PSC and ERCP

Paul R. Tarnasky, M.D.

Methodist Digestive Institute

Methodist Dallas Medical Center

PSC: Objectives

• Background

• Diagnostic options

• Treatment (Endoscopic)

• Endotherapy Complications

• Tissue Sampling

Challenging

Benign Biliary Strictures

• Postoperative stricture (OLT, biliary-enteric)

• Operative bile duct injury

• Chronic pancreatitis

• Papillary stenosis

• Radiation injury

• Traumatic injury

• Sclerosing cholangitis

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

• 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

Am J Gastroenterol 2012; 107:56-63

IgG4 cholangitis and AIP-SC overlap syndrome respond to steroids

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

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

>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

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

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

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

Diagnosis of PSC

Chapman et al. Hepatology 2010

Jaundice

ERC

• 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

MRCP Pitfall (Cirrhosis)

ERC-Cholangiography Technique

• Avoid pancreatography

• Consider wire-guided cannulation

• Sphincterotomy

• Early radiographs with minimal contrast

• Adjust scope position to visualize duct

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

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

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

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

Therapeutic ERCP Indications

Indications

•Spills

•Spasms

•Stones

•Strictures

• Endoscopic

• Retrieving

• Cutting

• Plumbing

• 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

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%)

80% at 1yr

Cumulative proportion of patients without endoscopic intervention

60% at 3yr

(Mean 11 days)

Am J Gastroenterol 1999;94:2304-2307

Am J Gastroenterol 2001; 96:1059-1066

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

Therapeutic ERCP for PSC

Clin Liver Dis 2010; 14:349-358

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

Balloon Dilation Alone

Balloon Dilation + Stenting

ERCP Complications in PSC

• Retrospective • Mayo Clinic• ERCPs in 2005• Overall 11%• Higher cholangitis

Am J Gastroenterol 2009;104:855-860

Gastrointest Endosc 2008;67:643-648

Cumulative complications per patient: PEP 4 (16%)

Gastrointest Endosc 1996;44:293-299

J Clin Gastroenterol 2008;42:1032-1039

>50% complications are PEP 106 patients had ERCP11% PEP per patient

• Laboratory (LFT, CA 19-9, IgG4)• Routine imaging (US, CT)• MRCP, EUS• ERCP Sensitivity Specificity

– Brush cytology ~50% >95%– Intraductal biopsy ~60% >95%– Cholangioscopy ~80% ~80%– Probe CLE ? ?– Combined >80%

Suspicious Strictures

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

Cholangioscopy & Biliary CLE

Intraductal Biopsies

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

Evaluation for Suspected CCA

Chapman et al. Hepatology 2010

? Laparotomy

q 6 – 12 weeks

New Method to Diagnose CCA?

Acrylonitrile, Methyl hexane, and Benzene

Gastrointest Endosc 2015;81:943-949

Cholangiocarcinoma

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

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

Bilateral Uncovered SEMS

Palliative Ablation of CCA

PSC Summary

• Varied clinical presentations

• Lack data

• Technically challenging

• Complications are common

• Limited treatment options

Not All Bad News