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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 Liver
Rosaye et al 2005-2011 2342 3.5% Abnormal Liver
Zhong et al 2000-2007 908 3.1% Abnormal Liver
Vigano 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 Liver
Zhou et al 2006-2009 124 0.5% Healthy Liver
Faber 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
Excluded
N = 312
Study Population
HCC
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-operative
Decompensation
N=29 (27.4%)
90-day Mortality
Post-op Liver Failure, N=2
Ascites and Sepsis, N = 1
Patients Alive with
Persitant Hepatic
Decompensation
Ascites, N=5
Jaundice, N=1
Persistent Ascites
When I plan a treatment to Mister
Durand, I think to Mister Dupond…
Who will be more beneficiated of
liver transplantation relatively to
resection ?
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 predictive
factor 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 rate
Urea rate
Rate of platelet
ICG Clearence
Hepatic 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 HCC
HVPG 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
hepatectomy
Right-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 HCC
In 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 cirrhosis
on 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 2016
6 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 LAP
32% in OPEN
OR 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
PosthepatectomyPVP(mmHg)
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 pts
New 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 elastography
and ICG in minor hepatectomy with MELD > 8
• Response to PVE before Right Hep in path liver
• Laparoscopic and portal pressure assessment

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How to predict po course before and during surgery for HCC

  • 1. How to predict post-operative course before and during surgery for HCC Pr Eric Vibert, MD, PhD Centre Hépato-Biliaire, Hop. Paul Brousse
  • 2. 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 ?
  • 3. 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 ?
  • 4. Mortality of Liver Resection for HCC Authors Period N 90 days Mortality Underlying Parenchyma Greco et al. 2001-2005 129 4.1% Abnormal Liver Rosaye et al 2005-2011 2342 3.5% Abnormal Liver Zhong et al 2000-2007 908 3.1% Abnormal Liver Vigano 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 Liver Zhou et al 2006-2009 124 0.5% Healthy Liver Faber 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)
  • 6. Nov 2014 – Aug 2016 N = 418 Liver Resection for HCC Other Indications Excluded N = 312 Study Population HCC 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
  • 7. Laparoscopy, N=29 (28%) Laparotomy, N=77 (73%) Minor Hepatectomy, N=69 (65%) Major Hepatectomy, N=37 (35%)
  • 8. 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%
  • 9. 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
  • 10. Persistent Hepatic Decompensation 9/67 pts (13%) (F3/F4) had liver decompensation after hepatectomy Post-operative Decompensation N=29 (27.4%) 90-day Mortality Post-op Liver Failure, N=2 Ascites and Sepsis, N = 1 Patients Alive with Persitant Hepatic Decompensation Ascites, N=5 Jaundice, N=1 Persistent Ascites
  • 11. When I plan a treatment to Mister Durand, I think to Mister Dupond… Who will be more beneficiated of liver transplantation relatively to resection ? Risk and Interest of oncologic hepatectomy ? VS
  • 12. 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 ?
  • 13. Feasibility of Surgery ? MELD < 10 MELD < 12 Independant predictive factor of mortality Cuccheti et al. Liver Transpl 2006Farges et al. Ann Surg 2012
  • 15. The location and the type of the unique HCC inferior to 5 cm ? LiverSP by SIGHT
  • 16. 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 rate Urea rate Rate of platelet ICG Clearence Hepatic venous pressure gradiant, 1996
  • 17. 2015
  • 18. Same portal hypertension and nodule But different location… Segmentectomy Segmentectomy 8 by Laparotomy Resection in Segment 3 by Lap’
  • 19. Portal Hypertension is an indirect method to assess of liver parenchyma
  • 20. Pathological liver classified as cirrhotic « Soft » cirrhosis post HBV « Hard » cirrhosis post HCV
  • 21. 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
  • 22. In absence of large right tumor Assessment by US on left side
  • 23. Liver Stiffness and Posthepatectomy complications Cescon et al, Ann Surg 2012 Wong et al, Ann Surg 2013 >16 kPa 12 kPa
  • 24. 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 HCC HVPG was measured intra-operatively when feasible (N=x) Rajakunnu et al., Vibert. Surgery 2017
  • 25. • Indocyanine Green Dye (ICG) – Intravenous injection • Passive hepatocytes captation and active biliary secretion • Decrease of the ICG secretion  Decrease of liver function
  • 26. 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 hepatectomy Right-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
  • 27. 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
  • 28. 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 HCC In 3 Frenchs Centers (PB, Marseille, Lyon) Le Roy et al, Vibert. Submitted to World J Surg
  • 29. 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
  • 30. 2003 PVE is an « effort test » for the pathological liver…
  • 31. 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
  • 32. 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 ?
  • 33. Impact of laparoscopic liver resection in patients with cirrhosis on 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 2016 6 French HPB Centers 343 Hepatectomy in F3/F4 89 pts by Lap (26%)
  • 34. RESULTS LAPOPEN Propensity score PHLF (ISGLS Grade B and C) 16% in LAP 32% in OPEN OR 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
  • 35. Intra Operative Portal Pressure ? 28 mm Hg…10 mm Hg
  • 36. Corrélation linéaire… YesNo PosthepatectomyPVP(mmHg) 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
  • 37. Intraoperative Portal Flow modulation MODHEP-1 : Phase I/II in Human (Hop. Paul Brousse – Villejuif), n=4 pts New Device now tested to improve it 1. Splenic Artery Ligation 2. Portal Caval Shunt (8 mm Goretex) Today… Tomorrow…
  • 38. 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
  • 39. Arterial Lactate > 3.0 mmol/L after abdominal closure  USI 2017
  • 40. Conclusion • Pathological liver is metastable situation • Acceptable po. Mortality is around 5% • Direct parenchyma and liver function could replaced indirect evaluation with elastography and ICG in minor hepatectomy with MELD > 8 • Response to PVE before Right Hep in path liver • Laparoscopic and portal pressure assessment