Portal vein embolization and colorectal liver metastases

Eric Vibert, MD, PhD

Centre Hépato-Biliaire

Plan

• Why we perform Portal Vein Occlusion ?

• How we perform Portal Vein Occlusion ?

• What are the consequences of PVE on

– Fonction ?

– Volume ?

– Histology of the liver ?

– Tumor ?

• Alternative to PVE ?

To avoid post-operative liver failure

< 20% of standard liver volume or 0.5% body weight

Liver SP Liver SP

Truant et al. JACS 2008Ribeiro, Vauthey et al. BJS 2007

No liver resection with a liver remnant volume < 0.5% of body weight ratio

2011

MHV

RHV

Vcongestion

NCLR : 29%

NCLR : 20%

Vascular reconstructionMise et al. BJS 2011

The middle hepatic vein is betweenthe right and the left liver…

Be careful to liver resection that cut middle hepatic vein

« Morphological » Vol. ≠ « Functional » Vol.

Tanaka et al. Surgery 2010

?

Pas de veine hépatique inf. droite

Foie gauche = 0,5%

Interhepatic vein anastomoses

e flow

Post-hepatectomy liver failure

At D3 et/ou D5 : Bilirubine > 50 µMol/L and TP < 50% 50 à 63% of 1 month mortality

50

J5

De J1 et J90 : Bilirubine > 120 µMol/L 70% of 3 month mortality

Balzan…Belghit et al. Ann Surg 2005 Paugam…Belghit et al. Ann Surg 2009 Mullen…Vauthey et al. JACS 2007

And /Or

n=1057 majors hepatectomies

in non cirrhotic liver

n=870 then n=436

hepatectomies

2011

Gp A

Gp B

Gp C

Post-operative liver failure is the consequence of macroscopic and

microscopic liver « desorganization »

Difference between fulminant hepatitis and major hepatectomy

Fulminant hepatitis Major hepatectomy

« The liver is not a Brocoli, it is 2 Brocolis »

INFLOW OUTFLOW

Sano et al,, Ann Surg 2002

The liver function is related to vascular surface between hepatocytes / sinusoids

Hoelme et al. PNAS 2010

Day 0 Day 4

Hepatocytes

proliferationEndothelial

proliferation

Before hepatectomy

Day 0 to Day 4 / major hepatectomy

Hepatocytes multiplication +++

Œdema Increase of portal pressure

Decrease of exchange surface between endoth. cell and hepatocytes Poor liver function

After Day 4 / major hepatectomy

Improve of « liver permeability »

Endothelial prolifération +++

Enlargment of surface exchange between LSEC and Hep. Function

PV

CLVHepatocytes

Endothelial Cell

Biliary cell

Patients and MethodsPortal Vein Pressure measurement

• When? 30 min to 1 hour after liver transection just before abdominal closure

• How? Transducer connected to a 25 gauge needle inserted into the portal trunk

There is a correlation of PVP with liver failure and 90-day mortality

YesNoPost

hep

atec

tom

y P

VP

(m

mH

g)

22.5 mmHg

15 mmHg

P < 0.001

Liver failure « 50-50 » criteria 90-day mortality

YesNo

15 mmHg

19 mmHg

P = 0.01

Optimal cutoff of PVP for each liver failure definition

« 50-50 » criteria Peak of serum bilirubin > 7 mg/dL

ISGLS grade 3 definition

22 mmHg 22 mmHg21 mmHg

Incidence of POLF after

hepatectomy for CRLM

Auteur Date Période Hépatectomie Mortalité po Hep.Maj Ins.Hep Ins.Hep/Maj.

N. % N. % %

Figueras et al. 2001 1991-2000 256 4,0 145 0,8 1,4

Tamandl et al. 2007 2001-2004 276 0,0 27 0,7 7,4

Finch et al. 2007 1993-2003 484 3,5 349 0,4 0,6

Gold 2008 1992-2003 443 2,9 380 0,5 0,5

Mehta 2008 2003-2005 173 4,0 127 1,2 1,6

Welsh et al. 2008 1987-2005 911 1,5 0,2

Kesmodel 2008 2004-2006 125 1,6 (3 mois) 77 1,6 2,6

Konopke 2009 1993-2008 107 0,9 49 1,9 4,1

Ferrero 2010 2002-2004 80 0,0 39 2,5 5,1

Schiesser 2008 1992-2005 197 2,5 126 1,0 1,6

Karanjia et al. 2008 1996-2006 283 2,1 151 0,7 1,3

2,1% 1% 2,6%

96

10

26

114

00

20

40

60

80

100

120

Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

34

6

22

14

7

2

0

5

10

15

20

25

30

35

40

Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

147 Hépatectomies mineures

85 Hépatectomies majeures

32% Gr 1-2 27% Gr 3-4-5

24% Gr 1-2 11% Gr 3-4-5

Morbidité 33% Mortalité 0%

Morbidité 59% Mortalité 2%

Morbidité grave

Morbidité grave

Maj + Min Mineure (<3 seg) Majeure (>2 seg) p

N=232 N=147 N=85N(%) or Moy±SD N(%) or Moy±SD N(%) or Moy±SD

Insuff. hép. post hep. 7 (3%) 1 (0,8%) 6 (7%) 0,002

Fistule Biliaire 19 (8) 11 (7) 8 (9) 0,04Ascite 17 (7) 3 (2) 14 (16) 0,0001Pneumopathie 15 (6) 9 (6) 6 (6) 0,77Confusion mentale 14 (6) 4 (3) 10 (11) 0,005Infection urinaire 12 (5) 6 (4) 6 (7) 0,32Collection péri-hépatique infecté

9 (4) 2 (1)7 (8) 0,009

Hémorragie 6 (2) 3 (2) 3 (3) 0,49Thrombose portale 2 (1) 0 2 (2) 0,06

Hospit. en Réanimation (jours) 2,3±3,3 1,8±2,3 3,1±4,5 0,007Hospitalisation globale (jours) 13,3±24 12,3±30,4 14,2±8,7 0,58

Toutes Hépatectomies(N=232)

Hépatectomies majeures (N=85)

RR (95% CI) p RR (95% CI) p

PO. Liver Failure 3,84 (1,01 – 14,4) 0,04 4,14 (1,29 – 14,8) 0,01

Mental Confusion 3,11 (1,37 – 7,14) 0,006 3,66 (1,18 – 12,5) 0,02

Infected Collection 2,87 (1,24 – 6,62) 0,01 -

Intraop Transf. 2,27 (1,21 – 4,09) 0,009 -

1er pronostic factor of long

term mortality after hep. for

colorectal liver met.

PO. Liver FailureSuivi moy. > 36 mois

C.H.B

J Am Coll Surg 1995; 181

C.H.B

Portal Puncture Under US Controle

Left Portal Branch

C.H.B

Right Portal Vein Embolization

C.H.B

Anatomical Hepatectomy after Fonctional Hepatectomy

2007

1 weeks

PVE allows to operate patient with finally the same overall result

2000

P=0.004

1995

2001

2009

2012

87 pts with PVE and chemotherapy to be operated

47 Slow responders : > 12 cycles of chemo.

40 Fast responders : < 12 cycles of chemo.

2012

PVE and chemo…

2008

Injection de cellule tumorale en intra splénique ou systémique et procédure à J7

In the liverIn the chest

Subcapsular hepatoma in rat thenlaparotomy, hep 30% or hep 60%

Evolution of the tumor ?

PV Ligation + In situ Splitting

« ALPPS » for Associated Liver Partition and Portal ligation for Staged hepatectomy

+ 72% in 9 days…

N=25

2012

To win time and volume….

The Solution to prevent small remnant liver ?

Or a dangerous method to explore with caution ?

Conclusion

• Portal vein embolization allows to decrease to the risk ofpo. Liver failure after major hepatectomy for colorectal livermetastasis

• Portal vein embolization increases the growth of colorectalliver metastases– Short term period between PVE / Hepatectomy– PVE and chemotherapy

• Alternative to PVE must be explored…– Major hepactomy seems did not increased malignancy– Portal flow modulation to prevent po. Failure with PVE

The future… Removable AdjustableVascular Ring around the portal vein