{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:06:59Z","timestamp":1788926819513,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K08775"],"award-info":[{"award-number":["22K08775"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Gastroent Surgery"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Resectability in colorectal liver metastases (CRLM) is traditionally defined by technical feasibility; however, a biologically based definition of borderline resectable disease has not been established. We evaluated the prognostic impact of\n KRAS<\/jats:italic>\n mutation and developed a model for biological risk stratification.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This multi\u2010institutional retrospective study included 584 patients undergoing initial hepatectomy for CRLM. The impact of\n KRAS<\/jats:italic>\n mutation was assessed according to primary tumor sidedness and tumor burden score (TBS). A nomogram predicting overall survival (OS) was constructed using independent prognostic factors and compared with established clinical risk scores.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n KRAS<\/jats:italic>\n mutation was identified in 36.8% of patients and was associated with worse OS (median survival: 47.3 vs. 70.6\u2009months,\n p<\/jats:italic>\n \u2009=\u20090.0006) and recurrence\u2010free survival. This adverse impact was observed in left\u2010sided tumors but not in right\u2010sided tumors. TBS stratified prognosis in\n KRAS<\/jats:italic>\n wild\u2010type but not in mutant cases, suggesting that tumor biology may outweigh morphology. A nomogram incorporating\n KRAS<\/jats:italic>\n status, TBS, CA19\u20109, primary nodal status, and extrahepatic disease demonstrated improved discriminatory ability compared with conventional models and stratified recurrence patterns, including extrahepatic recurrence.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The prognostic impact of\n KRAS<\/jats:italic>\n mutation depends on tumor sidedness and is independent of tumor morphology. Our nomogram provides a continuous biological risk assessment and may facilitate biological risk stratification and support future refinement of the concept of biologically borderline resectable CRLM.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ags3.70278","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:44:36Z","timestamp":1788925476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biological Resectability in Colorectal Liver Metastases: A Nomogram\u2010Based Continuous Risk Model to Define Borderline Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5778-6863","authenticated-orcid":false,"given":"Yuzo","family":"Umeda","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Pancreatic and Transplantation Surgery Ehime University Graduate School of Medicine Matsuyama Ehime Japan"},{"name":"Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9940-0570","authenticated-orcid":false,"given":"Toshiharu","family":"Mitsuhashi","sequence":"additional","affiliation":[{"name":"Center for Innovative Clinical Medicine, Medical Development Field Okayama University Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7107-6518","authenticated-orcid":false,"given":"Tomokazu","family":"Fuji","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Surgery Okayama Saiseikai General Hospital Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Koujima","sequence":"additional","affiliation":[{"name":"Department of Surgery Himeji Red Cross Hospital Himeji Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Surgery Tenwakai Matsuda Hospital Kurashiki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2043-9099","authenticated-orcid":false,"given":"Daisuke","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Surgery Hiroshima Citizens Hospital Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8049-2858","authenticated-orcid":false,"given":"Masaru","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Department of Surgery National Hospital Organization Fukuyama Medical Center Fukuyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosei","family":"Takagi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyoshi","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2407-14-810","article-title":"Treatment of Colorectal Liver Metastases in Germany: A Ten\u2010Year Population\u2010Based Analysis of 5772 Cases of Primary Colorectal Adenocarcinoma","volume":"14","author":"Hackl C.","year":"2014","journal-title":"BMC Cancer"},{"issue":"7260","key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1136\/bmj.321.7260.531","article-title":"Palliative Chemotherapy for Advanced Colorectal Cancer: Systematic Review and Meta\u2010Analysis. 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N.","year":"2007","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_13_33_1","doi-asserted-by":"crossref","first-page":"8198","DOI":"10.1245\/s10434-021-10220-w","article-title":"Liver\u2010First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients From the LiverMetSurvey Registry","volume":"28","author":"Giuliante F.","year":"2021","journal-title":"Annals of Surgical Oncology"},{"issue":"35","key":"e_1_2_13_34_1","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1200\/JCO.19.01340","article-title":"FOLFOXIRI Plus Panitumumab as First\u2010Line Treatment of RAS Wild\u2010Type Metastatic Colorectal Cancer: The Randomized, Open\u2010Label, Phase II VOLFI Study (AIO KRK0109)","volume":"37","author":"Modest D. 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