Innovations in HCC surgery

Pr Eric Vibert, MD, PhD

Centre Hépato-Biliaire,

Hop. Paul Brousse, Villejuif

Disclosures

• Fees from Bayer, BMS, Johnson&Johnson

• Consultant for Nanobiotix and MID

• Academic collaboration with EchoSens, Fluoptics and IntraSense

Surgery for HCC

Must be feasible Must be useful

Must continue to improve

Innovative Methods

To evaluate feasibility of surgery ?

To perform a useful surgery ?

To improve surgical gesture ?

Feasibility of Liver Surgery ?

MELD < 10

MELD < 12

Independant predictivefactor of mortality

Cuccheti et al. Liver Transpl 2006Farges et al. Ann Surg 2012 Bruix et al. Gastroenterology 1996

Mortality of Liver Resection for HCC

Authors Period N 90 days Mortality 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 LiverFrench HPB Registry 2012-2016 343 4.7% Abnormal liver

Kim et al 2005-2010 454 0.7% Healthy LiverZhou et al 2006-2009 124 0.5% Healthy Liver

Post-operative mortality in cirrhotic patient is inferior to 5%

3-months Mortality of Liver Transplantation : 9% (Adam et al. J Hep 2012)

Our patients are in metastable equilibrium

Clinical Ascitis and/or Jaundice and/or Encephalopathy at 3 months po.

Liver Decompensation

Metastable

Child A/B

When I plan a treatment to MisterDurand, I think to Mister Dupond…Who will be more beneficiated ofliver transplantation relatively toresection ?

Risk and Interest of oncologic hepatectomy ?

VS

De Novo recurrence

Postop. Courses

Local recurrence

Extra-hepatic DiseaseUtility of liver resection ?Response in the cancer…

Feasibility of liver resection ?Response in the liver…

Portal Hypertension is an indirect method to assess of liver parenchyma

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

Resection adapted to portal hypertensionTo decrease impact of portal hypertension

Ishizawa et al. Gastroenterology 20..

Same portal hypertension and nodule But different location…

Easy lap’ Segmentectomy 3 Hard lap’ Segmentectomy 8

The location of HCC is determinant…

LiverSP by SIGHT

Pathological liver classified as cirrhotic

« Soft » cirrhosis post HBV « Hard » cirrhosis post HCV

In absence of right large tumor

Direct and global liver parenchyma evaluation by physical measurement

Elastometry for Stifness and CAP for Steatosis

Liver Stiffness and Posthepatectomy complications

Cescon et al, Ann Surg 2012 Wong et al, Ann Surg 2013

>16 kPa 12 kPa

LSM was an independent Risk Factor of mortality and po. Liver decompensation

Parameter AUROC 95% CI Cut-off Se (%) Sp(%)

LSM

(kPa)0.80 0.64 - 0.97

12 86 67

15 43 82

22 43 93

HVPG

(mm Hg)0.71 0.497 – 0. 91 10 29 96

LSM was systematically measured preop. in 167 pts operated for HCCHVPG was measured intra-operatively

Rajakunnu et al., Vibert. Surgery 2017

Innovative Methods

To evaluate feasibility of surgery ?

To perform a useful surgery ?

To improve surgical gesture ?

De Novo recurrence

Postop. Courses

Local recurrence

Extra-hepatic DiseaseUtility of liver resection ?Response in the cancer…

Feasibility of liver resection ?Response in the liver…

Fantastic tools… for publication

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Rates of microvascular invasion among the patients

who underwent hepatic resection or transplantation (n=921)

P<0.0001

P=0.33

Patients who underwent hepatic resection or liver transplantation from January 1994 to May 2016 in Paul Brousse Hospital

AFP (ng/ml) at preoperation

AFP to evaluated HCC aggressiveness

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

2007

Margin : 1 cm vs 2 cm

Surgical margin impact depend of preop. AFP rate

Median of Follow-up : 17 months

75%

45% 51%

55%

AFP > 100 : Margin > 1 cm is mandatoy AFP < 100 : Margin > 1 cm is not mandatoy

2012- 2016 : 334 pts operated for HCC in 4 HPB Centers in France

#ILCA_17 congress – Poster XX

3 cm HCC deeply

located in segment 8

MELD 10 – FE 12 kPa

Local destruction Segmentectomy 8

AFP > 100 ng/mlAFP < 100 ng/ml

Margin > 1 cmMargin < 1 cm

Improved anatomical resection in all tumoral type

Improved Recurrence Free Survival in HCC

Golse, Cottin, Vibert et al.

Pessaux et al.

From virtual to real…

Open or Lap

Innovative Methods

To evaluate feasibility of surgery ?

To perform a useful surgery ?

To improve surgical gesture ?

Impact of laparoscopic liver resection in patients with cirrhosison post-operative liver failure : A Propensity Score Analysis

M. Prodeau, S. Truant, E. Vibert, O. Farges, J.Y. Mabrut,

J. Hardwigsen, J.M. Régimbeau, G. Millet, O. Soubrane,

R. Adam, D. Cherqui, F.R. Pruvot, E. Boleslawski

The ACHBT French Hepatectomy Study Group

Oct 2012 – June 20166 French HPB Centers

343 Hepatectomies in F3/F4 89 pts by Lap (26%)

Incidence of Post-Operative Liver Failure

Matched-LAP Matched-OPEN

Age (years) 65.3 65.3

BMI (kg/m²) 26.9 26.9

MELD 8.6 8.5

Platelets (x 1000/mm3) 167 167

ICG (15 min) 15.2 % 15.0 %

HVPG (mmHg) 7.9 8.1

LS (kPa) 21.8 21.9

RLV (%) 88.6 87.6

16% in LAP and 32% in OPEN

OR 0.31 [0.12-0.78]; p<0.001

Intra Operative Portal Pressure ?

28 mm Hg…10 mm Hg

Intraoperative Portal Flow modulation

MODHEP-1 : Phase I/II in Human(Hop. Paul Brousse – Villejuif), n=4 ptsNew Device now tested to improve it

1. Splenic Artery Ligation

2. Portal Caval Shunt (8 mm Goretex)

Today… Tomorrow…

75% Hepatectomy in Pig with or without Portal Flow Modulation from POD-0 to POD3

Lower Bilirubin at PO3 and POD5 and Higher ki67 index at POD3

2017

Fluorescent Guided Liver Surgery

Ishizawa. Cancer 2009 Ishizawa. Surg Endos 2016Ishizawa. Ann Surg Onc 2010

• Indocyanine Green Dye (ICG) – Intravenous injection

• Passive hepatocytes captation and active biliary secretion

• Decrease of the ICG secretion Decrease of liver function

26 patients (20 HCC – 6 Colorectal LM) : intraoperative exploration with ICG cam

Only to detect subcapsular lesion / No clear data on clinical rentability

Cancer 2009

HCC : Fluorescent spot CRLM : Fluorescent ring

HCC : No functional

hepatocytes

Camera Vert D’indo

170 patients operated by laparotomy for HCC who had received ICG (0.5 mg/kg) at least 48 hours before liver surgery

Intraop. detection of 21 new spots in 19 patients 14 HCC (8.2%) and 7 False-Positive

Low specificity in severe cirrhosis

With the courtesy of T. Ishizawa and M. Terasawa

Intraoperative Pathological Data

Macroscopic Scale and,in a very next future, atMicroscopic scale…

Conclusions

• Fibroscan is important tools to select patient• Tumoral biology should impact surgical strategy• Virtual Hepatectomy increased surgical quality• Laparoscopy decreased by 2 the risk of POLF• Fluorescent guided liver surgery seems useful

And surgeons must come to ILCA….