A prospective comparison of digital image analysis and routine cytology for the identification of malignancy in biliary tract strictures

Baron, Todd H.; Harewood, Gavin C.; Rumalla, Ashwin; Pochron, Nicole L.; Stadheim, Linda M.; Gores, Gregory J.; Therneau, Terry M.; Groen, Piet C. de; Sebo, Thomas J.; Salomão, Diva R.; Kipp, Benjamin R.

doi:10.1016/s1542-3565(04)00006-0

Cited by 187 publications

(100 citation statements)

References 24 publications

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“…The technique offers the clinician almost definitive diagnostic certainty when positive for malignancy (specificity 96 -100%) but has a poor ability to detect malignancy (sensitivity 18 -57%) (de Bellis et al, 2002b;Baron et al, 2004;Harewood et al, 2004;Moreno Luna et al, 2006). This proof of principle study has shown that the sensitivity of the automated immunofluorometric Mcm5 test on bile aspirates for detecting pancreaticobiliary malignancy was superior (four times more at the 1000 cells per well cut point) to that of brush cytology, while maintaining a high specificity.…”

Section: Discussionmentioning

confidence: 86%

“…Brush cytology is the most commonly used method of sampling a biliary stricture (De Bellis et al, 2002a) as it is relatively easy to perform, does not compromise resection margins in potentially resectable cases and has a high specificity (96 -100%) for malignancy. However, cytology has a low sensitivity (9 -57%) (de Bellis et al, 2002b;Baron et al, 2004;Harewood et al, 2004;Moreno Luna et al, 2006) for the detection of malignancy, which is even lower if cells are acquired from bile aspirates (6 -32%) (De Bellis et al, 2002a). The poor detection rate may stem from a number of factors, including the desmoplastic nature of biliary tract cancers, failure to obtain an adequate cellular yield and morphological changes induced by inflammation and necrosis.…”

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confidence: 99%

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Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in bile aspirates

et al. 2008

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Biliary brush cytology is the standard method of sampling a biliary stricture but has a low sensitivity for the detection of malignancy. We have previously shown that minichromosome maintenance (MCM) replication proteins (Mcm2 -7) are markers of dysplasia and have utilised these novel biomarkers of growth for the diagnosis of cervical and bladder cancer. We aimed to determine if MCM proteins are dysregulated in malignant pancreaticobiliary disease and if levels in bile are a sensitive marker of malignancy. In 30 tissue specimens from patients with malignant/benign biliary strictures, we studied Mcm2 and -5 expression by immunohistochemistry. Bile samples were also collected prospectively at endoscopic retrograde cholangiopancreatography from 102 consecutive patients with biliary strictures of established (n ¼ 42) or indeterminate aetiology (n ¼ 60). Patients with indeterminate strictures also underwent brush cytology as part of standard practice. Bile sediment Mcm5 levels were analysed using an automated immunofluorometric assay. In benign biliary strictures, Mcm2 and -5 protein expression was confined to the basal epithelial proliferative compartment -in contrast to malignant strictures where expression was seen in all tissue layers. The percentage of nuclei positive for Mcm2 was higher in malignant tissue (median 76.5%, range 42 -92%) than in benign tissue (median 5%, range 0 -33%) (Po0.0005), with similar results for Mcm5. Minichromosome maintenance protein 5 levels in bile were significantly more sensitive than brush cytology (66 vs 20%; P ¼ 0.004) for the detection of malignancy in patients with an indeterminate stricture, with a comparable positive predictive value (97 vs 100%; P ¼ ns). In this study, we demonstrate that Mcm5 in bile detected by a simple automated test is a more sensitive indicator of pancreaticobiliary malignancy than routine brush cytology.

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Section: Discussionmentioning

confidence: 86%

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confidence: 99%

Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in bile aspirates

et al. 2008

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“…These techniques are fluorescence insitu hybridization (FISH) (Fig. 5) and digital image analysis (DIA) (53,54). FISH utilizes fluorescent probes to identify chromosomal amplification (i.e., the actual number of a given chromosome in a cell) and DIA quantitates nuclear DNA as a ratio of normal ploidy (2N).…”

Section: Diagnosismentioning

confidence: 99%

Cholangiocarcinoma: Modern advances in understanding a deadly old disease

Malhi

Gores

2006

Journal of Hepatology

243

193

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Cholangiocarcinomas are tumors that arise anywhere in the biliary tract, presumably of cholangiocyte origin. The global incidence of this rare disease is on the rise. Several known risk factors exist, and link chronic biliary inflammation to the pathogenesis of cholangiocarcinoma. Among these, amplification of the epidermal growth factor receptor, the interleukin-6 signaling pathway, inducible nitric oxide, erb-2, and cyclooxygenase-2 are well defined. Most patients present late, with a median survival of months. Although, imaging studies and clinical context often indicate cholangiocarcinoma, pathologic and cytologic diagnosis is difficult to obtain. Advanced cytologic tests with fluorescent in situ hybridization or digital image analysis can increase diagnostic sensitivity. Surgical resection is the current therapy of choice for both intrahepatic and ductal cholangiocarcinomas. However, the 5 year survival is poor, with 60 to greater than 90% recurrence rates. In a single center experience, liver transplantation with neoadjuvant chemoirradiation, for highly selected patients has a 5 year disease free survival of greater than 80%. Future targeted therapies will depend on a better understanding of the cellular and molecular biology of cholangiocarcinomas.

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“…Aneuploidy, or the presence of increased amounts of DNA, is quantitated and, if present, suggests malignancy. DIA increases the sensitivity of routine brush cytology from 18%-40%, but decreased the specificity from 98%-77% [9] . Fluorescence in-situ hybridization (FISH) uses a commercial probe set to assess for polysomy of chromosomes 3, 7, 17, and 9p21.…”

Section: Ercpmentioning

confidence: 92%

Review of endoscopic techniques in the diagnosis and management of cholangiocarcinoma

Nguyen¹,

Sing²

2008

WJG

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A prospective comparison of digital image analysis and routine cytology for the identification of malignancy in biliary tract strictures

Cited by 187 publications

References 24 publications

Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in bile aspirates

Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in bile aspirates

Cholangiocarcinoma: Modern advances in understanding a deadly old disease

Review of endoscopic techniques in the diagnosis and management of cholangiocarcinoma

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