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Liver Transplantation for Hilar Cholangiocarcinoma

Liver Transplantation for Hilar Cholangiocarcinoma. Mary Douglas, RN, MSN,CCTC Clinical Transplant Coordinator University of Wisconsin- Madison. Case Study. 44 yo male with PSC/ UC. Dx with UC age 37, PSC at age 42 ERCP 5 years after diagnosis revealed adenocarcinoma via brushings

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Liver Transplantation for Hilar Cholangiocarcinoma

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  1. Liver Transplantation for Hilar Cholangiocarcinoma Mary Douglas, RN, MSN,CCTC Clinical Transplant Coordinator University of Wisconsin- Madison

  2. Case Study • 44 yo male with PSC/ UC. • Dx with UC age 37, PSC at age 42 • ERCP 5 years after diagnosis revealed adenocarcinoma via brushings • FISH positive for polysomy • Presented with weight loss, obstructive jaundice and abdominal discomfort

  3. Diagnosis of Cholangiocarcinoma • CCA is slow growing tumor that invades adjacent neural, lymphatic and hepatic tissue. Intertwining with bile ducts. • Brushings are 50% accurate, now use FISH ( fluorescence in situ hybridization) • Median survival of unresectable disease with only XRT is 9-12 months. • With surgical resection, median survival is 11-38 months with 5 year survival at 5-20%

  4. Liver Transplantation • 1980’s Liver txp was used for unresectable tumor, only 10-20% survived >5years. • CCA –contraindication for oltx

  5. Mayo Protocol • 1993 • Diagnosis of CCA established- • Biopsy( transluminal) positive for cancer • Positive or suspicious cytology on brush cytology • Stricture, and FISH polysomy • Mass lesion on cross-sectional imaging • Malignant-appearing stricture and CA19-9>100 or FISH polysomy

  6. Indeterminate Diagnostic Criteria • FISH trisomy ( 7 or 3) • Dysplasia • DIA>1.8 in isolation(FISH neg,cyt neg) • FISH polysomy in absence of malignant-appearing stricture • Malignant-appearing stricture in absence of mass lesion, positive cytology, biopsy, elevated CA19-9 or FISH polysomy

  7. Prior to protocol • EUS guided regional lymph node aspiration routinely before beginning neoadjuvant therapy. • The identification of lymph node metastases obviated the need for exploratory laparotomy and disqualified the patients from subsequent liver transplantation • With the introduction of EUS in 2002, the percentage of patients with a positive staging laparotomy has decreased from 30 to 15%.

  8. Mayo Protocol Neoadjuvant Therapy • Neoadjuvant therapy (4000-4500 cGy) is administered by external beam radiation in 30 fractions • Followed by transcatheter radiation (2000-3000cGy) with iridium-192 wires( brachytherapy) • These wires placed by ERCP or PTC • Infusional 5-FU is given during XRT, followed by oral capecitabine after the radiation therapy until the day of oltx.

  9. Protocol • Staging laparotomy is preformed upon completion of neoadjuvant radiotherapy. Usually within 2-3 weeks after brachy therapy. • This involves complete abdominal exploration with biopsy of any lymph nodes/nodules suspicious for tumor, examination of tumor, and routine biopsy of regional lymph nodes. At least one lymph node must be taken. (laparoscopic?) • If negative staging operation, then eligible for listing for OLTX • MELD exception=22 in Region 7. 10% MELD upgrade every 3 months if not transplanted

  10. Liver Transplantation • If LRD, do staging operation 1-2 days prior • If CAD, stage, waitlist, MELD exception • During oltx, if there is microscopic tumor involvement, a pancreaticoduodenectomy is also preformed • Unique complications with LRD vs. CAD with vessels due to XRT exposure.

  11. Outcomes • 1993-2008:167 patients • 12 deaths,2 txp elsewhere,10 received neoadjuvant rx. • 143 had irradiation and 5FU and staging • 27 were positive (19%), 2 waitlist, 1 death, 2 txp elsewhere • 111 transplants, 75 CAD,35 LRD,1 domino

  12. Outcomes • 1 -,3-, and 5-year patient survivals after the start of therapy(167) are 84%, 64% and 56%. • 1-,3-,and 5-year patient survivals after liver transplantaion ( N=111)are 96%, 83%, and 72%. No difference in survival regarding LRD vs.CAD • There have been 15 recurrences in 111 oltx (14%), occurring at a mean of 25 months after oltx (range: 7-64 months).

  13. Organ Allocation • To get MELD exception: • Transplant center submit formal patient care protocols to UNOS Liver /Intestinal Committee • Candidates satisfy accepted diagnostic criteria for CCA and be considered un-resectable on basis of technical considerations or underlying liver disease (PSC) • tumor mass <3cm diameter on imaging • imaging studies to r/o mets • negative exploratory lap • primary tumor cannot be biopsed

  14. Further investigations • OLTX is superior in outcomes to resection • Should this therapy be applied to other patients without liver disease ( PSC)? • Neoadjuvant therapy with XRT can damage bile ducts, which precludes biliary reconstruction after resection.

  15. Summary • Role of oltx in setting of CCA has undergone radical changes in past 20 years. • With rigorous patient selection,neoadjuvant XRT, operative staging and oltx, the protocol has achieved a 72% survival at 5 years. • We need to continue to work on advances in XRT, chemo agents, protocol development • Future role of this therapy for patients with resectable tumors, but outcomes not as positive as in liver transplantation.

  16. Patient Case Study • Patient went thru this protocol, exploratory lap was negative. MELD=22 • Got exception to 25 after 3 months • Transplanted 4 months after getting to list • CA19-9=125. Age<45 • Out 3 years to date. No recurrence

  17. Bibliography: Gores GJ. Cholangiocarcinoma: current concepts and insights. Hepatology 2003; 37: 961-969. De Vreede I, Steers JL, Burch PA, Rosen CB, Gunderson LL, Haddock MG, et al. Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma. Liver Transpl 2000; 6: 309-316. Sudan D, DeRoover A, Chinnakotla S, Fos I, ShawB, Jr, McCashland T, et al. Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant 2002;2: 774-779. Burak K, Angula P, Pasha TM, Egan K, Petz J, Lindor KD. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol 2004; 99: 523-526. Brandsaeter B, Isoniemi H, Broome U, Olausson M, Backman L, Hansen B, et al. Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliry malignancy. J Hepatol 2004; 40: 815-822 Heimbach J, Haddock M, Alberts S, Nyberg S, Ishitani M, Rosen C, Gores G. Transplantation for Hilar Cholangiocarcinoma. Liver Transplantation 2004; 10:S65-S68. Rea, DJ.,et.al,Liver Transplantation with Neoadjuvant Chemoradiation is More Effective than Resection for Hilar Cholangiocarcinoma. Annals of Surgery:242;3,Sept 2005 Lazaridis KN, Gores GJ. Semin Liver Dis.2006 Feb:26(1):42-51 Heimbach, JK, et.al.,Transplantation 2006 Dec 27:82(12):1703-7

  18. Bibliography • Rosen, CD, Heimbach, JK, Gores, GJ Surgery for cholangiocarcinoma: the role of liver transplantation. HPB 2008 June 1: 10(3): 186-189. • Rea, DJ, Rosen,CB,Nagorney,DM, Heimbach, JK, Gores, GJ Transplantation for Cholangiocarcinoma: When and for Whom? Surg Oncol Clin NAM 18(2009)325-337. • Heimback,JK, Gores, GJ, Haddock,MG, Alberts,SR,Pedersen, R, Kremers, W, Nyberg,Sl, Ishitani, MB, Rosen, CB. Predictors of Disease Recurrence Following Neoadjuvant Chemoradiotherapy and Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma

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