{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T13:21:20Z","timestamp":1772889680502,"version":"3.50.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Johann Wolfgang Goethe-Universit\u00e4t, Frankfurt am Main"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>MDRO-colonization has been shown to impair survival in patients with hematological malignancies and solid tumors as well as in patients with liver disease. Despite the increasing spread of multidrug-resistant organisms (MDRO), its impact on patients with hepatocellular carcinoma (HCC) has not been studied. We conducted this retrospective study to analyze the impact of MDRO-colonization on overall prognosis in HCC patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Materials and methods<\/jats:title>\n                <jats:p>All patients with confirmed HCC diagnosed between January 2008 and December 2017 at the University Hospital Frankfurt were included in this study. HCC patients with a positive MDRO screening before or within the first 90\u00a0days after diagnosis of HCC were defined as colonized HCC patients, HCC patients with a negative MDRO screening were defined as noncolonized HCC patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>59 (6%) colonized and 895 (94%) noncolonized HCC patients were included. <jats:italic>Enterobacterales<\/jats:italic> with extended-spectrum \u03b2-lactamase-like phenotype with or without resistance to fluoroquinolones (ESBL\/\u2009\u00b1\u2009FQ) were the most frequently found MDRO with 59%, followed by vancomycin-resistant <jats:italic>Enterococcus faecium<\/jats:italic> with 37%. Colonized HCC patients had more severe cirrhosis and more advanced HCC stage compared to noncolonized HCC patients. Colonized HCC patients showed an impaired survival with a median OS of 189\u00a0days (6.3\u00a0months) compared to a median OS of 1001\u00a0days (33.4\u00a0months) in noncolonized HCC patients. MDRO-colonization was identified as an independent risk factor associated with survival in multivariate analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>MDRO-colonization is an independent risk factor for survival in patients with HCC highlighting the importance of regular MDRO screening, isolation measures as well as interdisciplinary antibiotic steward-ship programs to guide responsible use of antibiotic agents.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-021-03741-0","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T12:03:27Z","timestamp":1626782607000},"page":"1465-1472","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Colonization with multidrug-resistant organisms impairs survival in patients with hepatocellular carcinoma"],"prefix":"10.1007","volume":"148","author":[{"given":"Vera","family":"Himmelsbach","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mate","family":"Knabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip G.","family":"Ferstl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai-Henrik","family":"Peiffer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan A.","family":"Stratmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Wichelhaus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hogardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volkhard A. J.","family":"Kempf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Waidmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Finkelmeier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-1988","authenticated-orcid":false,"given":"Olivier","family":"Ballo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"issue":"22","key":"3741_CR1","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1056\/NEJMra1914900","volume":"382","author":"V Arroyo","year":"2020","unstructured":"Arroyo V, Moreau R, Jalan R (2020) Acute-on-chronic liver failure. N Engl J Med 382(22):2137\u20132145","journal-title":"N Engl J Med"},{"issue":"4","key":"3741_CR2","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1053\/j.gastro.2010.06.019","volume":"139","author":"V Arvaniti","year":"2010","unstructured":"Arvaniti V, D\u2019Amico G, Fede G, Manousou P, Tsochatzis E, Pleguezuelo M et al (2010) Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology 139(4):1246\u20131256","journal-title":"Gastroenterology"},{"issue":"1","key":"3741_CR3","doi-asserted-by":"publisher","first-page":"e0210991","DOI":"10.1371\/journal.pone.0210991","volume":"14","author":"O Ballo","year":"2019","unstructured":"Ballo O, Tarazzit I, Stratmann J, Reinheimer C, Hogardt M, Wichelhaus TA et al (2019) Colonization with multidrug resistant organisms determines the clinical course of patients with acute myeloid leukemia undergoing intensive induction chemotherapy. PLoS ONE 14(1):e0210991","journal-title":"PLoS ONE"},{"issue":"9","key":"3741_CR4","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1016\/S1473-3099(17)30325-0","volume":"17","author":"D Baur","year":"2017","unstructured":"Baur D, Gladstone BP, Burkert F, Carrara E, Foschi F, Dobele S et al (2017) Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis 17(9):990\u20131001","journal-title":"Lancet Infect Dis"},{"key":"3741_CR5","unstructured":"Bundesministerium der Justiz und f\u00fcr Verbraucherschutz. IfSG-Gesetz zur Verh\u00fctung und Bek\u00e4mpfung von Infektionskrankheiten beim Menschen; 2019 [cited 2019 Jul 22]. Available from: http:\/\/www.gesetze-im-internet.de\/ifsg\/BJNR104510000.html"},{"key":"3741_CR6","unstructured":"Centers for Disease Control and Prevention (2013) Antibiotic resistance threats in the United States, 2013 (https:\/\/www.cdc.gov\/drugresistance\/threat-report-2013\/pdf\/ar-threats-2013-508.pdf)."},{"issue":"11","key":"3741_CR7","doi-asserted-by":"publisher","first-page":"3285","DOI":"10.1007\/s10620-007-9750-3","volume":"52","author":"OF Couto","year":"2007","unstructured":"Couto OF, Dvorchik I, Carr BI (2007) Causes of death in patients with unresectable hepatocellular carcinoma. Dig Dis Sci 52(11):3285\u20133289","journal-title":"Dig Dis Sci"},{"issue":"4","key":"3741_CR8","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/j.jhep.2011.12.001","volume":"56","author":"European Association for the study of the L European Organisation for R, Treatment of C","year":"2012","unstructured":"European Association for the study of the L European Organisation for R, Treatment of C (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56(4):908\u2013943","journal-title":"J Hepatol"},{"issue":"1","key":"3741_CR9","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.jhep.2018.03.019","volume":"69","author":"European Association for the Study of the Liver","year":"2018","unstructured":"European Association for the Study of the Liver (2018) Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 69(1):182\u2013236","journal-title":"J Hepatol"},{"issue":"6","key":"3741_CR10","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1002\/hep.28330","volume":"63","author":"J Fernandez","year":"2016","unstructured":"Fernandez J, Tandon P, Mensa J, Garcia-Tsao G (2016a) Antibiotic prophylaxis in cirrhosis: good and bad. Hepatology 63(6):2019\u20132031","journal-title":"Hepatology"},{"issue":"5","key":"3741_CR11","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.jhep.2016.08.006","volume":"65","author":"J Fernandez","year":"2016","unstructured":"Fernandez J, Bert F, Nicolas-Chanoine MH (2016b) The challenges of multi-drug-resistance in hepatology. J Hepatol 65(5):1043\u20131054","journal-title":"J Hepatol"},{"issue":"10","key":"3741_CR12","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1111\/liv.13438","volume":"37","author":"PG Ferstl","year":"2017","unstructured":"Ferstl PG, Filmann N, Brandt C, Zeuzem S, Hogardt M, Kempf VAJ et al (2017) The impact of carbapenem resistance on clinical deterioration and mortality in patients with liver disease. Liver Int 37(10):1488\u20131496","journal-title":"Liver Int"},{"issue":"1","key":"3741_CR13","doi-asserted-by":"publisher","first-page":"e0245091","DOI":"10.1371\/journal.pone.0245091","volume":"16","author":"PG Ferstl","year":"2021","unstructured":"Ferstl PG, Filmann N, Heilgenthal EM, Schnitzbauer AA, Bechstein WO, Kempf VAJ et al (2021) Colonization with multidrug-resistant organisms is associated with in increased mortality in liver transplant candidates. PLoS ONE 16(1):e0245091","journal-title":"PLoS ONE"},{"issue":"20","key":"3741_CR14","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","volume":"382","author":"RS Finn","year":"2020","unstructured":"Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al (2020) Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382(20):1894\u20131905","journal-title":"N Engl J Med"},{"issue":"6","key":"3741_CR15","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1093\/jac\/dku035","volume":"69","author":"P Gastmeier","year":"2014","unstructured":"Gastmeier P, Schroder C, Behnke M, Meyer E, Geffers C (2014) Dramatic increase in vancomycin-resistant enterococci in Germany. J Antimicrob Chemother 69(6):1660\u20131664","journal-title":"J Antimicrob Chemother"},{"issue":"6","key":"3741_CR16","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1200\/JCO.2014.57.9151","volume":"33","author":"PJ Johnson","year":"2015","unstructured":"Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL et al (2015) Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol 33(6):550\u2013558","journal-title":"J Clin Oncol"},{"issue":"2","key":"3741_CR17","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1053\/jhep.2001.22172","volume":"33","author":"PS Kamath","year":"2001","unstructured":"Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL et al (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33(2):464\u2013470","journal-title":"Hepatology"},{"issue":"3","key":"3741_CR18","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1055\/s-2007-1007122","volume":"19","author":"JM Llovet","year":"1999","unstructured":"Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19(3):329\u2013338","journal-title":"Semin Liver Dis"},{"issue":"5","key":"3741_CR19","doi-asserted-by":"publisher","first-page":"e0127448","DOI":"10.1371\/journal.pone.0127448","volume":"10","author":"M Merli","year":"2015","unstructured":"Merli M, Lucidi C, Di Gregorio V, Falcone M, Giannelli V, Lattanzi B et al (2015) The spread of multi drug resistant infections is leading to an increase in the empirical antibiotic treatment failure in cirrhosis: a prospective survey. PLoS ONE 10(5):e0127448","journal-title":"PLoS ONE"},{"issue":"8","key":"3741_CR20","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/bjs.1800600817","volume":"60","author":"RN Pugh","year":"1973","unstructured":"Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60(8):646\u2013649","journal-title":"Br J Surg"},{"issue":"2","key":"3741_CR21","doi-asserted-by":"publisher","first-page":"30110","DOI":"10.2807\/1560-7917.ES.2016.21.2.30110","volume":"21","author":"C Reinheimer","year":"2016","unstructured":"Reinheimer C, Kempf VA, Gottig S, Hogardt M, Wichelhaus TA, O\u2019Rourke F et al (2016) (2016) Multidrug-resistant organisms detected in refugee patients admitted to a University Hospital, Germany June December 2015. Euro Surveill 21(2):30110","journal-title":"Euro Surveill"},{"issue":"1","key":"3741_CR22","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12879-016-2105-y","volume":"17","author":"C Reinheimer","year":"2017","unstructured":"Reinheimer C, Kempf VA, Jozsa K, Wichelhaus TA, Hogardt M, O\u2019Rourke F et al (2017) Prevalence of multidrug-resistant organisms in refugee patients, medical tourists and domestic patients admitted to a German university hospital. BMC Infect Dis 17(1):17","journal-title":"BMC Infect Dis"},{"key":"3741_CR23","unstructured":"Robert Koch Institut (2012) Hygienema\u00dfnahmen bei Infektionen oder Besiedlung mit multiresistenten gram-negativen Sta\u00e4bchen. Empfehlung der Kommission f\u00fcr Krankenhaushygiene und Infektionspr\u00e4vention (KRINKO) beim Robert Koch-Institut (RKI). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 55(10):1311\u20131354."},{"issue":"11","key":"3741_CR24","doi-asserted-by":"publisher","first-page":"e0242544","DOI":"10.1371\/journal.pone.0242544","volume":"15","author":"JA Stratmann","year":"2020","unstructured":"Stratmann JA, Lacko R, Ballo O, Shaid S, Gleiber W, Vehreschild M et al (2020) Colonization with multi-drug-resistant organisms negatively impacts survival in patients with non-small cell lung cancer. PLoS ONE 15(11):e0242544","journal-title":"PLoS ONE"},{"key":"3741_CR25","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/nyas.12537","volume":"1323","author":"E Temkin","year":"2014","unstructured":"Temkin E, Adler A, Lerner A, Carmeli Y (2014) Carbapenem-resistant Enterobacteriaceae: biology, epidemiology, and management. Ann N Y Acad Sci 1323:22\u201342","journal-title":"Ann N Y Acad Sci"},{"issue":"6","key":"3741_CR26","doi-asserted-by":"crossref","first-page":"568 e1-13","DOI":"10.1016\/j.jamda.2012.04.004","volume":"13","author":"LW van Buul","year":"2012","unstructured":"van Buul LW, van der Steen JT, Veenhuizen RB, Achterberg WP, Schellevis FG, Essink RT et al (2012) Antibiotic use and resistance in long term care facilities. J Am Med Dir Assoc 13(6):568 e1\u201313","journal-title":"J Am Med Dir Assoc"},{"issue":"15","key":"3741_CR27","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1056\/NEJMra1713263","volume":"380","author":"A Villanueva","year":"2019","unstructured":"Villanueva A (2019) Hepatocellular carcinoma. N Engl J Med 380(15):1450\u20131462","journal-title":"N Engl J Med"},{"issue":"7","key":"3741_CR28","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1136\/gutjnl-2014-309104","volume":"64","author":"O Waidmann","year":"2015","unstructured":"Waidmann O, Kempf VA, Brandt C, Zeuzem S, Piiper A, Kronenberger B (2015) Colonisation with multidrug-resistant bacteria is associated with increased mortality in patients with cirrhosis. Gut 64(7):1183\u20131184","journal-title":"Gut"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-021-03741-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-021-03741-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-021-03741-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T07:05:25Z","timestamp":1652771125000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-021-03741-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["3741"],"URL":"https:\/\/doi.org\/10.1007\/s00432-021-03741-0","relation":{},"ISSN":["0171-5216","1432-1335"],"issn-type":[{"value":"0171-5216","type":"print"},{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]},"assertion":[{"value":"3 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Vera Himmelsbach: nothing to declare. Mate Knabe: nothing to declare. Philip G. Ferstl: consultancies: SNIPR Biome. Kai-Henrik Peiffer: nothing to declare. Jan A. Stratmann: nothing to declare. Thomas Wichelhaus: nothing to declare. Michael Hogardt: nothing to declare. Volkhard Kempf: nothing to declare. Stefan Zeuzem: speaker\u2019s fees: Abbvie, Gilead, Merck\/MSD, consultancy: Abbvie, Gilead, Intercept, Janssen. Oliver Waidmann: consultancies: Amgen, Bayer, BMS, Celgene, Eisai, Incyte, Ipsen, Merck Serono, MSD, Novartis, Roche, Servier, Shire; Speaker\u2019s fees: Bayer, BMS, Celgene, Eisai, Ipsen, Novartis, Roche, Shire; Travel support: Abbvie, Bayer, BMS, Gilead, Ipsen, Merck; Grants: Basilea, Incyte, Else Kr\u00f6ner-Fresenius-Stiftung, Medac, Merck Serono, MSD Fabian Finkelmeier: speaker fees from Abbvie, Ipsen, Eisai, and MSD Olivier Ballo: nothing to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was performed in accordance with the Declaration of Helsinki. The study was approved by the institutional review board of the Frankfurt University Hospital.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Patients provided informed written consent and patient data was provided after approval by the local Ethics Committee.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Patients provided informed written consent and patient data was provided after approval by the local Ethics Committee.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}