Parameters affecting the enhanced permeability and retention effect: the need for patient selection

The enhanced permeability and retention (EPR) effect constitutes the rationale by which nanotechnologies selectively target drugs to tumors. Despite promising pre-clinical and clinical results, these technologies have, in our view, underachieved compared to their potential, possibly due to a suboptimal exploitation of the EPR effect. Here, we have systematically analyzed clinical data to identify key parameters affecting the extent of the EPR effect. An analysis of 17 clinical studies showed that the magnitude of the EPR effect was varied and was influenced by tumor type and size. Pancreatic, colon, breast, and stomach cancers showed the highest levels of accumulation of nanomedicines. Tumor size also had an effect on the accumulation of nanomedicines, with large size tumors having higher accumulation than both medium- and very large- sized tumors. However, medium tumors had the highest percentage of cases (100% of patients) with evidence of the EPR effect. Moreover, tumor perfusion, angiogenesis, inflammation in tumor tissues, and other factors also emerged as additional parameters that might affect the accumulation of nanomedicines into tumors. At the end of the commentary, we propose two strategies for identification of suitable patient sub-populations, with respect to the EPR effect, in order to maximize therapeutic outcome

Ultrasound biomicroscopy in diagnosis of anterior segment pathology

Introduction. Ultrasound biomicroscopy (UBM) is a non-invasive diagnostic procedure, developed in order to achieve better visualization of the anterior segment of the eye. The first clinical images were made in March 1990. The use of UBM at the Institute for Eye Diseases, Clinical Centre of Serbia, began in February 2007. Outline of Cases. Due to a drop in visual acuity, the first patient was sent to the Institute for Eye Diseases, Clinical Centre of Serbia. The existence of the ciliary body tumour was suspected, so she underwent a UBM diagnostic procedure. UBM showed fibrin in the anterior chamber of the eye, occlusion of the pupil, and the absence of tumour. The second patient had a part of the chamber angle filled with solid lesion. UBM showed a solid tumour lesion filling the chamber angle in the lower part of the anterior chamber. The origin of the tumour was the ciliary body rather than the choroid which was shown by the B scan ultrasound. Lipodermoid was found by clinical examination of the third patient. He underwent UBM in order to exclude the involvement of the sclera under the lesion. UBM visualized a subconjunctival lesion lying on the sclera, reaching the limbus of the cornea. The difference in ultrasound reflection of the two tissues helped us to confirm that the sclera was not involved. Our fourth patient underwent an antiglaucomatous procedure, and the assessment of the chamber angle opening was the reason for the UBM examination. Parameters measured in the lower quadrants (6 o'clock) that we managed to obtain were the following: AOD (250 μm) - 180 μm, AOD (500 μm) - 400 μm, TIA - 34.39 deg., ARA - 0.25 mm2. Comparing them to normal values, we came to the conclusion that the chamber angle was open in the lower part of the anterior chamber. Conclusion. Ultrasound biomicroscopy gives us plenty of useful information when it comes to diagnosing the anterior chamber pathology

The redox state of young female handball players following acute exercise and a one-month precompetitive training period

Although the relationship between exercise and oxidative stress has been intensively investigated for over 3 decades, there remains a lack of empirical data on exercise-induced oxidative stress in athletes engaged in sporting games, specifi cally among the population of elite female athletes. Blood samples were taken from female handball players on the Serbian U20 national team at the beginning and end of a one-month preparatory training period, as well as immediately before and after acute treadmill exercise. Levels of superoxide anion radical, hydrogen peroxide, nitric oxide and lipid peroxidation were measured in plasma samples, while levels of reduced glutathione and the activity of superoxide dismutase and catalase were measured in erythrocytes. Both experimental protocols demonstrated signifi cant increases in plasma levels of hydrogen peroxide and decreases in superoxide dismutase activity in erythrocytes. Despite the increase in plasma levels of hydrogen peroxide after both the treadmill exercise and the one-month training period, the levels of the two antioxidants responsible for eliminating H2O2 hydrogen peroxide were not signifi cantly diff erent, as may be expected. Moreover, the marker of lipid peroxidation, TBARS, was not signifi cantly increased. Th ese fi ndings suggest that the fi rst line of antioxidative defence was eff ective in the prevention of oxidative stress among young female handball players

The Utility of Conventional CT, CT Perfusion and Quantitative Diffusion-Weighted Imaging in Predicting the Risk Level of Gastrointestinal Stromal Tumors of the Stomach: A Prospective Comparison of Classical CT Features, CT Perfusion Values, Apparent Diffusion Coefficient and Intravoxel Incoherent Motion-Derived Parameters

Background: The role of advanced functional imaging techniques in prediction of pathological risk categories of gastrointestinal stromal tumors (GIST) is still unknown. The purpose of this study was to evaluate classical CT features, CT-perfusion and magnetic-resonance-diffusion-weighted-imaging (MR-DWI)-related parameters in predicting the metastatic risk of gastric GIST. Patients and methods: Sixty-two patients with histologically proven GIST who underwent CT perfusion and MR-DWI using multiple b-values were prospectively included. Morphological CT characteristics and CT-perfusion parameters of tumor were comparatively analyzed in the high-risk (HR) and low-risk (LR) GIST groups. Apparent diffusion coefficient (ADC) and intravoxel-incoherent-motion (IVIM)-related parameters were also analyzed in 45 and 34 patients, respectively. Results: Binary logistic regression analysis revealed that greater tumor diameter (p < 0.001), cystic structure (p < 0.001), irregular margins (p = 0.007), irregular shape (p < 0.001), disrupted mucosa (p < 0.001) and visible EFDV (p < 0.001), as well as less ADC value (p = 0.001) and shorter time-to-peak (p = 0.006), were significant predictors of HR GIST. Multivariate analysis extracted irregular shape (p = 0.006) and enlarged feeding or draining vessels (EFDV) (p = 0.017) as independent predictors of HR GIST (area under curve (AUC) of predicting model 0.869). Conclusion: Although certain classical CT imaging features remain most valuable, some functional imaging parameters may add the diagnostic value in preoperative prediction of HR gastric GIST

CT and FDG-PET/CT findings in progressive mediastinal idiopathic fibrosis as a benign mimicker of esophageal carcinoma: a case report

Idiopathic mediastinal fibrosis, also called sclerosing or fibrosing mediastinitis, is a very rare and aggressive fibroinflammatory process characterized by fibrous tissue proliferation in the mediastinal region. Herein, we present a rare case of idiopathic mediastinal fibrosis presenting with esophageal obstruction, most likely associated with immunoglobulin G (IgG4)-related disease, affecting the posterior mediastinum with intrapulmonary infiltration. Computed tomography revealed a narrowed lumen and thickened wall of the distal esophagus surrounded by a necrotic mass with infiltration into the nearby structures, suggesting a locally advanced malignant process. Positron emission tomography revealed intense accumulation of 18F-fluorodeoxyglucose, indicating an active inflammatory component, which complicates further differential diagnosis of mediastinal masses. Thoracoscopic biopsy and immunohistochemical analysis confirmed a fibroinflammatory process with perivascular lymphoid cell infiltration that was cluster of differentiation (CD)3 (++) and CD20 (++), with massive numbers of IgG4-immunoreactive plasma cells. Although a benign condition, sclerosing mediastinitis is a close mimicker of esophageal carcinoma, which cannot be differentiated by computed tomography or positron emission tomography and must be considered in a differential diagnosis