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
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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
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Andrew Y. Wang, MD
Differential diagnosis of IBDS • Benign
– Chronic pancreatitis• Malignant
– Cholangiocarcinoma– Post-surgical– PSC– Autoimmune pancreatitis– IgG4-related cholangiopathy– Ischemic injury– Radiation stricture– Inflammatory stricture
– Pancreatic cancer– Gallbladder cancer– HCC– Metastatic malignancy
• Breast cancer• Renal cell cancer
– LymphomaInflammatory stricture• Stones, trauma, acute panc
– Mirizzi’s syndrome– Cystic duct neuromas– Infections
• HIV, parasitic
• Porta hepatis or hilar LN
Topazian M. Clin Endosc 2012;45:328-330
Ideal endoscopic sampling technique:High sensitivity few false negativesPerfect specificity no false positives
Harewood GC. Curr Opin Gastroenterol 2008
1975
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Andrew Y. Wang, MD
Clinical clues
• ReassuringY ti t
• ConcerningW i ht l– Younger patient
– h/o pancreatitis– h/o biliary stones– ? Normal CA 19-9– Elevated IgG4– Prior hepatobiliary
– Weight loss– ? Elevated CA 19-9– Long-term PSC– Longer stricture (>1 cm)– Asymmetric stricture– Anomalous pancreatico-Prior hepatobiliary
surgery• Cholecystectomy
Anomalous pancreaticobiliary junction
– Choledochal cyst
44 y.o. FTB 1.5ALT 170s/p chole for stonesh/o GS pancreatitis
44 y.o. MTB 4.0ALT 184s/p choleh/o PSC
42 y.o. MTB 2.5ALT 236h/o biliary NHL 4 yrs agos/p XRT
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Andrew Y. Wang, MD
• 44 y.o. M with mild chronic RUQ and fluctuating abnormal LFTs for 3 months
• Referred to hepatology• Liver biopsy – chronic hepatitis with biliary
features suggestive of PSC• Contrasted MRI/MRCP – suspicion for PSC
Brushings:Adenocarcinoma
Bile duct biopsies:Moderate to poorly differentiatedadenocarcinoma
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Andrew Y. Wang, MD
Borderline or
Petersen BT. Indeterminate Biliary Stricture. ERCP 2008
CholedochoscopyIDUSFISH/DIAConfocalSurgery ???
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
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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
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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
– Better for all around
( , y )– 50% of the dose is taken
up and excreted by hepatocytes
– Greater hepatobiliary phase parenchymal enhancement
– Hepatobiliary phaseBetter for all around problem-solving
Hepatobiliary phase images are acquired 20-40 minutes after injection
– Best for FNH and staging metastatic disease
Fowler KJ et al. Hepatology 2011;54:2227-2237
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Andrew Y. Wang, MD
Dynamic MRI with IV contrastEarly Early delayed
Late delayedhypointense on T1 moderate
progressive and concentric filling
hypointense on T1 moderate peripheral enhancement
MRC vs. ERC
Berstad et al. Clin Gastroenterol Hepatol 2006;4:514-520
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Andrew Y. Wang, MD
MRC vs. ERC
Charatcharoenwitthaya P et al. Heaptology 2008;48:1106-1117
MRCP
3DERC
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Andrew Y. Wang, MD
ERCP technique• Pre-procedural antibiotics• Stent non-draining
opacified segments
Early vs. late images on selective ERC
• Full-strength contrast• Broad views for reference• Magnified images to
sharpen detail• Use the least contrast
needed• Use CT or MRCP to plan
Rotate pt RT or C-arm LT to expose hilum (if prone)
pERCP
• Some lesions still might require PTC
Petersen BT. Indeterminate Biliary Stricture. ERCP 2008
Fluoroscopy-guided biopsies
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Andrew Y. Wang, MD
Single-operator fiberoptic choledochoscopy
DAVE project
• A total of 26 patients (17 cancer positive/9 cancer negative) were enrolled
• Each patient underwent triple sampling with cholangioscopy-guided
Brush vs. biopsy vs. choledochoscopic biopsy
mini-forceps, cytology brushing, and standard forcepsDraganov PV et al. Gastrointest Endosc 2012;75:347-53
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Andrew Y. Wang, MD
Video-choledochoscopy and NBI
NBI choledochoscopy
Itoi T et al. Gastrointest Endosc 2007;66:730-6
Well differentiated adenocarcinoma Malignant tumor vessels
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Andrew Y. Wang, MD
Endoscopic ultrasonography for IBDS• Bile duct wall thickness of ≥ 3 mm on EUS
Sensitivity: 79% Specificity: 79%– Sensitivity: 79% Specificity: 79%– PPV: 73% NPV: 80%
Lee JH et al. Am J Gastroenterol 2004;99:1069-73
Gastrointest Endosc 2011;73:71-8
228 patients with biliary strictures undergoing EUS were identified
Gastrointest Endosc 2011;73:71 8
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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
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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
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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
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Andrew Y. Wang, MD
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)
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Andrew Y. Wang, MD
Test characteristics are affected by prevalence (pre-test probability)
Prevalence = 0.1 Prevalence = 0.5 Prevalence = 0.9
Sens Spec PPV NPV PPV NPV PPV NPV
MRI/MRCP 75% 65% 0.19 0.96 0.68 0.72 0.95 0.22
ERCP 90% 63% 0.21 0.89 0.71 0.86 0.96 0.41
Biopsy 29% 100% 1 0.93 1 0.58 1 0.14
Brush 25% 100% 1 0.92 1 0.57 1 0.13
EUS 79% 79% 0.29 0.97 0.79 0.79 0.97 0.29
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
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Andrew Y. Wang, MD
Thank you
SAVE THE DATE!Updates in GI and Liver TransplantUpdates in GI and Liver Transplant
Evening Poster Symposium: May 30, 2014Conference: May 31, 2014
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