how to predict po course before and during surgery for hcc

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How to predict post-operative course before and during surgery for HCC Pr Eric Vibert, MD, PhD Centre Hépato-Biliaire, Hop. Paul Brousse

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How to predict post-operative course before and during surgery for HCC

Pr Eric Vibert, MD, PhD

Centre Hépato-Biliaire,

Hop. Paul Brousse

Plan

• Mortality and Morbidity of HCC surgery ?

• Which pre-operative parameters were relevant in Child A/B patient before surgery ?

• How to predict and, perhaps, improve the post-operative courses ?

Plan

• Mortality and Morbidity of HCC surgery ?

• Which pre-operative parameters were relevant in Child A/B patient before surgery ?

• How to predict and, perhaps, improve the post-operative courses ?

Mortality of Liver Resection for 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%

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

ACHBT Web Prospective Registry

Nov 2014 – Aug 2016

N = 418 Liver Resection for HCC

Other Indications ExcludedN = 312

Study PopulationHCC

N = 106

Web Prospective Registry

MELD ≤12, platelet count ≥80,000

No preoperative HVPG assessment

TACE than PVE before Right Hep. in abnormal liver

Hepatectomy for HCC in last 2 years in Paul Brousse Hospital - Villejuif

Laparoscopy, N=29 (28%) Laparotomy, N=77 (73%)

Minor Hepatectomy, N=69 (65%) Major Hepatectomy, N=37 (35%)

90-day Post-operative Outcomes

Overall Cohort, N = 106 Advanced Liver Disease Cohort (F3/F4), N = 67

* Five patients died in 90-day postoperative period: 2 from liver failure, 1 with ascites and sepsis from

colonic perforation, 1 with biliary sepsis and 1 from suspected cardiac event after discharge

Minor N=81(76.4%)

Major N=25(23.6%)

Minor N=51(76.1%)

Major N=16(23.9%)

4.7%

Specific Complication Pathological Liver

CHILD A/B CHILD CNormal Liver

Metastable

3 types of Equilibrium

Stable Unstable

Liver Surgery

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

Liver Decompensation

Persistent Hepatic Decompensation

9/67 pts (13%) (F3/F4) had liver

decompensation after hepatectomy

Post-operativeDecompensation

N=29 (27.4%)

90-day MortalityPost-op Liver Failure, N=2 Ascites and Sepsis, N = 1

Patients Alive withPersitant HepaticDecompensation

Ascites, N=5Jaundice, N=1

Persistent Ascites

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

Plan

• Mortality and Morbidity of HCC surgery ?

• Which pre-operative parameters were relevant in Child A/B patient before surgery ?

• How to predict and, perhaps, improve the post-operative courses ?

Feasibility of Surgery ?

MELD < 10

MELD < 12

Independant predictivefactor of mortality

Cuccheti et al. Liver Transpl 2006Farges et al. Ann Surg 2012

BCLC B BCLC C

The location and the type of the unique HCC inferior to 5 cm ?

LiverSP by SIGHT

29 patients operated by laparotomy 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

2015

Same portal hypertension and nodule But different location…

Segmentectomy

Segmentectomy 8 by Laparotomy Resection in Segment 3 by Lap’

Portal Hypertension is an indirect method to assess of liver parenchyma

Pathological liver classified as cirrhotic

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

How to improve pre-operative assessment of po. Course ?

• Liver biopsy

• Elastometry (LS) and Controlled Attenuation Par. (CAP)

• Indocyanine Green (Global liver function)

• Scintigraphy (Global and localized liver function)

By Direct liver parenchyma and function evaluation

In absence of large right tumor

Assessment by US on left side

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 when feasible (N=x)

Rajakunnu et al., Vibert. Surgery 2017

• Indocyanine Green Dye (ICG) – Intravenous injection

• Passive hepatocytes captation and active biliary secretion

• Decrease of the ICG secretion Decrease of liver function

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 reserve

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

ICG-15’ was superior to Platelet rate to predict 3-month post-operative ascitis

Pre-operative ICG-R15’ > 15%

34% of po. Ascitis

2012-2014 : 147 pts operated for HCCIn 3 Frenchs Centers (PB, Marseille, Lyon)

Le Roy et al, Vibert. Submitted to World J Surg

Major Hepatectomy in cirrhotic patient

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

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

MELD Score < 10

2003

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

Global Liver Function (ICG) is relevant

Global Liver Function (ICG) is not relevant

Image de Scinti post PVE

Image de Scinti sans PVE

Ref about ICG post PVE

Plan

• Mortality and Morbidity of HCC surgery ?

• Which pre-operative parameters were relevant in Child A/B patient before surgery ?

• How to predict and, perhaps, improved the post-operative courses ?

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

RESULTS

LAPOPEN

Propensity score

PHLF (ISGLS Grade B and C)16% in LAP32% in OPENOR 0.31 [0.12-0.78]; p<0.001

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

Intra Operative Portal Pressure ?

28 mm Hg…10 mm Hg

Corrélation linéaire…

YesNo

Post

hep

atec

tom

y P

VP

(m

mH

g)

22.5 mmHg

15 mmHg

P < 0.001

Liver failure « 50-50 » criteria

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

277 hépatectomies majeures sur foie non cirrhotique

2013

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

Arterial Lactate > 3.0 mmol/L after abdominal closure USI

2017

Conclusion

• Pathological liver is metastable situation

• Acceptable po. Mortality is around 5%

• Direct parenchyma and liver function could replaced indirect evaluation with elastographyand ICG in minor hepatectomy with MELD > 8

• Response to PVE before Right Hep in path liver

• Laparoscopic and portal pressure assessment