1. University Hospital 12 de Octubre, Madrid, Spain
•
Capital City Madrid (pop. 4,512,500) (2006 est.) .The Madrid metro area now exceeds 5.9
million
~1200 beds
~1.000.000 population
Juan Carlos Meneu-Diaz MD PhD
Chief Hepatobiliary Unit and Transplantation
Surgical treatment of hepatocellular carcinoma.
Partial liver resection vs liver transplantation.

2. University Hospital 12 de Octubre, Madrid, Spain

3. University Hospital 12 de Octubre, Madrid, Spain

4. LIVER TRANSPLANTATION
ACTIVITY (1986-2007)
0
10
20
30
40
50
60
70
80
90
100
1987
1989
1991
1993
1995
1997
1999
2001
2003
2005
University Hospital 12 de Octubre, Madrid, Spain
N=1394

5. University Hospital 12 de Octubre, Madrid, Spain

6. Surgical treatment of hepatocellular carcinoma.
Partial liver resection vs liver transplantation.
Juan Carlos Menéu-Diaz MD PhD
Baltasar Perez Saborido MD PhD
Almudena Moreno MD PhD
Yiliam Fundora MD PhD
Manuel Abradelo MD PhD,
Alberto Gimeno MD PhD,
Santos Jiménez Galanes
Vanesa Barra
Hepatobiliary Unit and Transplantation
Part of the team

7. Introduction: HCC Worldwide
•Hepatocellular carcinoma (HCC) is the fifth most
common cancer worldwide
•More than half a million new cases yearly
•In some areas of Asia and the Middle East, HCC ranks as
the first cause of death due to cancer
•The incidence of HCC is increasing in Europe and the
United States, and it is currently the leading cause of
death among cirrhotic patients.

8. Major causes of HCC worldwide

9. ParikhS.TheAmericanJournalofMedicine(2007)
120,194-202
Surveilleance for HCC Liver Nodule
?

10. Non-cirrhotic liver  Affordable resection: 80 % of liver volume
Functional reserve
Hepatic Insufficience
Hepatic failure
Dead
Limited resectionPreneoplastic condition
Tumoral recurrence
The problem
Llovet JM. J Gastroenterol 2005; 40:225–235

11. • Tumor variables
• Hepatic function reserve
• Tumor involvement
• Patient status
• Hospital posibilities
Better survival
Lower morbimortality
Lower Recurrence
HCC: Management depends on…
Compagnon P. Transplantation. 2008 Oct 27;86(8):1068-76

12. HCC: Management options
Surgical therapy
1. Partial liver resection
2. Total liver resection and
orthotopic liver transplantation
Locoregional therapies
1. EPI
2. Acetic acid PI
3. Criotherapy
4. Microwaves
5. Radiofrecuency
6. Chemoembolization
7. Radiotherapy
8. Chemotherapy
• Systemic
• Transarterial
9. Hormonotherapy
10. Inmunotherapy
11. Genetic therapy
Kim DY. World J Gastroenterol 2006 November 21; 12(43): 6992-6997

13. Literature Review

14. Liver transplant and HCC
Wong LL. Am J Surg 2002 183:309-16

15. Liver Transplant and HCC
• Primary tumor along with…
• Cirrhotic liver
Reduce tumor
recurrence!
Waiting time
Disease recurrence
Inmunosuprresion therapy
Tumor progression
Tumor recurrence risk
Infectous complications
New tumors
Chapman WC. Ann Surg. 2008 Oct;248(4):617-25.

16. Surgical treatment algorithm

17. HCC: Management options
Locoregional therapies
1. EPI
2. Acetic acid PI
3. Criotherapy
4. Microwaves
5. Radiofrecuency
6. Chemoembolization
7. Radiotherapy
8. Chemotherapy
• Systemic
• Transarterial
9. Hormonotherapy
10. Inmunotherapy
11. Genetic therapy
Kim DY. World J Gastroenterol 2006 November 21; 12(43): 6992-6997

19. LRT for HCC. Pathologic response

20. LRT for HCC. Survival benefit

21. LRT for HCC. Survival benefit

22. Liver Transplantation for HCC at
The Uniiversity Hospital 12 de Octubre
Milan Criteria  LT
LDLT /Split liver transplantation/NHBD
MELD priority (MELD 22 for stage II)
Locoregional treatment
TACE
RFA
Europe
EEUU
Spain~ 7 months
Waiting list
drop-outs
time
Perez B, Meneu-Diaz JC, M Elola A et al. Tumor recurrence after liver transplantation for hepatocellular
carcinoma: recurrence pathway and prognostic factors.
Transplant Proc. 2007 Sep;39(7):2304-7.

23. Patients and method
• Retrospective, case-control study (April´86-December´01)Retrospective, case-control study (April´86-December´01)
 Follow-up: 2003Follow-up: 2003
 164 HCC patients164 HCC patients Surgically treatedSurgically treated
 Two groupsTwo groups::
• Resection GroupResection Group:: 93 pts93 pts
 Solitary HCCSolitary HCC
 Good functional status (Child A/ICG <15%)Good functional status (Child A/ICG <15%)
• OLT GroupOLT Group:: 71 pts (8,3% of total liver trasnplants)71 pts (8,3% of total liver trasnplants)
 Child B-CChild B-C
 From 1996From 1996  Mazzaferro´s (Milan) criteriaMazzaferro´s (Milan) criteria
» Solitary tumor less than 5 cmSolitary tumor less than 5 cm
» Less than 3 nodules less than 3 cmLess than 3 nodules less than 3 cm
Perez B, Meneu-Diaz JC, M Elola A et al.
Liver transplantation for hepatocellular carcinoma: our experience from 1986.
Transplant Proc. 2003 Aug;35(5):1825

24. LT Technique
 Vena cava preservationVena cava preservation
 Arterial anastomosis (GDA-GDA)Arterial anastomosis (GDA-GDA)
 End-to-end porto-portal anastomosisEnd-to-end porto-portal anastomosis
 Biliary reconstruction: duct-to-ductBiliary reconstruction: duct-to-duct
 85.7 % blood operative transfussion85.7 % blood operative transfussion

25. Partial liver resection technique
 Minor/Mayor resection: 51.6%/48.4%Minor/Mayor resection: 51.6%/48.4%
 Pringle maneuver: 34.4%Pringle maneuver: 34.4%
 (mean time: 13.35 minutes)(mean time: 13.35 minutes)
 CUSA: 24.7%CUSA: 24.7%
 53.8% without transfussion53.8% without transfussion
 (Mean transfussion: 894 cc)(Mean transfussion: 894 cc)
 Operative US as neededOperative US as needed

26. Follow up
 US+AFP level every 3 months first yearUS+AFP level every 3 months first year 
every 6 months second yearevery 6 months second year  every yearevery year
 Histological confirmation is not neededHistological confirmation is not needed
 Mean follow-up time:Mean follow-up time:
– PLR: 34.56PLR: 34.56 ± 29 months± 29 months
– LT: 44.66 ± 45 monthsLT: 44.66 ± 45 months

27. Preoperative variables
Comparative LT/PLR
VariableVariable RESECTIONRESECTION TRANSPLANTATIONTRANSPLANTATION pp
Male/FemaleMale/Female 78.5%/21.5%78.5%/21.5% 79%/21.1%79%/21.1% nsns
Mean ageMean age 59.459.4 ± 13 y± 13 y 5454 ± 8.7 y± 8.7 y 0.0040.004
CirrhosisCirrhosis 82%82% 100%100% nsns
VHC cirrhosVHC cirrhos 48.7%48.7% 64.8%64.8% 0.040.04
VHB cirrhosVHB cirrhos 22.4%22.4% 8.5%8.5% 0.020.02
Child A/B-CChild A/B-C 87.1%/87.1%/12.9%12.9% 21.1%/21.1%/78.9%78.9% 0.00010.0001
Okuda I/II-IIIOkuda I/II-III 80.6%/80.6%/19.4%19.4% 19.7%/19.7%/80.3%80.3% 0.00010.0001

28. Pathology
Comparative LT/PLR
VariableVariable RESECTIONRESECTION TRANSPLANTATIONTRANSPLANTATION pp
SolitarySolitary 82.8%82.8% 63.4%63.4% 0.0050.005
< 3 cm< 3 cm 17.2%17.2% 52.1%52.1% 0.00010.0001
Both lobulesBoth lobules 4.3%4.3% 9.9%9.9% nsns
MD-PDMD-PD 21.5%21.5% 12.7%12.7% nsns
Vascular InvVascular Inv 16.1%16.1% 16.9%16.9% nsns
EncapsulatedEncapsulated 23.7%23.7% 64.8%64.8% 0.00010.0001
SattelitosisSattelitosis 16.1%16.1% 11.3%11.3% nsns
pTNM IVpTNM IV 6.5%6.5% 22.5%22.5% 0.0030.003
MazzaferroMazzaferro 48.3%48.3% 73.2%73.2% 0.010.01

29. Postoperative course
Comparative LT/PLR
RESECTIONRESECTION TRANSPLANTATIONTRANSPLANTATION pp
HospitalHospital
mortalitymortality
6.5%6.5% 11%11% nsns
MorbidityMorbidity 60%*60%* 71%#71%# nsns
TransfussionTransfussion 46.2%46.2% 85.7%85.7% 0.0010.001
Mean postopMean postop
staystay
16.5 days16.5 days 26.4 days26.4 days 0.0090.009
**Surgical complications more frequent
# Medical complications more frequent

30. Crude patient Survival
Follow-up status
PLRLT
Count
100
90
80
70
60
50
40
30
20
10
0
STATUS
Alive
Dead
3754
63
46
p=0.03
p =0.03

31. Actuarial patient survival
Kaplan-Meier survival
Follo-up time (months)
10896847260483624120
Cumsurvival
1,0
,8
,6
,4
,2
0,0
p = 0.047
LT
PLR
40%
p = 0,047
58.9 %

32. Mortality causes
Follow-up mortality causes
PLRLT
Count
100
90
80
70
60
50
40
30
20
10
0
Medical causes
New tumors
Liver disease
Tumoral recurrence
528
14
16
21
78
38
p=0.0001

33. Tumor recurrence
Tumoral recurrence incidence
PLRLT
%
100
90
80
70
60
50
40
30
20
10
0
Recurrence
Yes
No
6219
38
81
p=0.0001
Liver 0 %
Extrahepatic 66,7 %
Both 33,3 %
43.4 % first year
75 % first year
Liver 78.2 %
Extrahepatic 16.4 %
Both 5.5 %

34. Disease-free survival
Disease-free survival
Follow-up without recurrence (months)
96847260483624120
Cumsurvival
1,0
,8
,6
,4
,2
0,0
p = 0.0006
LT
PLR
59,8%
22,4 %

35. ParikhS.TheAmericanJournalofMedicine(2007)
120,194-202
Surveilleance for HCC Liver Nodule
?

36. Needle biopsy and DFS
156.68 ± 23.16 months
48.79 ± 9.28 months

37. Conclusions
 LT can achieve better survival rates than PLR in a patientLT can achieve better survival rates than PLR in a patient
with liver cirrhosis and HCCwith liver cirrhosis and HCC
 Recurrence rate is lower with LT than PLRRecurrence rate is lower with LT than PLR
 However in the presence of poor pathological factorsHowever in the presence of poor pathological factors
(larger than 5 cm, more than 3 nodules, bilateral, MD-PD,(larger than 5 cm, more than 3 nodules, bilateral, MD-PD,
vascular invasion, sattelite nodules or pTNM stage IV) LTvascular invasion, sattelite nodules or pTNM stage IV) LT
does not offer a benefit over PLRdoes not offer a benefit over PLR
So, LT is better curative option than PLR to be offer to aSo, LT is better curative option than PLR to be offer to a
patient with liver cirrhosis and HCCpatient with liver cirrhosis and HCC

38. Thank you!
Come and visit MADRID, SPAIN