Treating ischaemia-reperfusion injury with prostaglandin E1 reduces the risk of early hepatocellular carcinoma recurrence following liver transplantation.
BACKGROUND
Surgical stress by hepatic ischaemia-reperfusion (I/R) is supposed to promote intra- and extrahepatic tumour recurrence. Treatment with prostaglandin E1 (PGE1) has been shown to attenuate hepatic I/R injury in liver transplant patients, but the potential anti-cancer effects have not been analysed.


OBJECTIVE
To evaluate the impact of PGE1 therapy on risk of hepatocellular carcinoma (HCC) recurrence in liver transplant patients.


METHODS
A retrospective review of 106 liver transplant patients with HCC was conducted. Fifty-nine patients underwent early post-liver transplantation (LT) treatment with the stable PGE1 analogue alprostadil. Administration of alprostadil was correlated with outcome in uni- and multivariate analysis. Subgroup analysis focused on patients with HCC beyond the Milan criteria (Milan Out) on radiographic imaging.


RESULTS
Three- and 5-year recurrence-free survival rates were 87.9% and 85.7% in the PGE1-group, but only 65.3% and 63.1% in the non-PGE1-population (P = 0.003). Multivariate Cox regression analysis identified absence of PGE1-treatment (HR = 11.42), along with presence of poor tumour grading (HR = 2.69) and microvascular tumour invasion (HR = 35.8) to be independently associated with early (within 12 months) HCC recurrence. In Milan Out-patients, only therapy with PGE1 (HR = 5.09) and well/moderate tumour differentiation (HR = 6.51) were independent promoters of recurrence-free survival.


CONCLUSIONS
Treating hepatic ischaemia-reperfusion injury with alprostadil reduces the risk of early HCC recurrence following LT. In particular patients with HCC exceeding the Milan criteria seem to benefit from PGE1-treatment. The molecular mechanisms of the anti-tumour effects need to be further assessed.
Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany.
A
A
Kornberg
Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany.
U
U
Witt
Department of Anaesthesiology, Klinikum Großhadern, LMU Munich, Munich, Germany.
J
J
Kornberg
Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany.
H
H
Friess
Institute of Pathology, Helios Klinikum, Berlin, Germany.
K
K
Thrum
D000328:Adult; D000368:Aged; D000527:Alprostadil / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000601:surgery; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000150:complications / Q000517:prevention & control*; D011859:Radiography; D015427:Reperfusion Injury / Q000150:complications* / Q000188:drug therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
D000527:Alprostadil