{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:17:35Z","timestamp":1790709455966,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health through Fondazione Italiana Malattie Pancreas","award":["FIMP_CUP E37G25000440001"],"award-info":[{"award-number":["FIMP_CUP E37G25000440001"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Circulating bile acid (BA) profiles are increasingly explored in pancreatic cancer, although their interpretation is often complicated by biliary obstruction and its clinical management. In this study, we characterized plasma BA profiles in pancreatic ductal adenocarcinoma (PDAC) and assessed the relative contributions of tumor localization, histological subtype, cholestasis, and cholestasis-related interventions. Methods: Plasma BAs were quantified by LC-MS\/MS in patients with PDAC of the pancreatic head (hPDAC, n = 132), PDAC of the body-tail (tPDAC, n = 42), and non-PDAC tumors of the pancreatic head (hnonPDAC, n = 34). BA concentrations and derived ratios were log-transformed and standardized, and their associations with bilirubin were examined using multivariable linear models, LOESS, and multivariate longitudinal analyses. Results: UDCA therapy was associated with markedly increased circulating UDCA, higher total BA concentrations, and enrichment of secondary BA species. Direct bilirubin explained more variability in BA composition than binary jaundice classification and showed a non-linear association with BA remodeling, with a distinct metabolic profile emerging only at high bilirubin levels. Longitudinally, BA profiles changed substantially over time in hPDAC, largely in parallel with bilirubin, whereas they remained comparatively stable in tPDAC. After adjustment for bilirubin, tumor-related differences were modest and context-dependent. Conclusions: Overall, circulating BA profiles in pancreatic cancer appear to be driven predominantly by cholestasis and its management rather than by tumor-related features alone.<\/jats:p>","DOI":"10.3390\/cancers18152481","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:17:40Z","timestamp":1785737860000},"page":"2481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Interpreting Circulating Bile Acid Profiles in Pancreatic Cancer: The Role of Cholestasis and Its Management"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2454-0410","authenticated-orcid":false,"given":"Elisa","family":"Danese","sequence":"first","affiliation":[{"name":"Section of Clinical Biochemistry, Department of Engineering for Innovation Medicine, University of Verona, 37129 Verona, 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Pastena","sequence":"additional","affiliation":[{"name":"Department of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, 37129 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1880-0669","authenticated-orcid":false,"given":"Fabio","family":"Del Ben","sequence":"additional","affiliation":[{"name":"Immunopathology and Cancer Biomarkers Unit, Department of Cancer Research and Advanced Diagnostics, CRO Aviano National Cancer Institute IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4635-3680","authenticated-orcid":false,"given":"Gabriella","family":"Lionetto","sequence":"additional","affiliation":[{"name":"Department of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, 37129 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5732-7327","authenticated-orcid":false,"given":"Alessia","family":"Scirpoli","sequence":"additional","affiliation":[{"name":"Department of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, 37129 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Mariateresa","family":"Rizza","sequence":"additional","affiliation":[{"name":"Section of Clinical Biochemistry, Department of Engineering for Innovation Medicine, University of Verona, 37129 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3514-8473","authenticated-orcid":false,"given":"Roberto","family":"Salvia","sequence":"additional","affiliation":[{"name":"Department of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, 37129 Verona, 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