CP 1081584 1 Cumulative incidence of cholangiocarcinoma Incidence
- Slides: 49
CP 1081584 -1
Cumulative incidence of cholangiocarcinoma (%) Incidence of Cholangiocarcinoma Years since PSC diagnosis CP 1042831 -1
Relationship Between the Natural History of a Disease and Effective Screening Ineffective therapy Biologic onset Early clinical diagnosis Usual clinical diagnosis Effective therapy CP 1164484 -1
CP 1081584 -2
ROC for CA 19 -9 in Identifying Cholangiocarcinoma in PSC 41 128 100 180 Sensitivity 200 CA 19 -9>100 Sensitivity Specificity Chalasani et al: Hepatology 31: 7 -11, 2000 75% 80% 1 -specificity CP 925977 -1
Performance for Routine Cytology Interpretation Harewood et al Am J Gastro, 2004
Advances in Diagnostic Modalities CP 901472 - 7
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
Fluorescent In Situ Hybridization (FISH) • Fluorescent hybridization oligonucleotides chromosome 3 chromosome 17 chromosome 7 locus 9 p 21
Prospective Study of DIA vs Brush Cytology • Consecutive patients with bile duct strictures (n=97) • Classification of benign vs malignant Surgical specimens Follow-up CP 1037610 -6
Percent Sensitivity and Specific of Cytology, DIA, and FISH for Malignant Biliary Strictures Cytology N=130, 69 malignant and 61 benign DIA FISH
FISH • Polysomy of 2 or more chromosomes = cholangiocarcinoma • Trisomy of chromosome 7 can be observed without cholangiocarcinoma - 50% no cancer - ? Early marker of neoplasia
CEP 7/EGFR Probe PROBES CEP 7=Green EGFR=Red
Hypothesis EGFR amplification Trisomy 7 EGFR inhibition Growth advance Cancer CP 1164484 -3
PSC Screening? ERCP with cytology for FISH (1 -2 years) Trisomy 7 EGFR Inhibitor ? Chemoprevention
Position Emission Tomography (PET) • ? Cholangiocarcinoma
Utility of PET scanning in cholangiocarcinoma (n=21) • Primary tumor sensitivity 92% specificity 93% • Metastases sensitivity 15% Kluge, et al, Hepatololgy, 2001
Initial Diagnosis of Symptomatic PSC PET scan ? PSC Brushings/biopsies • DIA • FISH Serum CA 19 -9 CP 1037610 -3
Evaluation of Indeterminate Stricture Pathology (DIA, FISH) Postive Negative CA 19 -9 >100 U/m. L Treat as malignant <100 U/m. L MRI + feredex Suspicious Negative PET CP 1037610 -4
Cholangiocarcinoma • • • Incidence Risk factors Diagnosis Staging Treatment
Staging Cholangiocarcinoma Periductal Extension Submucosal tumor CP 1041236 -2
Staging of Cholangiocarcinoma MR studies • Cholangiogram • Feredex • Angiogram EUS • FNA of lymph nodes CP 1037610 -1
Feredex MR Feredex • Fe based • Kupffer cells • signal on MR Allows visualizaton of bile duct tumors CP 1037610 -5
EUS and Staging Cholangiocarcinoma Endoscope Lymph node metastasis CP 1041236 -1
Lymph Node
Utility of EUS in the Staging of Cholangiocarcinoma 30 patients • Operative candidates • Negative CT scans for nodal metastases EUS with FNA • Positive in 17% CP 1037610 -2
Cholangiocarcinoma • • • Incidence Risk factors Diagnosis Staging Treatment
Surgical Resction for Cholangiocarcinoma
Survival Following Resection for Perihilar Cholangiocarcinoma Survival rate (%) Rea et al: Archives of Surgery 139: 54, 2004 Time (yr) CP 1156855 -2
Liver Transplantation for Cholangiocarcinoma
Liver Transplantation for Hepatobiliary Malignancy in PSC No HB-malignancy HCC Survival probability Brandsaeter et al: J Hept 40: 815, 2004 GBC CCA n=192 n=9 n=4 n=17 Years post-transplantation CP 1156855 -1
Criteria for LTx • Unresectable, perihilar • Mass if present <3 cm • If PSC, any ductal tumor <3 cm CP 1041236 -3
Diagnosis of Cholangiocarcinoma • Cytology - routine cytology, positive DIA, or positive FISH • Malignant appearing stricture with CA-19 > 100 U/L in the absence of cholangitis
Treatment Protocol External beam radiation therapy Brachytherapy Capecitabine Abdominal exploration for staging Liver transplantation CP 1084287 -3
RESULTS 1993 - 2004 71 patients Irradiation + 5 -FU 57 staging operation 4 deaths 4 disease progression 6 waiting for lap 14 positive 5 awaiting transplantation 38 liver transplantation 31 Alive 7 deaths CP 1084287 -6
Patient Demographics at Enrollment into Protocol Characteristic Age Transplanted (n=38) 45 (+) staging lap. (n=14) 45 Male: Female 28: 10 8: 6 PSC 29 (76%) 11 (78%) IBD 10 (26%) 7 (50%) Cirrhosis 12 (31%) 6 (43%) CA 19 -9 100 13 (34%) 6 (43%) CA 19 -9 >100 3 (8%) 4 (14%)
PATIENT SURVIVAL AFTER TRANSPLANTATION
Patient Survival OLT Survival (%) No OLT Years CP 1084287 -7
Cause of Death Recurrent CCA 4 Sudden death 1 Complications following LDLT 2 HAT, retransplant, bile leak, sepsis, MOF Bile leak, sepsis CP 1084287 -8
Rationale for Screening PSC Patients for Cholangiocarcinoma Biologic onset Early Dx: ERCP + RC/FISH/DIA Usual clinical diagnosis Ineffective therapy ? EGFR inhibition Liver Tx CP 1164484 -2
CP 1081584 -4
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