1. Two-Stage Hepatectomy for Unresectable Metastases :
R. Adam, D.A. Wicherts, R. Miller,
R.J. de Haas, G. Bitsakou, E. Vibert, L.A. Veilhan,
D. Azoulay, H. Bismuth, D. Castaing
Hôpital Paul Brousse,
Université Paris-Sud, France

2. Survival benefit 40% at 5 yrs
Resectable 10–20%
Non resectable 80–90%
15–30 %
1-2%
Survival benefit 40% at 5 yrs
RESECTABILITY: a new end point of the strategy

4. MULTINODULAR COLORECTAL LIVER METASTASES
HOW TO MAKE A COMPLETE RESECTION
WHILE SAVING 30% LIVER REMNANT ?

5. BILATERAL HUGE LIVER METASTASES
HOW TO MAKE A COMPLETE RESECTION ?

6. TWO-STAGE HEPATECTOMY
Concept
Two sequential liver resections aiming to
resect multinodular hepatic tumors
irresectable by a single procedure
Regeneration following hepatectomy
Planned strategy at the time of 1st hepatectomy -
(1) Adam R, et al. Ann Surg 2000; 232:777-85

7. Two-Stage Hepatectomy (1) Adam R, et al. Ann Surg 2000; 232:777-85
155 cc 1 I
440 cc IV I 2
(1) Adam R, et al. Ann Surg 2000; 232:777-85

8. 262 Pts initially Unresectable
Two-Stage Hepatectomy: Patients and Methods
Oct Oct. 2006:
817 pts resected for CLM
100%
32%
262 Pts initially Unresectable
100%
51 Pts
2-stage hepatectomy
20% 6%

9. Two-Stage Hepatectomy: Evolution in time%
Conventional Hepatectomy
Two-stage
14% 8% 5% 7% 2%

10. Two-Stage Hepatectomy: Results
Feasibility
35/51 (69%)
16 patients ineligible for a second resection because:
Disease Progression
- Intrahepatic
- Intra- and extrahepatic
Bad Performance Status
15 (29%)
6 (12%)
9 (18%)
1 (2%)

11. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Outcome of failed patients (N = 16)
Alive with disease (13%) (N=2)
Dead (88%) (N=14)
Median time to death 12.3 mo ( )

12. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Patient and Primary tumor characteristics
N = 35
17 (49%)
18 (51%)
27 (77%)
8 (23%)
5 (26%)
14 (74%)
4 (22%)
14 (78%)
Mean age + SD
Female
Male
Colon
Rectum
T - 0-2
T - 3-4
N - 0
N - 1-2

13. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Liver Metastases Diagnosis
N = 35
28 (80%)
7 (20%)
6 (17%)
Synchronous
Metachronous
Mean number + SD
Mean max size + SD
Mean CEA + SD
Mean CA SD
Extrahepatic disease

14. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Chemotherapy
N =35
Before 1st Hepatectomy (N = 34) (97%)
Mean number of lines + SD
Mean number of cycles + SD
Before 2nd Hepatectomy (N = 27) (77%)
All patients received 1 line.
After 2nd Hepatectomy (N = 26) (74%)

15. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Time interval between 1st and 2nd hepatectomy
Mean + SD (months)
< 3 months
3-6 months
> 6 months
N = 35
13 (37%)
17 (49%)
5 (14%)

16. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Hepatic resection
1st
4 (11%)
0 (0%)
2 (6%)
27 (77%)
2nd
26 (74%)
1 (3%)
4 (11%) - P
< 0.001
0.41 -
Major resection (> 3 segm)
Local treatment
RFA
Cryotherapy
Portal Vein Embolization

17. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Short-term outcome
1st -
8 (23%)
3 (9%)
6 (17%)
1 (3%)
2nd
3 (9%)
22 (63%)
10 (29%)
20 (57%)
2 (6%)
9 (26%) P -
< 0.01
0.03
0.56
60-day Mortality
Morbidity
General complications
Hepatic complications
Relaparotomy
Percutaneous drainage
Mean hospital stay + SD

18. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Recurrences after second hepatectomy
N = 19 (54%)
Intra- and Extrahepatic (31%)
No (46%)
Extrahepatic (9%)
Hepatic (14%)
Median follow-up 26.0 months (range: )

19. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Repeat hepatectomy
Extrahepatic resection
Both
Recurrence
N = 19 (54%)
6 (32%)
4 (21%)
3 (16%)

20. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Total number of procedures
35 Pts
81 Hepatectomies
34 Adjuvant Procedures
(PVE + Local Ablation)
15 EH Resections
130 Procedures in 35 Patients
3,7 Procedures per Patient

21. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Overall Survival - Intention to treat (N = 51) .2 .4 .6 .8 1
Overall Survival 2 3 4 5
Years
44%
30%
Patients at risk
Total
1 yr
2 yrs
3 yrs
4 yrs
5 yrs 51 34 19 10 6 4

22. Two-Stage Hepatectomy (Oct 1992 - Oct 2006)
Overall Survival .2 .4 .6 .8 1
Overall Survival 2 3 4 5
Years
Two-stage effective (N = 35)
Two-stage failed (N = 16)
Log rank P < 0.001
57%
39%
Patients at risk
Total
1 yr
2 yrs
3 yrs
4 yrs
5 yrs
Two-stage 35 27 19 10 6 4
Failed 16 7 -

23. Prognostic Factors of Overall Survival
Two-Stage Hepatectomy (Oct Oct 2006)
Multivariate Analysis
Prognostic Factors of Overall Survival
after effective Two-Stage procedure
HR [95% CI] P
> 6 Metastases at diagnosis
Concomitant Extrahepatic Disease
No chemotherapy after second hepatectomy
0.01
0.02
< 0.01
18.4 [ ]
5.3 [ ]
12.8 [ ]

24. Two-Stage Hepatectomy
Conclusions
1) Established strategy to increase resectability in
selected patients with advanced bilobar disease
2) Feasibility rate: 69%
3) Second resection (more extensive) had higher
morbidity than first resection
4) Five-year survival 39% for patients that completed
the total strategy, close to that of patients with a
single procedure.

25. Portal Embolization Hepatectomy + RxF or Cryo 2-Stage Hepatectomy
NON RESECTABLE « HEPATIC » PATIENTS
Multi Unilobar
Multi Bilobar
Multi Bilobar
Remnant Liver<30%
≤3 nod. ≤30 mm
>3 nod >30 mm
Portal Embolization
Hepatectomy +
RxF or Cryo
2-Stage Hepatectomy