ahtidtitapproach to indeterminate biliary...

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


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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

Darden Business SchoolCharlottesville VACharlottesville, VA


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ahtidtitapproach to indeterminate biliary...

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