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Differentiation of Pancreatic Cyst Types by Analysis of Rheological Behavior of Pancreatic Cyst Fluid.

ABSTRACT: Differentiation between mucinous and non-mucinous pancreatic cysts is exceedingly important and challenging, particularly as the former bears malignant transformation potential. Pancreatic cyst fluid (PCF)-based diagnostics, including analyses of biochemical markers, as well as cytology, has shown inadequate accuracy. Herein, a preliminary single-center study of 22 PCF samples, collected by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), assessed the rheological behavior of PCF and its correlation with lesion type. The dependence of PCF shear viscosity on shear rate was found to follow a power law and could be fitted using Ostwald-de Waele model. Three types of flow curves were identified, where two types correlated with non-mucinous cysts, differing by their power law exponent, and the third type corresponding to mucinous cysts. Viscosity measured at a high shear rate was shown to serve as an accurate and independent marker distinguishing between mucinous and non-mucinous cysts, with an optimal cutoff value of ?_c?=?1.3?cP The accuracy of this novel technique proved superior to string-sign, cytology, carcinoembryonic antigen, and amylase assessments. Moreover, the combined predictive value of ?_c and patient age provided for sensitivity and specificity of 100% and 95.5%, respectively. This simple and rapid diagnostic tool can be immediately implemented after EUS-FNA sampling.

SUBMITTER: Khamaysi I

PROVIDER: S-EPMC5372360 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Differentiation of Pancreatic Cyst Types by Analysis of Rheological Behavior of Pancreatic Cyst Fluid.

Khamaysi Iyad I Abu Ammar Aiman A Vasilyev Gleb G Arinstein Arkadii A Chowers Yehuda Y Zussman Eyal E

Scientific reports 20170330

Differentiation between mucinous and non-mucinous pancreatic cysts is exceedingly important and challenging, particularly as the former bears malignant transformation potential. Pancreatic cyst fluid (PCF)-based diagnostics, including analyses of biochemical markers, as well as cytology, has shown inadequate accuracy. Herein, a preliminary single-center study of 22 PCF samples, collected by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), assessed the rheological behavior of PCF an ...[more]

PMID: 28358122

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Project description:BACKGROUND:DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanced neoplasia. Several studies recently demonstrated the ability of next-generation sequencing (NGS) analysis to detect DNA mutations in pancreatic CF, but few studies have performed a systematic comparative analysis between pancreatic CF and neoplastic surgical tissue (NT). The value of CF-NGS analysis indicators for determining surgical resection necessitates evaluation. AIM:To confirm whether CF genomic profiles are a reliable malignancy predictor by comparing NGS mutational analyses of CF and NT. METHODS:Patients requiring surgery for high-risk pancreatic cysts were included in a multicenter prospective pilot study. DNA from CF (collected by endoscopic ultrasound-guided fine needle aspiration (known as EUS-FNA)) and NT (collected by surgery) were analyzed by NGS. The primary objective was to compare the mutation profiles of paired DNA samples. The secondary objective was to correlate the presence of specific mutations (KRAS/GNAS, RAF/ PTPRD/CTNNB1/RNF43/POLD1/TP53) with a final cancer diagnosis. Sensitivity and specificity were also evaluated. RESULTS:Between December 2016 and October 2017, 20 patients were included in this pilot study. Surgery was delayed for 3 patients. Concordant CF-NT genotypes were found in 15/17 paired DNA, with a higher proportion of mutated alleles in CF than in NT. NGS was possible for all pancreatic CF collected by EUS-FNA. In 2 cases, the presence of a KRAS/GNAS mutation was discordant between CF and NT. No mutations were found in 3 patients with NT or pancreatic cysts with high-grade dysplasia. The sensitivity and specificity of KRAS/GNAS mutations in CF to predict an appropriate indication for surgical resection were 0.78 and 0.62, respectively. The sensitivity and specificity of RAF/PTPRD/CTNNB1 /RNF43/POLD1/TP53 mutations in CF were 0.55 and 1.0, respectively. CONCLUSION:Mutational analyses of CF and NT were highly concordant, confirming the value of NGS analysis of CF in the preoperative malignancy assessment. However, these results need to be confirmed on a larger scale.

Project description:BackgroundThe application of advanced imaging technologies for identifying pancreatic cysts has become widespread. However, accurately differentiating between low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive intraductal papillary mucinous neoplasms (IPMNs) remains a diagnostic challenge with current biomarkers, necessitating the development of novel biomarkers that can distinguish IPMN malignancy.MethodsCyst fluid samples were collected from nine IPMN patients (3 LGD, 3 HGD, and 3 invasive IPMN) during their pancreatectomies. An integrated proteomics approach that combines filter-aided sample preparation, stage tip-based high-pH fractionation, and high-resolution MS was applied to acquire in-depth proteomic data of pancreatic cyst fluid and discover marker candidates for IPMN malignancy. Biological processes of differentially expressed proteins that are related to pancreatic cysts and aggressive malignancy were analyzed using bioinformatics tools such as gene ontology analysis and Ingenuity pathway analysis. In order to confirm the validity of the marker candidates, 19 cyst fluid samples were analyzed by western blot.ResultsA dataset of 2992 proteins was constructed from pancreatic cyst fluid samples. A subsequent analysis found 2963 identified proteins in individual samples, 2837 of which were quantifiable. Differentially expressed proteins between histological grades of IPMN were associated with pancreatic diseases and malignancy according to ingenuity pathway analysis. Eighteen biomarker candidates that were differentially expressed across IPMN histological grades were discovered-7 DEPs that were upregulated and 11 that were downregulated in more malignant grades. HOOK1 and PTPN6 were validated by western blot in an independent cohort, the results of which were consistent with our proteomic data.ConclusionsThis study demonstrates that novel biomarker candidates for IPMN malignancy can be discovered through proteomic analysis of pancreatic cyst fluid.

Dataset Information

Differentiation of Pancreatic Cyst Types by Analysis of Rheological Behavior of Pancreatic Cyst Fluid.

Publications

Differentiation of Pancreatic Cyst Types by Analysis of Rheological Behavior of Pancreatic Cyst Fluid.

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