{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:19:55Z","timestamp":1768569595313,"version":"3.49.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Statins have been proven to be cytotoxic to human cholangiocarcinoma cells by inhibiting cell division and inducing apoptosis. We aimed to determine the effect of statin use on the risk of cancer development and survival in patients with extrahepatic cholangiocarcinoma (ECC), including perihilar cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>A total of 394 patients with ECC and hyperlipidemia who received care at Mayo Clinic Rochester between 2005 and 2015 were matched by age, sex, race, ethnicity, and residency to 788 controls with hyperlipidemia. Clinical and outcome data were abstracted. The odds ratios (ORs) for risk and hazard ratios for outcomes were calculated. The mean age and standard deviation (SD) for cases and controls was 65.6\u00a0years (13.8). The number of statin users in cases and controls was 73 (19%) and 403 (51%), respectively. Hepatitis C virus infection (OR,\u00a015.84; 95% confidence interval [CI], 4.06\u201061.87; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.001) was the most significant risk factor for pCCA followed by inflammatory bowel disease and cirrhosis, whereas other liver disease, including biliary stone disease (OR,\u00a04.06; CI, 2.24\u20107.36; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.001), was the only significant risk factor for dCCA. Statin use was associated with significantly reduced risk for all ECC (OR,\u00a00.22; CI, 0.16\u20100.29) as well as for the subtypes pCCA (OR,\u00a00.3; CI, 0.21\u20100.41) and dCCA (OR,\u00a00.06; CI, 0.03\u20100.14), all <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.0001. Moderate\u2010intensity dosage was found to decrease the risk of ECC (OR,\u00a00.48; CI, 0.34\u20100.67; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.001). Comparing statin ever users to nonusers, patients with dCCA who used statins had significantly overall better survival (hazard ratio\u00a0=\u00a00.53; CI, 0.29\u20100.97; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.04).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This case\u2010control study suggests that statins decrease the risk of ECC and may improve survival in patients with dCCA. Additional validation studies are warranted.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31146","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T13:52:47Z","timestamp":1583157167000},"page":"1298-1309","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":21,"title":["Effect of Statins on the Risk of Extrahepatic Cholangiocarcinoma"],"prefix":"10.1097","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-3852","authenticated-orcid":false,"given":"Sravanthi","family":"Lavu","sequence":"first","affiliation":[{"name":"Division of Gastroenterology & Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1490-6711","authenticated-orcid":false,"given":"Terry M.","family":"Therneau","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics,Mayo Clinic,Rochester,MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William S.","family":"Harmsen","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics,Mayo Clinic,Rochester,MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8783-0191","authenticated-orcid":false,"given":"Kristin C.","family":"Mara","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics,Mayo Clinic,Rochester,MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8676-413X","authenticated-orcid":false,"given":"Nicha","family":"Wongjarupong","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-8811","authenticated-orcid":false,"given":"Mohamed","family":"Hassan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2671-0532","authenticated-orcid":false,"given":"Hamdi A.","family":"Ali","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2372-9489","authenticated-orcid":false,"given":"Samuel","family":"Antwi","sequence":"additional","affiliation":[{"name":"Division of Epidemiology,Mayo Clinic,Jacksonville,FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasra H.","family":"Giama","sequence":"additional","affiliation":[{"name":"Department of Nursing,University of Minnesota,Rochester,MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4915-9835","authenticated-orcid":false,"given":"Katsuyuki","family":"Miyabe","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7885-8574","authenticated-orcid":false,"given":"Lewis R.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2020,10,9]]},"reference":[{"key":"hep31146-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12876-016-0527-z","article-title":"Increasing mortality in the 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