{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:04:57Z","timestamp":1792839897466,"version":"4.5.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The concept and definition of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), an extremely rare condition accounting for only 1% of all primary liver cancers, has shifted in recent years. The latest World Health Organization Classification (fifth edition) includes two types of cHCC-CCAs, (i) the classical type described in the previous edition, which contains a mixture of distinctly differentiated components of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) and (ii) intermediate cell carcinoma wherein all cells comprising the tumor express both hepatocellular and cholangiocellular features. However, the pathogenesis of cHCC-CCA, including its origins, remains controversial even among experts. Treatment strategies for cHCC-CCA in clinical practice have been determined based on imaging findings, tumor markers, and pathologically predominant tumor components for either HCC or ICC, suggesting that cHCC-CCA has yet to be been established as an independent disease entity. As with HCC and ICC, the treatment strategy for HCC-CCA involves initially considering resectability. Although systemic therapy has been considered for patients unsuitable for local treatment, no prospective clinical trials have evaluated the efficacy and safety of systemic therapy for cHCC-CCA, which could explain the lack of a standard of care. In recent years, however, studies have demonstrated the efficacy of immune checkpoint inhibitors for HCC and ICC, with therapeutic results having been reported for cHCC-CCA. Hence, further accumulation of cases is expected to facilitate the establishment of a consensus on treatment strategies in the near future.<\/jats:p>","DOI":"10.1093\/jjco\/hyaf029","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T07:50:50Z","timestamp":1739346650000},"page":"327-333","source":"Crossref","is-referenced-by-count":12,"title":["Diagnosis, clinical characteristics, and treatment of combined hepatocellular-cholangiocarcinoma"],"prefix":"10.1093","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1052-0101","authenticated-orcid":false,"given":"Takeshi","family":"Terashima","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Kanazawa University Hospital , 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences , 13-1, Takaramachi, Kanazawa, Ishikawa 920-8641 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Kanazawa University Hospital , 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"2025040711073431200_ref1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"2025040711073431200_ref2","doi-asserted-by":"publisher","first-page":"426","DOI":"10.2188\/jea.JE20200416","article-title":"Updated trends in cancer in Japan: incidence in 1985\u20132015 and mortality in 1958\u20132018\u2013a sign of decrease in cancer incidence","volume":"31","author":"Katanoda","year":"2021","journal-title":"J Epidemiol"},{"key":"2025040711073431200_ref3","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.jhep.2024.06.004","article-title":"Rare primary liver cancers: an EASL position paper","volume":"81","author":"Wege","year":"2024","journal-title":"J Hepatol"},{"key":"2025040711073431200_ref4","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1007\/s00535-022-01920-5","article-title":"The epidemiology of rare types of hepatobiliary and pancreatic cancer from national cancer registry","volume":"57","author":"Satake","year":"2022","journal-title":"J Gastroenterol"},{"key":"2025040711073431200_ref5","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1097\/00000441-190309000-00004","article-title":"Primary carcinoma of the liver","volume":"126","author":"Wells","year":"1903","journal-title":"Am J Med Sci"},{"key":"2025040711073431200_ref6","first-page":"647","article-title":"Combined liver cell and bile duct carcinoma","volume":"25","author":"Allen","year":"1949","journal-title":"Am J Pathol"},{"key":"2025040711073431200_ref7","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/1097-0142(19850101)55:1&lt;124::AID-CNCR2820550120&gt;3.0.CO;2-Z","article-title":"Combined hepatocellular-cholangiocarcinoma. 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