1. Gastroenterology Grand Rounds
October 31, 2013
Fellow: David Tang, M.D.
Faculty: Clark Hair, M.D.

2. Case Presentation 30 year old Hispanic woman
[2010] Diagnosed with Ulcerative Colitis
Started on Mesalamine and Azathioprine
Three flares since diagnosis each resolved after starting steroid taper

3. Case Presentation
[8/26] Presented to Houston area hospital with RUQ abdominal pain x 4 days
AST
144
ALT
266
Alk Phos
522
Total Bilirubin
4.1
Direct Bilirubin
3.6
Total Protein
7.2
Albumin
3.7

4. Case Presentation [8/26] RUQ Abdominal Ultrasound [8/29] MRCP
Hydropic gallbladder with an associated stone at the gallbladder neck. No intrahepatic or extrahepatic biliary ductal dilation.
[8/29] MRCP
Subtle contour irregularity within the intrahepatic biliary system suggesting PSC
1.2 cm segment of proximal extrahepatic common bile duct is smoothly narrowed with possible adjacent are of soft tissue prominence

5. [8/30] ERCP
1. Beading appearance of the intra and extra hepatic bile ducts 2. 2cm distal CHD/proximal CBD stricture s/p biopsies and brushings 3. S/p 10F x 7cm biliary stent placement

6. [9/4] Colonoscopy
Path: CHRONIC ACTIVE COLITIS WITH CRYPT ARCHITECTURAL DISARRAY AND CRYPT LOSS; No dysplasia, no granulomas

7. [9/23] EUS
There was an ill-defined heterogeneous hypoechoic 23 x 18mm porta hepatis lesion around the proximal-mid bile duct

8. Courtesy of Dr. Zarrin-Khameh, Pathology
FNA of the porta hepatis has large cells (red circle) with high nuclear to cytoplasmic ratio and prominent nucleoli. This is a Pap stain. Red cells are seen in the background. You can compare the size of these cells with a lymphocytes (red arrow)
Courtesy of Dr. Zarrin-Khameh, Pathology

9. Courtesy of Dr. Zarrin-Khameh, Pathology
This is the cell block (we spin down the material and make a cell block; which we treat like a small biopsy). This is H&E stain (hematoxilin and eosin). The tumor cells with high nuclear to cytoplasmic ratio and prominent nucleoli are seen. A tumor giant cell is note (green). A huge tumor cells with irregular nuclear borader and very large nucleoli is seen (blue)
Courtesy of Dr. Zarrin-Khameh, Pathology

10. Pathological Diagnosis
Cholangiocarcinoma

11. Clinical Questions
What is the epidemiological relationship of Cholangiocarcinoma to PSC?
Is concomitant IBD a risk for developing Cholangiocarcinoma? What are the other risk factors?
What is the utility of CA 19-9 in the diagnosis of Cholangiocarcinoma? How should it be used in screening patients with PSC?

12. Prevalence of CCA in PSC
Cohort Size
Prevalence
Median Follow Up
Broome
305 8%
5.3 years
Bergquist
604
13.3%
5.7 years
Boberg
394
12.2%
4.7 years
Burak
161
6.8%
11.5 years
Tischendorf
273
14.3%
6.3 years
Fevery
123
6.9%
9 years
Charatcharoenwitthaya
230
10%
4.1 years
Claessen
211
7.1%

13. Prevalence of IBD in PSC
Size
Population
Concomitant IBD
Concomitant UC
Concomitant CD
Berquist
604
Sweden
79%
69% 7%
Boberg
394
Europe
82%
65% -
Weisner
174
Minnesota
71%
Takikawa
192
Japan
21%
19.8% 1%
Kochlar 18
India
50%

14. Does concomitant IBD increase risk of CCA in PSC?
Multicenter European retrospective cohort study with 394 PSC patients
Median follow up 4.7 years
12.2% of patients developed Cholangiocarcinoma

15. Does concomitant IBD increase risk of CCA in PSC?

16. Predisposing factors for Cholangiocarcinoma in PSC
Retrospective cohort study of 161 patients with PSC at Mayo Clinic
Median follow up 11.5 years
6.8 % of patients developed Cholangiocarcinoma
History of variceal bleeding, lack of symptoms at baseline, and proctocolectomy associated with increased risk of Cholangiocarcinoma
Burak

17. Predisposing factors for Cholangiocarcinoma in PSC
Multicenter case-control study of 26 cases of Cholangiocarcinoma in PSC matched with 87 patients with PSC alone
Duration of IBD was not a significantly associated with Cholangiocarcinoma from 8 cases and 33 controls
However, a smaller case control trial showed no difference for duration of IBD. Chalasani

18. Predisposing factors for Cholangiocarcinoma in PSC
In the same study, Mayo risk score and CP class did not differ. Chalasani

19. Predisposing factors for Cholangiocarcinoma in PSC
Chalasani

20. Utility of CA 19-9 in Diagnosis of Cholangiocarcinoma
CA 19-9 cut off of > 100 U/mL was 75% sensitive and 80% specific for Cholangiocarcinoma
AUC = 0.84
Chasani

21. Utility of CA 19-9 in Diagnosis of Cholangiocarcinoma
Cross sectional study of 333 patients with PSC from 1984 to 1997
13% with Cholangiocarcinoma
CA 19-9 cut off of > 180 U/mL was 75% sensitive and 97% specific for Cholangiocarcinoma
AUC = 0.76
Siqueira

22. Utility of CA 19-9 in Diagnosis of Cholangiocarcinoma
Retrospective cohort study of 208 patients at Mayo clinic who had PSC and serial CA 19-9 measurements
Mean follow up 2.6 years
CA 19-9 cut off of > 129 U/mL was 78.6% sensitive and 98% specific for Cholangiocarcinoma
Only 2 out of 14 patients with Cholangiocarcinoma were resectable
AUC = 0.95
Levy
14/ % with CCA

23. Utility of CA 19-9 in Diagnosis of Cholangiocarcinoma
AUC
0.79
Cutoff
20 U/mL Sn 78 Sp 67
23/230
4.1 years
Charat

24. Combination of cross sectional imaging and CA 19-9 for diagnosis of Cholangiocarcinoma

25. Combination of cross sectional imaging and CA 19-9 for diagnosis of Cholangiocarcinoma

26. Proposed algorithm for screening and diagnosis of Cholangiocarcinoma