Two-Stage Hepatectomy Two-Stage Hepatectomy

for Unresectable for Unresectable

Metastases : Metastases :

Hôpital Paul Brousse, Université Paris-Sud, France

R. Adam, D.A. Wicherts, R. Miller,

R.J. de Haas, G. Bitsakou, E. Vibert, L.A. Veilhan,

D. Azoulay, H. Bismuth, D. Castaing

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Survival benefit40% at 5 yrs

Resectable 10–20% Non resectable 80–90%

1-2%15–30 %

RESECTABILITY: a new end point of the strategy

MULTINODULAR COLORECTAL LIVER METASTASES

HOW TO MAKE A COMPLETE RESECTIONWHILE SAVING 30% LIVER REMNANT ?

BILATERAL HUGE LIVER METASTASES

HOW TO MAKE A COMPLETE RESECTION ?

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

I

(1) Adam R, et al. Ann Surg 2000; 232:777-85

Two-Stage Hepatectomy

155 cc

440 cc

IVI

1

2

Oct. 1992 - Oct. 2006: 817 pts resected for CLM

Two-Stage Hepatectomy: Patients and Methods

51 Pts2-stage hepatectomy

262 Pts initially Unresectable

6%

32%

100%

100%

20%

Two-Stage Hepatectomy: Evolution in time

0

10

20

30

40

50

60

70

80

90

100

1992-1994 1995-1997 1998-2000 2001-2003 2004-2006

%

Conventional HepatectomyTwo-stage

14%8%

5%7%2%

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%)

Two-Stage Hepatectomy: Results

Outcome of failed patients (N = 16)

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

Dead (88%) (N=14)

Median time to death 12.3 mo (3.6 - 18.8)

Alive with disease (13%) (N=2)

Patient and Primary tumor characteristics

Mean age + SD

FemaleMale

ColonRectum

T - 0-2T - 3-4N - 0N - 1-2

N = 35

57.5 + 10.3

17 (49%)18 (51%)

27 (77%)8 (23%)

5 (26%)14 (74%)4 (22%)14 (78%)

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

N = 35

28 (80%)7 (20%)

9.6 + 5.450.2 + 25.1

290.6 + 655.4187.2 + 320.0

6 (17%)

Liver Metastases Diagnosis

SynchronousMetachronous

Mean number + SDMean max size + SD

Mean CEA + SDMean CA 19.9 + SD

Extrahepatic disease

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

Chemotherapy

Before 1st Hepatectomy (N = 34) (97%)Mean number of lines + SDMean number of cycles + SD

Before 2nd Hepatectomy (N = 27) (77%)All patients received 1 line.Mean number of cycles + SD

After 2nd Hepatectomy (N = 26) (74%)

N =35

1.5 + 0.711.0 +

3.8

4.2 + 1.8

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

Time interval between 1st and 2nd hepatectomy

Mean + SD (months)

< 3 months3-6 months> 6 months

N = 35

4.3 + 3.1

13 (37%)17 (49%)5 (14%)

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

Hepatic resection

1st

4 (11%)

0 (0%)2 (6%)

27 (77%)

Major resection (> 3 segm)

Local treatment RFA Cryotherapy

Portal Vein Embolization

2nd

26 (74%)

1 (3%)4 (11%)

-

P

< 0.001

0.41

-

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

Short-term outcome

1st

-

8 (23%)

3 (9%)

6 (17%)

1 (3%)

1 (3%)

11.7 +

4.2

2nd

3 (9%)

22 (63%)

10 (29%)

20 (57%)

2 (6%)

9 (26%)

20.6 +

17.1

60-day Mortality

Morbidity

General complications

Hepatic complications

Relaparotomy

Percutaneous drainage

Mean hospital stay + SD

P

-

< 0.01

0.03

< 0.01

0.56

< 0.01

< 0.01

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

Recurrences after second hepatectomy

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

No (46%)

Hepatic (14%)

Extrahepatic (9%)

Intra- and Extrahepatic (31%)

Median follow-up 26.0 months (range: 3.7 - 130.3)

N = 19 (54%)

6 (32%)

4 (21%)

3 (16%)

Repeat hepatectomy

Extrahepatic resection

Both

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

N = 19 (54%)Recurrence

Total number of procedures

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

0

10

20

30

40

50

60

70

80

90

Hep Adj Proc EHD Res

81 Hepatectomies

34 Adjuvant Procedures (PVE + Local Ablation)

15 EH Resections

130 Procedures in 35 Patients3,7 Procedures per Patient

35 Pts

Overall Survival - Intention to treat (N = 51)

Patients at risk

Total 1 yr 2 yrs

3 yrs

4 yrs

5 yrs

51 34 19 10 6 4

0

.2

.4

.6

.8

1

Overa

ll S

urv

ival

0 1 2 3 4 5 Years

44%

30%

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

Overall Survival

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 - - - -

0

.2

.4

.6

.8

1O

vera

ll S

urv

ival

0 1 2 3 4 5 Years

Two-stage effective (N = 35)Two-stage failed (N = 16)

Log rank P < 0.001

57%

39%

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

Prognostic Factors of Overall Survivalafter 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 [2.1-161.3]

5.3 [1.3-21.0]

12.8 [2.9-56.0]

Two-Stage Hepatectomy (Oct 1992 - Oct 2006)

Multivariate Analysis

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.

Two-Stage Hepatectomy

NON RESECTABLE « HEPATIC » PATIENTS

Multi Unilobar Multi Bilobar Multi Bilobar

Remnant Liver<30% ≤3 nod. ≤30 mm >3 nod >30 mm

Hepatectomy +RxF or Cryo

2-Stage Hepatectomy

Portal Embolization