Approach hto Indeterminate Biliary Strictures

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1 Approach hto Indeterminate t 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 Intrahepatic ti BD >40% of parallel lintrahepatic ti PV Main question for the patient and the endoscopist: Is this cancer? Spencer G, Kochman ML. Dilated Bile Duct. ERCP

2 Indeterminate bile duct stricture when basic work-up including transabdominal imaging i and ERCP with routine cytologic brushing are non-diagnostic Victor DW, Sherman SS et al. World J Gastroenterol 2012;18: includes those without a definite diagnosis after cross-sectional sectional imaging and ERCP with intraductal sampling Topazian M. Clin Endosc 2012;45: 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 2

3 Differential diagnosis of IBDS Benign Chronic pancreatitis Post-surgical PSC Autoimmune pancreatitis IgG4-related cholangiopathy Ischemic injury Radiation stricture Inflammatory stricture Stones, trauma, acute panc Mirizzi s syndrome Cystic duct neuromas Infections HIV, parasitic Malignant Cholangiocarcinoma Pancreatic cancer Gallbladder cancer HCC Metastatic malignancy Breast cancer Renal cell cancer Lymphoma Porta hepatis or hilar LN Topazian M. Clin Endosc 2012;45: Ideal endoscopic sampling technique: High sensitivity few false negatives Perfect specificity no false positives Harewood GC. Curr Opin Gastroenterol

4 Clinical clues Reassuring Younger patient t h/o pancreatitis h/o biliary stones? Normal CA 19-9 Elevated IgG4 Prior hepatobiliary surgery Cholecystectomy Concerning Weight htloss? Elevated CA 19-9 Long-term PSC Longer stricture (>1 cm) Asymmetric stricture Anomalous pancreaticobiliary junction Choledochal cyst 44 y.o. F TB 1.5 ALT 170 s/p chole for stones h/o GS pancreatitis 44 y.o. M TB 4.0 ALT 184 s/p chole h/o PSC 42 y.o. M TB 2.5 ALT 236 h/o biliary NHL 4 yrs ago s/p XRT 4

5 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 differentiated adenocarcinoma 5

6 Borderline or Choledochoscopy IDUS FISH/DIA Confocal Surgery??? Petersen BT. Indeterminate Biliary Stricture. ERCP 2008 ABIM-style question A 68-year-old man develops painless jaundice. He otherwise feels well. Abdominal ultrasound shows gallstones and dilated intrahepatic ti bile ducts. The common bile duct tis 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 abdomen B) Magnetic resonance cholangiopancreatography (MRCP) C) Laparoscopic cholecystectomy with intra-operative cholangiography D) ERCP GESAP VI 6

7 Range: 64-95% Range: 71-80% Ruys AT et al. British J Radiol 2012;85: 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:

8 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: Study of 192 liver lesions (32% malignant), DWI combined with dynamic contrast-enhanced MRI demonstrated a diagnostic accuracy of 93% Kenis C et al. Eur J Radiol. 2012;81: MRI contrast agents Gadobenate dimeglumine (MultiHance, Bracco) 3%-5% taken up and excreted by hepatocytes (rest kidney) Hepatobiliary phase images acquired 1-2 hours after injection Better for all around problem-solving Gadoxetate disodium (Eovist, Bayer) 50% of the dose is taken up and excreted by hepatocytes Greater hepatobiliary phase parenchymal enhancement Hepatobiliary phase images are acquired minutes after injection Best for FNH and staging metastatic disease Fowler KJ et al. Hepatology 2011;54:

9 Dynamic MRI with IV contrast Early Early delayed hypointense on T1 Late delayed moderate peripheral enhancement progressive and concentric filling MRC vs. ERC Berstad et al. Clin Gastroenterol Hepatol 2006;4:

10 MRC vs. ERC Charatcharoenwitthaya P et al. Heaptology 2008;48: MRCP 3D ERC 10

11 ERCP technique Early vs. late images on selective ERC Pre-procedural antibiotics Stent non-draining opacified segments Full-strength contrast Broad views for reference Magnified images to sharpen detail Use the least contrast needed Use CT or MRCP to plan ERCP Some lesions still might require PTC Rotate pt RT or C-arm LT to expose hilum (if prone) Petersen BT. Indeterminate Biliary Stricture. ERCP 2008 Fluoroscopy-guided biopsies 11

12 Single-operator fiberoptic choledochoscopy DAVE project Brush vs. biopsy vs. choledochoscopic biopsy A total of 26 patients (17 cancer positive/9 cancer negative) were enrolled Each patient underwent triple sampling with cholangioscopy-guided mini-forceps, cytology brushing, and standard forceps Draganov PV et al. Gastrointest Endosc 2012;75:

13 Video-choledochoscopy and NBI NBI choledochoscopy Well differentiated adenocarcinoma Malignant tumor vessels Itoi T et al. Gastrointest Endosc 2007;66:

14 Endoscopic ultrasonography for IBDS Bile duct wall thickness of 3 mm on EUS Sensitivity: 79% Specificity: 79% PPV: 73% NPV: 80% Lee JH et al. Am J Gastroenterol 2004;99: Gastrointest Endosc 2011;73: patients with biliary strictures undergoing EUS were identified 14

15 EUS/FNA in IDBS: PPV 100%, NPV 50-57% Khashab MA et al. Gastrointest Endosc 2012;76: Intraductal ultrasonography (IDUS) Farrell RJ et al. Gastrointest Endosc 2002;56:

16 Wallace M et al. Endoscopy 2011; 43: Biliary confocal endomicroscopy Normal Fine reticular gray pattern Cancer Dark, irregular structures (black arrow) interspersed with bright areas of tortuous dilated blood vessel (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:

17 Fluorescence in situ hybridization Each colored spot = 1 chromosome 2 spots/color normal diploid >2 spots for >1 color polysomy Mahli et al. J Hepatol 2006;45: Advanced molecular markers and imaging Cholangiography, h 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 histology who 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:

18 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 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: The quest continues Indiana Jones and the Last Crusade (1989) 18

19 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% ERCP 90% 63% Biopsy 29% 100% Brush 25% 100% EUS 79% 79% 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? Discuss the findings and options in clinic i Review risks/benefits of surgery vs. watchful waiting Consider surgery in pts with concerning clinical features who are good operative candidates 19

20 Thank you SAVE THE DATE! Updates in GI and Liver Transplant Evening Poster Symposium: May 30, 2014 Conference: May 31, 2014 Darden Business School Charlottesville, VA 20