{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:43:03Z","timestamp":1792201383091,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ANZ Journal of Surgery"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for distal cholangiocarcinoma (dCCA) uses depth of invasion (DOI) for T classification; however, it does not consider invasion into adjacent organs such as the pancreas. We investigated the prognostic significance of DOI and pancreatic invasion in patients with dCCA.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We retrospectively analyzed 130 patients with dCCA who underwent pancreatoduodenectomy between 2003 and 2016. The optimal DOI cutoff for predicting overall survival (OS) was determined using time\u2010dependent receiver operating characteristic analysis. Associations between clinicopathological factors, pancreatic invasion, and prognosis were evaluated using Kaplan\u2013Meier survival analysis and Cox proportional hazards models.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The optimal DOI cutoff for OS was 4\u2009mm. Patients with DOI >\u20094\u2009mm had significantly poorer survival than those with DOI \u2264\u20094\u2009mm (\n p<\/jats:italic>\n \u2009<\u20090.0001). Pancreatic invasion was associated with worse prognosis (\n p<\/jats:italic>\n \u2009<\u20090.001) and was more prevalent in tumors with greater DOI. Among patients with DOI >\u20094\u2009mm, pancreatic invasion significantly worsened OS (\n p<\/jats:italic>\n \u2009<\u20090.05), whereas no prognostic impact was observed in patients with DOI \u2264\u20094\u2009mm. Multivariate analysis identified the combination of DOI >\u20094\u2009mm and pancreatic invasion, lymph node metastasis, histological type, and positive resection margin as independent adverse prognostic factors. A novel classification incorporating DOI, pancreatic invasion, and lymph node status provided improved prognostic stratification.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The combination of DOI >\u20094\u2009mm and pancreatic invasion is an independent predictor of poor prognosis in dCCA. Incorporating pancreatic invasion into DOI\u2010based classification may improve prognostic assessment beyond the current AJCC staging system.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ans.71009","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:27:16Z","timestamp":1792200436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pancreatic Invasion in Distal Cholangiocarcinoma Is a Poor Prognostic Factor: A New Approach Integrating Tumor Depth of Invasion"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4829-1130","authenticated-orcid":false,"given":"Hirokazu","family":"Ogasawara","sequence":"first","affiliation":[{"name":"Department of Gastroenterological Surgery Hirosaki University Graduate School of Medicine Hirosaki Japan"},{"name":"Department of Anatomic Pathology Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8136-3281","authenticated-orcid":false,"given":"Tadashi","family":"Yoshizawa","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Ogasawara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Hirosaki University Graduate School of Medicine Hirosaki Japan"},{"name":"Department of Anatomic Pathology Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Kasai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Nagase","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0585-3024","authenticated-orcid":false,"given":"Norihisa","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0342-1199","authenticated-orcid":false,"given":"Keinosuke","family":"Ishido","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kijima","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Hirosaki University Graduate School of Medicine Hirosaki Japan"},{"name":"Department of Health Science Education Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6513-1202","authenticated-orcid":false,"given":"Kenichi","family":"Hakamada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"AJCC Cancer Staging Manual","author":"Edge S. 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W.","year":"2017","journal-title":"World Journal of Surgery"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.3390\/diagnostics13223406","article-title":"Subserosal Layer and\/or Pancreatic Invasion Based on Anatomical Features as a Novel Prognostic Indicator in Patients With Distal Cholangiocarcinoma","volume":"13","author":"Yoshii H.","year":"2023","journal-title":"Diagnostics"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.hpb.2020.12.001","article-title":"The Evaluation of the 8th and 7th Edition of the American Joint Committee on Cancer Tumor Classification for Distal Cholangiocarcinoma: The Proposal of a Modified New Tumor Classification","volume":"23","author":"Tamura S.","year":"2021","journal-title":"HPB"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1097\/PAS.0000000000001244","article-title":"Validation Study of Tumor Invasive Thickness for Postoperative Prognosis in 110 Patients Who Underwent Pancreatoduodenectomy for Distal Cholangiocarcinoma at a Single Institution","volume":"43","author":"Zhao Y.","year":"2019","journal-title":"American Journal of Surgical Pathology"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/modpathol.3800380","article-title":"Superficial vs Deep Pancreatic Parenchymal Invasion in the Extrahepatic Bile Duct Carcinomas: A Significant Prognostic Factor","volume":"18","author":"Hong S. M.","year":"2005","journal-title":"Modern Pathology"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1002\/bjs.10869","article-title":"Reappraisal of Classification of Distal Cholangiocarcinoma Based on Tumour Depth","volume":"105","author":"Aoyama H.","year":"2018","journal-title":"British Journal of Surgery"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1245\/s10434-010-1325-4","article-title":"Prognostic Factors After Surgical Resection for Intrahepatic, Hilar, and Distal Cholangiocarcinoma","volume":"18","author":"Murakami Y.","year":"2011","journal-title":"Annals of Surgical Oncology"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.ejso.2015.05.013","article-title":"Intrahepatic, Peri\u2010Hilar and Distal Cholangiocarcinoma: Three Different Locations of the Same Tumor or Three Different Tumors?","volume":"41","author":"Ercolani G.","year":"2015","journal-title":"European Journal of Surgical Oncology"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.14701\/ahbps.2019.23.4.319","article-title":"Comparison of the Clinical Results of Surgical Resection for Extrahepatic Cholangiocarcinomas: Hilar Cholangiocarcinoma and Mid\u2010To\u2010Distal Cholangiocarcinoma","volume":"23","author":"Jung P.","year":"2019","journal-title":"Annals of Hepato\u2010Biliary\u2010Pancreatic Surgery"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.4174\/astr.2022.102.2.100","article-title":"Comparison of Oncologic Outcomes of Extrahepatic Cholangiocarcinoma According to Tumor Location: Perihilar Cholangiocarcinoma Versus Distal Bile Duct Cancer","volume":"102","author":"Lee J. M.","year":"2022","journal-title":"Annals of Surgical Treatment and Research"},{"key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.21037\/jgo-21-776","article-title":"Specific Genomic Alterations and Prognostic Analysis of Perihilar Cholangiocarcinoma and Distal Cholangiocarcinoma","volume":"12","author":"Zheng Y.","year":"2021","journal-title":"Journal of Gastrointestinal Oncology"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1080\/14728222.2021.2013801","article-title":"Molecular Characterization of Extrahepatic Cholangiocarcinoma: Perihilar and Distal Tumors Display Divergent Genomic and Transcriptomic Profiles","volume":"25","author":"Simbolo M.","year":"2021","journal-title":"Expert Opinion on Therapeutic Targets"},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/modpathol.2017.22","article-title":"Dichotomy in Intrahepatic Cholangiocarcinomas Based on Histologic Similarities to Hilar Cholangiocarcinomas","volume":"30","author":"Akita M.","year":"2017","journal-title":"Modern Pathology"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1053\/j.gastro.2013.10.013","article-title":"Pathogenesis, Diagnosis, and Management of Cholangiocarcinoma","volume":"145","author":"Ilyas S. 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