Tratamiento endoscópico de la CEP. En quien como y cuando?
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1 Tratamiento endoscópico de la CEP. En quien como y cuando? Andrés Cárdenas, MD, MMSc, PhD, AGAF, FAASLD GI / Liver Unit, Hospital Clinic Institut de Malalties Digestives i Metaboliques University of Barcelona Barcelona, Spain
2 Primary Sclerosing Cholangitis ü Chronic cholestatic liver disease ü Characterized by stricturing of intra/extra- hepatic biliary tree ü Variable rate of progression ü Diagnosis of exclusion ü Unclear pathogenesis genetic and environmental risk factors Hirschfield GM et al. Lancet 2013
3 Diagnosis Combination of : Cholestatic biochemical profile multifocal strictures on cholangiography exclusion of secondary sclerosing cholangitis ERCP: Gold standard, but has side effects (more therapeutic than diagnostic) MRCP Considered the initial diagnostic test of choice, sensitivity (80%) and specificity (88%) AASLD Guidelines, Hepatology. 2010
4 Diagnosis Chronic cholestasis Multifocal strictures on cholangiogram Liver biopsy seldom required* Asymptomatic Pruritus Symptoms of advanced liver disease Inflammatory bowel disease? Small duct PSC Overlap cases Labs: ALP, autoantibodies, high IgG, high IgM (50%); 10% elevated IgG4 High IgG4 possibly associated with faster progression
5 MRCP Is The Preferred Imaging Modality ERCP MRCP False- Positives MRCP: cirrhosis ERCP: Incomplete biliary distension False- Negatives MRCP: Very mild/early changes ERCP: High grade strictures Berstad et al CGH 2006 Talwalkar et al Hepatology 2004
6 MRCP is good, but beware of overcall!
7 Differential Diagnosis Cholangiocarcinoma Choledocholithiasis IgG 4 related sclerosing cholangitis AIDS cholangiopathy Ischemic cholangitis Portal hypertensive biliopathy Diffuse intrahepatic metastasis Surgical biliary trauma Recurrent pyogenic cholangitis Recurrent pancreatitis Sclerosing cholangitis in critically ill Intra- arterial chemotherapy
8 Strictures
9 Clinical Picture IgG4- Related Sclerosing Cholangitis ü Biliary manifestation of IgG4- related disease ü Most are male (8M : 1F) ü Middle aged ü Obstructive jaundice; pruritus ü 90% have pancreatic involvement: anorexia, steatorrhea, weight loss ü History of allergies/ atopy; high IgE in 40-60% ü Presence of IBD more suggestive of PSC ü 5% of patients with IgG4- SC have IBD Beurs U, et al Dig Dis. 2015;;
10 Diagnosis HISORt Criteria Diagnostic Criterion Histology of bile duct Imaging of bile duct Serology Other organ involvement Response to Steroids Description Bile duct bx with > 10 IgG4+ cells/hpf (or >50 if surgical specimen) One or more strictures IH, proximal EH, or intrapancreatic. Fleeting biliary strictures Increased IgG 4 levels Pancreas classic features of AIP, or suggestive features* Retroperitoneal fibrosis Renal lesions (low attenuation, round, wedge- shaped or diffuse patchy) Salivary /lacrimal gland enlargement Normalization of enzymes and resolution of strictures
11 ACG Guidelines - PSC Recommendationsfor Diagnosis MRCP is preferred over ERCP Liver biopsy is not necessary Liver biopsy recommended in cases of suspected small duct PSC or to exclude other conditions, such as overlap with autoimmune hepatitis Anti- mitochondrial antibody can help exclude PBC Test for IgG4 at least once Lindor KD et al. Am J Gastro 2015
12 Endoscopic Therapy Who and When Abnormal liver tests and right upper quadrant pain Pruritus Cholangitis Dominant strictures and cholestasis Common bile duct stones Strictures and alarm symptoms Law R, Baron TH. CLD 2014 Thosani, Banerjee. Clin Liv Disease 2015
13 Endoscopic Therapy - Goals Improve liver function, minimize symptoms, and delay the need for liver transplantation. Reduce the serum alkaline phosphatase level to below 1.5 times the upper limit of normal Improved survival and a reduced risk of CCA in patients with PSC Law R, Baron TH. CLD 2014 Thosani, Banerjee. Clin Liv Disease 2015
14 Endoscopic Therapy How? 1. Sphincterotomy always perform, but not effective not alone 2. Stricture dilation alone *preferred 3. Dilation and short term stenting Refractory strictures and acute cholangitis Supported by AASLD and ACG guidelines Modha. World J Hepatol Lindor KD et al. Am J Gastro 2015 AASLD Guidelines, Hepatology. 2010
15 Therapy of strictures ERCP with balloon dilation with diameters of 4-8 mm Dilate only the dominant stricture Follow up with ALP and liver enzymes. Success > 80% AASLD and ASGE recommend antimicrobial therapy before ERCP Law R, Baron TH. CLD 2014 Thosani, Banerjee. Clin Liv Disease 2015 Lindor KD et al. Am J Gastro 2015
16 Dominant Strictures Stenosis with a diameter of 1.5 mm in the CBD or 1 mm in the intra- or extrahepatic ducts First ERCP session Sphincterotomy At 1-2 weeks Balloon Dilate to 4 mm Re- dilate (4-6 mm) Insert Plastic Stent (10Fr) Follow up 1. REFRACTORY STRICTURES AFTER FAILURE OF DILATION * twice 2. CHOLANGITIS Lindor KD et al. Am J Gastro 2015 AASLD Guidelines, Hepatology. 2010
17 Endoscopic therapy (A) Dominant strictures (B) Balloon dilatation of the strictures. (C) Placement of a 10F plastic biliary stent above the hilar stricture. (D) Stricture resolution noted on follow- up cholangiogram.
18 Dominant Strictures Stenosis < 1.5 mm in the CBD or < 1mm in the hepatic ducts within 2 cm from bifurcation Occur in 60% May cause sudden worsening with jaundice and cholangitis Up to 40 % may develop DS in 5 yr of follow up More frequently benign, but 22-26% are malignant Need to rule out CCA Culver EL and Chapman R. AP&T 2011; Chapman MH et al. Eur J Gastro & Hepatol 2012; Rudolph et al. J Hepatology 2009; Tischendorf et al. Endoscopy 2006; Lindor KD AJG 2015
19 Dominant Strictures: Role of endoscopic Improvement in jaundice Reduced rates of hospitalization Radiological improvement of strictures Retrospective studies show reduced mortality compared to predicted survival per Mayo Risk Score Dilatation +/- short term stenting preferred therapy Stiehl A. Semin Liver Dis 2006; Johnson GK et al. GIE 1991; Lee JG et al. Hepatology 1995; Kaya M et al AJG 2001; Balayut et al. GIE 2001; Gluck et al J Clin Gastroent
20 Bacterial Cholangitis May be the initial presentation of PSC Associated with bacterial colonization of the biliary tree Risk Factors: dominant strictures intraductal stones endoscopic/percutaneous intervention surgical exploration Often require therapeutic drainage with stent in addition to antibiotics Culver EL and Chapman R. AP&T 2011
21 Complications of ERCP 7.3% to 10%. Hospitalization > 24 hours in 10 % Cholangitis 4% Pancreatitis - 5-7% Duct perforation Liver abscess J Clin Gastroenterol 2008;42(9): J Hepatol 2009;51(1): Am J Gastroenterol. 2009;104(4):855.
22 ACG Guidelines PSC Endoscopic Management -ERCP with balloon dilatation is recommended for dominant strictures causing pruritus and/or cholangitis to relieve symptoms -PSC with dominant stricture seen on imaging should have ERCP with cytology/bx/fish to exclude cholangiocarcinoma -PSC patients undergoing ERCP should always receive prophylactic antibiotics -Routine stenting after dilatation is not required. Short term stenting may be needed for severe stricture
23 Beware of Cholangiocarcinoma CCA develops in 10% to 15%of patients with PSC Meta- analysis (>700 patients) - brush cytology is highly specific (97%) but has poor sensitivity (30-40%) In addition to routine cytologic evaluation, FISH (fluorescent in situ hybridization test) has sensitivity of 73% and specificity of 95%. Thosani, Banerjee. Clin Liv Disease 2015
24 ACG Guidelines - Surveillance Surveillance Strategies: Hepatobiliary and GB CA Based on expert opinion, very low quality of evidence Cross sectional imaging every 6-12 months Serum CA 19-9 every 6-12 months Cholecystectomy for polyps > 8 mm Future direction: targeted screening based on risk assessment of genetic markers Current guidelines do not support surveillance for cholangiocarcinoma in children Lindor KD et al. AJG 2015
25 Summary PSC is a diagnosis of exclusion MRCP is the preferred initial diagnostic test ERCP confirms diagnosis and allows therapy Endoscopic therapy in indicated in those with: Dominant strictures, cholestasis, cholangitis and CDB stones ERCP is the preferred 1 st line therapy with dilation of the stricture alone ERCP with dilatation and short term stenting is indicated for refractory strictures and those acute cholangitis CCA should always be ruled out
26 Thanks for your attention!
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