The recently identified claudins are dominant components of tight junctions, responsible for cell adhesion, polarity and paracellular permeability. Certain claudins have been shown to have relevance in tumor development, with some of them, especially claudin-4, even suggested as future therapeutic target. The aim of the present study was to analyze the expression of claudin-4 in the biliary tree, biliary tract cancers and hepatocellular carcinomas. A total of 107 cases were studied: 53 biliary tract cancers, 50 hepatocellular carcinomas, 10 normal liver and 10 normal extrahepatic biliary duct samples. Immunohistochemical analysis was performed on conventional specimens and on tissue microarrays as well. Claudin-4 was further investigated by Western blot analysis and real-time RT-PCR. Intense membranous immunolabeling was found for claudin-4 in all biliary tract cancers unrelated to the primary site of origin, namely intrahepatic, extrahepatic or gallbladder cancers. Normal biliary epithelium showed weak positivity for claudin-4. In contrast, normal hepatocytes and tumor cells of hepatocellular carcinomas did not express claudin-4. The results of Western immunoblot analysis and real-time RT-PCR were in correlation with the immunohistochemical findings. Cytokeratins, as CK7 (92%) and CK19 (83%) were mostly positive in biliary tract cancers, however, one-third of hepatocellular carcinomas also expressed CK7 (34%). HSA antibody (HepPar1) reacted with the majority of hepatocellular carcinomas (86%), while being positive in a low percentage of the biliary tract cancers (8%). In conclusion, this is the first report of a significantly increased claudin-4 expression in biliary tract cancers, which represents a novel feature of tumors of biliary tract origin. Claudin-4 expression seems to be a useful marker in differentiating biliary tract cancers from hepatocellular carcinomas and could well become a potential diagnostic tool.

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BackgroundContinuous Glucose Monitoring (CGM) has become an increasingly investigated tool, especially with regards to monitoring of diabetic and critical care patients. The continuous glucose data allows the calculation of several glucose variability parameters, however, without specific application the interpretation of the results is time-consuming, utilizing extreme efforts. Our aim was to create an open access software [Glycemic Variability Analyzer Program (GVAP)], readily available to calculate the most common parameters of the glucose variability and to test its usability.MethodsThe GVAP was developed in MATLAB® 2010b environment. The calculated parameters were the following: average area above/below the target range (Avg. AUC-H/L); Percentage Spent Above/Below the Target Range (PATR/PBTR); Continuous Overall Net Glycemic Action (CONGA); Mean of Daily Differences (MODD); Mean Amplitude of Glycemic Excursions (MAGE). For verification purposes we selected 14 CGM curves of pediatric critical care patients. Medtronic® Guardian® Real-Time with Enlite® sensor was used. The reference values were obtained from Medtronic®’s own software for Avg. AUC-H/L and PATR/PBTR, from GlyCulator for MODD and CONGA, and using manual calculation for MAGE.ResultsThe Pearson and Spearman correlation coefficients were above 0.99 for all parameters. The initial execution took 30 minutes, for further analysis with the Windows® Standalone Application approximately 1 minute was needed.ConclusionsThe GVAP is a reliable open access program for analyzing different glycemic variability parameters, hence it could be a useful tool for the study of glycemic control among critically ill patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12938-015-0035-3) contains supplementary material, which is available to authorized users.

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