Invited conference at IHBA Congress - Argentina

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

16. <40%
2013

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