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Biliary fistulas, though usually less severe, can occur after pancreaticoduodenectomy and, when combined with pancreatic fistulas, increase morbidity and mortality. This study is the first to investigate, whether bile enhances the harmful effects of pancreatic fluid on sealant integrity in a short-term\n                      <jats:italic>ex vivo<\/jats:italic>\n                      model using a fibrin-based sealant, thereby contributing to fistula formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We developed and validated an improved ex-vivo setup to simulate the conditions during pancreatic surgery: the physiological incubation bio-simulator 2 (PIBS 2). A defined defect in porcine pleura was sealed with the fibrin sealant TachoSil\n                      <jats:sup>\u00ae<\/jats:sup>\n                      and exposed to various fluids from human origin (pancreatic fluid, bile fluid and a combination of both) for 60\u00a0min in a physiological environment. Electrolyte solution served as control. We evaluated the overall leakage rates and time to leakage. Results were plotted as Kaplan-Meier survival curves and analyzed using the log-rank test (Mantel-Cox) and Fisher\u2019s exact test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PIBS 2 achieved stable defect closure for the electrolyte solution. Pancreatic fluid demonstrated the highest leakage rates (75%) and significantly impaired sealant stability (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), whereas bile fluid alone showed no significant effect on sealant integrity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.63). When combined, bile and pancreatic fluid resulted in a significantly lower leakage rate compared to pancreatic fluid alone (47% vs. 75%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.041; odds ratio 3.31).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study replicates previous results, showing that pancreatic fluid is highly aggressive towards fibrin-based sealants. In contrast to clinical findings, the addition of bile did not significantly increase this effect in this ex-vivo model, suggesting that morbidity in patients with combined fistulas may not be primarily caused by increased aggressiveness of pancreatic fluid after its combination with bile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00423-026-04300-2","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:47:00Z","timestamp":1791290820000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bile does not increase the aggressiveness of pancreatic fluid towards fibrin-based sealants in a short-term ex-vivo setting"],"prefix":"10.1007","volume":"411","author":[{"given":"Nora Katharina","family":"Drees","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Malzkorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-9880","authenticated-orcid":false,"given":"Britta","family":"Majchrzak-Stiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7847-6138","authenticated-orcid":false,"given":"Johanna","family":"Strotmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1021-3487","authenticated-orcid":false,"given":"David","family":"Wiedemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0919-7666","authenticated-orcid":false,"given":"Chris","family":"Braumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7719-3192","authenticated-orcid":false,"given":"Waldemar","family":"Uhl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2913-9690","authenticated-orcid":false,"given":"Philipp","family":"H\u00f6hn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"1","key":"4300_CR1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1080\/13651820600641357","volume":"9","author":"S Crippa","year":"2007","unstructured":"Crippa S, Salvia R, Falconi M, Butturini G, Landoni L, Bassi C (2007) Anastomotic leakage in pancreatic surgery. 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All procedures were performed according to a protocol approved by the Ethics Committee of Ruhr-University Bochum (permission no. 19-6737-BR). Written informed consent was obtained from all patients in accordance with local ethical guidelines. This study was conducted in accordance with the principles of the Declaration of Helsinki.","order":1,"name":"Ethics","label":"Statement of ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"265"}}