Transcript Liver Transplantation for Hilar Cholangiocarcinoma - wi

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
• FISH positive for polysomy
• Presented with weight loss, obstructive
jaundice and abdominal discomfort
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%
Liver Transplantation
• 1980’s Liver txp was used for unresectable
tumor, only 10-20% survived >5years.
• CCA –contraindication for oltx
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 CA199>100 or FISH polysomy
Indeterminate Diagnostic Criteria
•
•
•
•
FISH trisomy ( 7 or 3)
Dysplasia
DIA>1.8 in isolation(FISH neg,cyt neg)
FISH polysomy in absence of malignantappearing stricture
• Malignant-appearing stricture in absence
of mass lesion, positive cytology, biopsy,
elevated CA19-9 or FISH polysomy
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%.
Mayo Protocol Neoadjuvant
Therapy
• Neoadjuvant therapy (4000-4500 cGy) is
administered by external beam radiation in 30
fractions
• Followed by transcatheter radiation (20003000cGy) 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.
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
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.
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
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).
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
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.
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.
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
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
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