Advanced Cytologic Techniques for the Detection of Malignant Pancreatobiliary Strictures

Luna, Laura E. Moreno; Kipp, Benjamin R.; Halling, Kevin C.; Sebo, Thomas J.; Kremers, Walter K.; Roberts, Lewis R.; Fritcher, Emily G. Barr; Levy, Michael J.; Gores, Gregory J.

doi:10.1053/j.gastro.2006.08.021

Cited by 297 publications

(254 citation statements)

References 29 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%

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%

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

et al. 2008

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“…Conversely, individual tests generally have suboptimal performance characteristics. For example, conventional brush cytology has excellent specificity (nearly 100%) but limited sensitivity (ranging from 18%‐40%) in diagnosing CCA 15, 35, 36, 37, 38, 39. Similarly, while serum CA 19‐9 has a reported sensitivity and specificity of 79% and 98%, respectively, at a cut‐off value of 130 U/mL,40 its levels may become elevated in the setting of nonmalignant obstruction or acute cholangitis, and it is undetectable in Lewis blood antigen‐negative patients (and remains so even in the presence of CCA) 41.…”

Section: Discussionmentioning

confidence: 99%

Dominant strictures in primary sclerosing cholangitis: A multicenter survey of clinical definitions and practices

Hilscher

Tabibian

Carey

et al. 2018

Hepatology Communications

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Dominant strictures (DSs) of the biliary tree occur in approximately 50% of patients with primary sclerosing cholangitis (PSC) and may cause significant morbidity. Nevertheless, the definition and management of DSs lacks consensus. We aimed to better understand current perceptions and practices regarding PSC‐associated DSs. We conducted an anonymous, 23‐question, survey‐based study wherein electronic surveys were distributed to 131 faculty in the Division of Gastroenterology and Hepatology at the three Mayo Clinic campuses (Rochester, Scottsdale, and Jacksonville) as well as the affiliated practice network. Responses were aggregated and compared, where applicable, to practice guidelines of the American Association for the Study of Liver Diseases and European Association for the Study of the Liver. A total of 54 faculty (41.2%) completed the survey, of whom 24 (44.4%) were hepatologists, 21 (38.9%) gastroenterologists, and 9 (16.7%) advanced endoscopists. One of the major study findings was that there was heterogeneity among participants' definition, evaluation, management, and follow‐up of DSs in PSC. The majority of participant responses were in accordance with societal practice guidelines, although considerable variation was noted. Conclusion: Despite the prevalence and morbidity of DSs in PSC, clinical perceptions and practices vary widely among hepatologists, gastroenterologists, and advanced endoscopists who manage these patients, even within a single health care system. Further studies are needed to address these variations, develop general and evidence‐based consensus, and increase adherence to societal guidelines. (Hepatology Communications 2018;2:836‐844)

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“…Fluorescence in situ hybridization (FISH) has been increasingly used to facilitate the identification of neoplastic cells in cytologic specimens [27] . In one study, 20% of patients with cholangiocarcinoma missed by conventional cytology were identified by FISH without affecting the specificity [28] . Several studies have evaluated the diagnostic yield of endoscopic US fine needle aspiration in patients with biliary strictures [29][30][31][32] .…”

Section: Discussionmentioning

confidence: 99%

Differentiation of malignant and benign proximal bile duct strictures: The diagnostic dilemma

Kloek¹,

Delden²,

Erdogan³

et al. 2008

WJG

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AIM:To identify the criteria for the differentiation of hilar cholangiocarcinoma (HCCA) from benign strictures. METHODS: A total of 68 patients underwent resection of lesions suspicious for HCCA between 1998 and 2006. The results of laboratory investigations, imaging studies and brush cytology were collected. These findings were analyzed to obtain the final diagnosis. RESULTS: Histological examination of the resected specimens confirmed HCCA in 58 patients (85%, group Ⅰ) whereas 10 patients (15%, group Ⅱ) were diagnosed to have benign strictures. The most common presenting symptom was obstructive jaundice in 77% patients (79% group Ⅰ vs 60% group Ⅱ, P = 0.23). Laboratory findings showed greater elevation of transaminase levels in group Ⅰ compared to group Ⅱ. The various imaging modalities showed vascular involvement exclusively in the malignant group (36%, P < 0.05). Brush cytology was positive for malignant cells in only 50% patients in group Ⅰ whereas none in group Ⅱ showed malignant cells. CONCLUSION: Despite improvements in imaging techniques, 10 patients (15%) with a presumptive diagnosis of HCCA were ultimately found to have benign strictures. Except for vascular involvement which was associated significantly with malignancy, there were no conclusive features of malignancy on regular imaging modalities. This uncertainty should be taken into account when patients with a suspicious lesion at the liver hilum are considered for resection.

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Advanced Cytologic Techniques for the Detection of Malignant Pancreatobiliary Strictures

Cited by 297 publications

References 29 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

Dominant strictures in primary sclerosing cholangitis: A multicenter survey of clinical definitions and practices

Differentiation of malignant and benign proximal bile duct strictures: The diagnostic dilemma

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