PowerPoint Presentation Titledrpauthor: WTBKLast, AB SubdrpJob

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CP1081584-1
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Incidence of Cholangiocarcinoma
Cumulative incidence ofcholangiocarcinoma ()
Years since PSC diagnosis
CP1042831-1
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Relationship Between the Natural History of a
Disease and Effective Screening
Ineffectivetherapy
Biologiconset
Earlyclinicaldiagnosis
Usualclinicaldiagnosis
Effectivetherapy
CP1164484-1
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CP1081584-2
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ROC for CA 19-9 in Identifying Cholangiocarcinoma
in PSC
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128
100
180
Sensitivity
200
CA 19-9gt100 Sensitivity 75 Specificity 80
Chalasani et alHepatology 317-11, 2000
1-specificity
CP925977-1
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Performance for Routine Cytology Interpretation
Harewood et al Am J Gastro, 2004
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Advances in Diagnostic Modalities
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Digital Image Analysis Improves the Diagnostic
Yield of Brush Cytology

• Feulgen dye to stain DNA
• Employs computer-assisted technology to assess
  DNA content of cells
• Quantitates ploidy at the single cell level
• Aneuploidy malignancy

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Fluorescent In Situ Hybridization (FISH)

• Fluorescent hybridization oligonucleotides
• chromosome 3
• chromosome 17
• chromosome 7
• locus 9p21

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Prospective Study of DIA vsBrush Cytology

• Consecutive patients with bile duct strictures
  (n97)
• Classification of benign vs malignant
• Surgical specimens
• Follow-up

CP1037610-6
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Sensitivity and Specific of Cytology, DIA, and
FISH for Malignant Biliary Strictures
Percent
Cytology
DIA
FISH
N130, 69 malignant and 61 benign
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FISH

• Polysomy of 2 or more chromosomes
• cholangiocarcinoma
• Trisomy of chromosome 7 can be observed without
  cholangiocarcinoma
• - 50 no cancer
• - ? Early marker of neoplasia

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CEP7/EGFR Probe
PROBES
CEP7Green EGFRRed
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Hypothesis
EGFR amplification
Trisomy 7
EGFRinhibition
Growthadvance
Cancer
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PSC Screening?
ERCP with cytology for FISH (1-2 years)

Trisomy 7
EGFR Inhibitor
? Chemoprevention
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Position Emission Tomography(PET)

• ? Cholangiocarcinoma

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Utility of PET scanning in cholangiocarcinoma
(n21)

• Primary tumor
• sensitivity 92
• specificity 93
• Metastases
• sensitivity 15

Kluge, et al, Hepatololgy, 2001
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Initial Diagnosis of Symptomatic PSC
PET scan
?

• Brushings/biopsies
• DIA
• FISH

PSC
Serum CA 19-9
CP1037610-3
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Evaluation of Indeterminate Stricture
Pathology (DIA, FISH)
Postive
Negative
CA 19-9
gt100 U/mL Treat as malignant
lt100 U/mL
MRI feredex
Suspicious
Negative
PET
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Cholangiocarcinoma

• Incidence
• Risk factors
• Diagnosis
• Staging
• Treatment

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Staging Cholangiocarcinoma Periductal Extension
CP1041236-2
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Staging of Cholangiocarcinoma

• MR studies
• Cholangiogram
• Feredex
• Angiogram
• EUS
• FNA of lymph nodes

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Feredex MR

• Feredex
• Fe based
• Kupffer cells
• ? signal on MR
• Allows visualizaton of bile duct tumors

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EUS and Staging Cholangiocarcinoma
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Lymph Node
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Utility of EUS in the Staging of
Cholangiocarcinoma

• 30 patients
• Operative candidates
• Negative CT scans for nodal metastases
• EUS with FNA
• Positive in 17

CP1037610-2
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Cholangiocarcinoma

• Incidence
• Risk factors
• Diagnosis
• Staging
• Treatment

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Surgical Resction for Cholangiocarcinoma
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Survival Following Resection for Perihilar
Cholangiocarcinoma
Survival rate ()
Rea et al Archives of Surgery 13954, 2004
Time (yr)
CP1156855-2
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Liver Transplantation for Cholangiocarcinoma
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Liver Transplantation for Hepatobiliary
Malignancy in PSC
No HB-malignancy
n192
HCC
n9
GBC
Survivalprobability
n4
CCA
n17
Brandsaeter et al J Hept 40815, 2004
Years post-transplantation
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• Criteria for LTx
• Unresectable, perihilar
• Mass if present lt3 cm
• If PSC, any ductal tumor lt3 cm

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Diagnosis of Cholangiocarcinoma

• Cytology - routine cytology, positive DIA, or
  positive FISH
• Malignant appearing stricture with CA-19 gt 100
  U/L in the absence of cholangitis

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Treatment Protocol
External beam radiation therapy Brachytherapy Cape
citabine Abdominal exploration for
staging Liver transplantation
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RESULTS 1993 - 2004
71 patients
4 deaths
Irradiation 5-FU
4 disease progression
6 waiting for lap
57 staging operation
14 positive
5 awaiting transplantation
38 liver transplantation
7 deaths
31 Alive
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Patient Demographics at Enrollment into Protocol
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PATIENT SURVIVAL AFTER TRANSPLANTATION
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Patient Survival
OLT
Survival ()
No OLT
Years
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Cause of Death
Recurrent CCA 4 Sudden death 1 Complications
following LDLT 2 HAT, retransplant, bile leak,
sepsis, MOF Bile leak, sepsis
CP1084287-8
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Rationale for Screening PSC Patients for
Cholangiocarcinoma
Ineffectivetherapy
Biologiconset
Early DxERCP RC/FISH/DIA
Usualclinicaldiagnosis
? EGFRinhibition Liver Tx
CP1164484-2
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CP1081584-4
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