Is there is a place for livertransplantation 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

Surv

ie C

um

.

0 1 2 3 4 5 6 7 8 9 10

Years

Graft Survival

Primary Cancers vs Non CancerMay 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 diameterintrahepatic cholangiocarcinoma

24%

39%33%

52%

Ribeiro et al. Arch Surg 2012

Bridgewater. ILCA guidelines. J Hepatol 2014

Liver Transplantation (LT) is notrecommended for IntrahepaticCholangiocarcinoma (iCCA) orHepatocholangiocarcinoma (HCA) becauseresults are well below those published forstandard indications

Transplantation for Intra HepaticCholangiocarcinoma

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=0.0457%

Disease-free survival / Milan criteria

2016

48 pts with iCCA on the liver explant

Bridgewater. ILCA guidelines. J Hepatol 2014

Liver Transplantation (LT) is recommendedfor non resectable peri hilarcholangiocarcinoma and/or developed onsclerosing cholangitis. This assumption isbased on results of Mayo Clinic protocol

Transplantation for Peri hilarCholangiocarcinoma

11 Patients

Disease Free Survial: 45 %Mean Follow-up : 7 years !...

Transplantation for local recurrence in patient initially treated with palliative intentby 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 withlimits 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

CapecitabineExt RT (50 grays)

LaparotomyLymph 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