Revolutionizing Glioblastoma Treatment: A Comprehensive Overview of Modern Therapeutic Approaches.

Glioblastoma is the most common malignant primary brain tumor in the adult population, with an average survival of 12.1 to 14.6 months. The standard treatment, combining surgery, radiotherapy, and chemotherapy, is not as efficient as we would like. However, the current possibilities are no longer limited to the standard therapies due to rapid advancements in biotechnology. New methods enable a more precise approach by targeting individual cells and antigens to overcome cancer. For the treatment of glioblastoma, these are gamma knife therapy, proton beam therapy, tumor-treating fields, EGFR and VEGF inhibitors, multiple RTKs inhibitors, and PI3K pathway inhibitors. In addition, the increasing understanding of the role of the immune system in tumorigenesis and the ability to identify tumor-specific antigens helped to develop immunotherapies targeting GBM and immune cells, including CAR-T, CAR-NK cells, dendritic cells, and immune checkpoint inhibitors. Each of the described methods has its advantages and disadvantages and faces problems, such as the inefficient crossing of the blood-brain barrier, various neurological and systemic side effects, and the escape mechanism of the tumor. This work aims to present the current modern treatments of glioblastoma.

Magnetic resonance imaging (MRI) for local staging before salvage radical prostatectomy: a meta-analysis.

PURPOSE: The reliability of magnetic resonance imaging (MRI) as a local and nodal staging tool in radio-recurrent prostate cancer (PCa) is still unclear. The present study aims at evaluating the predictive value of MRI in the detection of extracapsular extension (ECE), seminal vesical invasion (SVI) and nodal involvement (LNI) in patients after primary radio (EBRT) and/or brachytherapy (BT) before salvage radical prostatectomy (SRP). METHODS: This systematic review and meta-analysis were performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Pubmed, Scopus, and Web of Science databases were systemically reviewed to extract the data on diagnostic performance of MRI in radio-recurrent PCa. RESULTS: Four studies comprising 94 radio-recurrent PCa patients were included. The pooled prevalence of ECE, SVI, and LNI was 61%, 41%, and 20%, respectively. The pooled sensitivity for ECE, SVI and LNI detection was 53% (CI 95% 19.8-83.6%), 53% (CI 95% 37.2-68%) and 33% (CI 95% 4.7-83.1%) respectively, whereas specificity was 75% (CI 95% 40.6-92.6%), 88% (CI 95% 71.7-95.9%) and 92% (CI 95% 79.6-96.8%). The sensitivity analysis revealed that a single outlying study using only T2-weighted imaging instead of multiparametric MRI reported significantly higher sensitivity with significantly lower specificity. CONCLUSIONS: This is the first meta-analysis reporting reliability of staging MRI in a radio-recurrent setting. MRI provides poor sensitivity while maintaining high specificity for local and nodal staging before SRP. However, current evidence is limited to the low number of heterogenous studies at meaningful risk of bias.

Intraobserver and Interobserver Agreement between Six Radiologists Describing mpMRI Features of Prostate Cancer Using a PI-RADS 2.1 Structured Reporting Scheme.

Clinical practice has revealed ambiguities in PI-RADS v2.1 scoring, but a limited number of studies are available that validate the interreader and intrareader reproducibility of the mpMRI PI-RADS lexicon. We decomposed the PI-RADS rules into a set of common data elements to evaluate the inter- and intraobserver agreement in assessing the individual features included in the PI-RADS lexicon. Six radiologists (three highly experienced, three less experienced) in two sessions independently read thirty-two lesions in the peripheral and transition zone using the structured reporting tool, blinded to clinical MRI indication. The highest agreement between radiologists was observed for the abnormality detection, the evaluation of the type of signal intensity, and the characteristic of benign prostatic hyperplasia. Moderate agreement was reported for dynamic contrast-enhanced images. This resulted in a decrease in abnormality detection (PA = 76.5%) and enhancement indication (PA = 77.3%). The lowest agreement was observed for highly subjective features: shape, signal intensity level, and type of lesion margins. The results indicate the limitations of the PI-RADS v2.1 lexicon in relation to interreader and intrareader reproducibility. We have demonstrated that it is possible to develop structured reporting systems standardized according to the PI-RADS lexicon.

Exosome secretion and cellular response of DU145 and PC3 after exposure to alpha radiation.

Exosomes are spherical membrane nanovesicles secreted from cells, and they play an important role in tumor immune response, metastasis, angiogenesis, and survival. Studies investigating exosomes isolated from cells exposed to photon radiation commonly used in conventional radiotherapy demonstrate the influence of this type of radiation on exosome characteristics and secretion. There is currently no research investigating the effects of densely ionizing particles such as protons and alpha radiation on exosomes. Thus we have evaluated the cellular response of human prostate cancer cells exposed to 0, 2, and 6 Gy of alpha radiation emitted from the Am-241 source. Irradiated PC3 and DU145 cell lines, characterized by differences in radiosensitivity, were studied using apoptosis, LDH, and IL-6 assays. Additionally, the corresponding concentration and size of isolated exosomes were measured using NTA. We found that exposure to ionizing radiation resulted in gross changes in viability and cell damage. There were increased amounts of apoptotic or necrotic cells as a function of radiation dose. We demonstrated that irradiated PC3 cells secrete higher quantities of exosomes compared to DU145 cells. Additionally, we also found no statistical difference in exosome size for control and irradiated cells.

Brownian Motion Influence on AFM Exosomes' Size Measurements.

Extracellular vesicles are evaluated by nanoparticle tracking analysis (NTA), providing information on their hydrodynamic diameters, and by atomic force microscopy (AFM) to calculate their geometric diameters. The aim of this study is to explore the influence of Brownian movements in a sample drop and preparation time on imaging-based measurements and to determine the relationship between the geometric and hydrodynamic sizes of the extracellular vesicles measured by the AFM and the NTA, respectively. Exosomes derived from the human prostate cancer cell line PC3 were evaluated by NTA and AFM, and those results were compared with Monte Carlo simulations. The mean size, evaluated by AFM shortly after application on the mica substrate, is less than its real value. It obtains the correct value faster for a thinner sample drop. Fitting the log-normal distribution to the geometric and hydrodynamic diameters leads to the conclusion that the latter could arise from the former by linear scaling by a factor that could be used to characterize the analyzed extracellular vesicles. The size of the vesicles attached to the mica substrate depends on time. The effect of Brownian motion and stretch of the lipid bilayer should be considered in the context of exosome AFM studies.

Associations between Patient Report of Pain and Intervertebral Foramina Changes Visible on Axial-Loaded Lumbar Magnetic Resonance Imaging.

The intervertebral foramen may influence spinal nerve roots and, therefore, be related to the corresponding dermatomal pain. In vivo evaluation of the intervertebral foramen-dermatome relationship is essential for understanding low back pain (LBP) pathophysiology. The study aimed to correlate the lumbar MRI unloaded-loaded foraminal area changes with dermatomal pain in the patient's pain drawings. Dynamic changes of the dermatomal pain distribution related to the intervertebral foramen area changes between quantitative conventional supine MRI (unloaded MRI) and axial-loading MRI (alMRI) were analyzed. The MRI axial-loading intervertebral foramen area changes were observed, and the most significant effect of reducing the foraminal area (-6.9%) was reported at levels of L2-L3. The incidence of pain in the dermatomes increases linearly with the spine level, from 15.6% at L1 to 63.3% at L5 on the right and from 18.9% at L1 to 76.7% at L5 on the left. No statistically significant effect of changes in the intervertebral foramen area on the odds of pain along the respective dermatomes was confirmed. Changes in the foraminal area were observed between the unloaded and loaded phases, but differences in area changes between foramen assigned to painful dermatomes and foramen assigned to non-painful dermatomes were not significant.

High-resolution, three-dimensional magnetic resonance imaging axial load dynamic study improves diagnostics of the lumbar spine in clinical practice.

BACKGROUND: The response to axial physiological pressure due to load transfer to the lumbar spine structures is among the various back pain mechanisms. Understanding the spine adaptation to cumulative compressive forces can influence the choice of personalized treatment strategies. AIM: To analyze the impact of axial load on the spinal canal's size, intervertebral foramina, ligamenta flava and lumbosacral alignment. METHODS: We assessed 90 patients using three-dimensional isotropic magnetic resonance imaging acquisition in a supine position with or without applying an axial compression load. Anatomical structures were measured in the lumbosacral region from L1 to S1 in lying and axially-loaded magnetic resonance images. A paired t test at α = 0.05 was used to calculate the observed differences. RESULTS: After axial loading, the dural sac area decreased significantly, by 5.2% on average (4.1%, 6.2%, P < 0.001). The intervertebral foramina decreased by 3.4% (2.7%, 4.1%, P < 0.001), except for L5-S1. Ligamenta flava increased by 3.8% (2.5%, 5.2%, P < 0.001), and the lumbosacral angle increased. CONCLUSION: Axial load exacerbates the narrowing of the spinal canal and intervertebral foramina from L1-L2 to L4-L5. Cumulative compressive forces thicken ligamenta flava and exaggerate lumbar lordosis.

Relationship Among the Foraminal Area and Demographic and Clinical Characteristics of Patients with Low Back Pain.

OBJECTIVE: Our study aims to contribute to existing knowledge by evaluating patients with low back pain to provide a more accurate relationship between the diameter of the intervertebral foramen and the clinical, demographic, and lumbar spine anatomic factors such as age, sex, body mass index, the Zurich Claudication Questionnaire, facet joint, intervertebral disc, ligamentum flavum, and spinal canal. METHODS: We studied 90 consecutive patients who had undergone evaluation for low back pain. We used magnetic resonance imaging to assess the cross-sectional areas of the intervertebral foramina at each level of the lumbar spine together with the ligamentum flavum area and the dural sac cross-sectional area (DSCSA) measurements. The presence of disc and facet joint degeneration was evaluated and data on symptoms were obtained. RESULTS: Age (P < 0.0001), lumbar disc degeneration grade (P = 0.016), and DSCSA (P < 0.0001) were found to statistically significantly influence the foraminal area (FA). The mean FA at all lumbar levels increased with increasing DSCSA. The mean FA decreased with age at all levels except L5/S1. Lumbar disc degeneration grade 1-3 increased the mean FA at L5/S1, but not at other levels. No statistically significant effects of the side of the measurement, sex, body mass index, Zurich Claudication Questionnaire score, ligamentum flavum area, or facet joint degeneration were found. CONCLUSIONS: The results of the present study allow us to quantify the effect of age, DSCSA, and lumbar disc degeneration grade on the FA.

Axially Loaded Magnetic Resonance Imaging Identification of the Factors Associated with Low Back-Related Leg Pain.

This retrospective observational study was conducted to identify factors associated with low back-related leg pain (LBLP) using axially loaded magnetic resonance imaging (AL-MRI). Ninety patients with low back pain (LBP) underwent AL-MRI of the lumbar spine. A visual analog scale and patient pain drawings were used to evaluate pain intensity and location and determine LBLP cases. The values of AL-MRI findings were analyzed using a logistic regression model with a binary dependent variable equal to one for low back-related leg pain and zero otherwise. Logistic regression results suggested that intervertebral joint effusion (odds ratio (OR) = 4.58; p = 0.035), atypical ligamenta flava (OR = 5.77; p = 0.003), and edema of the lumbar intervertebral joint (OR = 6.41; p = 0.003) were more likely to be present in LBLP patients. Advanced disc degeneration (p = 0.009) and synovial cysts (p = 0.004) were less frequently observed in LBLP cases. According to the AL-MRI examinations, the odds of having LBLP are more likely if facet effusion, abnormal ligamenta flava, and lumbar facet joint edema are present on imaging than if not. The assessment of lumbar spine morphology in axial loaded MRI adds value to the potential understanding of LBLP, but further longitudinal and loaded-unloaded comparative studies are required to determine the role of acute dynamic changes and instability in LBLP development.

Computed tomography-guided percutaneous radiofrequency and laser ablation for the treatment of osteoid osteoma - long-term follow-up from 5 to 10 years.

PURPOSE: The impact of computed tomography (CT)-guided, percutaneous radiofrequency ablation and interstitial laser ablation (ILA) on the management of patients with osteoid osteoma was studied. This was carried out by assessing immediate and long-term clinical outcomes, the complication rate, and repeat therapy effectiveness in recurrent patients who have already experienced percutaneous ablation. MATERIAL AND METHODS: Consecutive patients with osteoid osteoma were assessed before the interventional treatment in a single centre from 2010 to 2015. Patient demographics, complications, and recurrence were recorded. The pain was evaluated with Visual Analogue Scale (VAS). Percutaneous procedures were performed by means of radiofrequency thermoablation or ILA. Epidural or regional anaesthesia in the CT suite was applied in all procedures. Success, whether primary or secondary, was measured as complete pain relief without evidence of recurrence after the first or second procedure, respectively. Osteoid osteoma characteristics, procedure overview, and technical success were looked for in pre-procedural and procedural scans. RESULTS: Eighty-three per cent of osteoid osteomas were located in lower extremities, 56% of tumours were intracortical, and 83% of osteoid osteomas were extra-articular. The mean pre-procedure VAS score was 8.5 ± 0.8, while the overall primary success rate of radiofrequency thermoablation and ILA was 87.5%. No major complications were noted. The mean follow-up period for patients in was 7.5 years (5.0-10.2 years). CONCLUSIONS: Percutaneous, CT-guided thermoablation proved to be effective and should become the method of choice in osteoid osteoma treatment because of its minimal invasiveness. Our results show that there is no risk of very late recurrence after achieving primary and secondary treatment success.

Current Perspectives on Clinical Use of Exosomes as a Personalized Contrast Media and Theranostics.

An appropriate combination of biomarkers and imaging technologies will become standard practice in the future. Because the incidence of and mortality from cancers is rising, the further study of new approaches for the early detection and precise characterization of tumors is essential. Extracellular vesicles (EVs), including exosomes, prove to have great potential when it comes to diagnosis and targeted therapy. Due to their natural ability to pass through biological barriers, depending on their origin, EVs can accumulate at defined sites, including tumors, preferentially. This manuscript discusses the difficulties and simplicities of processing cell-derived materials, packaging diverse groups of agents in EVs, and activating the biological complex. Developing exosome-based diagnostic techniques to detect disease precisely and early as well as treat disease marks a new era of personalized radiology and nuclear medicine. As circulating drug delivery vehicles for novel therapeutic modalities, EVs offer a new platform for cancer theranostic.

Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers.

Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. Exosomes are involved in angiogenesis in cancer progression by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and microRNAs. Exosomes promote angiogenesis by suppressing expression of factor-inhibiting hypoxia-inducible factor 1 (HIF-1). Uptake of tumor-derived exosomes (TEX) by normal endothelial cells activates angiogenic signaling pathways in endothelial cells and stimulates new vessel formation. TEX-driven cross-talk of mesenchymal stem cells (MSCs) with immune cells blocks their anti-tumor activity. Effective inhibition of tumor angiogenesis may arrest tumor progression. Bevacizumab, a VEGF-specific antibody, was the first antiangiogenic agent to enter the clinic. The most important clinical problem associated with cancer therapy using VEGF- or VEFGR-targeting agents is drug resistance. Combined strategies based on angiogenesis inhibitors and immunotherapy effectively enhances therapies in various cancers, but effective treatment requires further research.

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy.

Tumor-derived exosomes (TEX) are involved in cancer development, metastasis, and disease progression. They can modulate angiogenesis to elevate the malignant degree of tumor cells. TEX carry immunosuppressive factors affecting the antitumor activities of immune cells. Tumor cells as well as immune cells secrete immunologically active exosomes which affect intercellular communication, antigen presentation, activation of immune cells, and immune surveillance. Cell proliferation and immune response suppression create a favorable microenvironment for tumor. TEX can inhibit immune cell proliferation, induce apoptosis of activated CD8+ Teffs, suppress NK cell activity, interfere with monocyte differentiation, and promote Treg as well as MDSC expansion. Exosomes of microenvironment cells may also contribute to the development of drug resistance in cancer therapy. An important role of TEX in modulating the sensitivity of tumor cells to immunotherapy is a promising area of research to make the cancer therapy more successful.

Exosomes in Prostate Cancer Diagnosis, Prognosis and Therapy.

Prostate cancer (PCa) is the second most common cause of cancer-related mortality among men in the developed world. Conventional anti-PCa therapies are not effective for patients with advanced and/or metastatic disease. In most cases, cancer therapies fail due to an incomplete depletion of tumor cells, resulting in tumor relapse. Exosomes are involved in tumor progression, promoting the angiogenesis and migration of tumor cells during metastasis. These structures contribute to the dissemination of pathogenic agents through interaction with recipient cells. Exosomes may deliver molecules that are able to induce the transdifferentiation process, known as "epithelial to mesenchymal transition". The composition of exosomes and the associated possibilities of interacting with cells make exosomes multifaceted regulators of cancer development. Extracellular vesicles have biophysical properties, such as stability, biocompatibility, permeability, low toxicity and low immunogenicity, which are key for the successful development of an innovative drug delivery system. They have an enhanced circulation stability and bio-barrier permeation ability, and they can therefore be used as effective chemotherapeutic carriers to improve the regulation of target tissues and organs. Exosomes have the capacity to deliver different types of cargo and to target specific cells. Chemotherapeutics, natural products and RNA have been encapsulated for the treatment of prostate cancers.

Predicting side-specific prostate cancer extracapsular extension: a simple decision rule of PSA, biopsy, and MRI parameters.

OBJECTIVE: To develop an easy-to-use side-specific tool for the prediction of prostate cancer extracapsular extension (ECE) using clinical, biopsy, and MRI parameters. MATERIALS AND METHODS: Retrospective analysis of patients who underwent radical prostatectomy preceded by staging multiparametric MRI of the prostate was performed. Multivariate logistic regression analysis was used to choose independent predictors of ECE. Continuous variables were transformed to categorical ones by choosing threshold values using spline knots or testing thresholds used in previously described models. Internal validation of the rule was carried out as well as validation of other algorithms on our group was performed. RESULTS: In the analyzed period of time, 88 out of 164 patients who underwent radical prostatectomy met inclusion criteria. ECE was evidenced at radical prostatectomy in 41 patients (46.6%) and in 53 lobes (30.1%). In the multivariate analysis PSA, total percentage of cancerous tissue in cores (%PCa) and maximum tumour diameter (MTD) of Likert 3-5 lesions on MRI were independent predictors of ECE. The following rule for predicting side-specific ECE was proposed: %PCa ≥ 15% OR MTD ≥ 15 mm OR PSA ≥ 20 ng/mL. Internal validation of the algorithm revealed safe lower confidence limits for sensitivity and NPV, proving that model offers accurate risk grouping that can be safely used in decision-making. CONCLUSION: The rule developed in this study makes ECE prediction fast, intuitive, and side-specific. However, until validated externally it should be used with caution.

Diagnostic Benefits of Axial-Loaded Magnetic Resonance Imaging Over Recumbent Magnetic Resonance Imaging in Obese Lower Back Pain Patients.

STUDY DESIGN: Single center before-after case series study. OBJECTIVE: To determine when and in which kind of lower back pathologies, axial-loaded magnetic resonance imaging (MRI) provides additional benefit over recumbent MRI. SUMMARY AND BACKGROUND DATA: Systems simulating physiological axial loading of the spine in patients examined in the supine position have recently been introduced in clinical practice. However, indications for examinations with axial loading have yet to be clearly specified. METHODS: Ninety patients (46 men, 44 women, aged 20-90 yr) with lower back pain underwent lumbar spine MRI with and without axial loading. MRI was performed in a supine position on a 1.5 T system using a compression device. A high-resolution 3D T2-weighted sequence was used for image acquisition. Clinical characteristics of patients were established using questionnaire surveys and demographic data. MR images were assessed for the appearance of changes after axial loading. After determining which patients showed significant changes, logistic regression analysis was performed with 15 independent variables (clinical, demographic, and imaging-related). RESULTS: After axial loading, 48.9% of patients showed additional changes. Multivariate analysis revealed that only obesity was a statistically significant predictor of the occurrence of changes (P < 0.05). After axial loading, 11 potentially clinically relevant changes appeared in seven patients, the most common being absolute spinal stenosis (n = 7). CONCLUSION: Axial loading may increase the diagnostic value of lumbar spine MRI in patients with obesity and/or those with suspected spinal canal stenosis. LEVEL OF EVIDENCE: 4.

The value of ultrasonography in the diagnosis of varicocele.

A varicocele is described as pathologically enlarged, tortuous veins of the pampiniform plexus, leading to an increased testicular temperature and adrenal metabolite reflux into the testes. Varicocele can impair spermatogenesis and is considered to be the most common cause of male infertility. Patients may palpate a thickening in the scrotum or complain of dull scrotal or inguinal pain, which increases when standing or during erection. In the case of a sudden onset of varicocele in elderly men, it is necessary to exclude renal tumor and extend diagnostic ultrasound with the assessment of the abdominal cavity. The diagnosis of varicocele is based on medical history and physical examination, which involves palpation and observation of the scrotum at rest and during the Valsalva maneuver. Ultrasound is the imaging method of choice. The width and the number of vessels in the pampiniform plexus as well as the evaluation and measurement of regurgitation during the Valsalva maneuver are typical parameters analyzed during ultrasound assessment. However, diagnostic ultrasound is still a controversial method due to numerous and often divergent classification systems for varicocele assessment as well as its poor correlation with clinical manifestations. As a result of introduction of clear ultrasound criteria as well as the development of elastography and nuclear magnetic resonance, diagnostic imaging can play an important role in assessing the risk of damage to the testicular parenchyma, qualifying patients for surgical treatment and predicting the effects of therapy.

Percutaneous thermoablation of osteoid osteoma--a case study.

Osteoid osteoma has been traditionally treated by curettage and en bloc resection. These methods are now being replaced by low-invasive techniques. We present the description of a percutaneous thermoablation of a femoral neck osteoid osteoma performed under CT guidance in a 22-year-old female patient.

MinK gene polymorphism in the pathogenesis of lone atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is the most common type of complex arrhythmia found in everyday clinical practice. Lone AF is a particular form occurring in 2% to 31% of patients with confirmed AF. Genetic factors may underline this arrhythmia. AIM: To determine the relationship between G38S polymorphism in the MinK gene and the incidence of lone AF, and to evaluate this polymorphism as a genetic marker of susceptibility to AF. METHODS: The study involved 69 patients with lone AF and 60 control healthy subjects. Both groups included patients aged up to 65 years without cardiovascular or thyroid disease. MinK genotype was determined with PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). The MinK gene was present in two allelic forms: G and S. RESULTS: The MinK G allele was found significantly more often in patients with AF (62.32%) compared to control subjects (41.80%) (p=0.009). In the AF group GS occurred more frequently (55.07%) than GG (34.78%) and SS genotypes (10.14%). In a logistic regression model the presence of G variant was associated with increase of AF risk in the study population (OR 2.39; 95% CI 0.88-6.54; p=0.084). Presence of GG genotype was associated with significant, over 10-fold, increase of AF risk. Presence of S allele of the MinK gene met criteria of protective factor against AF in the study population. CONCLUSIONS: 1. G38S polymorphism in the MinK gene seems to be associated with incidence of lone AF in the study population. 2. GG genotype carrier state may significantly relate to increased risk of AF in the study group. 3. G38S polymorphism in the MinK gene could be used as a genetic marker of risk of lone AF.