{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:47:52Z","timestamp":1792597672769,"version":"4.5.0"},"reference-count":65,"publisher":"American Medical Association (AMA)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Surg"],"abstract":"<jats:sec id=\"ab-srv260006-1\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy, and incidence is increasing worldwide. Despite advances in multimodal therapy, 5-year overall survival remains approximately 9%, underscoring the urgent need for improved therapeutic strategies and comprehensive understanding of current management approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-srv260006-2\">\n                    <jats:title>Observations<\/jats:title>\n                    <jats:p>\n                      Surgical resection with regional lymphadenectomy remains the cornerstone of curative therapy, with adjuvant capecitabine established as standard of care after resection. Neoadjuvant chemotherapy may be strongly considered for patients with iCCA with high-risk features, including at least 1 of the following: tumor size larger than 5 cm, multifocal disease, vascular invasion, lymph node involvement, and elevated carbohydrate antigen 19-9. For unresectable, liver-confined disease, locoregional therapies, including transarterial chemoembolization, Y-90 radioembolization, hepatic artery infusion pump chemotherapy, thermal ablation, and radiotherapy, may provide meaningful survival benefits. Liver transplant is emerging as a viable option in highly selected patients with very early iCCA or sustained response to neoadjuvant therapy. In advanced disease, chemoimmunotherapy with gemcitabine\/cisplatin plus durvalumab or pembrolizumab has become the first-line treatment. Comprehensive molecular profiling identifies actionable targets in 30% to 40% of patients, including\n                      <jats:italic toggle=\"yes\">FGFR2<\/jats:italic>\n                      fusions\/rearrangements,\n                      <jats:italic toggle=\"yes\">IDH1<\/jats:italic>\n                      variants, and other alterations amenable to targeted therapies approved by the US Food and Drug Administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-srv260006-3\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>The management of iCCA has evolved substantially with neoadjuvant chemoimmunotherapy for high-risk resectable disease, enhanced locoregional strategies for liver-confined tumors, chemoimmunotherapy as first-line systemic therapy for advanced disease, and precision oncology approaches targeting recurrent molecular alterations. Multidisciplinary evaluation and comprehensive genomic profiling are essential for optimal patient outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamasurg.2026.4971","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:00:29Z","timestamp":1792594829000},"source":"Crossref","is-referenced-by-count":0,"title":["Intrahepatic Cholangiocarcinoma"],"prefix":"10.1001","author":[{"given":"Diamantis I.","family":"Tsilimigras","sequence":"first","affiliation":[{"name":"Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Ntanasis-Stathopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy 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