Liver Transplantation for Cholangiocarcinoma

Eric Vibert, MD, PhD
Eric Vibert, MD, PhDProfesseur de Chirurgie Digestive au Centre Hépato-Biliaire - Chirurgie Hépato-biliaire et Transplantation um Centre Hépato-Biliaire
Is there is a place for liver
transplantation in cholangiocarcinoma ?
Pr Eric Vibert
Centre Hépato-Biliaire
Hopital Paul Brousse, Villejuif, Paris
N
Survival
Recurrence
rate1 yr 3 yrs 5 yrs
Meyer 2000 IH-CC + HIL-CC 207 72% 48% 23% 51%
Shimoda 2001
EH-CC 9 86% 31% - 22%
IH-CC 16 62% 39% - 54%
Ghali 2005 Incidental 10 - 30% - 80%
Robles 2004
HIL-CC 36 82% 53% 30% 53%
IH-CC 23 77% 65% 42% 35%
Kaiser 2008 HIL-CC 47 - 31% 22% -
Rapport AFC
HIL-CC 72 78% 38% 30%
IH-CC 26 78% 44% 34% 60%
Upfront Liver Transplantation for
Cholangiocarcinoma
0
,2
,4
,6
,8
1
SurvieCum.
0 1 2 3 4 5 6 7 8 9 10
Years
Graft Survival
Primary Cancers vs Non Cancer
May 1968 – March 2016
Klatskin (n=358)
HCC (n=22075)
CCC (n=637)
84%
65%
52%
71%
37%
30%
66%
30%
21%CCC vs Klatskin p=0.02 CCC vs Non Cancer p<0.001
CCC vs CHC p<0.001 Klatskin vs Non Cancer p<0.001
Klatskin vs CHC p<0.00 HCC vs Non Cancer p<0.001
Non Cancer (n=87243)
75%
66%
<1% des indications de TH
4.4%
Biliary Cancer are Lymphophil
Globally 40% of operated liver cancer had lymph node invasion
Farges et al. Ann Surg 2011 Gugliemi et al. J Gastro. Surg 2013 Aoba et al. Ann Surg 2013
Bismuth Type Lymph Node Incidence
Type 1 (n=19) 21%
Type 2 (n=22) 27%
Type 3 (n=135) 41%
Type 4 (n=144) 55%
2013
Correlated with the diameter
intrahepatic cholangiocarcinoma
24%
39%
33%
52%
Ribeiro et al. Arch Surg 2012
Bridgewater. ILCA guidelines. J Hepatol 2014
Liver Transplantation (LT) is not
recommended for Intrahepatic
Cholangiocarcinoma (iCCA) or
Hepatocholangiocarcinoma (HCA) because
results are well below those published for
standard indications
Transplantation for Intra Hepatic
Cholangiocarcinoma
Sapisochin. Am J Transpl 2014
Overall survival of patients with
iCCA on native liver
Patient survivial with an iCCA
≤ 2 cm « very early » versus > 2 cm
45%
71%
34%
P=0.2
Multicentric Spanish Study – 29 pts
Multicentric US Study – 32 pts
including 16 iCCA and 16 HCA
Facciuto. Transplantation 2014
Overall survival
78%
32%
P=0.04
57%
Disease-free survival / Milan criteria
2016
48 pts with iCCA on
the liver explant
Bridgewater. ILCA guidelines. J Hepatol 2014
Liver Transplantation (LT) is recommended
for non resectable peri hilar
cholangiocarcinoma and/or developed on
sclerosing cholangitis. This assumption is
based on results of Mayo Clinic protocol
Transplantation for Peri hilar
Cholangiocarcinoma
11 Patients
Disease Free Survial: 45 %
Mean Follow-up : 7 years !...
Transplantation for local recurrence in patient initially treated with palliative intent
by external radiotherapy and curietherapy with Iridium Needle
2002
2005
287 Patients
25% of drop-out
Gastroenterology, Juillet 2012
<40%
2013
Nagino M et al., Ann Surg 2013
pN0 pN1
Overall Survival After Surgery
For the Scheme to Reality
Fibrotic and Infiltrative little tumor with
limits often difficult to define...
True R0 is difficult to
obtain by liver surgery
Resectable Unresectable
Actual Policy in Peri Hilar CholangioK.
Extended Right Hep Extended Left Hep
RT-CT then
Liver Transplant. Palliative Chemo
Is Mayo Clinic Protocol should be
used in resectable patient ?
Perihilar Cholangiocarcinoma < 3 cm and without transhepatic biliary drainage
Primary Investigator Pr. Eric VIBERT
Scientific Responsible Pr. Emmanuel BOLESLAWSKI
Inclusion Criteria
• 18 to 68 year-old
• Perihilar cholangiocarcinoma inferior to 3 cm of
maximal diameter in axial CT-Scan
• Resectable R0
• No pathological liver including Sclerosing Chol.
• No percutaneous drainage
2 arms : Chirurgie Vs Mayo Clinic
Exhaustive Exploration (including Laparoscopy)
To exclude Intra- ou Extra Metastatic Disease
RANDOMIZATION 1:1
Capecitabine
Ext RT (50 grays)
Laparotomy
Lymph Node ?
6 Weeks
1-2 Weeks
PVE
Hepatectomy
TRANSPHIL Study : Inclusion Curve (06.09.2017)
Aim : 60 patients to have 54 randomized (27 pts x 2)
Arm RCT-LT (n=12)  9 LT
Arm Liver Res (n=13)  10 Res
Conclusion
• Upfront liver transplantation is a bad treatment of
cholangiocarcinoma, excepted perhaps in unique
intra-hepatic CCA < 2 cm
• Mayo Clinic Protocol had drastically changed the
prognosis of non resectable peri-hilar
cholangiocarcinoma, despite 25% of drop-out
• Role of Radio-Chemotherapy and transplantation
in resectable peri-hilar cholangiocarcinoma will be
determined by TRANSPHIL in 2021
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Liver Transplantation for Cholangiocarcinoma

  • 1. Is there is a place for liver transplantation in cholangiocarcinoma ? Pr Eric Vibert Centre Hépato-Biliaire Hopital Paul Brousse, Villejuif, Paris
  • 2. N Survival Recurrence rate1 yr 3 yrs 5 yrs Meyer 2000 IH-CC + HIL-CC 207 72% 48% 23% 51% Shimoda 2001 EH-CC 9 86% 31% - 22% IH-CC 16 62% 39% - 54% Ghali 2005 Incidental 10 - 30% - 80% Robles 2004 HIL-CC 36 82% 53% 30% 53% IH-CC 23 77% 65% 42% 35% Kaiser 2008 HIL-CC 47 - 31% 22% - Rapport AFC HIL-CC 72 78% 38% 30% IH-CC 26 78% 44% 34% 60% Upfront Liver Transplantation for Cholangiocarcinoma
  • 3. 0 ,2 ,4 ,6 ,8 1 SurvieCum. 0 1 2 3 4 5 6 7 8 9 10 Years Graft Survival Primary Cancers vs Non Cancer May 1968 – March 2016 Klatskin (n=358) HCC (n=22075) CCC (n=637) 84% 65% 52% 71% 37% 30% 66% 30% 21%CCC vs Klatskin p=0.02 CCC vs Non Cancer p<0.001 CCC vs CHC p<0.001 Klatskin vs Non Cancer p<0.001 Klatskin vs CHC p<0.00 HCC vs Non Cancer p<0.001 Non Cancer (n=87243) 75% 66%
  • 4. <1% des indications de TH 4.4%
  • 5. Biliary Cancer are Lymphophil Globally 40% of operated liver cancer had lymph node invasion Farges et al. Ann Surg 2011 Gugliemi et al. J Gastro. Surg 2013 Aoba et al. Ann Surg 2013
  • 6. Bismuth Type Lymph Node Incidence Type 1 (n=19) 21% Type 2 (n=22) 27% Type 3 (n=135) 41% Type 4 (n=144) 55% 2013
  • 7. Correlated with the diameter intrahepatic cholangiocarcinoma 24% 39% 33% 52% Ribeiro et al. Arch Surg 2012
  • 8. Bridgewater. ILCA guidelines. J Hepatol 2014 Liver Transplantation (LT) is not recommended for Intrahepatic Cholangiocarcinoma (iCCA) or Hepatocholangiocarcinoma (HCA) because results are well below those published for standard indications Transplantation for Intra Hepatic Cholangiocarcinoma
  • 9. Sapisochin. Am J Transpl 2014 Overall survival of patients with iCCA on native liver Patient survivial with an iCCA ≤ 2 cm « very early » versus > 2 cm 45% 71% 34% P=0.2 Multicentric Spanish Study – 29 pts
  • 10. Multicentric US Study – 32 pts including 16 iCCA and 16 HCA Facciuto. Transplantation 2014 Overall survival 78% 32% P=0.04 57% Disease-free survival / Milan criteria
  • 11. 2016 48 pts with iCCA on the liver explant
  • 12. Bridgewater. ILCA guidelines. J Hepatol 2014 Liver Transplantation (LT) is recommended for non resectable peri hilar cholangiocarcinoma and/or developed on sclerosing cholangitis. This assumption is based on results of Mayo Clinic protocol Transplantation for Peri hilar Cholangiocarcinoma
  • 13. 11 Patients Disease Free Survial: 45 % Mean Follow-up : 7 years !... Transplantation for local recurrence in patient initially treated with palliative intent by external radiotherapy and curietherapy with Iridium Needle 2002
  • 14. 2005
  • 15. 287 Patients 25% of drop-out Gastroenterology, Juillet 2012
  • 17. Nagino M et al., Ann Surg 2013 pN0 pN1 Overall Survival After Surgery
  • 18. For the Scheme to Reality Fibrotic and Infiltrative little tumor with limits often difficult to define... True R0 is difficult to obtain by liver surgery
  • 19. Resectable Unresectable Actual Policy in Peri Hilar CholangioK. Extended Right Hep Extended Left Hep RT-CT then Liver Transplant. Palliative Chemo
  • 20. Is Mayo Clinic Protocol should be used in resectable patient ? Perihilar Cholangiocarcinoma < 3 cm and without transhepatic biliary drainage
  • 21. Primary Investigator Pr. Eric VIBERT Scientific Responsible Pr. Emmanuel BOLESLAWSKI
  • 22. Inclusion Criteria • 18 to 68 year-old • Perihilar cholangiocarcinoma inferior to 3 cm of maximal diameter in axial CT-Scan • Resectable R0 • No pathological liver including Sclerosing Chol. • No percutaneous drainage
  • 23. 2 arms : Chirurgie Vs Mayo Clinic Exhaustive Exploration (including Laparoscopy) To exclude Intra- ou Extra Metastatic Disease RANDOMIZATION 1:1 Capecitabine Ext RT (50 grays) Laparotomy Lymph Node ? 6 Weeks 1-2 Weeks PVE Hepatectomy
  • 24. TRANSPHIL Study : Inclusion Curve (06.09.2017) Aim : 60 patients to have 54 randomized (27 pts x 2) Arm RCT-LT (n=12)  9 LT Arm Liver Res (n=13)  10 Res
  • 25. Conclusion • Upfront liver transplantation is a bad treatment of cholangiocarcinoma, excepted perhaps in unique intra-hepatic CCA < 2 cm • Mayo Clinic Protocol had drastically changed the prognosis of non resectable peri-hilar cholangiocarcinoma, despite 25% of drop-out • Role of Radio-Chemotherapy and transplantation in resectable peri-hilar cholangiocarcinoma will be determined by TRANSPHIL in 2021