Hepato-Gastroenterology 2011; 58:1873-1876 doi 10.5754/hge10367
© H.G.E. Update Medical Publishing S.A., Athens
Οriginal Paper
1873 BILIARY TREE
Adoption of New Selection Criteria on
Living Donor Liver Transplantation for
Hepatocellular Carcinoma and their
Impact on the Outcome
Ayman Z Azzam
1
and Koichi Tanaka
2
1
Lecturer of General Surgery, Department of General Surgery, Alexandria University, Alexandria, Egypt
2
Director, Institute of Biochemical Research and Innovation, Kobe, Japan
Corresponding author: Dr. Ayman Zaki Azzam, Liver Transplant Surgeon, King Faisal Specialist Hospital and Research
Center, MBC: 72, P.O.Box 3354 Riyaddh 11211, Saudi Arabia; Tel.: +96 6-1-464-7272 Ext 39474,
Fax: +96 6-1-442-4817, E-mail:aazzam70@yahoo.com
ABSTRACT
Background/Aims: In cadaveric liver transplanta-
tion, the Milan criteria have been accepted as the se-
lection criteria for HCC in considering organ allocation.
However, the situation in LDLT is different. Method-
ology: This is a retrospective study on 518 recipients
who underwent LDLT. The exclusion criteria included
HCC with extrahepatic spread and HCC extending to
the major hepatic vessels detected during the preop-
erative evaluation. Results: HCC was the indication in
96 patients (18.5%); 52/96 patients (54.2%) fulfilled
Milan criteria and 44/96 patients (45.8%) did not. The
5-year survival rate among patients fulfilling Milan cri-
teria was 40/52 (77.0%) while for those who did not
30/44 (68.0%). Although these results show better sur-
vival rates among patients with HCC within the Milan
criteria, they are insignificant (p=0.01) and they clearly
demonstrate that patients with HCC outside the Milan
criteria have nearly the same survival rate as patients
with HCC within Milan criteria. Conclusions: Trans-
plantation is the best treatment option for patients with
HCC if a careful search reveals no extra-hepatic disease.
The application of the Milan criteria for all patients with
HCC would have denied many patients who can survive
after transplantation. In LDLT programs, where the pa-
tient has a special living donor, the Milan criteria are not
necessarily relevant.
Key Words:
HCC Recurrence;
Milan criteria;
Mortality;
Microvascular
invasion;
Macrovascular
invasion.
INTRODUCTION
Hepatocellular carcinoma (HCC) is the most common
primary liver malignancy and a leading cause of death
(1). Liver transplantation (LT) was recognized as the best
treatment option for patients with early HCC and end
stage liver disease (2). Introduction of the Milan criteria,
by Mazzaferro et al. in 1996 (3), namely, tumors 5cm or
less in diameter in patients with single HCC and no more
than 3 tumors nodules of 3cm or less in diameter each, in
patients with multiple tumors, resulted in 5-year surviv-
al rates among HCC patients fulfilling the criteria, almost
comparable with those of patients transplanted for non-
malignant indications (4-6). The Milan criteria have been
accepted as selection criteria for allocation of cadaveric
liver to patients with small unresectable HCC (5,7). How-
ever, the situation is different in living donor liver trans-
plantation (LDLT), in which, graft donation may only de-
pend on the donor’s strong will to save the life of a be-
loved relative.
METHODOLOGY
This is a retrospective study on 518 recipients who
underwent LDLT at the Liver Transplantation and Im-
munology Department, Kyoto University Hospital, from
May 1999 to May 2004. Hepatocellular carcinoma (HCC)
was the indication in 96/518 cases (18.5%). The inclu-
sion criteria were all unresectable HCC, with no limita-
tions for the number and size. The exclusion criteria in-
cluded HCC with extrahepatic spread and HCC extending
to the major hepatic vessels detected during the preop-
erative evaluation. Preoperative assessment of all recip-
ients included head, chest and abdominal CT and bone
scintigraphy. During the operation, tumor localization
was confirmed again. Ascites was also collected and sent
for cytological study to rule out tumor dissemination. Pa-
tients who were diagnosed with TNM stage III or IVa dis-
ease before transplantation received epirubicin infusion
(chemotherapy) at 10mg/m
2
during the anhepatic peri-
od without any critical side effects. Adjuvant chemothera-
py was continued after the operation using the same drug
and dose, weekly for 10 weeks, for those with TNM stage
III or IVa disease when their general condition allowed it.
Statistical analysis
Statistical calculations for mean values and standard
deviations were performed using the SPSS 12.0 soft-
ware package (SPSS Inc., Chicago, IL, USA). Results were
expressed as the mean and standard deviation (SD) af-
ter verification of normal distribution or median (inter-
quartile range) for quantitative variables. ANOVA pro-
cedure and Pearson correlation coefficient were used to
compare between different values, a p<0.05 was consid-
ered statistically significant.
RESULTS
Age of the patients ranged 21.8-70 years (median 52).
Hepatocellular carcinoma (HCC) was the indication of
liver transplantation in 96/518 cases (18.5%). HCC as-