Clinical Journal of Gastroenterology

, Volume 12, Issue 2, pp 128–134 | Cite as

Combined hepatocellular-cholangiocarcinoma successfully treated with sorafenib: case report and review of the literature

  • Yuka Futsukaichi
  • Kazuto TajiriEmail author
  • Saito Kobayashi
  • Kohei Nagata
  • Satoshi Yasumura
  • Terumi Takahara
  • Masami Minemura
  • Ichiro Yasuda
Case Report


Sorafenib, a multiple kinase inhibitor, has been established as first-line standard systemic chemotherapy for patients with advanced hepatocellular carcinoma (HCC). We encountered a patient with combined hepatocellular and cholangiocarcinoma (CHC) who achieved complete remission in response to sorafenib treatment. A 58-year old man with hepatitis C virus (HCV)-induced liver cirrhosis was diagnosed with CHC in segments 6th and 7th of the liver and underwent partial surgical resection. Three months later, CHC recurred as metastases at multiple intrahepatic sites, lymph nodes, and bones, making surgery impossible. Treatment with sorafenib was initiated at 400 mg b.i.d., later reduced to 400 mg/day. After 6 months of sorafenib administration, he no longer showed abnormal uptake on fluorodeoxyglucose positron emission tomography. He was continued on sorafenib for 2.5 years, but later discontinued due to adverse events. He has shown no evidence of tumor recurrence more than 1 year after sorafenib discontinuation. His HCV was eradicated by direct-acting antivirals, and he remains in good health.


Combined hepatocellular-cholangiocarcinoma Sorafenib Cirrhosis Hepatitis C virus Systemic chemotherapy 


Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Human/animal Rights

All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed Consent

Informed consent was obtained from a patient for being included in the study.


  1. 1.
    Goodman ZD, Ishak KG, Langloss JM, et al. Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer. 1985;55:124–35.CrossRefGoogle Scholar
  2. 2.
    Allen RA, Lisa JR. Combined liver cell and bile duct carcinoma. Am J Pathol. 1949;25:647–55.Google Scholar
  3. 3.
    Theise ND, Nakashima O, Park YN, Nakanuma Y. Combined hepatocellular-cholangiocarcinoma. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC Press; 2010. p. 225–57.Google Scholar
  4. 4.
    Yano Y, Yamamoto J, Kosuge T, et al. Combined hepatocellular and cholangiocarcinoma: a clinicopathologic study of 26 resected cases. Jpn J Clin Oncol. 2003;33:283–7.CrossRefGoogle Scholar
  5. 5.
    Kassahun WT, Hauss J. Management of combined hepatocellular and cholangiocarcinoma. Int J Clin Pract. 2008;62:1271–8.CrossRefGoogle Scholar
  6. 6.
    Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64:7099–109.CrossRefGoogle Scholar
  7. 7.
    Ekstrom V, Kumar R, Zhao Y, et al. Real world experience with pegylated interferon and ribavirin in hepatitis C genotype 1 population with favourable IL28B polymorphism. Gastroenterol Rep (Oxf). 2017;5:208–12.Google Scholar
  8. 8.
    Sammon J, Fischer S, Menezes R, et al. MRI features of combined hepatocellular- cholangiocarcinoma versus mass forming intrahepatic cholangiocarcinoma. Cancer Imaging. 2018;18:8.CrossRefGoogle Scholar
  9. 9.
    Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.CrossRefGoogle Scholar
  10. 10.
    Kim GM, Jeung HC, Kim D, et al. A case of combined hepatocellular-cholangiocarcinoma with favorable response to systemic chemotherapy. Cancer Res Treat. 2010;42:235–8.CrossRefGoogle Scholar
  11. 11.
    Rogers JE, Bolonesi RM, Rashid A, et al. Systemic therapy for unresectable, mixed hepatocellular-cholangiocarcinoma: treatment of a rare malignancy. J Gastrointest Oncol. 2017;8:347–51.CrossRefGoogle Scholar
  12. 12.
    Chakunta HR, Sunderkrishnan R, Kaplan MA, et al. Cholangiocarcinoma: treatment with sorafenib extended life expectancy to greater than 4 years. J Gastrointest Oncol. 2013;4:E30-2.Google Scholar
  13. 13.
    El-Khoueiry AB, Rankin CJ, Ben-Josef E, et al. SWOG 0514: a phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma. Invest New Drugs. 2012;30:1646–51.CrossRefGoogle Scholar
  14. 14.
    Bengala C, Bertolini F, Malavasi N, et al. Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial. Br J Cancer. 2010;102:68–72.CrossRefGoogle Scholar
  15. 15.
    Pan TT, Wang W, Jia WD, et al. A single-center experience of sorafenib monotherapy in patients with advanced intrahepatic cholangiocarcinoma. Oncol Lett. 2017;13:2957–64.CrossRefGoogle Scholar
  16. 16.
    Luo X, Jia W, Huang Z, et al. Effectiveness and safety of sorafenib in the treatment of unresectable and advanced intrahepatic cholangiocarcinoma: a pilot study. Oncotarget. 2017;8:17246–57.Google Scholar
  17. 17.
    Kobayashi S, Terashima T, Shiba S, et al. Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. Cancer Sci. 2018;1–9.Google Scholar
  18. 18.
    Sugiyama H, Onuki K, Ishige K, et al. Potent in vitro and in vivo antitumor activity of sorafenib against human intrahepatic cholangiocarcinoma cells. J Gastroenterol. 2011;46:779–89.CrossRefGoogle Scholar
  19. 19.
    Fraveto A, Cardinale V, Bragazzi MC, et al. Sensitivity of human intrahepatic cholangiocarcinoma subtypes to chemotherapeutics and molecular targeted agents: a study on primary cell cultures. PLoS One. 2015;10:e0142124.CrossRefGoogle Scholar
  20. 20.
    Fujimoto A, Furuta M, Totoki Y, et al. Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer. Nat Genet. 2016;48:500–9.CrossRefGoogle Scholar
  21. 21.
    Sasaki M, Sato H, Kakuda Y, et al. Clinicopathological significance of ‘subtypes with stem-cell feature’ in combined hepatocellular-cholangiocarcinoma. Liver Int. 2015;35:1024–35.CrossRefGoogle Scholar
  22. 22.
    Park JG, Tak WY, Park SY, et al. Long-term follow-up of complete remission of advanced hepatocellular carcinoma following sorafenib therapy: a case report. Oncol Lett. 2017;14:4853–6.CrossRefGoogle Scholar

Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  1. 1.Department of GastroenterologyToyama University HospitalToyamaJapan

Personalised recommendations