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Two-Stage Hepatectomy
vs ALPPS for
Unresectable Metastases
R Adam,
K Imai, C Castro, MA Allard,
E Vibert, A Sa Cunha, D
Cherqui, H Baba, D Castaing
Hôpital Paul Brousse, Villejuif, France
Université Paris-Sud, France
Multi Unilobar Multi Bilobar Multi Bilobar
Remnant Liver <30% ≤3 nod. ≤30 mm >3 nod. >30 mm
Hepatectomy +
Local Ablation
2-Stage
Hepatectomy
Portal Vein
Embolization
Two-Stage Hepatectomy: Patient Selection
Standard 2-Stage ALPPS
Portal vein
ligation
Tumorectomy
of liver remnant
Hypertrophy of
liver remnant
Stage 1 Stage 2
>30% of
total liver
4-8 weeks
Removal of the
deportalized lobe
Portal vein
embolization
Clavien et al. Strategies for safer liver surgery. NEJM, 2017
The Selective Staged method…
Two-stage Hepatectomy
Exclusion Pts
in progression
Portal vein
ligation
Tumorectomy
of liver remnant
Hypertrophy of
liver remnant
Stage 1 Stage 2
>30% of
total liver
9 days
Removal of the
deportalized lobe
Portal vein
embolization
Clavien et al. Strategies for safer liver surgery. NEJM, 2017
The fast-surgery method…: ALPPS
Present status
• Higher feasibility of complete resection with ALPPS
• Faster hypertrophy rate of liver remnant
Are the oncological results better than conventional
2-stage ?
Pending question
Results: flow chart
January 2000 – June 2014
248 Pts Resected of CLM at Paul Brousse Hospital
56 Two stage hepatectomy (23%)
TSH (N = 41)
15 Failure
(36%)
26 Complete
(64%)
ALPPS (N = 17)
Patient Selection
• Two-stage hepatectomy and ALPPS : indicated in
patients with bilobar colorectal liver metastases not
resectable by a single-stage hepatectomy with or without
portal vein embolization or local ablation therapy.
• ALPPS was favoured in patients with an estimated
smaller liver remnant volume irrespective of other tumour
or patient characteristics
Male 65 yrs
Synchronous Bilateral Irresectable LMCCR
FOLFOX AVASTIN 6 Courses
ACE 228 --- 83
FLR: 313cc ( < 0.5% ratio to Body weight)
Methods
• Between January 2010 and June 2014,
• 58 consecutive patients who underwent either
ALPPS (n=17) or two-stage hepatectomy (n=41)
for colorectal liver metastases were enrolled in
the study.
• Short-term and oncological outcomes were
compared.
Methods: ALPPS or TSH?
Bilobar multiple CLM
Unresectable with a single hepatectomy
even with portal vein embolization
Estimated small remnant liver
(requiring right hepatetomy
extended to segment IV)
ALPPS or Two stage hepatectomy?
Possibility to spare
segment IV
Methods: Techniques for ALPPS
• Clairance of future remnant liver
• Portal vein embolization
• Parenchymal transection
12 days later….
Right hepatectomy extended to segment IV
1st stage
Methods: End points
Oncological outcomes on intention to treat
• Overall survival
• Disease-free survival
Two stage vs ALPPS: baseline characteristics
Study group (n=58)
ALPPS
(n=17)
TSH
(n=41)
P value
Sex (M/F) 12/5 23/18 0.30
Age 58 (23-75) 58 (32-75) 0.90
T-stage CR tumour (1-2/3-4) 15 (88) 30 (73) 0.53
Site of primary tumour (colon/rectum) 13 (76) 27 (66) 0.42
Liver metastases: synchronous 15 (88) 38 (93) 0.59
No of liver lesions at diagnosis 10 (3-20) 10 (2-35) 0.37
Largest size at diagnosis (mm) 40 (13-145) 50 (10-150) 0.39
No of liver lesions at hepatectomy 8 (3-32) 10 (3-30) 0.39
Largest size at hepatectomy (mm) 38 (8-140) 43 (10-140) 0.26
CEA at hepatectomy (ng/mL) 8 (1-1195) 7.9 (0.5-940) 0.90
Preoperative chemotherapy 17 (100) 41 (100) 1
Progression at last line 0 0 1
Concomitant extra-hepatic disease 6 (35.3%) 12 (29.3%) 0.65
Two stage vs ALPPS: operative data
Study group (n=58)
ALPPS
(n=17)
TSH (n=41) P value
Percentage of estimated FLR before first-stage (%) 24 (11-38) 30 (19-53) 0.056
Percentage of estimated FLR before 2nd-stage (%) 36 (26-49) 40 (25-55) 0.12
Portal vein embolization 17 38 0.14
First-stage
Radiofrequency ablation 1 6 0.32
Red blood cell transfusion 4 2 0.044
No. of treated tumours* 2 (0-7) 4 (1-18) 0.04
Interval chemotherapy (days) 0 35 <0.0001
Time interval between the stages (day) 12 (9-39) 103 (19-450) <0.0001
Second-stage
Radiofrequency ablation 0 1 0.31
Red blood cell transfusion 4 8 0.60
No. of treated nodules* 8 (1-25) 6 (2-15) 0.53
Two stage vs ALPPS: operative data
Study group (n=58)
ALPPS
(n=17)
TSH (n=41) P value
Percentage of estimated FLR before first-stage (%) 24 (11-38) 30 (19-53) 0.056
Portal vein embolization 17 38 0.14
First-stage
Radiofrequency ablation 1 6 0.32
Red blood cell transfusion 4 2 0.044
No. of treated tumours* 2 (0-7) 4 (1-18) 0.04
Interval chemotherapy (days) 0 35 <0.0001
Time interval between the stages (day) 12 (9-39) 103 (19-450) <0.0001
Second-stage
Radiofrequency ablation 0 1 0.31
Red blood cell transfusion 4 8 0.60
No. of treated nodules* 8 (1-25) 6 (2-15) 0.53
Total (completed)
No. of treated nodules* 9 (2-32) 8 (1-30) 0.36
ALPPS vs Two stage Hep: early outcome
ALPPS (N = 17) TSH (N = 41) P value
90-day mortality 0 (0) 1 (2.4) 0.91
Dindo-Clavien ≥ III 7 (41) 16 (39) 0.88
Overall Survival after ALPPS vs TSH
in ITT after hepatectomy
Overall Survival after ALPPS vs TSH
in ITT after the diagnosis of liver metastases
Overall Survival after Matching for ALPPS vs TSH
in ITT after the diagnosis of liver metastases
Patient Outcome after ALPPS procedure
Cohort updated to 24 pts:
Months
OSprobability
0 12 24 36 48
0.00.20.40.60.81.0
41 35 18 9 3 Two stage
24 13 3 ALPPS
P = 0.005
MS : 28.9 mo
MS : Not reached
Two stage
ALPPS
Conclusions
• Despite a higher feasibility (100% vs 63%)
• …the absence of 90 day-mortality and a
comparable morbidity
• Survival of ALPPS group was lower than TSH,
in intention to treat (42 vs 77 % at 2 years)
• DFS was similar with however a higher
proportion of liver recurrences (100 vs 53%) and
a lower use of repeat surgery .
Summary
The higher feasibility rate of ALPPS did not seem
to translate into a better oncological outcome
compared to two-stage hepatectomy.

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Hepatectomie en 2 temps - Pr René Adam

  • 1. Two-Stage Hepatectomy vs ALPPS for Unresectable Metastases R Adam, K Imai, C Castro, MA Allard, E Vibert, A Sa Cunha, D Cherqui, H Baba, D Castaing Hôpital Paul Brousse, Villejuif, France Université Paris-Sud, France
  • 2. Multi Unilobar Multi Bilobar Multi Bilobar Remnant Liver <30% ≤3 nod. ≤30 mm >3 nod. >30 mm Hepatectomy + Local Ablation 2-Stage Hepatectomy Portal Vein Embolization Two-Stage Hepatectomy: Patient Selection Standard 2-Stage ALPPS
  • 3. Portal vein ligation Tumorectomy of liver remnant Hypertrophy of liver remnant Stage 1 Stage 2 >30% of total liver 4-8 weeks Removal of the deportalized lobe Portal vein embolization Clavien et al. Strategies for safer liver surgery. NEJM, 2017 The Selective Staged method… Two-stage Hepatectomy Exclusion Pts in progression
  • 4.
  • 5. Portal vein ligation Tumorectomy of liver remnant Hypertrophy of liver remnant Stage 1 Stage 2 >30% of total liver 9 days Removal of the deportalized lobe Portal vein embolization Clavien et al. Strategies for safer liver surgery. NEJM, 2017 The fast-surgery method…: ALPPS
  • 6. Present status • Higher feasibility of complete resection with ALPPS • Faster hypertrophy rate of liver remnant Are the oncological results better than conventional 2-stage ? Pending question
  • 7. Results: flow chart January 2000 – June 2014 248 Pts Resected of CLM at Paul Brousse Hospital 56 Two stage hepatectomy (23%) TSH (N = 41) 15 Failure (36%) 26 Complete (64%) ALPPS (N = 17)
  • 8. Patient Selection • Two-stage hepatectomy and ALPPS : indicated in patients with bilobar colorectal liver metastases not resectable by a single-stage hepatectomy with or without portal vein embolization or local ablation therapy. • ALPPS was favoured in patients with an estimated smaller liver remnant volume irrespective of other tumour or patient characteristics
  • 9. Male 65 yrs Synchronous Bilateral Irresectable LMCCR FOLFOX AVASTIN 6 Courses ACE 228 --- 83 FLR: 313cc ( < 0.5% ratio to Body weight)
  • 10. Methods • Between January 2010 and June 2014, • 58 consecutive patients who underwent either ALPPS (n=17) or two-stage hepatectomy (n=41) for colorectal liver metastases were enrolled in the study. • Short-term and oncological outcomes were compared.
  • 11. Methods: ALPPS or TSH? Bilobar multiple CLM Unresectable with a single hepatectomy even with portal vein embolization Estimated small remnant liver (requiring right hepatetomy extended to segment IV) ALPPS or Two stage hepatectomy? Possibility to spare segment IV
  • 12. Methods: Techniques for ALPPS • Clairance of future remnant liver • Portal vein embolization • Parenchymal transection 12 days later…. Right hepatectomy extended to segment IV 1st stage
  • 13. Methods: End points Oncological outcomes on intention to treat • Overall survival • Disease-free survival
  • 14. Two stage vs ALPPS: baseline characteristics Study group (n=58) ALPPS (n=17) TSH (n=41) P value Sex (M/F) 12/5 23/18 0.30 Age 58 (23-75) 58 (32-75) 0.90 T-stage CR tumour (1-2/3-4) 15 (88) 30 (73) 0.53 Site of primary tumour (colon/rectum) 13 (76) 27 (66) 0.42 Liver metastases: synchronous 15 (88) 38 (93) 0.59 No of liver lesions at diagnosis 10 (3-20) 10 (2-35) 0.37 Largest size at diagnosis (mm) 40 (13-145) 50 (10-150) 0.39 No of liver lesions at hepatectomy 8 (3-32) 10 (3-30) 0.39 Largest size at hepatectomy (mm) 38 (8-140) 43 (10-140) 0.26 CEA at hepatectomy (ng/mL) 8 (1-1195) 7.9 (0.5-940) 0.90 Preoperative chemotherapy 17 (100) 41 (100) 1 Progression at last line 0 0 1 Concomitant extra-hepatic disease 6 (35.3%) 12 (29.3%) 0.65
  • 15. Two stage vs ALPPS: operative data Study group (n=58) ALPPS (n=17) TSH (n=41) P value Percentage of estimated FLR before first-stage (%) 24 (11-38) 30 (19-53) 0.056 Percentage of estimated FLR before 2nd-stage (%) 36 (26-49) 40 (25-55) 0.12 Portal vein embolization 17 38 0.14 First-stage Radiofrequency ablation 1 6 0.32 Red blood cell transfusion 4 2 0.044 No. of treated tumours* 2 (0-7) 4 (1-18) 0.04 Interval chemotherapy (days) 0 35 <0.0001 Time interval between the stages (day) 12 (9-39) 103 (19-450) <0.0001 Second-stage Radiofrequency ablation 0 1 0.31 Red blood cell transfusion 4 8 0.60 No. of treated nodules* 8 (1-25) 6 (2-15) 0.53
  • 16. Two stage vs ALPPS: operative data Study group (n=58) ALPPS (n=17) TSH (n=41) P value Percentage of estimated FLR before first-stage (%) 24 (11-38) 30 (19-53) 0.056 Portal vein embolization 17 38 0.14 First-stage Radiofrequency ablation 1 6 0.32 Red blood cell transfusion 4 2 0.044 No. of treated tumours* 2 (0-7) 4 (1-18) 0.04 Interval chemotherapy (days) 0 35 <0.0001 Time interval between the stages (day) 12 (9-39) 103 (19-450) <0.0001 Second-stage Radiofrequency ablation 0 1 0.31 Red blood cell transfusion 4 8 0.60 No. of treated nodules* 8 (1-25) 6 (2-15) 0.53 Total (completed) No. of treated nodules* 9 (2-32) 8 (1-30) 0.36
  • 17. ALPPS vs Two stage Hep: early outcome ALPPS (N = 17) TSH (N = 41) P value 90-day mortality 0 (0) 1 (2.4) 0.91 Dindo-Clavien ≥ III 7 (41) 16 (39) 0.88
  • 18. Overall Survival after ALPPS vs TSH in ITT after hepatectomy
  • 19. Overall Survival after ALPPS vs TSH in ITT after the diagnosis of liver metastases
  • 20. Overall Survival after Matching for ALPPS vs TSH in ITT after the diagnosis of liver metastases
  • 21. Patient Outcome after ALPPS procedure
  • 22. Cohort updated to 24 pts: Months OSprobability 0 12 24 36 48 0.00.20.40.60.81.0 41 35 18 9 3 Two stage 24 13 3 ALPPS P = 0.005 MS : 28.9 mo MS : Not reached Two stage ALPPS
  • 23. Conclusions • Despite a higher feasibility (100% vs 63%) • …the absence of 90 day-mortality and a comparable morbidity • Survival of ALPPS group was lower than TSH, in intention to treat (42 vs 77 % at 2 years) • DFS was similar with however a higher proportion of liver recurrences (100 vs 53%) and a lower use of repeat surgery .
  • 24. Summary The higher feasibility rate of ALPPS did not seem to translate into a better oncological outcome compared to two-stage hepatectomy.