Indeterminate biliary strictures refer to biliary strictures without an identifiable cause on imaging. The endoscopist's role is to determine if the stricture is benign or malignant and offer treatment options. Available tools for evaluation include ERCP, cholangioscopy, intraductal ultrasound (IDUS), and endoscopic ultrasound (EUS). ERCP allows for tissue sampling but has a sensitivity of only 30-55%. Newer techniques like fluorescence in-situ hybridization and confocal endomicroscopy can increase sensitivity. Direct visualization with cholangioscopy may improve detection over standard ERCP. IDUS provides high accuracy in differentiating benign from malignant strictures without direct sampling. EUS allows for

1. 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

2. What is an “indeterminate”
biliary stricture ?
 Biliary stricture without an identifiable
cause (e.g. mass) on imaging (CT, MRI)
 +/- prior negative tissue sampling

3. Endoscopist’s role in evaluatingEndoscopist’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?

4. Available tools for evaluatingAvailable tools for evaluating
biliary strictures:biliary strictures:
 ERCP
 Cholangioscopy
 Intraductal US (IDUS)
 Endoscopic ultrasound (EUS)

5. ERCP in indeterminate stx:ERCP in indeterminate stx:
 Assess presence /
extent
 tissue sampling

6. 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 cytology 42% (30-57%; 8 studies with n=578)* over-the-wire, easy
forceps biopsies 56% (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

7. 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

8. Cholangioscopy for indeterminateCholangioscopy 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

9. Cholangioscopy for stricturesCholangioscopy for strictures
Technology Pros Cons
mother-baby
(fiberoptic / video)
allows biopsy
reasonable image quality
2 operators
2 processors
fragile, easily damaged
Single-operator fiberoptic
disposable
allows biopsy
4-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 available
allows biopsy
best imaging quality
technically challenging
difficult for prox. Stx
Nguyen NQ, Binmoeller KF, Shah JN. Tech Review GIE 2009

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

11. Cholangioscopy -Cholangioscopy -
fiberoptic mother-babyfiberoptic mother-baby

12. Cholangioscopy -Cholangioscopy -
video mother-babyvideo mother-baby

13. Cholangioscopy - ultraslim gastroscopeCholangioscopy - ultraslim gastroscope

14. 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

15. IDUSIDUS

16. 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

17. 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
DeWitt
GIE 2006
24 pts 77%
Eloubeidi
Clin Gast Hep 2004
28 pts 86%
Fritscher-Ravens
AJG 2004
44 pts 89%

18. EUS - biliary stricture

19. EUS-FNA of stricture

20. Summary: evaluating
indeterminate biliary strictures
ductoscopyIDUS
EUS
ERCP
- brush / bx
- DIA / FISH
- OCT / confocal

21. 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

22. Thank you...