title: Prospective evaluation of advanced molecular markers and imaging techniques in patients with indeterminate bile duct strictures.
abstract: OBJECTIVE
  Standard techniques for evaluating bile duct strictures have poor sensitivity for detection of malignancy. Newer imaging modalities, such as intraductal ultrasound (IDUS), and advanced cytologic techniques, such as digital image analysis (DIA) and fluorescence in situ hybridization (FISH), identify chromosomal abnormalities, and may improve sensitivity while maintaining high specificity. Our aim was to prospectively evaluate the accuracy of these techniques in patients with indeterminate biliary strictures.
  
  
  METHODS
  Cholangiography, routine cytology (RC), intraductal biopsy, DIA, FISH, and IDUS were performed in 86 patients with indeterminate biliary strictures. Patients were stratified based on the presence or absence of primary sclerosing cholangitis (PSC).
  
  
  RESULTS
  RC provided low sensitivity (7-33%) but high specificity (95-100%) for PSC and non-PSC patients. The composite DIA/FISH results (when considering trisomy-7 [Tri-7] as a marker of benign disease) yielded a 100% specificity and increased sensitivity one- to fivefold in PSC patients versus RC, and two- to fivefold in patients without PSC, depending on how suspicious cytology results were interpreted. 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.
  
  
  CONCLUSIONS
  DIA, FISH, and IDUS enhance the accuracy of standard techniques in evaluation of indeterminate bile duct strictures, allowing diagnosis of malignancy in a substantial number of patients with false-negative cytology and histology. These findings support the routine use of these newer diagnostic modalities in patients with indeterminate biliary strictures.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Levy
authors.forename: Todd H
authors.initials: TH
authors.lastname: Baron
authors.forename: Amy C
authors.initials: AC
authors.lastname: Clayton
authors.forename: Felicity B
authors.initials: FB
authors.lastname: Enders
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gostout
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Halling
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Kipp
authors.forename: Bret T
authors.initials: BT
authors.lastname: Petersen
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Roberts
authors.forename: Ashwin
authors.initials: A
authors.lastname: Rumalla
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sebo
authors.forename: Mark D
authors.initials: MD
authors.lastname: Topazian
authors.forename: Maurits J
authors.initials: MJ
authors.lastname: Wiersema
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gores
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D001652:Bile Ducts / Q000473:pathology; D001706:Biopsy; D002758:Cholangiography; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D002779:Cholestasis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018084:Ultrasonography, Interventional
chemical_list: D004273:DNA, Neoplasm