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Digestive Diseases and Sciences

, Volume 60, Issue 9, pp 2832–2839 | Cite as

Extended Ischemia Times Promote Risk of HCC Recurrence in Liver Transplant Patients

  • Arno Kornberg
  • Ulrike Witt
  • Jennifer Kornberg
  • Helmut Friess
  • Katharina Thrum
Original Article

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.

Aims

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 18F-fluoro-deoxy-glucose (18F-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, 18F-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).

Conclusion

Prolongation of ischemia times promotes the risk of HCC recurrence after LT, especially in patients with unfavorable tumor biology on PET imaging.

Keywords

Liver transplantation Hepatocellular carcinoma Ischemia–reperfusion injury PET Ischemia time Cold ischemia time Warm ischemia time 

Abbreviations

IRI

Ischemia–reperfusion injury

HCC

Hepatocellular carcinoma

LT

Liver transplantation

18F-FDG

18F-Fluoro-deoxy-glucose

PET

Positron emission tomography

CIT

Cold ischemia time

WIT

Warm ischemia time

TIT

Total ischemia time

CT

Computed tomography

MRI

Magnetic resonance imaging

AFP

Alpha-fetoprotein

HR

Hazard ratio

MELD

Model for end-stage liver disease

TACE

Transarterial chemoembolization

CsA

Cyclosporine A

Tac

Tacrolimus

AZA

Azathioprine

MMF

Mycophenolate mofetil

DRI

Donor risk index

OT

Operation time

EBL

Estimated blood loss

RBC

Red blood cell

MVI

Microvascular invasion

LVI

Lymphovascular invasion

STD

Standard deviation

CTC(s)

Circulating tumor cell(s)

DCD

Donor after cardiac death

DBD

Donor after brain death

AST

Aspartate aminotransferase

Notes

Acknowledgments

The authors have no financial support to declare.

Conflict of interest

The authors have no conflicts of interest to declare.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Arno Kornberg
    • 1
  • Ulrike Witt
    • 1
  • Jennifer Kornberg
    • 2
  • Helmut Friess
    • 1
  • Katharina Thrum
    • 3
  1. 1.Department of Surgery, Klinikum rechts der IsarTechnical University MunichMunichGermany
  2. 2.Department of Anaesthesiology, Klinikum GroßhadernLMU MunichMunichGermany
  3. 3.Institute of PathologyHelios Klinikum BerlinBerlinGermany

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