Cholangiocarcinoma: Not an Indication for Hepatic Transplantation. Joon Lee UCHSC Surgery Intern

Transcription

1 Cholangiocarcinoma: Not an Indication for Hepatic Transplantation Joon Lee UCHSC Surgery Intern

2 Objectives 1. Very brief overview of cholangiocarcinoma 2. Review current standards of care for patients with perihilar cholangiocarcinomas 3. Current statistics regarding OLT in the US, actuarial estimates of survival 4. Review of historical data of orthotopic liver transplantation (OLT) for cholangiocarcinoma 5. Neoadjuvant therapy for cholangiocarcinoma

3 Cholangiocarcinoma Malignancy of biliary duct system 1 -Intrahepatic -Extrahepatic Perihilar 60%-80% -Distal 10-30% Perihilar (Klatskin) classified by anatomic location 2 : I. Confined to common hepatic duct II. Bifurcation w/o secondary intrahepatic duct involvement III. a) Right intrahepatic duct extension III. b) Left intrahepatic duct extension IV. Both intrahepatic duct involvement

4 Bismuth-Corlette Classifications2

5 Cholangiocarcinoma: AJCC TNM Staging 3 T1 Tumor confined to bile duct T2 Tumor invades beyond the wall of the bile duct T3 Tumor invades the liver, gallbladder, pancreas, and/or unilateral branches of the portal vein (right or left) or hepatic artery (right or left) T4 Tumor invades any of the following: main portal vein or its branches bilaterally, common hepatic artery, or other adjacent structures, such as the colon, stomach, duodenum, or abdominal wall N0 No regional lymph node metastasis N1 Regional lymph node metastasis M0 No distant metastasis M1 Distant metastasis Stage Grouping IA T1 N0 M0 IB T2 N0 M0 IIA T3 N0 M0 IIB T1 N1 M0, T2 N1 M0, T3 N1 M0 III T4 Any N M0 IV Any T Any N M1

6 Cholangiocarcinoma:Current surgical therapy 4 Types I and II without vascular involvement : Local tumor excision + Portal lymphadenectomy + Cholecystectomy + CBD excision + Bilateral ReY hepaticojejunostomies Types IIIa and IIIb : All of the above including appropriate hepatic lobectomy Type IV : No curative surgical therapy palliation with or without surgery.

7 UNOS/OPTN Data for Liver Transplantation 5 Kaplan-Meier Patient Survival Rates : Malignant neoplasms All 1 Year 86.3% 82.5% 3 Year 70.0% 73.5% 5 Year 57.3% 67.2% Burden of proof of studies relies on survival rates versus figures listed above. Only malignancy that is indication for OLT is HCC

8 OLT for Cholangiocarcinoma 1997 Meyer et al. 6 Retrospective review of Cincinnati Transplant Tumor Registry pts transplanted for cholangiocarcinoma -34% living at date of publication -51% recurrence, 4% survival with recurrence -1,2, & 5 yr survival estimates 72, 48, & 23%

9 OLT for Cholangiocarcinoma 1997 Meyer et al. 6 Retrospective review of Cincinnati Transplant Tumor Registry pts transplanted for cholangiocarcinoma -34% living at date of publication -51% recurrence, 4% survival with recurrence -1,2, & 5 yr survival estimates 72, 48, & 23% 1998 Iwatsuki et al. 7 Retrospective analysis of Univ of Pittsburg experience of hepatic resection vs OLT -n=72, 38 w OLT -1, 3, 5yr survival: 60, 32, 25%.

10 OLT for Cholangiocarcinoma 2000 Figueras et al. 8 Spanish retrospective analysis -n=28, 20 resections, 8 OLT -5 YSR of 36% w OLT

11 OLT for Cholangiocarcinoma 2000 Figueras et al. 8 Spanish retrospective analysis -n=28, 20 resections, 8 OLT -5 YSR of 36% w OLT 2001 Shimoda et al. 9 Los Angeles retrospective analysis of all OLT at 2 sites:ucla and Cedars Sinai -n=25, 1 & 3 year survival rates of 71 & 35% -1&3 year disease-free survival 67 and 42% -Affecting disease-free survival: tumor size (>3cm), extension to other organs, single versus multiple nodules.

12 OLT for Cholangiocarcinoma 2003 Robles et al. 10 Spanish retrospective multicenter study. -n=36 OLT for hilar cholangiocarcinoma -53% recurred. 1,3 & 5 YSR of 82, 53 & 30%

13 OLT for Cholangiocarcinoma 2003 Robles et al. 10 Spanish retrospective multicenter study. -n=36 OLT for hilar cholangiocarcinoma -53% recurred. 1,3 & 5 YSR of 82, 53 & 30% 2005 Ghali et al. 11 Canadian retrospective study -n=10 during period during 1996 to All stage I or II, none w +LN -2/10 survived, actuarial 3 yr SR of 30%

14 Neoadjuvant therapies: Chemo/Radiotherapy 2002 Sudan et al. 12 Prospective trial of intraluminal bile duct irradiation (6000 cgy) and systemic chemotherapy (5-FU), followed by OLT. -Neoadjuvant therapy provided daily until transplant. -n=17, 6 inoperable, 11 OLT. Mean age 45 -median waiting time 87d ( days).

15 Neoadjuvant therapies: Chemo/Radiotherapy 2002 Sudan et al. -5 of 11 patients (45.5%) alive at end of study -mean survival 4.2 years -mean survival of 6 pts who died: 0.6 years Chemotherapy and radiotherapy preceding OLT represents a significant contribution to early postoperative fatality.

16 Neoadjuvant therapies: Chemo/Radiotherapy 2005 Rea et al. 13 Prospective study of neoadjuvant therapy with OLT to 2004.

17 2005 Rea et al. 1, 3 & 5 YSR of all 71 pts 79, 61, and 58% 1, 3 & 5 YSR of 38 OLT pts 98, 86, and 81%

18 Neoadjuvant therapies: Chemo/Radiotherapy 2005 Rea et al. Problems with study 1. Mean age disparity in control vs OLT group -63 years old versus /38 explanted livers free of residual tumor 3. Establishment of diagnosis in treatment group made by brush cytology OR CA 19-9 greater than 100ng/ml w radiographic malignant stricture 4. 5 year actuarial survival estimates of 14 patients treated nonsurgically greater than that of resection patients.

19 Neoadjuvant therapies: Chemo/Radiotherapy 2005 Rea et al. Critical conclusions 1. Control resection group was retrospective review of resection during same time period 2. Chemo- and radiation therapy without resection better than resection. 3. No attempt at using neoadjuvant therapy in combination with resection may be unrealistic. 4. Burden of imposing operable share of 4000 cases of cholangiocarcinoma diagnosed annually. 1

20 UNOS/OPTN Data for Liver Transplantation 5 7/01/2005 to 6/30/2006 National figures On waitlist 17,492 Total OLT 6,550 Transplant rate 38% Died on waitlist without transplant within one year of listing 9.4% = 1047 people.

21 Conclusions Prior studies prove failure of cholangiocarcinoma as an indication for OLT Neoadjuvant therapies in combination with OLT have shown success, but no trials to date with Mayo protocol and resection Our burdened organ transplantation system will be taxed by cholangiocarcinoma as new indication for OLT Is there a Milan Criteria/UCSF Criteria extractable from Mayo Study?

22 References 1. M Feldman (ed.) Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed CHAPTER 66 Tumors of the Gallbladder, Bile Ducts, and Ampulla. W.B. Saunders, St. Louis CM Townsend (ed.) Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice. 17 th ed Chapter 52 The Biliary Tract. W.B. Saunders, St. Louis RS Chamberlain and LH Blumgart. Hilar Cholangiocarcinoma: A Review and Commentary. Annals of Surgical Oncology. 2000; 7: FC Brunicardi. Schwartz s Principles of Surgery. 8 th ed Chapter 31 Gallbladder and the Extrahepatic Biliary System. McGraw-Hill, New York Scientific Registry of Transplant Recipients, Accessed March 29, CG Meyer, I Penn, and L James. Liver Transplantation for Cholangiocarcinoma: Results in 207 patients. Transplantation. 2000; 69: S Iwatsuki, S Todo, JW Marsh, JR Madariaga, RG Lee, I Dvochik, JJ Fung, and TE Starzl. Treatment of Hilar Cholangiocarcinoma (Klatskin Tumors) with Hepatic Resection or Transplantation. Journal of the American College of Surgeons. 1998; 187: J Figueras, L Llado, C Valls, T Serrano, E Ramos, J Fabregat, A Rafecas, J Torras and E Jaurrieta. Changing Strategies in Diagnosis and Management of Hilar Cholangiocarcinoma. Liver Transplantation. 2000; 6:

23 References 9. M Shimoda, DG Farmer, SD Colquhoun, M Rosove, RM Ghobrial, H Yersiz, P Chen and RW Busuttil. Liver Transplantation for Cholangiocellular Carcinoma: Analysis of a Singer-Center Experience and Review of the Literature. Liver Transplantation. 2001; 7: R Robles, J Figueras, VS Turrion, C Margarit, A Moya, E Varo, J Calleja, A Valdivieso, JC Garcia-Valdecasas, P. Lopez, M. Gomez, E de Vicente, C Loinaz, J Santoyo, D Casanova, A Bernardos, JA Fernandez, C Marin, P Ramirez, FS Bueno, E Jaurrieta, and P Parrilla. Liver Transplantation for Hilar Cholangiocarcinoma: Spanish Experience. Transplantation Proceedings. 2003; 35: P Ghali, PJ Marotta, EM Yoshida, VG Bain, D Marleau, K Peltekian, P Metrakos and M Deschenes. Liver Transplantation for Incidenctal Cholangiocarcinoma: Analysis of the Canadian Experience. Liver Transplantation. 2005; 11: D Sudan, A DeRoover, S Chinnakotla, I Fox, B Shaw Jr, T McCashland, M Sorrell, M Tempero and A Langnas. Radiochemotherapy and Transplantation Allow Long-Term Survival for Nonresectable Hilar Cholangiocarcinoma. American Journal of Transplantation. 2002; 2: DJ Rea, JK Heimbach, CB Rosen, MG Haddock, SR Alberts, WK Kremers, GJ Gores, and DM Nagorney. Liver Transplantation with Neoadjuvant Chemoradiation is More Effective than Resection for Hilar Cholangiocarcinoma. Annals of Surgery. 2005; 242: