Majors rules in HCC treatment

1. Liver Resection For HCC
Eric Vibert, MD, PhD
Centre Hépato-Biliaire,
Hop. Paul Brousse

3. 10 years Recurrence Free Survival
22.4%
Février 2011

4. 2006
HCC < 2 cm
54 pts HBV versus 285 pts HCV
Différence à plus de 2 ans
28%
62%
15%
43%

5. 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%

6. 2013
CHC < 3 cm

7. 1200 à 1500 Liver Graft / year in France….

8. Which type of hepatectomy ?
AnatomicNon anatomic
Unique and inferior to 5 cm

9. Marge : 1 cm vs 2 cm
Suivi moyen : Marge 1 cm (39±17 mois) ; Marge 2 cm (43±15)
2007

11. Prognosis was in Satellite Nodules

12. 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 if
Platelet > 150 000

13. 2005
Not the same liver, not the same resection…

14. Recurrence free-survival was similar except in poor differenciated HCC

15. 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)

16. Very good accuracy to evaluate tumoral grading for CHC < 5 cm
81 Patients operated for unique CHC unique with preop. Percut. Biopsy
2011

17. First Message
Agressive HCC (Satellite nod, AFP kinetic and poor
differentiated HCC) must be treated aggressively
with margin AND anatomical resection
Is feasible ?
The location is higly
determinant
No choice Choice

18. Minor hepatectomy

19. 2006
1997 – 2004 : 157 hepatectomies on cirrhosis
Child A : 93% / Minor resection 95% / Mortalité 7%
Insuf. Hépatique
post-operatoire
Complications
post-operatoires

20. 2006
No liver resection on cirrhosis if MELD > 11

21. 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 rate
Urea rate
Rate of platelet
ICG Clearence
Hepatic venous pressure gradiant,
1996
Ascite at 3 months po

22. BCLC B BCLC C

23. 2008
1994-2004 : 455 pts opérés pour CHC / Suivi moy.: 46 mois
384 pts avec fibroscopie pré-opératoire
Child A / Sans HTP
56%
71%
Child A / Avec HTP
Définition de l’HTP : VO et/ou
plq < 100 000/ml + Splénomégalie

24. 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%
Assessment of ICG preoperatively

25. 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 cirrhosis
Mort : 2% - Liver Decomp : 34% (Ascite 93%)
ICG is the only preoperative data to predict Liver Decomp.

26. 90 pts including including 17 major hep. : 30% of liver decompensation (20% ascite)

27. > 16 kpA: Ascite and/or POLF

28. No evident difference between Laparoscopy and Laparotomy
70%
40%

29. Foie Non Tumoral
Foie Tumoral
Si Récidive
Salvage
Rehépatectomie ?
De Principe
Bridge
Récidive Précoce
Récidive Tardive
CI à la TH
?
Le test of time…
Scatton et al. Liver Transpl.
Fuks et al. Hepatology

30. N= 35 malades

31. Second Message
Minor hepatectomy is feasible if MELD < 12 and
FibroScan < 17-20 kPa (or ICG-15’ < 13%)
Laparoscopy facilitates subsequent liver transplantation
and must be used if oncological rules are respected

32. 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

33. 2003
PVE is an « effort test » for
the pathological liver…

34. 2000-2010 : N= 231 pts (US) / 3 Centres
Plaquette Préop < 150.000 / mLCourbe ROC / Maj. Compl.
134 Maj. Hep / 3% PVE
JACS, Avril 2011

35. Be careful… Hepatofugal flow…
No effect of portal vein embolization and risk of portal thrombosis

36. TACE PVE Major Hep.
Rational of this strategy
1 PVE increases arterial flow and increases HCC vascularization
2 Intra tumoral arterioportal shunt decrease PVE efficacy
3 Blockage of intra-operative portal metastases
2003

37. 2011

38. 2009
PVE only or upfront hepatectomy…

39. 2006
Circulating Cells
Ant App. decrease
Massive Hemorrhage
(> 2 l) : 28% vs 7%
But no impact of
recurrence…

41. 2000 – 2011 : 62 pts – 84% diabete
32 (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

42. Non transplantable patient (Med 70 years) and CHC > 10 cm (75%)
Liver biopsy is mandatory to evaluated precisely parenchyma
Protection of the liver parenchyma…. Clamping seems deleterious

43. Third Message
No major hepatectomy in abnormal
parenchyma without preoperative PVE,
especially before Right Hepatectomy
TACE before PVE in HCC < 5 cm improved survival

44. Surgery is Usefull or not ?
Macroscopic Vascular Invasion

45. BCLC B BCLC C

46. 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 ablation
25% TACE as 1st treatment

48. HKLC I
HKLC IIa
HKLC IIb
HKLC Va (TH)
HKLC IIIa
HKLC IIIb
HKLC IVa
HKLC Vb

50. 2046 patients including 297 pts BCLC C / Mort. 2.7%
25%
50%
2013

51. 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….

52. But perhaps a role of adjuvant treatment
p=0.011
N=34
N=44
25.2 m9.4 m
Constantin et al. Submitted to EASL
To explore…. Which treatment…

53. 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