Long-term follow-up of patients with a clinically benign extrahepatic biliary stenosis and K-ras mutation in endobiliary brush cytology

Heek, N. Tjarda van; Rauws, Erik A.; Caspers, Eric; Drillenburg, Paul; Gouma, Dirk J.

doi:10.1067/mge.2002.124561

Cited by 8 publications

(10 citation statements)

References 22 publications

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“…96 Eleven studies considered here assessed the role of K-ras gene mutations in bile or pancreatic fluids, including patients with benign and malignant pancreaticobiliary diseases, 95,[97][98][99] and metastatic lesions of solid tumors or lymphomas, each affecting the biliary system (Table 4). [100][101][102][103][104][105][106] The diagnostic yield for K-ras lesions has been found to be noticeably lower in CC as com-pared with pancreatic carcinoma (27% versus 63%). 100 Focusing the results on CC, the incidence of K-ras alterations as detected in bile ranged from 17 72 to 66% 106 (Table 4).…”

Section: K-ras and P53 Gene Mutationsmentioning

confidence: 99%

“…Recently, Gores 6 has highlighted the cross-talk of genetic alterations and their functional implications for CC such as avoiding apoptosis or inducing DNA damage, promotion of tissue invasion and metastatic spread, as well as sustained proliferation (e.g., by COX-2). Molecular candidate markers have been proposed, and recent reports by our group and others have [96][97][98][99][100][101][102][103][104][105][106]127 demonstrated the feasibility of detecting molecular lesions within endoscopically retrieved bile specimens or blood samples.…”

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confidence: 99%

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Serum and Bile Markers for Cholangiocarcinoma

2004

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Surgery remains the only curative treatment option for cholangiocarcinoma (CC). Currently, both early identification of CC in affected individuals at high risk and accurate diagnosis of unexplained biliary strictures are problematic. However, growing insights into biochemical and molecular mechanisms underlying biliary carcinogenesis have suggested serum and bile markers for the diagnosis of CC. These tools include tumor antigens or products (e.g., carbohydrate antigen [CA] 19-9), cytokines (e.g., interleukin-6), metabolic products (e.g., lactate), proteases (e.g., trypsinogen-2), regulatory peptides (e.g., pancreatic polypeptide), and (epi-)genetic lesions (e.g., K- ras and p53 mutations, p16 (INK4a) or p14 (ARF) promoter hypermethylation). In this article we discuss these new potential tumor markers for the diagnosis of CC.

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Section: K-ras and P53 Gene Mutationsmentioning

confidence: 99%

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confidence: 99%

Serum and Bile Markers for Cholangiocarcinoma

2004

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“…Cytologic evaluation not only aids in the diagnosis but also can spare the patient unnecessary surgery. In addition, cytologic samples can be used for molecular diagnostics and DNA image analysis, which may increase diagnostic sensitivity compared with cytology alone 9, 10. Conventionally, bile duct brushing samples are smeared on glass slides, air‐dried or wet‐fixed, and stained with Diff‐Quik (Baxter, McGraw Park, IL) or Papanicolaou (Pap) stains.…”

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Comparison of ThinPrep and conventional smears in detecting carcinoma in bile duct brushings

Siddiqui

Gokaslan

Saboorian

et al. 2003

Cancer

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BACKGROUND.Bile duct brushing cytology is a common procedure for the exclusion of adenocarcinoma in the bile duct. The authors evaluated the use of ThinPrep (TP) to determine whether the information obtained is equivalent to that found with conventional smear cytology (CS). METHODS.Thirty-eight prospectively collected endoscope retrograde cholangiopancreatography-guided bile duct brushing samples were split in the following manner. First, two to four CS were prepared and immediately spray-fixed or wet-fixed. Second, the remaining sample was rinsed in PreservCyt™ (Cytyc Corp., Boxborough, MA). In the laboratory, one TP slide was prepared from each sample.TP and CS were stained by routine Papanicolaou stain. For the current study, TP and CS were reviewed independently by two cytopathologists. The diagnoses made by the two methods were compared with the final histology. RESULTS.The cytologic diagnoses for both TP and CS were categorized into five main groups: 1) unsatisfactory, 2) negative, 3) reactive, 4) suspicious for malignancy, and 5) malignant. The diagnoses on the 38 TP bile duct brushings and CS were categorized as follows: 1) unsatisfactory-2, 4; 2) negative-7, 4; 3) reactive-10, 14; 4) suspicious for malignancy-9, 9; and 5) malignant-10, 7, respectively. Histologic follow-up was available in 14 cases (reactive-4, suspicious for malignancy-1, and malignant-9). The sensitivity was 77% for TP and 66% for CS. The specificity was 100% for both methods.CONCLUSIONS. The two methods described in the current study detected equivalent disease on bile duct brushings. TP was found to provide better preservation and cytologic detail. However, the diagnostic criteria may require modification. Cancer (Cancer Cytopathol)

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“…[36][37][38] In a previous study on the same 312 consecutive patients, we performed a longterm follow up of the eight patients with a K-ras mutation detected in brushings of clinically benign EBS. 11 After a median follow up of 65 months all eight were considered to be confirmed false positives. Few publications exist on patients who develop pancreatic cancer after an interval of more than 65 months.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the novel quantitative ARMS assay and an enriched PCR–ASO assay for K-rasmutations with conventional cytology on endobiliary brush cytology from 312 consecutive extrahepatic biliary stenoses

Heek

2005

J Clin Pathol

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Background: Extrahepatic biliary stenosis (EBS) has malignant and benign causes. Patients with EBS are at risk of having or developing malignancy. Accurate diagnostic tests for early detection and surveillance are needed. The sensitivity of biliary cytology for malignancy is low. K-ras mutation analysis on brush cytology is a valuable adjunct, but specificity is low. A quantitative test for K-ras mutations has been developed: the amplification refractory mutation system (ARMS). Aim: To assess the test characteristics and additional value of ARMS in diagnosing the cause of EBS. Methods: Brush samples from endoscopic retrograde cholangiopancreatography were collected from 312 patients with EBS. K-ras mutation analysis was performed using ARMS-allele specific amplification was coupled with real time fluorescent detection of PCR products. Results were compared with conventional cytology and K-ras mutation analysis using allele specific oligonucleotide (ASO) hybridisation, and evaluated in view of the final diagnosis. Results: The test characteristics of ARMS and ASO largely agreed. Sensitivity for detecting malignancy was 49% and 42%, specificity 93% and 88%, and positive predictive value (PPV) 96% and 91%, respectively. The sensitivity of ARMS and cytology combined was 71%, and PPV was 93%. The specificity of ARMS could be increased to 100% by setting limits for the false positives, but reduced sensitivity from 49% to 43%. Conclusions: ARMS can be considered supplementary to conventional cytology, and comparable to ASO in diagnosing malignant EBS. A specificity of 100% can be achieved with ARMS, which should be considered in the surveillance of patients at risk for pancreatic cancer.

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Long-term follow-up of patients with a clinically benign extrahepatic biliary stenosis and K-ras mutation in endobiliary brush cytology

Cited by 8 publications

References 22 publications

Serum and Bile Markers for Cholangiocarcinoma

Serum and Bile Markers for Cholangiocarcinoma

Comparison of ThinPrep and conventional smears in detecting carcinoma in bile duct brushings

Comparison of the novel quantitative ARMS assay and an enriched PCR–ASO assay for K-rasmutations with conventional cytology on endobiliary brush cytology from 312 consecutive extrahepatic biliary stenoses

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