1. PSC and ERCP Paul R. Tarnasky, M.D. Methodist Digestive Institute Methodist Dallas Medical Center

2. PSC: Objectives Background Diagnostic options Treatment (Endoscopic) Endotherapy Complications Tissue Sampling

3. Challenging

4. Benign Biliary Strictures Postoperative stricture (OLT, biliary-enteric) Operative bile duct injury Chronic pancreatitis Papillary stenosis Radiation injury Traumatic injury Sclerosing cholangitis

5. Terminology Primary Sclerosing Cholangitis –Idiopathic but likely immune mediated Small-duct Sclerosing Cholangitis –Histologic diagnosis Overlap Syndromes – PSC features plus –Autoimmune hepatitis or Pancreatitis Secondary Sclerosing Cholangitis –Obstruction, Infection, Ischemia, Toxin, Histiocytosis X, IgG4 Cholangitis

6. May progress to large-duct PSC Better long-term prognosis, longer transplant-free survival May recur after liver transplant Cholangiocarcinoma is less common unless progression to large-duct PSC

7. Am J Gastroenterol 2012; 107:56-63 IgG4 cholangitis and AIP-SC overlap syndrome respond to steroids

8. Primary Sclerosing Cholangitis Chronic cholestatic liver disease - Idiopathic –Mean age at diagnosis =40yrs, ≈75% Male –Fatigue, jaundice, pruritus or no symptoms –+ANA (≈30%), +ASMA (≈60%) +ANCA (≈80%) Clinical diagnosis + cholangiopathy Decreased survival –Median survival after diagnosis ≈ 12 years –10 year survival ≈70%, 20 year survival ≈65% Potential sequelae –Cholangitis, Biliary cirrhosis, Malignancy

9. Best Pract & Research Clin Gastroenterol 25:741-752, 2011

10. >50% (up to 80%) have IBD (usually UC) –5% of IBD (colon disease) have PSC –Independent of disease activity 10X  risk for colon cancer (>10% lifetime) –Screening colon exam yearly at dx of PSC  risk for GB CA and HCC (2-5% lifetime) –annual U/S, CCX if lesion/polyp independent of size OR > 8mm PSC, IBD and Malignancy

11. PSC and Cholangiocarcinoma Risk of 1.5% per year after dx of PSC 30% of CCA dx within 2 years of PSC dx Nearly >150X  risk for CCA c/t general ≈ 20% lifetime risk for CCA Screening strategy not defined –CA 19-9 (>130 U/ml) ≈ 70% sensitivity, 98% specificity –Annual imaging

12. Cholangiography in PSC Stenosis alternating with dilation- “beaded” Diffuse intra- and extra-hepatic 25% Intra-hepatic only 5% Extra-hepatic only 5-15% Histologic only (Small-duct PSC) “Dominant Stricture” eventually in 20-50% –diameter < 1mm for CHD, < 1.5mm for CBD ? Concomitant cancer if long stricture

13. Liver Biopsy for PSC ? Not required if cholangiogram is abnormal Required to diagnose small-duct PSC –25% progress to large-duct PSC Consider if  transaminases and suspected PSC-AIH overlap syndrome

14. Diagnosis of PSC Chapman et al. Hepatology 2010 Jaundice ERC

15. MRCP had high sensitivity and specificity for diagnosis of PSC (> 80% for both) MRCP may avoid risks of ERCP Possible false + MRCP in cirrhosis Possible false - MRCP in “early PSC” Radiology 2010;256:387-396

16. MRCP Pitfall (Cirrhosis)

17. ERC-Cholangiography Technique Avoid pancreatography Consider wire-guided cannulation Sphincterotomy Early radiographs with minimal contrast Adjust scope position to visualize duct

18. Diagnosis of PSC: Summary Suspect if AMA-negative cholestasis Ultrasound to rule-out obstruction MRCP helpful (if not cirrhotic) Check IgG4 (IgG4-associated cholangitis) ANCA supportive (suspect colon disease) ANA +/- liver biopsy if  transaminases ERCP: to confirm diagnosis, jaundice, e/o dominant stricture or increased CA19-9

19. Medical Management of PSC Screen for malignancy Immunizations for viral hepatitis Screen for osteopenia q 3 years Screen for varices (if e/o cirrhosis) Monitor for fat soluble vitamin deficiency Management of pruritus (similar to PBC) Refer for OLT (≈25% recurrence in 10 yrs) –Refractory cholangitis and/or ESLD

20. Therapy for Cholangitis in PSC Antibiotic therapy –Quinolone for 10-14 days –Prophylactic cyclical for recurrent cholangitis: Quinolone and/or metronidazole for 2 weeks every 2 months UDCA is not recommended Surgical Percutaneous ERCP

21. Interventional Therapy for PSC ≈ 20 - 50% develop biliary obstruction Percutaneous therapy is effective, increased morbidity c/t endoscopic therapy, required if failed endoscopic therapy fails, more common with hilar obstruction Surgical therapy (bypass, resection or OLT) –No benefit & might worsen OLT outcomes –Consider for suspected cholangiocarcinoma or if failed endoscopic or percutaneous therapy

22. Therapeutic ERCP Indications Indications Spills Spasms Stones Strictures E ndoscopic R etrieving C utting P lumbing

23. Biliary sphincterotomy Stricture dilation (dominant strictures) –Balloon dilation –Catheter dilation Stent placement (short term) Limited data suggest improved outcomes –Improved transplant-free survival –No randomized controlled trials Therapeutic ERCP for PSC Goal: Reduce alkaline phosphatase to < 1.5X UNL

24. Gastrointest Endosc 1996;44:293-299 25 pts treated over 10 years Treated with stents +/- stricture dilation Stents removed or exchanged q 2-3 mo or if evidence of stent dysfunction Complicated by cholangitis in 10 (40%)

25. 80% at 1yr Cumulative proportion of patients without endoscopic intervention 60% at 3yr (Mean 11 days) Am J Gastroenterol 1999;94:2304-2307

26. Am J Gastroenterol 2001; 96:1059-1066

27. 171 pts with up to 20 yr f/u 96 (56%) had endotherapy Sphincterotomy Balloon Dilation q 4 wk until stricture resolved Mean 5.2 dilations (1-17) 6 (4%) developed CCA 20 (12%) underwent OLT Actuarial survival free of OLT Gastrointest Endosc 2010; 71:527-534

28. Therapeutic ERCP for PSC Clin Liver Dis 2010; 14:349-358

29. Therapeutic ERCP for PSC Biliary access (can be difficult) Balloon dilation preferred Short-term stent placement –Persistent stricture after dilation –Recent biliary sepsis Strictures >2cm proximal to CHD are ineffectively treated, ? Indicate need OLT Increased risk for post-ERCP pancreatitis

30. Balloon Dilation Alone

31. Balloon Dilation + Stenting

32. ERCP Complications in PSC Retrospective Mayo Clinic ERCPs in 2005 Overall 11% Higher cholangitis Am J Gastroenterol 2009;104:855-860

33. Gastrointest Endosc 2008;67:643-648

34. Cumulative complications per patient: PEP 4 (16%) Gastrointest Endosc 1996;44:293-299

35. J Clin Gastroenterol 2008;42:1032-1039 >50% complications are PEP 106 patients had ERCP 11% PEP per patient

36. Laboratory (LFT, CA 19-9, IgG4) Routine imaging (US, CT) MRCP, EUS ERCPSensitivity Specificity –Brush cytology ~50% >95% –Intraductal biopsy ~60% >95% –Cholangioscopy ~80% ~80% –Probe CLE?? –Combined >80% Suspicious Strictures

37. Gastrointest Endosc 2014;79:943-950 8 studies involving 828 patients with PSC Sensitivity = 68% Specificity = 70% High Cost Recommended if high pretest probability Or if standard brush cytology is negative

38. Cholangioscopy & Biliary CLE

39. Intraductal Biopsies

40. Suspect Cholangiocarcinoma Mass on surveillance imaging Increased CA 19-9 (> 130 U/mL) –80% sensitivity, 98% specificity Rapid recurrent cholestasis after endotherapy (< 12 weeks) Long-segment stricture Atypical cytology

41. Evaluation for Suspected CCA Chapman et al. Hepatology 2010 ? Laparotomy q 6 – 12 weeks

42. New Method to Diagnose CCA? Acrylonitrile, Methyl hexane, and Benzene Gastrointest Endosc 2015;81:943-949

43. Cholangiocarcinoma

44. Cholangiocarcinoma with PSC Long and/or early recurrent strictures Poor prognosis: < 20% 3 yr survival even after surgical resection Consider OLT protocol (< 3cm mass) Preoperative drainage is controversial Frequently unresectable (>80%) Confirmation of cancer is difficult (~50%) Palliation is goal –Stenting +/- Ablation

45. Palliative Stenting for Hilar CCA Define lesion to target drainage Only 25-50% of liver needs drainage Guidewire access of desired duct Opacify only ducts that are to be drained Single plastic stent preoperatively Bilateral drainage for Type II (long-term) Uncovered SEMS preferable (inoperable) Percutaneous and/or Endoscopic

46. Bilateral Uncovered SEMS

47. Palliative Ablation of CCA

48. PSC Summary Varied clinical presentations Lack data Technically challenging Complications are common Limited treatment options Not All Bad News