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Liver Transplantation for Cholangiocarcinoma
1) Liver transplantation has generally not proven effective for cholangiocarcinoma except possibly for very small (less than 2 cm) intrahepatic cholangiocarcinoma. 2) The Mayo Clinic protocol of neoadjuvant radiation and chemotherapy followed by liver transplantation for non-resectable perihilar cholangiocarcinoma has significantly improved outcomes compared to standard treatments, though 25% of patients drop out of the protocol. 3) The ongoing TRANSPHIL study aims to determine if the Mayo Clinic protocol provides any benefit compared to surgery alone for resectable perihilar cholangiocarcinoma less than 3 cm by randomizing eligible patients to each treatment.
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Liver Transplantation for Cholangiocarcinoma
- 1. Is there isa place for liver transplantation in cholangiocarcinoma ? Pr Eric Vibert Centre Hépato-Biliaire Hopital Paul Brousse, Villejuif, Paris
- 2. N Survival Recurrence rate1 yr 3yrs 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 23 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 indicationsde TH 4.4%
- 5. Biliary Cancer areLymphophil 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 LymphNode 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 thediameter 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 JTranspl 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 withiCCA 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 FreeSurvial: 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.
- 15. 287 Patients 25% ofdrop-out Gastroenterology, Juillet 2012
- 16.
- 17. Nagino M etal., Ann Surg 2013 pN0 pN1 Overall Survival After Surgery
- 18. For the Schemeto 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 Policyin Peri Hilar CholangioK. Extended Right Hep Extended Left Hep RT-CT then Liver Transplant. Palliative Chemo
- 20. Is Mayo ClinicProtocol 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 • 18to 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 livertransplantation 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