Surgery at the Borderline

Eric Vibert, MD, PhD

Centre Hépato-Biliaire,

Hop. Paul Brousse

The actual results of surgery in HCC

Authors Period N 90 days Mortality Underlying Parenchyma

Greco et al. 2001-2005 129 4.1% Abnormal LiverRosaye et al 2005-2011 2342 3.5% Abnormal LiverZhong et al 2000-2007 908 3.1% Abnormal LiverVigano et al 2000-2012 192 2.1% Abnormal Liver

Donadon et al 2004-2013 336 2% Abnormal Liver

Kim et al 2005-2010 454 0.7% Healthy LiverZhou et al 2006-2009 124 0.5% Healthy LiverFaber et a; 2000-2010 148 0% Healthy Liver

« Acceptable » post-operative mortality in cirrhotic patient is inferior to 5%

BCLC B BCLC C

These guidelines were no more followed…

2005-2011 : Cohort BRIDGE 8656 patients

70% No Surgery (n=6134 )

30% Surgery (n=2342 )70% Out BCLC Guidelines (n=1624)

30% In BCLC Guidelines (n=718 )

2% BCLC Guideline for Surg (n=123)

2015

Overall survival in the 3 groups

35%

65%

90 Postoperative Mortality : 1.2% (In BCLC) vs 4.5% (Out BCLC)

In BCLC A : Unique Or 3 nod ≤ 3 cm

The location of HCC is very important…

LiverSP by SIGHT

Same portal hypertension level and same nodule.. but different location…

Segmentectomy

Segmentectomy 8 by Laparotomy Resection in Segment 3 by Lap’

X3 PO. Mortality: 6.1% (38/618) vs 2.8% (32/1274)

X2 PO. Liver Failure : 17% vs 7%

2008

1994-2004 : 455 pts included 130 with PHT : No impact…

Child A / Sans HTP

56%

71%

Child A / Avec HTP

No early impact but lower longtime survival after resection of PHT

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%

Adapted liver resection to liverhemodynamics assessed by ICG-R15

Impact of portal hypertension dependsof the remnant liver volume

Volume of the Remnant Liver

Portal Hypertension

Major Hepatectomy in cirrhotic patient

Truant et al. JACS 2008

MELD Score ≤ 10 and no clinical portal hypertension

Cucchetti et al. Liver Transpl 2006

2003

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

2000-2010 : 231 pts including 134 maj. hepatectomies with only 3% of PVE

In such condition, major impact of préoperative platelet rate < 150.000 / mL

22%

6%

Global Post OperativeMortality : 9%

2011

TACE PVE Major Hep.

Rational of TACE before PVE strategy

1. Avoiding increased HCC arterial vascularization after PVE2. Occlusion of tumoral arterioportal shunt to increase PVE efficacy

2003

After ArterialRepermeabilization

2 weeks 3 weeks

2011

TACE then PVE in HCC inferior to 5 cm : Increased Liver Volume and Tumoral Necrosis

Correlation is linear…

YesNo

Post

hep

atec

tom

y P

VP

(m

mH

g)

22.5 mmHg

15 mmHg

P < 0.001

Liver failure « 50-50 » criteria

Portal pressure at the end of liver resection

An independent predictor of liver failure and mortalityafter major resection (N = 277) in humans1

1. Allard….. Vibert - Ann Surg. 2013 Nov;258(5):822-9

Intraoperative Portal Flow modulation

MODHEP-1 : Phase I/II in Human(Hop. Paul Brousse – Villejuif)

1. Splenic Artery Ligation fisrt

2. Portal Caval Shunt (8 mm Goretex)

Today… Tomorrow…

First Message

Portal hypertension is not, per se, a contra-indication to resection if the extent of hepatectomy is adapted to degree of portal hypertension….

The HCC location must be included in therapeutic guidelines….

After Technical…Oncological limits

Image Ferrière : CHC Multiple

Adenopathie +

Macroscopic Vascular Invasion

Portal Invasion

Multiple Nodule

Huge Lesion

Ruptured HCC Hepatic Vein / Caval Invasion Ruptured HCC

No impact of HCC diameter in T1 lesionT1 : No vascular invasion on the specimen

Vauthey et al. J. Clin Oncol 2002

203 patients

5-years Overall Survival : 55%

Analysis of preoperative imagery

50%

Annals of Surgery 2009 Br. Journal of Surgery 2006

Same Size but different aspect…

Large HCC on non-cirrhotic liver

30% of 5-years OS >50% of 5-years OS

Extended Right HepatectomyWell Differenciated HCC – R1 Resection

2006

Circulating Cells

Ant App. decreaseMassive Hemorrhage

(> 2 l) : 28% vs 7%

But no impact of recurrence…

2009

PVE only or upfront hepatectomy…

No TACE before hepatectomy for large HCC without macroscopic vascular invasion

Resectable… No more resectable…

No impact of high Value of AFP

Surgery, 2015

Large tumor in large and old patient….

2000 – 2011 : 62 pts – CHC > 10 cm (75%) 52% of major hepatectomy

15% of pts in 2010

38 pts with liver abnormalities (32% F1/F2 / 29% F3/F4) 18% of post operative mortality

2013

No tolerance of clamping…

Protection of the liver and kidney duringlarge hepatectomy in fragile patients

Br. Journal of Surgery 2009Annals of Surgery 2005

Mergental et al. , J. Hepatol 2012

ELTR : 105 patients in 10 years…

49%

60%70%

Récidive < 12 mois

Second Message

Size is not the problem to decideresection or not for huge HCC…

Tumor and Patient Morphology are more important….

Surgery is Usefull or not ?

Macroscopic Vascular Invasion

Impact of Portal Vein Extension

Vp1 Vp2

Vp3 Vp4

5-year Survival around 10-15% in Vp3/Vp4

Author PeriodPortal VeinExtension

N. PtsPO.

Mort.Median

3-years OS

5-years OS

Matono et al. 1985-2005 Vp3/Vp4 29 3% 16.6 24% 17%

Ikai et al. 1990-2002 Vp3/Vp4 78 3.8% 8,8 21% 11%

Pawlick 1984-1999 Vp3 102 5.8% 11 17% 10%

Minigawa 1989-1998 Vp2/Vp3/Vp4 18 5.5% 18 42% 42%

Peng 2002-2007 Vp2 27 51% 37%

Vp3 68 17% 17%

Vp4 83 4% 4%

LeTreut 1988-2004 Vp2/Vp3/Vp4 26 11% 9 13%

Zhou Vp2/Vp3/Vp4 386 12%

Personnal Exp. 1992-201 Vp2/Vp3/Vp4 43 10% 7 19%

Selection by TACE before Surgery

Vp2

N=9(50%)

Vp3

N=9(50%)

2001

Surgery vs TACE in HCC with PVT

Vp1 Vp2

Vp3 Vp4

Peng et al. Cancer 2012

Paul Brousse Experience

1992 – 2014 : 43 pts

Vp1/Vp2 : 8 ptsVp3/Vp4 : 35 pts

50%

30%

19%

35%

Atrophy of the liver on the side of the tumoral thrombus is the only prognostic factor

Atrophy is a surrogate factor of a slowly growing tumor

Macroscopic Hepatic Vein

Microscopic or Peripherical Venous Invasion = Macroscopic Venous Invasion

2015

50%

Associated to Vp1/Vp2 >>> Vp3/Vp4

It is still intra hepatic lesion

Third (and last..) Message…

• Surgery is an emergency for HCC with intrahepaticmacroscopic portal vein or hepatic vein extension….

• Upfront surgical treatment of HCC with macroscopicvascular extension into large portal branch (Vp3) or portal Trunk (Vp4) is more debetable…

• Neo-Adjuvant (or Adjuvant ?…) treatments in thesepatients must be developped

Ruptured HCC

33%13%

45%

Surgery or Local destruction are justified if they are not performed in emergency

Aoki et al. Ann Surg 2013 Yang et al. Br J Surg 2013

Loc. Dest = Surgery

Conclusions and Perspectives

Therapeutic guidelines must nowinvolve the location of the tumor inthe liver and intra/extrahepaticmacroscopic vascular extension tostratify and treat correctly pts withHCC…