Prospective evaluation of advanced molecular markers and imaging techniques in patients with indeterminate bile duct strictures

Michael J. Levy, Todd H. Baron, Amy C. Clayton, Felicity T Enders, Christopher J. Gostout, Kevin C. Halling, Benjamin R. Kipp, Bret Thomas Petersen, Lewis Rowland Roberts, Ashwin Rumalla, Thomas J. Sebo, Mark Topazian, Maurits J. Wiersema, Gregory James Gores

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

BACKGROUND AND AIMS: 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.

Original languageEnglish (US)
Pages (from-to)1263-1273
Number of pages11
JournalAmerican Journal of Gastroenterology
Volume103
Issue number5
DOIs
StatePublished - May 2008

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Molecular Imaging
Bile Ducts
Pathologic Constriction
Sclerosing Cholangitis
Fluorescence In Situ Hybridization
Cell Biology
Histology
Neoplasms
Cholangiography
Trisomy
Chromosome Aberrations
Biopsy
Sensitivity and Specificity

ASJC Scopus subject areas

  • Gastroenterology

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Prospective evaluation of advanced molecular markers and imaging techniques in patients with indeterminate bile duct strictures. / Levy, Michael J.; Baron, Todd H.; Clayton, Amy C.; Enders, Felicity T; Gostout, Christopher J.; Halling, Kevin C.; Kipp, Benjamin R.; Petersen, Bret Thomas; Roberts, Lewis Rowland; Rumalla, Ashwin; Sebo, Thomas J.; Topazian, Mark; Wiersema, Maurits J.; Gores, Gregory James.

In: American Journal of Gastroenterology, Vol. 103, No. 5, 05.2008, p. 1263-1273.

Research output: Contribution to journalArticle

Levy, Michael J. ; Baron, Todd H. ; Clayton, Amy C. ; Enders, Felicity T ; Gostout, Christopher J. ; Halling, Kevin C. ; Kipp, Benjamin R. ; Petersen, Bret Thomas ; Roberts, Lewis Rowland ; Rumalla, Ashwin ; Sebo, Thomas J. ; Topazian, Mark ; Wiersema, Maurits J. ; Gores, Gregory James. / Prospective evaluation of advanced molecular markers and imaging techniques in patients with indeterminate bile duct strictures. In: American Journal of Gastroenterology. 2008 ; Vol. 103, No. 5. pp. 1263-1273.
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abstract = "BACKGROUND AND AIMS: 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.",
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AU - Baron, Todd H.

AU - Clayton, Amy C.

AU - Enders, Felicity T

AU - Gostout, Christopher J.

AU - Halling, Kevin C.

AU - Kipp, Benjamin R.

AU - Petersen, Bret Thomas

AU - Roberts, Lewis Rowland

AU - Rumalla, Ashwin

AU - Sebo, Thomas J.

AU - Topazian, Mark

AU - Wiersema, Maurits J.

AU - Gores, Gregory James

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N2 - BACKGROUND AND AIMS: 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.

AB - BACKGROUND AND AIMS: 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.

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