Liver Resection For HCC

Eric Vibert, MD, PhD

Centre Hépato-Biliaire,

Hop. Paul Brousse

10 years Recurrence Free Survival

22.4%

Février 2011

2006

HCC < 2 cm

54 pts HBV versus 285 pts HCV

Différence à plus de 2 ans

28%

62%

15%

43%

2000 – 2009 : 127 pts avec CHC sur cirrhose C / Résection R0

Diab. équilibré

Diab. non équilibré

Treatment of co-factor as diabete is also mandatory to decrease recurrence

En préop : BMI et plaquette plus élevés chez les diabétiques

RFS à 3 ans : 66% vs 27%

2013

CHC < 3 cm

1200 à 1500 Liver Graft / year in France….

Which type of hepatectomy ?

AnatomicNon anatomic

Unique and inferior to 5 cm

Marge : 1 cm vs 2 cm

Suivi moyen : Marge 1 cm (39±17 mois) ; Marge 2 cm (43±15)

2007

Prognosis was in Satellite Nodules

2013

16 / 132 pts (12%) Satellites Nod.

1990 – 2009 : New York + Milan- NY : Child A / No Portal Hypertension- Milan : Child A : ICG < 20%

132 pts / Mortalité Pst op 0.7%

Surgery > Local Destruction ifPlatelet > 150 000

2005

Not the same liver, not the same resection…

Recurrence free-survival was similar except in poor differenciated HCC

Kinetics of AFP (Doubling time < 1 month) is more important than level to detect agressive HCC that required margin

No correlation between level

and kinetic (Dbl time)

Very good accuracy to evaluate tumoral grading for CHC < 5 cm

81 Patients operated for unique CHC unique with preop. Percut. Biopsy

2011

First Message

Agressive HCC (Satellite nod, AFP kinetic and poordifferentiated HCC) must be treated aggressively

with margin AND anatomical resection

Is feasible ?

The location is higlydeterminant

No choice Choice

Minor hepatectomy

2006

1997 – 2004 : 157 hepatectomies on cirrhosis

Child A : 93% / Minor resection 95% / Mortalité 7%

Insuf. Hépatique post-operatoire

Complications post-operatoires

2006

No liver resection on cirrhosis if MELD > 11

29 patients operated for HCC on Child A cirrhosis

Only hepatic venous pressure gradient > 10 mmHg was significant in multivariate analysis for decompensated cirrhosis after hepat.

Risk factor in univariate analysis

Bilirubin rateUrea rateRate of plateletICG ClearenceHepatic venous pressure gradiant,

1996

Ascite at 3 months po

BCLC B BCLC C

2008

1994-2004 : 455 pts opérés pour CHC / Suivi moy.: 46 mois384 pts avec fibroscopie pré-opératoire

Child A / Sans HTP

56%

71%

Child A / Avec HTP

Définition de l’HTP : VO et/ouplq < 100 000/ml + Splénomégalie

Makuuchi et al., Semin Surg Oncol 1993

Ascites

None or controlled Not controlled

ICGR15 Limited resection Enucleation Not indicated for hepatectomy

Trisectorectomy bisectorectomy

Left-sided hepatectomyRight-sided

sectoriectomy

Segmentectomy Limited resection Enucleation

Normal 1.1 – 1.5 mg/dL 1.6 – 1.9 mg/dL > 2.0 mg/dL

Total bilirubin level

Normal 10% - 19% 30% - 39% > 40%20% - 29%

Assessment of ICG preoperatively

Hépatectomie mineure Hépatectomie majeure

AUC 0,78 [0,66-0,90]Valeur seuil: 12,75

Sensibilité: 74%Spécificité: 71%

AUC: 0,66 [0,66-0,87]Sensibilité: 50%Spécificité: 88%

p=0,33

2012-2014 : 89 pts operated for HCC on cirrhosisMort : 2% - Liver Decomp : 34% (Ascite 93%)

ICG is the only preoperative data to predict Liver Decomp.

90 pts including including 17 major hep. : 30% of liver decompensation (20% ascite)

> 16 kpA: Ascite and/or POLF

No evident difference between Laparoscopy and Laparotomy

70%

40%

Foie Non Tumoral

Foie Tumoral

Si Récidive

SalvageRehépatectomie ?

De Principe

Bridge

Récidive Précoce

Récidive Tardive

CI à la TH

?

Le test of time…

Scatton et al. Liver Transpl. Fuks et al. Hepatology

N= 35 malades

Second Message

Minor hepatectomy is feasible if MELD < 12 andFibroScan < 17-20 kPa (or ICG-15’ < 13%)

Laparoscopy facilitates subsequent liver transplantation and must be used if oncological rules are respected

Major hepatectomy

< 20% of standard liver volume or 0.5% body weight on non cirrhotic liver

Liver Surgical Planner (Available on iTunes)

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

2003

PVE is an « effort test » for the pathological liver…

2000-2010 : N= 231 pts (US) / 3 Centres

Plaquette Préop < 150.000 / mLCourbe ROC / Maj. Compl.

134 Maj. Hep / 3% PVE

JACS, Avril 2011

Be careful… Hepatofugal flow…

No effect of portal vein embolization and risk of portal thrombosis

TACE PVE Major Hep.

Rational of this strategy

1 PVE increases arterial flow and increases HCC vascularization2 Intra tumoral arterioportal shunt decrease PVE efficacy3 Blockage of intra-operative portal metastases

2003

2011

2009

PVE only or upfront hepatectomy…

2006

Circulating Cells

Ant App. decreaseMassive Hemorrhage

(> 2 l) : 28% vs 7%

But no impact of recurrence…

2000 – 2011 : 62 pts – 84% diabete32 (52%) Majors hepatectomies

TACE/PVE (n=8) et PVE (n=1)

38 (61%) abnormal liver parenchyma- F1/F2 ou Stéatohépatite (n=20)- F3/F4 (n=18)

15% des CHC réséqués en 2010

18% postop. mortality

Non transplantable patient (Med 70 years) and CHC > 10 cm (75%)

Liver biopsy is mandatory to evaluated precisely parenchymaProtection of the liver parenchyma…. Clamping seems deleterious

Third Message

No major hepatectomy in abnormalparenchyma without preoperative PVE,

especially before Right Hepatectomy

TACE before PVE in HCC < 5 cm improved survival

Surgery is Usefull or not ?

Macroscopic Vascular Invasion

BCLC B BCLC C

Early tumor : ≤5 cm AND ≤3 nod AND no vascular invasion

Intermediate tumor : ≤5 cm AND >3 nod OR with vascular invasion>5 cm AND ≤3 nod AND no vascular invasion

Locally advanced tumor : ≤5 cm AND >3 nod AND with vascular invasion>5 cm AND >3 nod AND/OR vascular invasion

ECOG Performance Status1- Général status of pts:

Score de Child-Pugh2- Function reserve:

3 – Tumoral status:

4 - Envahissement extra-hépatique : Vasculaire et/ou métastatique

3856 ps – 79% HVB 38% resection, LT or ablation25% TACE as 1st treatment

HKLC I

HKLC IIaHKLC IIb

HKLC Va (TH)

HKLC IIIa

HKLC IIIbHKLC IVa

HKLC Vb

2046 patients including 297 pts BCLC C / Mort. 2.7%

25%

50%

2013

Chir (n=70) vs Nexavar (n=44) in BCLC C in 4 Centers in France (Bondy, Creteil, Grenoble, Paul Brousse)

N=17

N=16

p=0.17

Propensity score to compare 2 populations

Constantin et al. Submitted to EASL

Globally no difference….

But perhaps a role of adjuvant treatment

p=0.011

N=34N=44

25.2 m9.4 m

Constantin et al. Submitted to EASL

To explore…. Which treatment…

Conclusions and Perspectives

• Oncological HCC resection imposed margin

– Prognostic value of margin according to diameter and genetic of HCC ?

• The location of HCC defined the type of surgery

– Staging of HCC must included also location

• Underlying liver parenchyma is the key

– Elastometry will replaced all and notably liver biopsy ?

• Surgical treatment of HCC BLCL C is feasible

– Adjuvant and perhaps neoadjuvant must be explored