Post on 04-Dec-2014
description
Liver Transplantation for Hilar Cholangiocarcinoma
Robin D Kim, MDExecutive Medical Director, Transplant Service Line
Director, Hepatobiliary Cancer ProgramHuntsman Cancer Institute and the University of Utah
The Cholangiocarcinoma FoundationFebruary 27 to 28, 2014
Surgical Options for Cholangiocarcinoma
- R0 resection or LT currently the only curative treatments for CCA
- 20% of patients who present with CCA are candidates for R0 surgery
- Distribution: Upper Extrahepatic/Hilar (UEH) 40-60%, Lower Extrahepatic (LEH) 30%, Intrahepatic (IH) 10%
- Location determines the operation required- UEH/Hilar requires liver/bile duct
resection or liver transplantation- LEH requires
pancreaticoduodenectomy- IH requires liver resection
- R0 candidacy is ascertained at a comprehensive Hepatobiliary/LT Center
IH
UEH/Hilar
LEH
LT for Hilar CCA- Early results for LT alone for CCA were uniformly poor due to a high incidence of recurrence and
mortality- Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 2000
- Protocol for neoadjuvant chemoXRT for unresectable hilar CCA then LT began at the Mayo Clinic- From 1993 – 2002, 38 pts receiving neoadjuvant tx then LT for unresectable hilar CCA were
compared to pts who were resected. LT provided superior outcomes, with 5-yr survival for LT vs resection of 82% vs 21%.
- Rea D, Heimbach JK, Rosen CB, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg 2005; 3:451–461.
- Follow up data on from 2006 showed that in 65 pts undergoing neoadjuvant tx then LT with mean follow-up of 32 months, 1 yr and 5 yr survival of 91% and 76%, respectively. These results are similar to those achieved for other standard indications for LT such as HCC and HCV cirrhosis.
- Heimbach JK, Gores GJ, Haddock MG, et al. Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma. Transplantation 2006; 12:1703–1707.
- A similar protocol employing higher dose brachytherapy without EBRT was undertaken at the University of Nebraska.
- Hassoun Z, Gores GJ, Rosen CB, et al. Preliminary experience with liver transplantation in selected patients with unresectable hilar cholangiocarcinoma. Surg Oncol Clin N Am 2002; 11:909–921.
Patients with hilar CCA Stage I or II (AJCC 5th Ed) may be considered for neoadjuvant chemoradiation followed by LT if the following criteria are met.
I. Inclusion Criteria (A, B, C must all be met) A) Patients with unresectable CCA (per experienced HPB surgeon) and/or CCA in PSC B) Dx of CCA established by (1 and 2 must be met) 1) CT, MRI/MRCP demonstrating an malignant-looking mass < or = 3 cm or a dominant stricture at the extrahepatic hilar bile duct and above the cystic duct 2) CCA confirmed by a) an intraluminal brush cytology or intraluminal biopsy showing cancer or suspicious cells, or b) biliary aneuploidy demonstrated with fluorescent in situ hybridization (FISH). In the absence of histologic confirmation, a Carbohydrate antigen 19-9 (CA 19-9) level greater than 100 ng/ml will be sufficient to diagnose CCA. II. Exclusion Criteria 1) Pre-treatment imaging demonstrating suspicious disease outside of the hilar bile duct (including skip met into the liver parenchyma, distant nodes, chest metastases) 2) Previous chemo or XRT, uncontrolled infection, a previous malignancy other than skin or cervical cancer within 5 years, medical conditions precluding LT, extrahepatic disease (including regional lymph node involvement), and operative biopsy or attempted resection of the tumor. 3) Patients with hilar tumors extending below the cystic duct. Vascular encasement and tumor size are not included in exclusion criteria. 4) Post-chemoradiation imaging or surgical staging demonstrating nodal disease, metastases, peritoneal metastases, extent of bile duct cancer below the cystic duct.
LT for Hilar CCA at the U of U and HCI
A) Pre-treatment workup:CT abdomen/pelvis dual phase or MRI with contrast and MRCP, 2) CT Chest, 3) Bone Scan, 4) ERCP with brushings and or biopsy with FISH, 5) CA 19-9, CEA, 6) EUS with biopsy of suspicious lymph nodes.B) Neoadjuvant chemo-radiationPTC guided flexible catheter will be inserted and remain for the entire protocol. EBRT administered to a target dose of 4500 cGy in 25 fractions with IV 5-FU at 500 mg / m2 as a daily bolus for the first 3 days of radiation. Two to 3 weeks after EBRT, a transluminal boost of radiation delivered using a transcatheter Iridium-192 brachytherapy wire, with a target dose of 2000cGy, given in 4 treatments over 2 days. A total of 4 radiation treatments, 500 cGy each, will be delivered over two days, with each treatment at least 6 hours apart. Total max boost dose of 14.4 Gy in 8 fractions. Following brachytherapy, patients will be treated with oral capecitabine (2000 mg/m2 per day in 2 divided doses, 2 out of every 3 weeks) until LT. C) Pre-listing assessment (4 to 6 weeks after chemoXRT and before listing): CT chest, abdomen and pelvis with IV contrast, 2) CA 19-9, CEA, 3) EUS with biopsy of any suspicious nodes. If EUS is not possible, then operative lymph node biopsy is required. 4) Operative staging 6 weeks after completion of chemoXRT and before listing.D) Follow-up while on the liver transplant list: Submission of recertification and upgrade per UNOS. This would include a CA 19-9, CEA and MRCP q 4 months, 2) Presentation of such recertification studies at Liver Tumor Planning Conference at the HCI.E) Liver Transplant
Ref: Rea DJ, Heimbach JK, Rosen CB, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005; 242: 451-461.
LT for Hilar CCA at the U of U and HCI
• LT for Hilar CCA Program began as a clinical trial in 2006• Program approved by UNOS for exception point accrual in 2012• 9 of 9 patients successfully transplanted since official
designation• 89% overall survival to date• All survivors in excellent health
LT for Hilar CCA at the U of U and HCI
Selected CCA-related Publications from the U of U and HCI
Darwish MS, Kim WR, Harnois DM, et al. Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology. 2012 Jul;143(1):88-98.e3
Schwartz JJ, Thiesset HF, Clayton F, et al. Using the modern Silverhawk™ atherectomy catheter to characterize biliary structures that appear malignant: review of initial experience. HPB (Oxford). 2011 Nov;13(11):823-9. doi: 10.1111/j.1477-2574.2011.00376.x.
Schwartz JJ, Sorensen JB, Kim RD (2013). Selection of Patients for Resection and Liver Transplantation. In Lau, WY (Eds.), Hilar Cholangiocarcinoma. New York: Springer.
Schwartz JJ, Thiesset HF, Hutson W, et al. Complete Resolution of a Malignant Biliary Stricture using Combined Neoadjuvant Chemoradiation and Brachytherapy Boost Prior to Orthotopic Liver Transplantation. Journal of Liver: Disease & Transplantation (Accepted for publication).
Hepatobiliary Cancer Research Program at the U of U and HCI
• Hepatobiliary Cancer group May 2013 was officially recognized as a Disease Oriented Team at the HCI to cific funding received for Hepatobiliary cancer research.
• Hepatobiliary cancer investigators are currently looking:• at a variety of conditions predisposing patients to cancer and genetic analysis
of molecular components in tissue and blood. Our staff currently consents patients and collects samples to ensure we can work to provide answers to all of the questions that cancer provides.
• We are currently looking at inflammatory bowel disease blood and tissue samples to potentially identify common molecular signatures with Cholangiocarcinoma.
• Furthermore, we are conducting epidemiological studies to determine pre-cursing diseases to Cholangiocarcinoma.
Hepatobiliary Research Program continued…
Hepatobiliary Patient Advocacy
Annual patient advocacy support meetings held in September
Annual newsletters and education flyers highlighting patients and research
Advocacy walks as part of the Huntsman Cancer Institute to raise funds for Hepatobiliary Cancers
Clinical program
The University of Utah and Huntsman Cancer Institute have been able to attract a robust Cholangiocarcinoma patient population due to the combined specialties found at an academic center.
We are able to offer our patients first line defense against hepatobiliary cancer with liver transplantation and resection. Furthermore, we are also able to provide chemoembolizations and radiation therapy.
Hepatobiliary Cancer Program
Surgeons, Medical Oncologists, Hepatologists, Radiologists, Radiation Oncologists, Gastroenterologists, Interventional Radiologists, Social Workers, Nurses, Coordinators, and other clinical staff work together to ensure patients get the best care possible.