McCullough AE, Barrett MT, Hunt K, Patel MD, Young SW, Collins JM, Silva AC, Condjella RM, Block M, McWilliams RR, Lazaridis KN, Klee EW, Bible KC, Harris P, Oliver GR, Bhavsar JD, Nair AA, Middha S, Asmann Y, Kocher JP, Schahl K, Kipp BR, Barr Fritcher EG, Baker A, J4 Aldrich, Kurdoglu A, Izatt T, Christoforides A, Cherni I, Nasser S, Reiman R, Phillips L, McDonald J, Adkins J, Mastrian SD, Placek P, Watanabe AT, Lobello J, Han H, Von Hoff D, Craig DW, Stewart AK, Carpten JD. Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma. PLoS Genet 2014;10:e1004135.

88. Fujimoto A, Furuta M, Shiraishi Y, Gotoh K, Kawakami Y, Arihiro K, Nakamura T, Ueno M, Ariizumi S, Nguyen HH, Shigemizu D, Abe T, Boroevich KA, Nakano K, Sasaki A, Kitada R, Maejima K, Yamamoto Y, Tanaka H, Shibuya T, Shibata T, Ojima H, Shimada K, Hayami S, Shigekawa Y, Aikata H, Ohdan H, Marubashi S, Yamada T, Kubo Hirano S M, Ishikawa O, Yamamoto M, Yamaue H, Chayama K, Miyano S, Tsunoda T, Nakagawa H. Whole-genome mutational landscape of liver cancers displaying biliary phenotype reveals hepatitis impact and molecular diversity. Nat Commun 2015;6:6120.

89. Gao Q, Zhao YJ, Wang XY, Guo WJ, Gao S, Wei L, Shi JY, Shi GM, Wang ZC, Zhang YN, Shi YH, Ding J, Ding ZB, Ke AW, Dai Z, Wu FZ, Wang H, Qiu ZP, Chen ZA, Zhang ZF, Qiu SJ, Zhou J, He XH, Fan J. Activating mutations in PTPN3 promote cholangiocarcinoma cell proliferation and migration and are associated with tumor recurrence in patients. Gastroenterology 2014;146:1397-407.

90. Boulter L, Guest RV, Kendall TJ, Wilson DH, Wojtacha D, Robson AJ, Ridgway RA, Samuel K, Van Rooijen N, Barry ST, Wigmore SJ, Sansom OJ, Forbes SJ. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J Clin Invest 2015;125:1269-85.

91. Chan-On W, Nairismägi ML, Ong CK, Lim WK, Dima S, Pairojkul C, Lim KH, McPherson JR, Cutcutache I, Heng HL, Ooi L, Chung A, Chow P, Cheow PC, Lee SY, Choo SP, Tan IBH, Duda D, Nastase A, Myint SS, Wong BH, Gan A, Rajasegaran V, Young Ng CC, Nagarajan S, Jusakul A, Zhang S, Vohra P, Yu W, Huang DC, Sithithaworn P, Yongvanit P, Wongkham S, Khuntikeo N, Bhudhisawasdi V, Popescu I, Rozen SG, Tan P, Teh BT. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat Genet 2013;45:1474-8.

92. Sia D, Losic B, Moeini A, Cabellos L, Hao K, Revill K, Bonal D, Miltiadous O, Zhang Z, Hoshida Y, Cornella H, Castillo-Martin M, Pinyol R, Kasai Y, Roayaie S, Thung SN, Fuster J, Schwartz ME, Waxman S, Cordon-Cardo C, Schadt E, Mazzaferro V, Llovet JM. Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma. Nat Commun 2015;6:6087.

93. Nault JC, Zucman-Rossi J. Genetics of hepatobiliary carcinogenesis. Semin Liver Dis 2011;31:173-87.

94. Chen CP, Haas-Kogan D. Neoplasms of the hepatobiliary system: clinical presentation, molecular pathways and diagnostics. Expert Rev Mol Diagn 2010;10:883-95.

95. Kumar M, Zhao X, Wang XW. Molecular carcinogenesis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: one step closer to personalized medicine? Cell Biosci 2011;1:5.

96. Yoon JH, Higuchi H, Werneburg NW, Kaufmann SH, Gores GJ. Bile acids induce cyclooxygenase-2 expression via the epidermal growth factor receptor in a human cholangiocarcinoma cell line. Gastroenterology 2002;122:985-93.

97. Yoon JH, Canbay AE, Werneburg NW, Lee SP, Gores GJ. Oxysterols induce cyclooxygenase-2 expression in cholangiocytes: implications for biliary tract carcinogenesis. Hepatology 2004;39:732-8.

98. Jaiswal M, LaRusso NF, Burgart LJ, Gores GJ. Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res 2000;60:184-90.

99. Jaiswal M, LaRusso NF, Shapiro RA, Billiar TR, Gores GJ. Nitric oxide-mediated inhibition of DNA repair potentiates oxidative DNA damage in cholangiocytes. Gastroenterology 2001;120:190-9.

100. Ishimura N, Bronk SF, Gores GJ. Inducible nitric oxide synthase upregulates cyclooxygenase-2 in mouse cholangiocytes promoting cell growth. Am J Physiol Gastrointest Liver Physiol 2004;287:G88-95.

101. Seol MA, Chu IS, Lee MJ, Yu GR, Cui XD, Cho BH, Ahn EK, Leem SH, Kim IH, Kim DG. Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma. BMC Cancer 2011;11:78.

102. Jinawath N, Chamgramol Y, Furukawa Y, Obama K, Tsunoda T, Sripa B, Pairojkul C, Nakamura Y. Comparison of gene expression profiles between Opisthorchis viverrini and non-Opisthorchis viverrini associated human intrahepatic cholangiocarcinoma. Hepatology 2006;44:1025-38.

103. Wang X, Chen W, Huang Y, Sun J, Men J, Liu H, Luo F, Guo L, Lv X, Deng C, Zhou C, Fan Y, Li X, Huang L, Hu Y, Liang C, Hu X, Xu J, Yu X. The draft genome of the carcinogenic human liver fluke Clonorchis sinensis. Genome Biol 2011;12:R107.

104. Young ND, Campbell BE, Hall RS, Jex AR, Cantacessi C, Laha T, Sohn WM, Sripa B, Loukas A, Brindley PJ, Gasser RB. Unlocking the transcriptomes of two carcinogenic parasites, Clonorchis sinensis and Opisthorchis viverrini. PLoS Negl Trop Dis 2010;4:e719.

105. Sriraksa R, Zeller C, El-Bahrawy MA, Dai W, Daduang J, Jearanaikoon P, Chau-In S, Brown R, Limpaiboon T. CpG-island methylation study of liver fluke-related cholangiocarcinoma. Br J Cancer 2011;104:1313-8.

106. Sakoda LC, Gao YT, Chen BE, Chen J, Rosenberg PS, Rashid A, Deng J, Shen MC, Wang BS, Han TQ, Zhang BH, Cohen-Webb H, Yeager M, Welch R, Chanock S, Fraumeni JF Jr, Hsing AW. Prostaglandin-endoperoxide synthase 2 (PTGS2) gene polymorphisms and risk of biliary tract cancer and gallstones: a population-based study in Shanghai, China. Carcinogenesis 2006;27:1251-6.

107. Kipp BR, Fritcher EG, Clayton AC, Gores GJ, Roberts LR, Zhang J, Levy MJ, Halling KC. Comparison of KRAS mutation analysis and FISH for detecting pancreatobiliary tract cancer in cytology specimens collected during endoscopic retrograde cholangiopancreatography. J Mol Diagn 2010;12:780-6.

108. Huang L, Frampton G, Liang LJ, Demorrow S. Aberrant DNA methylation profile in cholangiocarcinoma. World J Gastrointest Pathophysiol 2010;1:23-9.

109. Huang L, Frampton G, Rao A, Zhang KS, Chen W, Lai JM, Yin XY, Walker K, Culbreath B, Leyva-Illades D, Quinn M, McMillin M, Bradley M, Liang LJ, DeMorrow S. Monoamine oxidase A expression is suppressed in human cholangiocarcinoma via coordinated epigenetic and IL-6-driven events. Lab Invest 2012;92:1451-60.

110. Melum E, Karlsen TH, Schrumpf E, Bergquist A, Thorsby E, Boberg KM, Lie BA. Cholangiocarcinoma in primary sclerosing cholangitis is associated with NKG2D polymorphisms. Hepatology 2008;47:90-6.

111. Karamitopoulou E, Tornillo L, Zlobec I, Cioccari L, Carafa V, Borner M, Schaffner T, Brunner T, Diamantis I, Zimmermann A, Terracciano L. Clinical significance of cell cycle- and apoptosis-related markers in biliary tract cancer: a tissue microarray-based approach revealing a distinctive immunophenotype for intrahepatic and extrahepatic cholangiocarcinomas. Am J Clin Pathol 2008;130:780-6.

112. Miller G, Socci ND, Dhall D, D'Angelica M, DeMatteo RP, Allen PJ, Singh B, Fong Y, Blumgart LH, Klimstra DS, Jarnagin WR. Genome wide analysis and clinical correlation of chromosomal and transcriptional mutations in cancers of the biliary tract. J Exp Clin Cancer Res 2009;28:62.

113. Borger DR, Tanabe KK, Fan KC, Lopez HU, Fantin VR, Straley KS, Schenkein DP, Hezel AF, Ancukiewicz M, Liebman HM, Kwak EL, Clark JW, Ryan DP, Deshpande V, Dias-Santagata D, Ellisen LW, Zhu AX, Iafrate AJ. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 2012;17:72-97.

114. Yang B, House MG, Guo M, Herman JG, Clark DP. Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma. Mod Pathol 2005;18:412-20.

115. Oliveira DV, Zhang S, Chen X, Calvisi DF, Andersen JB. Molecular profiling of intrahepatic cholangiocarcinoma: the search for new therapeutic targets. Expert Rev Gastroenterol Hepatol 2017;11:349-56.

116. Rhee H, Ko JE, Chung T, Jee BA, Kwon SM, Nahm JH, Seok JY, Yoo JE, Choi JS, Thorgeirsson SS, Andersen JB, Lee HS, Woo HG, Park YN. Transcriptomic and histopathological analysis of cholangiolocellular differentiation trait in intrahepatic cholangiocarcinoma. Liver Int 2018;38:113-24.

117. Rizvi S, Gores GJ. Emerging molecular therapeutic targets for cholangiocarcinoma. J Hepatol 2017;67:632-44.

118. NakanumaY, SatoY. Cystic and papillary neoplasm involving peribiliary glands: a biliary counterpart of branch-type intraductal papillary mucinous [corrected] neoplasm? Hepatology 2012;55:2040-1.

119. Cardinale V, Wang Y, Carpino G, Mendel G, Alpini G, Gaudio E, Reid LM, Alvaro D. The biliary tree--a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol 2012;9:231-40.

120. Cardinale V, Renzi A, Carpino G, Torrice A, Bragazzi MC, Giuliante F, DeRose AM, Fraveto A, Onori P, Napoletano C, Franchitto A, Cantafora A, Grazi G, Caporaso N, D'Argenio G, Alpini G, Reid LM, Gaudio E, Alvaro D. Profiles of cancer stem cell subpopulations in cholangiocarcinomas. Am J Pathol 2015;185:1724-39.

121. Gandou C, Harada K, Sato Y, Igarashi S, Sasaki M, Ikeda H, Nakanuma Y. Hilar cholangiocarcinoma and pancreatic ductal adenocarcinoma share similar histopathologies, immunophenotypes, and development-related molecules. Hum Pathol 2013;44:811-21.

122. Nakanuma Y, Harada K, Sasaki M, Sato Y. Proposal of a new disease concept "biliary diseases with pancreatic counterparts." Anatomical and pathological bases. Histol Histopathol 2014;29:1-10.

123. Cardinale V, Gatto M, Alvaro D. Clinical features of intrahepatic cholangiocarcinoma. In: Brandi G, Ercolani G, editors. Cholangiocarcinoma. Nova Science Pub; 2015. pp. 125-34.

124. Rimola J, Forner A, Reig M, Vilana R, de Lope CR, Ayuso C, Bruix J. Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma. Hepatology 2009;50:791-8.

125. Iavarone M, Piscaglia F, Vavassori S, Galassi M, Sangiovanni A, Venerandi L, Forzenigo LV, Golfieri R, Bolondi L, Colombo M. Contrast enhanced CT-scan to diagnose intrahepatic cholangiocarcinoma in patients with cirrhosis. J Hepatol 2013;58:1188-93.

126. Kim SJ, Lee JM, Han JK, Kim KH, Lee JY, Choi BI. Peripheral mass-forming cholangiocarcinoma in cirrhotic liver. AJR Am J Roentgenol 2007;189:1428-34.

127. Weber SM, Ribero D, O'Reilly EM, Kokudo N, Miyazaki M, Pawlik TM. Intrahepatic cholangiocarcinoma: expert consensus statement. HPB (Oxford) 2015;17:669-80.

128. Chen J, He J, Deng M, Wu HY, Shi J, Mao L, Sun Q, Tang M, Fan XS, Qiu YD, Huang Q. Clinicopathologic, radiologic, and molecular study of 23 combined hepatocellular-cholangiocarcinomas with stem cell features, cholangiolocellular type. Hum Pathol 2017;64:118-27.

129. Khan SA, Davidson BR, Goldin RD, Heaton N, Karani J, Pereira SP, Rosenberg WM, Tait P, Taylor-Robinson SD, Thillainayagam AV, Thomas HC, Wasan H, Gastroenterology British Society of. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut 2012;61:1657-69.

130. Bledsoe JR, Shinagare SA, Deshpande V. Difficult diagnostic problems in pancreatobiliary neoplasia. Arch Pathol Lab Med 2015;139:848-57.

131. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009;51:237-67.

132. Lindor KD, Kowdley KV, Harrison ME, American College of Gastroenterology. ACG clinical guideline: primary sclerosing cholangitis. Am J Gastroenterol 2015;110:646-59; quiz 660.

133. Navaneethan U, Njei B, Lourdusamy V, Konjeti R, Vargo JJ, Parsi MA. Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis. Gastrointest Endosc 2015;81:168-76.

134. Arbelaiz A, Azkargorta M, Krawczyk M, Santos-Laso A, Lapitz A, Perugorria MJ, Erice O, Gonzalez E, Jimenez-Agüero R, Lacasta A, Ibarra C, Sanchez-Campos A, Jimeno JP, Lammert F, Milkiewicz P, Marzioni M, Macias RIR, Marin JJG, Patel T, Gores GJ, Martinez I, Elortza F, Falcon-Perez JM, Bujanda L, Banales JM. Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2017;66:1125-43.

135. Alvaro D. The challenge of cholangiocarcinoma diagnosis: the turning point is in extracellular vesicles? Hepatology 2017;66:1029-31.

136. Primrose JN, Fox R, Palmer DH, Prasad R, Mirza D, Anthoney DA, Corrie P, Falk S, Wasan HS, Ross PJ, Wall LR, Wadsley J, Evans TRJ, Stocken D, Praseedom R, Cunningham D, Garden OJ, Stubbs C, Valle JW, Bridgewater JA. Adjuvant capecitabine for biliary tract cancer: the BILCAP randomized study. J Clin Oncol 2017;35 Suppl 15:abstr4006.

137. Javle M, Lowery M, Shroff RT, Weiss KH, Springfeld C, Borad MJ, Ramanathan RK, Goyal L, Sadeghi S, Macarulla T, El-Khoueiry A, Kelley RK, Borbath I, Choo SP, Oh DY, Philip PA, Chen LT, Reungwetwattana T, Van Cutsem E, Yeh KH, Ciombor K, Finn RS, Patel A, Sen S, Porter D, Isaacs R, Zhu AX, Abou-Alfa GK, Bekaii-Saab T. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol 2018;36:276-82.

138. Bragazzi MC, Ridola L, Safarikia S, Matteo SD, Costantini D, Nevi L, Cardinale V. New insights into cholangiocarcinoma: multiple stems and related cell lineages of origin. Ann Gastroenterol 2018;31:42-55.

139. Rycaj K, Tang DG. Cell-of-origin of cancer versus cancer stem cells: assays and interpretations. Cancer Res 2015;75:4003-11.

140. Visvader JE. Cells of origin in cancer. Nature 2011;469:314-22.

141. Cardinale V, Wang Y, Carpino G, Reid LM, Gaudio E, Alvaro D. Mucin producing cholangiocarcinoma might derive from biliarytree stem/progenitor cells located in peribiliary glands. Hepatology 2012;55:2041-2.

142. Yamashita T, Wang XW. Cancer stem cells in the development of liver cancer. J Clin Invest 2013;123:1911-8.

143. Raggi C, Invernizzi P, Andersen JB. Impact of microenvironment and stem-like plasticity in cholangiocarcinoma: molecular networks and biological concepts. J Hepatol 2015;62:198-207.

144. Chen WT, Tseng CC, Pfaffenbach K, Kanel G, Luo B, Stiles BL, Lee AS. Liver-specific knockout of GRP94 in mice disrupts cell adhesion, activates liver progenitor cells, and accelerates liver tumorigenesis. Hepatology 2014;59:947-57.

145. Vander Borght S, Komuta M, Libbrecht L, Katoonizadeh A, Aerts R, Dymarkowski S, Verslype C, Nevens F, Roskams T. Expression of multidrug resistance-associated protein 1 in hepatocellular carcinoma is associated with a more aggressive tumour phenotype and may reflect a progenitor cell origin. Liver Int 2008;28:1370-80.

146. Govaere O, Komuta M, Berkers J, Spee B, Janssen C, de Luca F, Katoonizadeh A, Wouters J, van Kempen LC, Durnez A, Verslype C, De Kock J, Rogiers V, van Grunsven LA, Topal B, Pirenne J, Vankelecom H, Nevens F, van den Oord J, Pinzani M, Roskams T. Keratin 19: a key role player in the invasion of human hepatocellular carcinomas. Gut 2014;63:674-85.

147. Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 2012;21:283-96.

148. Moeini A, Sia D, Zhang Z, Camprecios G, Stueck A, Dong H, Montal R, Torrens L, Martinez-Quetglas I, Fiel MI, Hao K, Villanueva A, Thung SN, Schwartz ME, Llovet JM. Mixed hepatocellular cholangiocarcinoma tumors: Cholangiolocellular carcinoma is a distinct molecular entity. J Hepatol 2017;66:952-61.

149. Wei M, Lü L, Lin P, Chen Z, Quan Z, Tang Z. Multiple cellular origins and molecular evolution of intrahepatic cholangiocarcinoma. Cancer Letters 2016;379:253-61.

Hepatoma Research
ISSN 2454-2520 (Online) 2394-5079 (Print)

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/