{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T02:56:00Z","timestamp":1773370560256,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009336","name":"Bengt Ihres Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007687","name":"Svenska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001725","name":"Royal Swedish Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003748","name":"Svenska S\u00e4llskapet f\u00f6r Medicinsk Forskning","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003748","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Surg Oncol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumor multiplicity is a negative prognostic factor in intrahepatic cholangiocarcinoma (iCCA) and the role of surgical resection in multiple iCCA remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Data were extracted from the Swedish quality registry for cancers of the liver and biliary tract, for all patients undergoing surgery for iCCA (2010\u20132021). Validation was performed with all Swedish hepatobiliary referral centers, including a comparison cohort of patients with liver-only multiple iCCA and nonsurgical therapy. The primary endpoint was overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Out of 338 patients operated for iCCA, 284 had resectable tumors and 54 (16.0%) unresectable disease at exploration. In the resection and exploration groups, 46 (16.2%) and 11 patients (20.4%), respectively, had multiple lesions. A majority of patients with resection for multiple iCCA had two or three lesions (63.0%), with median OS 27.1 months (95% CI 18.8\u201335.5), compared with 5.3 months (95% CI 3.8\u20136.8) for patients with unresectable disease (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001). For patients with four or more lesions, OS with resection was similar as with unresectable disease (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.922). In multiple iCCA, resection was associated with better performance status (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.007), negative lymph nodes (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.028), and smaller tumors (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.004). With adjustment including these factors, resection was not significantly associated with OS (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.090).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Resection for multiple iCCA with four or more lesions was not associated with a survival benefit compared with exploration. With selection to surgery for patients with good performance status, smaller tumors and no signs of lymph node metastasis, resection for two or three lesions yielded median OS above 2 years.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1245\/s10434-025-18983-2","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T19:30:17Z","timestamp":1767641417000},"page":"2917-2925","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Outcomes After Resection for Multiple Intrahepatic Cholangiocarcinoma\u2014A National Population-Based Study"],"prefix":"10.1245","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1833-854X","authenticated-orcid":false,"given":"Hannes","family":"Jansson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Taflin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bergthor","family":"Bj\u00f6rnsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jozef","family":"Urdzik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oskar","family":"Hemmingsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny Lundmark","family":"Rystedt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Gilg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Sandstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernesto","family":"Sparrelid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"issue":"6","key":"18983_CR1","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1001\/jamasurg.2013.5137","volume":"149","author":"MN Mavros","year":"2014","unstructured":"Mavros MN, Economopoulos KP, Alexiou VG, Pawlik TM. Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: systematic review and meta-analysis. JAMA Surg. 2014;149(6):565\u201374. https:\/\/doi.org\/10.1001\/jamasurg.2013.5137.","journal-title":"JAMA Surg"},{"issue":"4","key":"18983_CR2","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.ejso.2023.01.006","volume":"49","author":"H Jansson","year":"2023","unstructured":"Jansson H, Villard C, Nooijen LE, Ghorbani P, Erdmann JI, Sparrelid E. Prognostic influence of multiple hepatic lesions in resectable intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. Eur J Surg Oncol. 2023;49(4):688\u201399. https:\/\/doi.org\/10.1016\/j.ejso.2023.01.006.","journal-title":"Eur J Surg Oncol"},{"issue":"6","key":"18983_CR3","doi-asserted-by":"publisher","first-page":"2311","DOI":"10.1002\/hep.31598","volume":"73","author":"A Lamarca","year":"2021","unstructured":"Lamarca A, Santos-Laso A, Utpatel K, et al. Liver metastases of intrahepatic cholangiocarcinoma: implications for an updated staging system. Hepatology. 2021;73(6):2311\u201325. https:\/\/doi.org\/10.1002\/hep.31598.","journal-title":"Hepatology"},{"issue":"2","key":"18983_CR4","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1002\/hep.31741","volume":"74","author":"XF Zhang","year":"2021","unstructured":"Zhang XF, Lv Y, Pawlik TM. Letter to the Editor: Does multiple intrahepatic cholangiocarcinoma worsen prognosis as \u201cM1\u201d stage? Hepatology. 2021;74(2):1128. https:\/\/doi.org\/10.1002\/hep.31741.","journal-title":"Hepatology"},{"issue":"7","key":"18983_CR5","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1001\/jamasurg.2022.1298","volume":"157","author":"S Franssen","year":"2022","unstructured":"Franssen S, Soares KC, Jolissaint JS, et al. Comparison of hepatic arterial infusion pump chemotherapy vs resection for patients with multifocal intrahepatic cholangiocarcinoma. JAMA Surg. 2022;157(7):590\u20136. https:\/\/doi.org\/10.1001\/jamasurg.2022.1298.","journal-title":"JAMA Surg"},{"issue":"6","key":"18983_CR6","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.jhep.2014.01.021","volume":"60","author":"J Bridgewater","year":"2014","unstructured":"Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60(6):1268\u201389. https:\/\/doi.org\/10.1016\/j.jhep.2014.01.021.","journal-title":"J Hepatol"},{"issue":"1","key":"18983_CR7","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jhep.2023.03.010","volume":"79","author":"European Association for the Study of the Liver","year":"2023","unstructured":"European Association for the Study of the Liver. EASL-ILCA Clinical Practice Guidelines on the management of intrahepatic cholangiocarcinoma. J Hepatol. 2023;79(1):181\u2013208. https:\/\/doi.org\/10.1016\/j.jhep.2023.03.010.","journal-title":"J Hepatol"},{"key":"18983_CR8","unstructured":"SweLiv Registry, Regional Cancer Centre West. Regional cancer centres in Sweden. https:\/\/cancercentrum.se\/diagnosbehandling\/cancerdiagnoser\/leverochgalla\/kvalitetsregister.7151.html. Accessed 5 Aug 2025"},{"issue":"6","key":"18983_CR9","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1097\/00000421-198212000-00014","volume":"5","author":"MM Oken","year":"1982","unstructured":"Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern cooperative oncology group. Am J Clin Oncol. 1982;5(6):649\u201355.","journal-title":"Am J Clin Oncol"},{"key":"18983_CR10","volume-title":"TNM classification of malignant tumours","author":"JD Brierley","year":"2017","unstructured":"Brierley JD. Union for international cancer C. In: TNM classification of malignant tumours. 8th edn. New York: Wiley Blackwell; 2017.","edition":"8"},{"key":"18983_CR11","doi-asserted-by":"publisher","first-page":"103208","DOI":"10.1016\/j.jbi.2019.103208","volume":"95","author":"PA Harris","year":"2019","unstructured":"Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208. https:\/\/doi.org\/10.1016\/j.jbi.2019.103208.","journal-title":"J Biomed Inform"},{"issue":"2","key":"18983_CR12","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1097\/01.sla.0000133083.54934.ae","volume":"240","author":"D Dindo","year":"2004","unstructured":"Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205\u201313. https:\/\/doi.org\/10.1097\/01.sla.0000133083.54934.ae.","journal-title":"Ann Surg"},{"issue":"7624","key":"18983_CR13","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1136\/bmj.39335.541782.AD","volume":"335","author":"E von Elm","year":"2007","unstructured":"von Elm E, Altman DG, Egger M, et al. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 2007;335(7624):806\u20138. https:\/\/doi.org\/10.1136\/bmj.39335.541782.AD.","journal-title":"BMJ"},{"issue":"4","key":"18983_CR14","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/0197-2456(96)00075-x","volume":"17","author":"M Schemper","year":"1996","unstructured":"Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17(4):343\u20136. https:\/\/doi.org\/10.1016\/0197-2456(96)00075-x.","journal-title":"Control Clin Trials"},{"issue":"10","key":"18983_CR15","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1093\/aje\/kwi307","volume":"162","author":"Z Zhou","year":"2005","unstructured":"Zhou Z, Rahme E, Abrahamowicz M, Pilote L. Survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods. Am J Epidemiol. 2005;162(10):1016\u201323. https:\/\/doi.org\/10.1093\/aje\/kwi307.","journal-title":"Am J Epidemiol."},{"issue":"5","key":"18983_CR16","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/S1470-2045(18)30915-X","volume":"20","author":"JN Primrose","year":"2019","unstructured":"Primrose JN, Fox RP, Palmer DH, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20(5):663\u201373. https:\/\/doi.org\/10.1016\/S1470-2045(18)30915-X.","journal-title":"Lancet Oncol"},{"issue":"4","key":"18983_CR17","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1093\/bjs\/znaf050","volume":"112","author":"J Kawashima","year":"2025","unstructured":"Kawashima J, Akabane M, Khalil M, et al. Tumour burden predicts outcomes after curative resection of multifocal intrahepatic cholangiocarcinoma. Br J Surg. 2025;112(4):50. https:\/\/doi.org\/10.1093\/bjs\/znaf050.","journal-title":"Br J Surg"},{"issue":"4","key":"18983_CR18","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1111\/hpb.12359","volume":"17","author":"P Tabrizian","year":"2015","unstructured":"Tabrizian P, Jibara G, Hechtman JF, et al. Outcomes following resection of intrahepatic cholangiocarcinoma. HPB (Oxford). 2015;17(4):344\u201351. https:\/\/doi.org\/10.1111\/hpb.12359.","journal-title":"HPB (Oxford)"},{"issue":"1","key":"18983_CR19","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s13304-010-0007-x","volume":"62","author":"G Nuzzo","year":"2010","unstructured":"Nuzzo G, Giuliante F, Ardito F, et al. Intrahepatic cholangiocarcinoma: prognostic factors after liver resection. Updates Surg. 2010;62(1):11\u20139. https:\/\/doi.org\/10.1007\/s13304-010-0007-x.","journal-title":"Updates Surg"},{"key":"18983_CR20","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.hbpd.2020.08.002","volume":"20","author":"F Bartsch","year":"2020","unstructured":"Bartsch F, Hahn F, Muller L, et al. Intrahepatic cholangiocarcinoma: Introducing the preoperative prediction score based on preoperative imaging. Hepatobiliary Pancreat Dis Int. 2020;20:330. https:\/\/doi.org\/10.1016\/j.hbpd.2020.08.002.","journal-title":"Hepatobiliary Pancreat Dis Int"},{"issue":"9","key":"18983_CR21","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1007\/s11605-018-4052-y","volume":"23","author":"P Addeo","year":"2019","unstructured":"Addeo P, Jedidi I, Locicero A, et al. Prognostic impact of tumor multinodularity in intrahepatic cholangiocarcinoma. J Gastrointest Surg. 2019;23(9):1801\u20139. https:\/\/doi.org\/10.1007\/s11605-018-4052-y.","journal-title":"J Gastrointest Surg"},{"issue":"9","key":"18983_CR22","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","volume":"17","author":"JM Banales","year":"2020","unstructured":"Banales JM, Marin JJG, Lamarca A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17(9):557\u201388. https:\/\/doi.org\/10.1038\/s41575-020-0310-z.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"10391","key":"18983_CR23","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1016\/S0140-6736(23)00727-4","volume":"401","author":"RK Kelley","year":"2023","unstructured":"Kelley RK, Ueno M, Yoo C, et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;401(10391):1853\u201365. https:\/\/doi.org\/10.1016\/S0140-6736(23)00727-4.","journal-title":"Lancet"},{"issue":"5","key":"18983_CR24","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/S1470-2045(20)30109-1","volume":"21","author":"GK Abou-Alfa","year":"2020","unstructured":"Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21(5):671\u201384. https:\/\/doi.org\/10.1016\/S1470-2045(20)30109-1.","journal-title":"Lancet Oncol"},{"issue":"8","key":"18983_CR25","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/S2468-1253(24)00095-5","volume":"9","author":"DY Oh","year":"2024","unstructured":"Oh DY, He AR, Bouattour M, et al. Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study. Lancet Gastroenterol Hepatol. 2024;9(8):694\u2013704. https:\/\/doi.org\/10.1016\/S2468-1253(24)00095-5.","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"4","key":"18983_CR26","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1093\/bjs\/znaf048","volume":"112","author":"K Soreide","year":"2025","unstructured":"Soreide K. Resection of multifocal intrahepatic cholangiocarcinoma. Br J Surg. 2025;112(4):48. https:\/\/doi.org\/10.1093\/bjs\/znaf048.","journal-title":"Br J Surg"},{"key":"18983_CR27","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001594","author":"T Wei","year":"2025","unstructured":"Wei T, Ma ZJ, Guo S, et al. Satellite lesions versus intrahepatic metastasis in multifocal intrahepatic cholangiocarcinoma: prognostic impact and genomic profiling. Hepatology. 2025. https:\/\/doi.org\/10.1097\/HEP.0000000000001594.","journal-title":"Hepatology"},{"issue":"3","key":"18983_CR28","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1093\/carcin\/bgaa124","volume":"42","author":"SH Lee","year":"2021","unstructured":"Lee SH, Simoneau EB, Karpinets T, et al. Genomic profiling of multifocal intrahepatic cholangiocarcinoma reveals intraindividual concordance of genetic alterations. Carcinogenesis. 2021;42(3):436\u201341. https:\/\/doi.org\/10.1093\/carcin\/bgaa124.","journal-title":"Carcinogenesis"},{"issue":"9","key":"18983_CR29","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1158\/1078-0432.CCR-21-1157","volume":"28","author":"S Chen","year":"2022","unstructured":"Chen S, Xie Y, Cai Y, et al. Multiomic analysis reveals comprehensive tumor heterogeneity and distinct immune subtypes in multifocal intrahepatic cholangiocarcinoma. Clin Cancer Res. 2022;28(9):1896\u2013910. https:\/\/doi.org\/10.1158\/1078-0432.CCR-21-1157.","journal-title":"Clin Cancer Res"}],"container-title":["Annals of Surgical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1245\/s10434-025-18983-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1245\/s10434-025-18983-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1245\/s10434-025-18983-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:47:22Z","timestamp":1773330442000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1245\/s10434-025-18983-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["18983"],"URL":"https:\/\/doi.org\/10.1245\/s10434-025-18983-2","relation":{},"ISSN":["1068-9265","1534-4681"],"issn-type":[{"value":"1068-9265","type":"print"},{"value":"1534-4681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]},"assertion":[{"value":"3 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors have no conflict of interest to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosures"}}]}}