Indeterminate Biliary Strictures:Indeterminate Biliary Strictures:Diagnosis by ERCP, IDUS, Diagnosis by ERCP, IDUS,

Cholangioscopy, and Tissue SamplingCholangioscopy, and Tissue Sampling

Janak N. Shah, MD

Director of Pancreatic / Biliary Endoscopy

Interventional Endoscopy Services - California Pacific Medical Center

Director of Endoscopy- SFVAMC

Associate Clinical Professor of Medicine - UCSF

San Francisco, CA

What is an “indeterminate” biliary stricture ?

Biliary stricture without an identifiable cause (e.g. mass) on imaging (CT, MRI)

+/- prior negative tissue sampling

Endoscopist’s role in evaluating Endoscopist’s role in evaluating indeterminate strictures:indeterminate strictures:

Determine the cause: Benign or Malignant? Diff dx: cholangioCA, pancreatic CA, PSC, autoimmune (IGG4),

inflammatory (chronic pancreatitis), bile duct injury

Offer treatment options: benign - candidate for endo therapy? stent? malignant - resectable or unresectable? Stenting?

Available tools for evaluating Available tools for evaluating biliary strictures:biliary strictures:

ERCP

Cholangioscopy

Intraductal US (IDUS)

Endoscopic ultrasound (EUS)

ERCP in indeterminate stx:ERCP in indeterminate stx:

Assess presence / extent

tissue sampling

ERCP tissue sampling techniquesERCP tissue sampling techniques

Technique Sensitivity Technical aspects

bile aspirate cytology

27% (6-32%; 6 studies with n=351)* easy

retrieved biliary stent cytology

32% (11-79%; 6 studies with n=197)*

easy; done at 2nd procedure

brush cytology42% (30-57%; 8 studies with

n=578)*over-the-wire, easy

forceps biopsies56% (43-81%; 6 studies with

n=343)*

more difficult;often requires

sphincterotomy

forceps + brushings

55% (in same study brush alone 30%; bx alone 43%)**

more difficult;often requires

sphincterotomy

* de Bellis M, GIE 2002** Jailwala J, GIE 2000

Improving yield at ERCP? Improving yield at ERCP? newer techniques in suspected malignancynewer techniques in suspected malignancy

Technique Method Utility

digital image analysis (DIA)

spectrophotometry to quantify DNA content

14% sensitivity in cyto-negative stx

*

fluorescence in-situ

hybridization (FISH)

fluorescently labeled DNA probes to detect loss / gain of chromosomes

62% sensitivity in cyto-negative stx

*

optical coherence

tomography (OCT)

catheter-based; cross-sectional, subsurface imaging (2mm) based on

measuring backscattered infrared light

1-2 abnl findings in 53-79% with

cancer **

confocal endomicroscopy

catheter-based, in-vivo microscopic imaging

abnl findings in 83% with cancer

***

* Levy MJ, AJG 2008** Arvanitakis M, Endosc 2009*** Giovannini M, Surg Endosc 2011

Cholangioscopy for indeterminate Cholangioscopy for indeterminate stricturesstrictures

Visualization of stricture and ability for direct tissue sampling

Some studies suggest improved detection of malignancy over standard ERCP techniques (e.g. brushings): 92% vs. 66% (p=0.25) tumor detection among 53 PSC

pts with dominant strictures * 89% tumor detection (16 of 18) among 62 pts with

“indeterminate strictures”, majority with prior neg sampling **

* Tischendorf JJ, Endosc 2006 ** Shah RJ, Clin Gastroenterol Hepatol 2006

Cholangioscopy for stricturesCholangioscopy for strictures

Technology Pros Cons

mother-baby(fiberoptic / video)

allows biopsyreasonable image quality

2 operators2 processorsfragile, easily

damaged

Single-operator fiberoptic disposable

allows biopsy4-way tip deflection

easier for proximal stx

inferior image quality compared to

others

Direct ductoscopy with ultraslim gastroscopes

(+/- overtube, wire-guided, anchoring balloon assistance)

widely availableallows biopsy

best imaging quality

technically challenging

difficult for prox. Stx

Nguyen NQ, Binmoeller KF, Shah JN. Tech Review GIE 2009

Cholangioscopy - Single-operator, Cholangioscopy - Single-operator, fiberoptic disposable systemfiberoptic disposable system

Cholangioscopy - Cholangioscopy - fiberoptic mother-babyfiberoptic mother-baby

Cholangioscopy - Cholangioscopy - video mother-babyvideo mother-baby

Cholangioscopy - ultraslim gastroscopeCholangioscopy - ultraslim gastroscope

IDUS for indeterminate stricturesIDUS for indeterminate strictures Catheter-based US probe, over-the-wire, 12-30 MHz Abnl features in suspected malignant stx:

hypoechoic, infiltrating mass notching or irregular outer border intraductal papillary growth suspicious LN

Improved tumor detection -- no direct tissue sampling malig dx accurately predicted in 89% among 34 PSC and 52 non-PSC

pts with indeterminate stx (higher in non-PSC); malign dx in 86% of 21 pts with negative cytology *

Retrospective blinded review of 30pts with indeterminate stx: benign vs. malign dx correct in 90% with IDUS vs. 67% with ERCP/cyto **

Other uses: assessing tumor extension for operative planning and resectability

* Levy MJ, AJG 2008** Vasquez-Sequeiros, GIE 2002

IDUSIDUS

EUS for indeterminate stricturesEUS for indeterminate strictures Bile duct (from ampulla to hilum) well visualized from

duodenum

Abnl features in suspected malignant stx: hypoechoic mass focal, irregular wall thickening intraductal papillary growth suspicious LN liver metastases and distant LN

Immediate tissue sampling / on-site analysis

Sensitivity of EUS-FNA for bile duct CA: Sensitivity of EUS-FNA for bile duct CA: indeterminate stx with prior negative samplingindeterminate stx with prior negative sampling

Study N Sensitivity

DeWittGIE 2006

24 pts 77%

EloubeidiClin Gast Hep 2004

28 pts 86%

Fritscher-RavensAJG 2004

44 pts 89%

EUS - biliary stricture

EUS-FNA of stricture

Summary: evaluating indeterminate biliary strictures

ductoscopyIDUS

EUS

ERCP- brush / bx- DIA / FISH

- OCT / confocal

Indeterminate biliary strictures:Approach at CPMC

EUS-FNA (with on-site cyto) +/- ERCP

diagnostic

ERCP if needed- biliary decompression- stent exchange- operative planning

non-diagnostic

ERCP- brushings / forceps bx- IDUS- consider cholangioscopy

Thank you...