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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.

Prehabilitation aims to increase the endurance capacity of patients who are awaiting major surgery. However, there are no studies investigating the implementation of this demanding and expensive intervention in lowincome countries. This study aimed to assess the impact of a 4-week trimodal prehabilitation program on the physical and psychological health of patients waiting for colorectal surgery compared with a control group managed according to enhanced recovery after surgery principles supplemented by nutritional care. This study was a single-centre, randomised controlled trial. The primary outcome measures for the physical aspects were 6-minute walking distance (6MWD) and incentive spirometry, whereas the psychological elements were measured using the 36-item short form survey questionnaire and the hospital anxiety and depression score. In total, data from 149 patients were analysed (77 in the prehabilitation group and 72 in the control group). At the time of surgery, patients in the prehabilitation group had improved 6MWD and incentive spirometry compared with the control group (median (IQR [range]) percentage improvement 131% (112-173 [68-376]) vs. 107% (99-120 [63-163]); p < 0.001 and 113% (100-125 [75-200]) vs. 100% (100-112 [86-167]); p < 0.001 respectively). Patients in the prehabilitation group also had reduced anxiety scores compared with the control group (mean (SD) anxiety score (4 (3) vs. 5 (3) respectively; p = 0.032). However, these effects did not translate into improvements in postoperative mortality and morbidity, or a reduction in duration of hospital stay. Trimodal (physical, emotional and nutritional) prehabilitation is able to improve functional status as well as some parameters of emotional and physical well-being of patients waiting for colorectal surgery.

In recent decades, imaging devices have become indispensable tools in the basic sciences, in preclinical research and in modern drug development. The rapidly evolving high-resolution in vivo imaging technologies provide a unique opportunity for studying biological processes of living organisms in real time on a molecular level. State of the art small-animal imaging modalities provide non-invasive images rich in quantitative anatomical and functional information, which renders longitudinal studies possible allowing precise monitoring of disease progression and response to therapy in models of different diseases. The number of animals in a scientific investigation can be substantially reduced using imaging techniques, which is in full compliance with the ethical endeavours for the 3R (reduction, refinement, replacement) policies formulated by Russell and Burch; furthermore, biological variability can be alleviated, as each animal serves as its own control. The most suitable and commonly used imaging modalities for in vivo small-animal imaging are optical imaging (OI), ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and finally the methods of nuclear medicine: positron emission tomography (PET) and single photon emission computed tomography (SPECT).

We highly recommend immunohistochemistry for clinically susceptible, nonactive chronic gastritis cases, if the conventional stain-based HP detection is negative. Moreover, we recommend to use IHC more widely as basic HP stain. Helicobacter pylori FISH technique is primarily recommended to determine bacterial clarithromycin resistance. Furthermore, it is another accurate diagnostic tool for HP.

Biliary tract cancers are relatively common malignant gastrointestinal tumors in the elderly. Claudins are integral components of tight junctions that play important roles in maintaining epithelial cell polarity, controlling paracellular diffusion, and regulating cell growth and differentiation. The expression profile of claudins has been extensively characterized, but few reports exist on their expression in the normal and neoplastic biliary tract. Our aim was therefore to study claudins by IHC reactions in normal and neoplastic biliary tract samples. We detected that claudin expressions differ in the normal sample groups: the normal gallbladder strongly expressed claudin-2, −3, −4, and −10, but only weak reactions were seen in normal intrahepatic bile ducts. Although each cancer type expressed several claudins with various intensities, only claudin-4 presented especially strong immunoreactions in extrahepatic bile duct cancers and gallbladder carcinomas, whereas claudin-1 and −10 presented in intrahepatic bile duct cancers. Comparing the normal and carcinoma groups, the most significant decrease was detected in the expression of claudin-10. In conclusion, the expression pattern of claudins is different in the various parts of the normal and neoplastic biliary tract; moreover, an unequivocal decrease was detected in the carcinomas compared with their corresponding normal samples. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

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