1) Portal hypertension is not necessarily a contraindication for resection of HCC if the extent of surgery is adapted to the degree of portal hypertension and the location of the tumor in the liver is considered. 2) The size of a HCC tumor is less important than the tumor morphology and patient condition in determining resectability for large HCC tumors. 3) Surgery may be useful for HCC with intrahepatic portal or hepatic vein invasion but is more debatable for invasion into a large portal branch or portal trunk, and neoadjuvant treatments should be developed for these patients.

1. Surgery at the Borderline
Eric Vibert, MD, PhD
Centre Hépato-Biliaire,
Hop. Paul Brousse

2. The actual results of surgery in 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. BCLC B BCLC C
These guidelines were no more followed…

4. 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

5. Overall survival in the 3 groups
35%
65%
90 Postoperative Mortality : 1.2% (In BCLC) vs 4.5% (Out BCLC)

6. In BCLC A : Unique Or 3 nod ≤ 3 cm

8. The location of HCC is very important…
LiverSP by SIGHT

9. Same portal hypertension level and
same nodule.. but different location…
Segmentectomy
Segmentectomy 8 by Laparotomy Resection in Segment 3 by Lap’

10. X3 PO. Mortality: 6.1% (38/618) vs 2.8% (32/1274)
X2 PO. Liver Failure : 17% vs 7%

11. 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

12. 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 liver
hemodynamics assessed by ICG-R15

13. Impact of portal hypertension depends
of the remnant liver volume
Volume of the Remnant Liver
Portal Hypertension

14. Major Hepatectomy in cirrhotic patient
Truant et al. JACS 2008
MELD Score ≤ 10 and no clinical portal hypertension
Cucchetti et al. Liver Transpl 2006

15. 2003
PVE is an « effort test » for
the pathological liver…

16. 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 Operative
Mortality : 9%
2011

17. TACE PVE Major Hep.
Rational of TACE before PVE strategy
1. Avoiding increased HCC arterial vascularization after PVE
2. Occlusion of tumoral arterioportal shunt to increase PVE efficacy
2003
After Arterial
Repermeabilization
2 weeks 3 weeks

18. 2011
TACE then PVE in HCC inferior to 5 cm : Increased Liver Volume and Tumoral Necrosis

19. Correlation is linear…
YesNo
PosthepatectomyPVP(mmHg)
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 mortality
after major resection (N = 277) in humans1
1. Allard….. Vibert - Ann Surg. 2013 Nov;258(5):822-9

20. 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…

21. 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….

22. 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

24. No impact of HCC diameter in T1 lesion
T1 : No vascular invasion on the specimen
Vauthey et al. J. Clin Oncol 2002
203 patients
5-years Overall Survival : 55%

25. Analysis of preoperative imagery
50%
Annals of Surgery 2009 Br. Journal of Surgery 2006

26. Same Size but different aspect…
Large HCC on non-cirrhotic liver
30% of 5-years OS>50% of 5-years OS

27. Extended Right Hepatectomy
Well Differenciated HCC – R1 Resection

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

29. 2009
PVE only or upfront hepatectomy…

30. No TACE before hepatectomy for large HCC
without macroscopic vascular invasion
Resectable… No more resectable…

31. No impact of high Value of AFP
Surgery, 2015

32. Large tumor in large and old patient….

33. 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

34. No tolerance of clamping…

35. Protection of the liver and kidney during
large hepatectomy in fragile patients
Br. Journal of Surgery 2009Annals of Surgery 2005

36. Mergental et al. , J. Hepatol 2012
ELTR : 105 patients in 10 years…
49%

37. 60%
70%
Récidive < 12 mois

38. Second Message
Size is not the problem to decide
resection or not for huge HCC…
Tumor and Patient Morphology are
more important….

39. Surgery is Usefull or not ?
Macroscopic Vascular Invasion

40. Impact of Portal Vein Extension
Vp1 Vp2
Vp3 Vp4

41. 5-year Survival around 10-15% in Vp3/Vp4
Author Period
Portal Vein
Extension
N. Pts
PO.
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%

42. Selection by TACE before Surgery
Vp2
N=9(50%)
Vp3
N=9(50%)
2001

43. Surgery vs TACE in HCC with PVT
Vp1 Vp2
Vp3 Vp4
Peng et al. Cancer 2012

44. Paul Brousse Experience
1992 – 2014 : 43 pts
Vp1/Vp2 : 8 pts
Vp3/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

45. 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

46. Third (and last..) Message…
• Surgery is an emergency for HCC with intrahepatic
macroscopic portal vein or hepatic vein extension….
• Upfront surgical treatment of HCC with macroscopic
vascular extension into large portal branch (Vp3) or
portal Trunk (Vp4) is more debetable…
• Neo-Adjuvant (or Adjuvant ?…) treatments in these
patients must be developped

48. Ruptured HCC

49. 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

50. Conclusions and Perspectives
Therapeutic guidelines must now
involve the location of the tumor in
the liver and intra/extrahepatic
macroscopic vascular extension to
stratify and treat correctly pts with
HCC…