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, FranceUniversité 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 HepatectomyPortal 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 2014248 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 yrsSynchronous Bilateral Irresectable LMCCRFOLFOX AVASTIN 6 CoursesACE 228 --- 83FLR: 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 0.30Age 58 (23-75) 58 (32-75) 0.90T-stage CR tumour (1-2/3-4) 15 (88) 30 (73) 0.53Site 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) 0.37Largest size at diagnosis (mm) 40 (13-145) 50 (10-150) 0.39No 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) 0.90Preoperative 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 0.14First-stage

Radiofrequency ablation 1 6 0.32Red blood cell transfusion 4 2 0.044No. 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-stageRadiofrequency ablation 0 1 0.31Red blood cell transfusion 4 8 0.60No. 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

  Resection margin (R0/R1/ Rrfa†) 2/14/1 5/18/3 0.61

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 0.14First-stage

Radiofrequency ablation 1 6 0.32Red blood cell transfusion 4 2 0.044No. 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-stageRadiofrequency ablation 0 1 0.31Red blood cell transfusion 4 8 0.60No. 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

  Resection margin (R0/R1/ Rrfa†) 2/14/1 5/18/3 0.61

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 TSHin ITT after hepatectomy

Overall Survival after ALPPS vs TSHin ITT after the diagnosis of liver metastases

Overall Survival after Matching for ALPPS vs TSHin ITT after the diagnosis of liver metastases

Patient Outcome after ALPPS procedure

Cohort updated to 24 pts:

Months

OS

pro

babi

lity

0 12 24 36 48

0.0

0.2

0.4

0.6

0.8

1.0

41 35 18 9 3 Two stage

24 13 3 ALPPS

P = 0.005MS : 28.9 mo

MS : Not reached

Two stageALPPS

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.