1. LIVER RESECTION VERSUS
LIVER RESECTION VERSUS
TRANSPLANTATION FOR
TRANSPLANTATION FOR
HEPATOCELLULAR CARCINOMA
HEPATOCELLULAR CARCINOMA
L. DE CARLIS
L. DE CARLIS
DEPT. OF SURGERY AND ABDOMINAL
DEPT. OF SURGERY AND ABDOMINAL
ORGAN TRANSPLANTATION
ORGAN TRANSPLANTATION
NIGUARDA HOSPITAL -- MILAN (ITALY)
NIGUARDA HOSPITAL MILAN (ITALY)
2. SURGICAL TREATMENT OF HCC
SURGICAL TREATMENT OF HCC
• Due to its direct link with liver cirrhosis, the
• Due to its direct link with liver cirrhosis, the
surgical therapy of HCC remains controversial.
surgical therapy of HCC remains controversial.
• Liver resection (LR) is limited by the severity of
• Liver resection (LR) is limited by the severity of
cirrhosis and tumor recurrence is a frequent
cirrhosis and tumor recurrence is a frequent
event in the cirrhotic liver remnant, which
event in the cirrhotic liver remnant, which
maintains its oncogenic potential.
maintains its oncogenic potential.
• Liver transplantation (LTx) is the only option to
• Liver transplantation (LTx) is the only option to
treat tumor and cirrhosis at the same time but
treat tumor and cirrhosis at the same time but
mortality and morbidity are higher and waiting
mortality and morbidity are higher and waiting
lists are crowded.
lists are crowded.
3. • Absence of randomized controlled
Absence of randomized controlled
trials
trials
• Treatment of HCC is not yet well
Treatment of HCC is not yet well
codified
codified
4. Aim of the study
Aim of the study
• Compare 2 large series of pts with HCC
Compare 2 large series of pts with HCC
treated with LR or OLTx
treated with LR or OLTx
• Determine tumor and patients chara-
Determine tumor and patients chara-
cteristic on survival and recurrence
cteristic on survival and recurrence
• Verify whether these parameters can
Verify whether these parameters can
identify the most appropriate treatment
identify the most appropriate treatment
option
option
5. LR and LTx for HCC
LR and LTx for HCC
(casistics 1985-2003)
(casistics 1985-2003)
• Liver Resection
Liver Resection 282
282
• Liver Transplantation
Liver Transplantation 187/654
187/654
(28,5%)
(28,5%)
6. LR and OLTx for HCC
LR and OLTx for HCC
analysis 1985-1999
analysis 1985-1999
• Liver Resection
Liver Resection 154
154
• Liver Transplantation
Liver Transplantation 121
121
7. LTx - Indication (121 pts)
LTx - Indication (121 pts)
• Unresectable single nodule <5
Unresectable single nodule <5
cm or 1-3 nodules ≤ 3 cm
cm or 1-3 nodules ≤ 3 cm
• Child B9 to C pts
Child B9 to C pts
28 pts with incidental HCC
28 pts with incidental HCC
Median diameter of the nodules → 3.7 cm
Median diameter of the nodules → 3.7 cm
(±2.5)
(±2.5)
8. LR - Indication (154 pts)
LR - Indication (154 pts)
• Child A-(B) pts
Child A-(B) pts
• Absence of portal hypertension
Absence of portal hypertension
• Single or multiple nodules in
Single or multiple nodules in
resectable position
resectable position
Major liver resections
Major liver resections 27 pts
27 pts
Segmentectomies
Segmentectomies 90 pts
90 pts
Wedge resection
Wedge resection 27 pts
27 pts
Multiple procedures
Multiple procedures 10 pts
10 pts
9. Patients characteristics
Patients characteristics
p
Age NS
Gender NS
Ethiology of liver disease NS
Child classification 0.05
pTNM 0.05
Tumor size 0.05
Number of nodules NS
Vascular infiltration NS
Presence of capsule NS
αFP / Histologic Grade NS
10. Perioperative mortality *
Perioperative mortality *
• LTx
LTx 22/121 (18.1%)
22/121 (18.1%)
• LR
LR 7/154 (4.5%)
7/154 (4.5%)
* (1996-2001 OLTx = 9% - LR ~ 0)
* (1996-2001 OLTx = 9% - LR ~ 0)
12. Causes of perioperative deaths
Causes of perioperative deaths
LR (7 pts)
LR (7 pts)
• Hepatic Failure
Hepatic Failure 5
5
• Haemorrhagic shock
Haemorrhagic shock 1
1
• Cerebrovascular accidents
Cerebrovascular accidents 1
1
13. Late Mortality
Late Mortality
Tumor Unrelated
Tumor Unrelated
• LTx
LTx 12
12
• LR
LR 21
21
Tumor Related
Tumor Related
• LTx
LTx 10
10
• LR
LR 55 (p0.0001)
55 (p0.0001)
14. Data at the end of follow-up
Data at the end of follow-up
Overall Recurrence
Overall Recurrence
• LTx
LTx 11
11 (9%)
(9%)
• LR
LR 74
74 (47.4%)
(47.4%)
Pts Survival With Recurrence
Pts Survival With Recurrence
• LTx
LTx 1*
1* (9%)
(9%)
• LR
LR 19
19 (25.6%)
(25.6%)
* 8,3 yrs
15. Final results of statistical analysis II
Final results of statistical analysis
Univariate Analysis
Univariate Analysis
• Capsule, Vascular Invasion, pTNM, αFP,
• Capsule, Vascular Invasion, pTNM, αFP,
seem important factors for 5 yrs survival and
seem important factors for 5 yrs survival and
recurrence rate in both groups
recurrence rate in both groups
• in LR number of nodules and age were
• in LR number of nodules and age were
significant for recurrence and 5 yrs survival
significant for recurrence and 5 yrs survival
while Child and size only for survival
while Child and size only for survival
• in LTx size of tumor was significant for
• in LTx size of tumor was significant for
recurrence and survival while viral cirrhosis
recurrence and survival while viral cirrhosis
for survival
for survival
16. Final results of statistical analysis II
Final results of statistical analysis II
Multivariate Analysis
Multivariate Analysis
• At multivariate analysis only αFP,
At multivariate analysis only αFP,
histological grade and vascular invasion
histological grade and vascular invasion
were indipendent variables for tumor
were indipendent variables for tumor
recurrence in both groups
recurrence in both groups
• In LR pTNM, αFP, Child and age were
In LR pTNM, αFP, Child and age were
indipendent variables for 5 yrs survival
indipendent variables for 5 yrs survival
• In LTx capsula, αFP, viral cirrhosis were
In LTx capsula, αFP, viral cirrhosis were
indipendent variables for 5 yrs survival
indipendent variables for 5 yrs survival
20. pT 1/2
pT 1/2
1.0 LR pT 1/2
Survival Distr.Funct.
LTx pT 1/2
0.8
0.6
0.4
0.2
p=0.3
0.0
0 1000 2000 3000 4000 5000
Days After Transplantation
21. SMALL TUMOR ( 5 cm)
SMALL TUMOR ( 5 cm)
1.0
LR 5cm
Survival Distr.Funct.
0.8 LTx 5cm
0.6
0.4
0.2
p=0.4
0.0
0 1000 2000 3000 4000 5000
Days After Transplantation
22. SMALL, ENCAPSULATED WITH
SMALL, ENCAPSULATED WITH
LOW αFP LEVELS
LOW αFP LEVELS
1.0
LR (n=32)
Survival Distr.Funct.
LT (n=26)
0.8
0.6
0.4
0.2
p=0.3
0.0
0 1000 2000 3000 4000 5000
Days After Transplantation
23. The best options for small
The best options for small
HCC
HCC
• Liver resection
Liver resection
• Liver transplantation
Liver transplantation
The same 3-5 years survival
The same 3-5 years survival
HCC recurrence in liver resection
HCC recurrence in liver resection
24. Conclusions II
Conclusions
• LTx appears to offer a better recurrence
LTx appears to offer a better recurrence
freedom than LR in patients with HCC.
freedom than LR in patients with HCC.
Nevertheless, many patients still live a long
Nevertheless, many patients still live a long
time after recurrence and mortality is often
time after recurrence and mortality is often
related to the progression of cirrhosis
related to the progression of cirrhosis
• Shortage of organs limits the possibility of
Shortage of organs limits the possibility of
offering this option to every pts with HCC
offering this option to every pts with HCC
• A strict selection should be made to
A strict selection should be made to
optimise organ allocation
optimise organ allocation
25. Conclusions II
Conclusions II
• LR should be considered a good therapeutic
• LR should be considered a good therapeutic
alternative in pts who do not fulfill LTx criteria
alternative in pts who do not fulfill LTx criteria
• The HCCs most suitable for LR are the same
• The HCCs most suitable for LR are the same
tumors that should have the best results when
tumors that should have the best results when
treated by LTx,, i.e. small, encapsulated tumors
treated by LTx i.e. small, encapsulated tumors
with low AFP levels.
with low AFP levels.
• In these cases other risk factors should be
• In these cases other risk factors should be
considered like the etiology of the disease, the
considered like the etiology of the disease, the
age of the patients, the severity of the cirrhosis
age of the patients, the severity of the cirrhosis
and, when available, the grade of the neoplasm.
and, when available, the grade of the neoplasm.
26. Conclusions III
Conclusions III
• Size and multifocality are not ‘per se’ signs of an
• Size and multifocality are not ‘per se’ signs of an
aggressive behavior of the tumor.
aggressive behavior of the tumor.
• AFP, vascular invasion, histological grade and an
• AFP, vascular invasion, histological grade and an
aggressive behavior during the waiting period,
aggressive behavior during the waiting period,
more likely reflect the risk of recurrence of the
more likely reflect the risk of recurrence of the
disease.
disease.
• Criteria for transplantation may undoubtedly be
• Criteria for transplantation may undoubtedly be
widened by including larger tumors in young
widened by including larger tumors in young
patients, but the length of the waiting time and
patients, but the length of the waiting time and
the appropriateness of the organ allocation limit
the appropriateness of the organ allocation limit
this procedure only to selected cases.
this procedure only to selected cases.
27. Open Problems
Open Problems
• Expanding indication for resectable HCC?
Expanding indication for resectable HCC?
• Expanding selection criteria for LTx ?
Expanding selection criteria for LTx ?
• LTx after downstaging the tumor ?
LTx after downstaging the tumor ?
“Nowadays the main problem of LTx is not the
“Nowadays the main problem of LTx is not the
definition of the best selection criteria, but the
definition of the best selection criteria, but the
low applicability of the treatment because of the
low applicability of the treatment because of the
lack of donors”
lack of donors”
(Lowet. Hepatology 1999; 30, 6, 1434)
(Lowet. Hepatology 1999; 30, 6, 1434)
