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 19 February 2018

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News

Genetic analyses increase detection of malignancies in biliary strictures

Mutation profile and fluorescence in situ hybridization analyses increase detection of malignancies in biliary strictures, reports this month's issue of the Clinical Gastroenterology & Hepatology.

News image

It is a challenge to detect malignancies in biliary strictures. 

Various sampling methods are available to increase diagnostic yield, but these require additional procedure time and expertize. 

Dr Tamas Gonda and colleagues evaluated the combined accuracy of fluorescence in situ hybridization (FISH) and polymerase chain reaction–based DNA mutation profiling of specimens collected using standard brush techniques.

The researchers performed a prospective study of 107 consecutive patients treated for biliary strictures by endoscopic retrograde cholangiopancreatography from 2012 through 2014. 

The team performed routine cytology and FISH analyses on cells collected by standard brush techniques, and analyzed supernatants for point mutations in KRAS and loss-of-heterozygosity mutations in tumor-suppressor genes at 10 loci. 

Cytology analysis identified patients with malignancies with 100% specificity
Clinical Gastroenterology & Hepatology
Strictures were determined to be nonmalignant based on repeat image analysis or laboratory test results 12 months after the procedure. 

The research team identified malignant strictures based on subsequent biopsy or cytology analyses, pathology analyses of samples collected during surgery, or death from biliary malignancy. 

The team determined the sensitivity and specificity with which FISH and DNA mutation profiling analyses detected malignancies using the exact binomial test.

The researchers' final analysis included 100 patients, of which 41% had biliary malignancies.

Cytology analysis identified patients with malignancies with 32% sensitivity and 100% specificity. 

Addition of FISH or DNA mutation profiling results to cytology results increased the sensitivity of detection to 51% without reducing specificity. 

The research team found that the combination of cytology, DNA mutation profiling, and FISH analyses detected malignancies with 73% sensitivity. 

FISH identified an additional 9 of the 28 malignancies not detected by cytology analysis, and DNA mutation profiling identified an additional 8 malignancies. 

The team observed that FISH and DNA mutation profiling together identified 17 of the 28 malignancies not detected by cytology analysis.

Dr Gonda's team concludes, "Addition of FISH and mutation analyses to cytology analysis significantly increased the level of sensitivity with which we detected malignancy in biliary strictures, with 100% specificity."

"These techniques can be performed using standard brush samples collected during endoscopic retrograde cholangiopancreatography, with mutations detected in free DNA in supernatant fluid of samples."

"The tests are complementary and therefore should be used sequentially in the diagnostic evaluation of biliary strictures."

Clin Gastroenterol Hepatol 2017: 15(6): 913–919.e1
20 June 2017

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