title: Extended Ischemia Times Promote Risk of HCC Recurrence in Liver Transplant Patients.
abstract: BACKGROUND
  There is increasing evidence that ischemia-reperfusion injury (IRI) promotes vasculogenesis and tumor outgrowth in the liver. Hepatic IRI is exaggerated by prolongation of ischemia times.
  
  
  OBJECTIVE
  The aim of this retrospective analysis was to assess the impact of ischemia times on risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Subgroup analysis focused on patients with (18)F-fluoro-deoxy-glucose ((18)F-FDG)-avid HCC on pretransplant positron emission tomography (PET).
  
  
  METHODS
  A total of 103 liver transplant patients with HCC were included in this study. The impact of cold (CIT), warm (WIT), and total ischemia times (TIT) along with other prognostic variables on posttransplant outcome was analyzed in uni- and multivariate analysis.
  
  
  RESULTS
  Twenty-four patients (23.3 %) developed tumor relapse after LT. Mean durations of CIT (468.0 vs. 375.5 min; P = 0.001), WIT (58.4 vs. 45.7 min; P = 0.001), and TIT (525.8 vs. 422.0 min; P < 0.001) were significantly longer in patients with compared to those without HCC recurrence. In multivariate regression analysis, (18)F-FDG-avid HCC (odds ratio [OR] 73.4), WIT >50 min (OR 52.5), alpha-fetoprotein level >400 IU/ml (OR 11.1), and Milan Out status (OR 7.4) were identified as independent predictors of HCC recurrence. In the subgroup of patients with PET-positive HCC, WIT remained the only independent variable to predict HCC recurrence (OR 15.5).
  
  
  CONCLUSIONS
  Prolongation of ischemia times promotes the risk of HCC recurrence after LT, especially in patients with unfavorable tumor biology on PET imaging.
authors: Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaningerstr. 22, 81675, Munich, Germany, ArnoKornberg@aol.com.
authors: Arno
authors: A
authors: Kornberg
authors: Ulrike
authors: U
authors: Witt
authors: Jennifer
authors: J
authors: Kornberg
authors: Helmut
authors: H
authors: Friess
authors: Katharina
authors: K
authors: Thrum
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000209:etiology* / Q000601:surgery; D050377:Cold Ischemia / Q000009:adverse effects*; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000209:etiology* / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D015427:Reperfusion Injury / Q000150:complications; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D052096:Warm Ischemia / Q000009:adverse effects*; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D019275:Radiopharmaceuticals; D000509:alpha-Fetoproteins; D019788:Fluorodeoxyglucose F18
references: Liver Transpl. 2009 Sep;15(9):1050-5
references: 19718649
references: Transpl Int. 2013 Jan;26(1):50-60
references: 23106431
references: Liver Transpl. 2007 Nov;13(11 Suppl 2):S36-43
references: 17969067
references: J Hepatol. 2014 Aug;61(2):278-85
references: 24713189
references: Liver Transpl. 2013 Nov;19(11):1214-23
references: 23907778
references: J Surg Res. 2002 Jun 15;105(2):243-7
references: 12121713
references: Am J Transplant. 2009 Mar;9(3):592-600
references: 19191771
references: Surgery. 2003 May;133(5):547-55
references: 12773983
references: Am J Transplant. 2011 Oct;11(10):2031-5
references: 21831154
references: ISRN Hepatol. 2014 Mar 04;2014:706945
references: 27335840
references: Liver Cancer. 2012 Nov;1(3-4):183-9
references: 24159583
references: PLoS One. 2014 Aug 25;9(8):e105679
references: 25153834
references: Ann Surg Oncol. 2008 May;15(5):1392-8
references: 18335279
references: Clin Transplant. 2009 Dec;23 Suppl 21:49-60
references: 19930317
references: Liver Transpl. 2011 Oct;17 Suppl 2:S44-57
references: 21695773
references: Clin Cancer Res. 2011 Jun 1;17(11):3783-93
references: 21527564
references: J Nucl Med. 2009 May;50(5):682-7
references: 19372474
references: Hepatology. 2005 Jul;42(1):165-75
references: 15962318
references: Am J Transplant. 2007 Jun;7(6):1601-8
references: 17511683
references: J Hepatol. 2014 Jan;60(1):103-9
references: 23994383
references: Hepatology. 2015 Mar;61(3):895-904
references: 25099130
references: Transplant Rev (Orlando). 2010 Jan;24(1):1-10
references: 19828306
references: World J Surg. 2013 Jan;37(1):192-201
references: 22965538
references: J Hepatol. 2012 Feb;56(2):474-85
references: 21782762
references: World J Gastroenterol. 2014 Jan 7;20(1):142-7
references: 24415867
references: Ann Surg. 2010 Dec;252(6):1020-6
references: 21107113
references: Liver Transpl. 2012 Jan;18(1):53-61
references: 21850692
references: Transplant Proc. 1999 Sep;31(6):2388-9
references: 10500633
references: Br J Surg. 2007 Jan;94(1):78-86
references: 17016793
references: Nat Rev Gastroenterol Hepatol. 2013 Feb;10(2):79-89
references: 23229329
references: J Surg Res. 2013 Oct;184(2):888-97
references: 23726239
references: J Gastroenterol. 2008;43(1):18-26
references: 18297431
references: Liver Transpl. 2012 Oct;18(10):1226-36
references: 22685095
references: J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:180-7
references: 21199530
references: Surg Clin North Am. 2010 Aug;90(4):665-77
references: 20637940