{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:17:26Z","timestamp":1786706246838,"version":"build-2736575974"},"reference-count":116,"publisher":"Georg Thieme Verlag KG","issue":"04","funder":[{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"crossref","award":["Premed-CHC"],"award-info":[{"award-number":["Premed-CHC"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Liver Dis"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver malignancy characterized by the coexistence of both hepatocellular and biliary morphological differentiation. It is thought to represent less than 5% of all primary liver cancers and is associated with a dismal clinical course. Due to its rarity and inherent diagnostic challenges, consensus guidelines for the management of patients with cHCC-CCA are lacking, and treatments are usually extrapolated from HCC or CCA guidelines. This review provides an overview of the main clinical and histo-molecular features of cHCC-CCA, along with its diagnostic and therapeutic challenges. Technological advances have allowed researchers to progressively elucidate cHCC-CCA's unique biology and heterogeneity. Several major questions, however, remain, such as the cHCC-CCA cell of origin. Integration of multi-modal data and use of artificial intelligence provide interesting perspectives to further improve patient management; however, they will need to be carefully assessed and validated. A better definition and understanding of this entity will be key to further planning clinical trials.<\/jats:p>","DOI":"10.1055\/a-2730-9074","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T23:08:13Z","timestamp":1761347293000},"page":"476-486","source":"Crossref","is-referenced-by-count":4,"title":["Combined Hepatocellular-Cholangiocarcinoma: A Clinical and Molecular Review"],"prefix":"10.1055","volume":"45","author":[{"given":"Shaodian","family":"Xu","sequence":"additional","affiliation":[{"name":"Team \u201cViruses, Hepatology, Cancer,\u201d Institut Mondor de Recherche Biom\u00e9dicale, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"},{"name":"MINT-Hep, Mondor Integrative Hepatology, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Calderaro","sequence":"additional","affiliation":[{"name":"Team \u201cViruses, Hepatology, Cancer,\u201d Institut Mondor de Recherche Biom\u00e9dicale, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"},{"name":"MINT-Hep, Mondor Integrative Hepatology, Cr\u00e9teil, France"},{"name":"Department of Pathology, Assistance Publique-H\u00f4pitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"issue":"03","key":"ref1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"03","key":"ref2","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.jhep.2019.06.001","article-title":"Molecular and histological correlations in liver cancer","volume":"71","author":"J Calderaro","year":"2019","journal-title":"J 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