Andrew Y. Wang, MD A ht Idt i t Approach to Indeterminate Biliary Strictures Andrew Y. Wang, MD, FACG, FASGE Associate Professor of Medicine Co-Medical Director of Endoscopy Director of Pancreatico-Biliary Services Division of Gastroenterology and Hepatology University of Virginia Health System Clinical relevance • What is the size of a normal bile duct? – Varies at different levels – US 6-8 mm – CT 8-10 mm – Essentially unknown • What constitutes a biliary stricture? – Proximal dilation It h ti BD 40% f ll li t h ti PV – Intrahepatic BD >40% of parallel intrahepatic PV • Main question for the patient and the endoscopist: “Is this cancer?” Spencer G, Kochman ML. Dilated Bile Duct. ERCP 2008 ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology 1
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Andrew Y. Wang, MD
A h t I d t i tApproach to Indeterminate Biliary Strictures
Andrew Y. Wang, MD, FACG, FASGEAssociate Professor of Medicine
Co-Medical Director of EndoscopyDirector of Pancreatico-Biliary Services
Division of Gastroenterology and HepatologyUniversity of Virginia Health System
Clinical relevance• What is the size of a normal bile duct?
– Varies at different levels– US 6-8 mm– CT 8-10 mm– Essentially unknown
• What constitutes a biliary stricture?– Proximal dilation
I t h ti BD 40% f ll l i t h ti PV– Intrahepatic BD >40% of parallel intrahepatic PV
• Main question for the patient and the endoscopist: “Is this cancer?”
Spencer G, Kochman ML. Dilated Bile Duct. ERCP 2008
ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology
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Andrew Y. Wang, MD
Indeterminate bile duct stricture…• …when basic work-up including
t bd i l i i d ERCP ithtransabdominal imaging and ERCP with routine cytologic brushing are non-diagnostic
Victor DW, Sherman SS et al. World J Gastroenterol 2012;18:6197-6205
• …includes those without a definite diagnosis after cross sectional imaging and ERCP withafter cross-sectional imaging and ERCP with intraductal sampling
Topazian M. Clin Endosc 2012;45:328-330
IBDS in clinical practice• No mass on cross-sectional imaging
– Typically contrasted CT or contrasted MRI/MRCP
• Conventional histopathology is non-diagnostic– ERCP with biliary brushings
ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology
ABIM-style question• A 68-year-old man develops painless jaundice. He otherwise
feels well. Abdominal ultrasound shows gallstones and dilated i t h ti bil d t Th bil d t i t llintrahepatic bile ducts. The common bile duct is not well seen.
• Which of the following is the most appropriate next step in evaluation of this patient’s biliary obstruction?
A) Contrast-enhanced CT of the abdomenB) Magnetic resonance cholangiopancreatography (MRCP)C) Laparoscopic cholecystectomy with intra-operative
cholangiographyD) ERCP
GESAP VI
ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology
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Andrew Y. Wang, MD
Range:64-95%
Ruys AT et al. British J Radiol 2012;85:1255–1262
Range:71-80%
Multiphasic CT
Hyperenhancement of the involved bile duct during the portal venous phase independently differentiates malignant from benign strictures
Choi SH et al. Radiology 2005;236:178-183
ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology
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Andrew Y. Wang, MD
MRI and MRCP• Non-invasive, avoids radiation exposure• Diagnostic imaging modality of choice for biliary strictures and
PSC– Comparable diagnostic accuracy to ERCP– Sensitivity of 80% and specificity of 87% for diagnosing PSC
Berstad et al. Clin Gastroenterol Hepatol 2006;4:514-520
• Study of 192 liver lesions (32% malignant), DWI combined with dynamic contrast-enhanced MRI demonstrated awith dynamic contrast enhanced MRI demonstrated a diagnostic accuracy of 93%
Kenis C et al. Eur J Radiol. 2012;81:1016-23
MRI contrast agents• Gadobenate dimeglumine
(MultiHance, Bracco)• Gadoxetate disodium
(Eovist, Bayer)( , )– 3%-5% taken up and
excreted by hepatocytes (rest kidney)
– Hepatobiliary phase images acquired 1-2 hours after injection
228 patients with biliary strictures undergoing EUS were identified
Gastrointest Endosc 2011;73:71 8
ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology
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Andrew Y. Wang, MD
Khashab MA et al. Gastrointest Endosc 2012;76:1024-33
EUS/FNA in IDBS: PPV 100%, NPV 50-57%
Intraductal ultrasonography (IDUS)
Farrell RJ et al. Gastrointest Endosc 2002;56:681-7
ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology
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Andrew Y. Wang, MD
Biliary confocal endomicroscopyWallace M et al. Endoscopy 2011; 43: 882–891
NormalFinereticular
CancerDark, irregularstructures
gray pattern (black arrow)interspersedwith bright areas of tortuous dilated bloodvessel (white arrow)
Probe-based confocal laser endomicroscopy (pCLE)
Smith IA et al. Gastroenterol Res Practice 2012
The overall inter-observer agreement for pCLE image interpretation in indeterminate biliary strictures ranges from poor to fair
Talreja JP et al. Dig Dis Sci 2012;57:3299–3302
ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology
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Andrew Y. Wang, MD
Fluorescence in situ hybridization
Mahli et al. J Hepatol 2006;45:856–867
Each colored spot = 1 chromosome2 spots/color normal diploid>2 spots for >1 color polysomy
Advanced molecular markers and imaging
Ch l i h i l (RC) i d l bi DIA FISH d IDUS• Cholangiography, routine cytology (RC), intraductal biopsy, DIA, FISH, and IDUS were performed in 86 patients with indeterminate biliary strictures
• For the most difficult-to-manage patients with negative cytology and histologywho were later proven to have malignancy (N = 21), DIA, FISH, composite DIA/FISH, and IDUS were able to predict malignant diagnoses in 14%, 62%, 67%, and 86%, respectively
Levy MJ et al. Am J Gastroenterol 2008;103:1263–1273
ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology
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Mutational analysis• Brush cytology specimens can yield supernatant fluid
enriched with DNA, probably from actively proliferating cells
• Mutational profiling can enhance the cytologic evaluation and characterization of specimens suspected to contain pancreatic or bile duct cancer– KRAS point mutation– Loss of heterozygosity (LOH) analysis of microsatellites locatedLoss of heterozygosity (LOH) analysis of microsatellites located
at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 21q, and 22q
• Few data to support this practice
Finkelstein SD et al. Acta Cytol 2012;56:439-47
The quest continues…
Indiana Jones and the Last Crusade (1989)
ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology
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Andrew Y. Wang, MD
Test characteristics are affected by prevalence (pre-test probability)
Persistent non-diagnosis: what now?• What was the pre-test(s) probability/initial clinical
suspicion?– Weight loss, older, chronic PSC, progressive stricture, no
history of gallstone disease
• Review available data at a multidisciplinary tumor board to reach consensus
• Has the patient withstood the test of time?Di th fi di d ti i li i• Discuss the findings and options in clinic– Review risks/benefits of surgery vs. watchful waiting
• Consider surgery in pts with concerning clinical features who are good operative candidates
ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology
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Andrew Y. Wang, MD
Thank you
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ACG Regional Postgraduate Course - Williamsburg, VA Copyright 2013 American College of Gastroenterology