Liver Transplantation for Hilar Cholangiocarcinoma

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

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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

• 1980s Liver txp was used for unresectable tumor,
  only 10-20 survived gt5years.
• CCA contraindication for oltx

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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 CA19-9gt100 or
  FISH polysomy

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Indeterminate Diagnostic Criteria

• FISH trisomy ( 7 or 3)
• Dysplasia
• DIAgt1.8 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

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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.

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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.

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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 exception22 in Region 7. 10 MELD upgrade
  every 3 months if not transplanted

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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.

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Outcomes

• 1993-2008167 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

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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 ( N111)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).

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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 lt3cm diameter on imaging
• imaging studies to r/o mets
• negative exploratory lap
• primary tumor cannot be biopsed

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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.

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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.

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Patient Case Study

• Patient went thru this protocol, exploratory lap
  was negative. MELD22
• Got exception to 25 after 3 months
• Transplanted 4 months after getting to list
• CA19-9125. Agelt45
• Out 3 years to date. No recurrence

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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 20022
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 10S65-S68. Rea,
DJ.,et.al,Liver Transplantation with Neoadjuvant
Chemoradiation is More Effective than Resection
for Hilar Cholangiocarcinoma. Annals of
Surgery2423,Sept 2005 Lazaridis KN, Gores GJ.
Semin Liver Dis.2006 Feb26(1)42-51 Heimbach,
JK, et.al.,Transplantation 2006 Dec
2782(12)1703-7
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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