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CP1081584-1. Incidence of Cholangiocarcinoma Cumulative incidence of cholangiocarcinoma (%) Years since PSC diagnosis CP1042831-1.

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Presentation on theme: "CP1081584-1. Incidence of Cholangiocarcinoma Cumulative incidence of cholangiocarcinoma (%) Years since PSC diagnosis CP1042831-1."— Presentation transcript:

1 CP

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3 Incidence of Cholangiocarcinoma Cumulative incidence of cholangiocarcinoma (%) Years since PSC diagnosis CP

4 Relationship Between the Natural History of a Disease and Effective Screening CP Biologic onset Early clinical diagnosis Usual clinical diagnosis Ineffective therapy Effective therapy

5 CP

6 ROC for CA 19-9 in Identifying Cholangiocarcinoma in PSC Sensitivity 1-specificity CA 19-9>100 Sensitivity75% Specificity80% CP Chalasani et al: Hepatology 31:7-11,

7 Performance for Routine Cytology Interpretation Harewood et al Am J Gastro, 2004

8 CP Advances in Diagnostic Modalities

9 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 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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11 Fluorescent In Situ Hybridization (FISH) Fluorescent hybridization oligonucleotides chromosome 3 chromosome 17 chromosome 7 locus 9p21 Fluorescent hybridization oligonucleotides chromosome 3 chromosome 17 chromosome 7 locus 9p21

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14 Prospective Study of DIA vs Brush Cytology CP Consecutive patients with bile duct strictures (n=97) Classification of benign vs malignant Surgical specimens Follow-up Consecutive patients with bile duct strictures (n=97) Classification of benign vs malignant Surgical specimens Follow-up

15 CytologyDIAFISH Percent N=130, 69 malignant and 61 benign Sensitivity and Specific of Cytology, DIA, and FISH for Malignant Biliary Strictures for Malignant Biliary Strictures

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

17 CEP7/EGFR Probe CEP7=Green EGFR=Red PROBES

18 Hypothesis CP Trisomy 7 EGFR amplification Growth advance Cancer EGFR inhibition

19 PSC Screening? ERCP with cytology for FISH (1-2 years) Trisomy 7 ? Chemoprevention EGFR Inhibitor

20 Position Emission Tomography (PET) ? Cholangiocarcinoma

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22 Utility of PET scanning in cholangiocarcinoma (n=21) Primary tumor sensitivity 92% specificity 93% Metastases sensitivity 15% Primary tumor sensitivity 92% specificity 93% Metastases sensitivity 15% Kluge, et al, Hepatololgy, 2001

23 Initial Diagnosis of Symptomatic PSC CP Brushings/biopsies DIA FISH Brushings/biopsies DIA FISH PET scan Serum CA 19-9 PSC ? ?

24 Evaluation of Indeterminate Stricture CP Pathology (DIA, FISH) Postive Negative CA 19-9 >100 U/mL Treat as malignant >100 U/mL Treat as malignant <100 U/mL MRI + feredex Suspicious Negative PET

25 Cholangiocarcinoma Incidence Risk factors Diagnosis Staging Treatment Incidence Risk factors Diagnosis Staging Treatment

26 Staging Cholangiocarcinoma Periductal Extension Staging Cholangiocarcinoma Periductal Extension CP Submucosal tumor

27 Staging of Cholangiocarcinoma CP MR studies Cholangiogram Feredex Angiogram EUS FNA of lymph nodes MR studies Cholangiogram Feredex Angiogram EUS FNA of lymph nodes

28 Feredex MR CP Feredex Fe based Kupffer cells  signal on MR Allows visualizaton of bile duct tumors Feredex Fe based Kupffer cells  signal on MR Allows visualizaton of bile duct tumors

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31 Endoscope CP EUS and Staging Cholangiocarcinoma Lymph node metastasis

32 Lymph Node

33 Utility of EUS in the Staging of Cholangiocarcinoma CP patients Operative candidates Negative CT scans for nodal metastases EUS with FNA Positive in 17% 30 patients Operative candidates Negative CT scans for nodal metastases EUS with FNA Positive in 17%

34 Cholangiocarcinoma Incidence Risk factors Diagnosis Staging Treatment Incidence Risk factors Diagnosis Staging Treatment

35 Surgical Resction for Cholangiocarcinoma

36 Survival Following Resection for Perihilar Cholangiocarcinoma CP Survival rate (%) Time (yr) Rea et al: Archives of Surgery 139:54, 2004

37 Liver Transplantation for Cholangiocarcinoma

38 Liver Transplantation for Hepatobiliary Malignancy in PSC CP Survival probability Years post-transplantation No HB-malignancy HCC GBC CCA n=192 n=9 n=4 n=17 Brandsaeter et al: J Hept 40:815, 2004

39 CP Criteria for LTx Unresectable, perihilar Mass if present <3 cm If PSC, any ductal tumor <3 cm

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

41 CP Treatment Protocol External beam radiation therapy Brachytherapy Capecitabine Abdominal exploration for staging Liver transplantation External beam radiation therapy Brachytherapy Capecitabine Abdominal exploration for staging Liver transplantation

42 CP CP RESULTS patients 4 deaths 4 disease progression 5 awaiting transplantation 57 staging operation 14 positive 38 liver transplantation Irradiation + 5-FU 7 deaths 6 waiting for lap 31 Alive

43 Patient Demographics at Enrollment into Protocol CharacteristicTransplanted (n=38) (+) staging lap. (n=14) Age45 Male: Female28:108:6 PSC29 (76%)11 (78%) IBD10 (26%)7 (50%) Cirrhosis12 (31%)6 (43%) CA 19-9  (34%)6 (43%) CA 19-9 >1003 (8%)4 (14%)

44 PATIENT SURVIVAL AFTER TRANSPLANTATION

45 CP Patient Survival Survival (%) Survival (%) Years OLT No OLT

46 CP Cause of Death Recurrent CCA4 Sudden death1 Complications following LDLT2 HAT, retransplant, bile leak, sepsis, MOF Bile leak, sepsis Recurrent CCA4 Sudden death1 Complications following LDLT2 HAT, retransplant, bile leak, sepsis, MOF Bile leak, sepsis

47 Rationale for Screening PSC Patients for Cholangiocarcinoma CP Biologic onset Early Dx: ERCP + RC/FISH/DIA Usual clinical diagnosis Ineffective therapy ? EGFR inhibition ? EGFR inhibition Liver Tx ? EGFR inhibition ? EGFR inhibition Liver Tx

48 CP

49 North Dakota Beer Cooler


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