2. Decision-Making Analysis for Surveillance
Population at Risk:
PSC
Surveillance Strategy:
Available
Accessible
Acceptable
Early Detection:
Treatment
Improved Outcomes:
Survival
Cost Effectiveness

3. PSC: Important CCA Risk Factor
26%
37%
37%
Proportion of all CCAs (%) 1 10
Time since PSC Diagnosis (years)
Leading source of mortality (1/3rd all deaths)
10-15% lifetime risk
Annual incidence ~1-2%
↑ CCA: late onset PSC, longer IBD duration.
↓ CCA: small duct & pediatric patients (very rare)
Weismuller TJ,. Gastroenterology 2017
Gulamhusein AF. Am J Gastroenterol 2016
Boonstra K, et al. Hepatology 2013
Eaton JE, J Gastroenterol Hepatol 2017

4. MRI/MRCP Imaging Modality of Choice for pCCA
Sensitivity
Specificity
Ultrasound
57% -
CT scan
75%
79%
PET Scan*
55%
33%
MRI/MRCP
88%
85%
Mass lesion with delayed venous enhancement nearly 100% specific for CCA
Alkhawaldeh Clin Nucl Med 2011
Schramm, Eaton Hepatology 2017

7. CP

8. Diagnosis

9. ROC for CA 19-9 in Identifying Cholangiocarcinoma in PSC41
128
100
180
Chalasani et al: Hepatology 31:7-11, 2000
Sensitivity
200
CA 19-9>100
Sensitivity 75%
Specificity 80%
1-specificity CP

11. Causes of Elevated CA 19-9 in PSC Patients without Cholangiocarcinoma
Normalization after endoscopic treatment n=7
Extrahepatic malignancy n=1
Persistent
Cholestasis
n=5
Recurrent
bacterial cholangitis n=6
Sinakos et al.
Clinical Gastroenterology and Hepatology 2011

12. Routine Cytology
Normal Atypical
Suspicious Positive

13. Limitations of Conventional Cytology
Difficult to access and obtain specimens
Cancers are highly desmoplastic
Specimens are frequently paucicellular
Diagnostic criteria are subjective
Sensitivity for malignancy 10-40%
Specificity ~100% - Still a Gold Standard

14. FISH chrom 3= red, chrom 7= green, chrom 17= aqua, locus 9p21= gold
Normal
Polysomy >5 cells
2 signals per color
≥ 2 signals in ≥ colors

15. Conventional Cytology and FISH Polysomy: PSC-Associated Strictures
Sensitivity
Specificity
100
100 % 47 18

17. Unresectable, perihilar
Criteria for LTx
Unresectable, perihilar
Mass, radial diameter <3 cm, no cut off for longitudinal diameter
If PSC, any ductal tumor <3 cm CP

20. Treatment Protocol External beam radiation therapy Brachytherapy
Capecitabine
Hand Assisted Laparoscopy
Liver transplantation

21. Recurrence-Free Survival: PSC vs. non-PSC
82% (76-88)
72% (63-81)
62% (48-76)
Recurrence-free survival (%)
70% (58-82)
51% (37-65)
51% (37-65)
Primary sclerosing cholangitis (PSC)
P=0.06
No PSC
Years
No. at risk
Cumulative no. events
PSC
No PSC
No. at risk
Cumulative no. events
Murad et al: Gastroenterology, 2012
©2012 MFMER |

22. Suspicious Cytology, FISH (-)
Indeterminate Stricture on MRI/MRCP
ERCP with Biopsy + Cytology + FISH
Cytology/Biopsy (+)
Cytology/Biopsy (-)
FISH (polysomy)
Suspicious Cytology, FISH (-)
Cytology/Biopsy, FISH
All (-)
CCA
CA19-9
≥ 129 U/mL
CA19-9 <129 U/mL
MRI/MRCP Surveillance
How do we synthesize that information and apply it to our clinical practice. This illustrates a guidance algorithm
Repeat ERCP
Probable CCA
Cytology (+)
Cytology (-)
FISH (polysomy)
Cytology (-)
FISH (-)
Probable CCA
MRI/MRCP surveillance

23. CCA Surveillance in PSC