Quantitative profiling of genes associated with cancer pathways in brain tumors.

BACKGROUND: Brain tumors are a heterogeneous group of malignancies characterized by inter- and intratumoral heterogeneity. Among them, the most aggressive and, despite advances in medicine, still incurable remains glioblastoma. One of the reasons is the high recurrence rate of the disease and resistance to temozolomide, a golden standard in chemotherapy of brain tumors. Therefore, mapping the pathways responsible for tumorigenesis at the transcriptional level may help to determine the causes and aggressive behavior among different glial tumors. PATIENTS AND METHODS: Biopsies from patients with astrocytoma (N = 6), glioblastoma (N = 22), and meningioma (N = 14) were included in the sample set. A control group consisted of RNA isolated from healthy human brain (N = 3). The reverse-transcribed cDNAs were analyzed using the Human Cancer PathwayFinder™ real-time PCR Array in a 96-well format. The expression of 84 genes belonging to 9 signaling pathways (angiogenesis, apoptosis, cell cycle and senescence, DNA damage and repair, epithelial-to-mesenchymal transition, hypoxia, overall metabolism, and telomere dynamics) was determined for each sample. RESULTS: By determining the relative expression of selected genes, we characterized the transcriptomic profile of individual brain malignancies in the context of signaling pathways involved in tumorigenesis. We observed deregulation in 50, 52.4 and 53.6% % of the genes in glioblastomas, meningiomas and astrocytomas, respectively. The most pronounced changes with statistical significance compared to control were observed in the genes associated with epithelial-to-mesenchymal transition (CDH2, FOXC2, GSC, SNAI2, and SOX10), cellular senescence (BMI1, ETS2, MAP2K1, and SOD1), DNA repair (DDB2, ERCC3, GADD45G, and LIG4), and dynamic of telomeres (TEP1, TERF2IP, TNKS, and TNKS2). CONCLUSION: Based on the obtained data, we can conclude that individual diagnoses differ in transcriptomic profile. An individual molecular approach is therefore necessary in order to provide comprehensive and targeted therapy on multiple metabolic pathways in the diagnosis of brain tumors.

Noninvasive study of brain tumours metabolism using phosphorus-31 magnetic resonance spectroscopy.

Phosphorus-31 magnetic resonance spectroscopy (31P MRS) is currently not accepted as a diagnostic tool in the neuro-oncological practice, although it provides useful non-invasive information about biochemical processes ongoing in the intracranial tumours. This pilot study was aimed to present the diagnostic capability of the 31P MRS in brain tumour examination, even its application on clinical 1.5T MR scanner.Seven patients with brain tumorous lesions (four glioblastomas, one ependymoma, and two lung metastasis) underwent multivoxel in vivo 31P MRS performed on clinical 1.5 T MR scanner within measurement time of 20 minutes. Comparing two selected voxels, one in the tumour and the other one in the normal-appearing brain tissue, enabled to investigate their metabolic differences. Enhanced markers of membrane phospholipids synthesis (significantly increased phosphomonoesters ratios) than markers of their degradation (significantly decreased phosphodiesters ratios) manifested a higher cell proliferation ongoing in tumours. High energetic tumorous tissue demands leading to anaerobic metabolic turnover were present as a significant decline in phosphocreatine ratios and adenosine triphosphates. Intracellular pH evaluation showed a tumorous tendency to alkalize. 31P MRS enables the non-invasive metabolic characterization of intracranial tumours and thus appears to be a clinically useful method for the determination of ongoing tumour pathomechanisms (Fig. 2, Ref. 26). Keywords: brain tumour, 31P MRS, 1.5 Tesla; energetic metabolism.

Quantitative analysis of 2-hydroxyglutarate as a controversial oncometabolite in malignant gliomas.

There is a great effort to connect the accumulation of 2-hydroxyglutarate (2-HG) oncometabolite with cellular onco-epigenetic status and subsequently predict the prognoses of glioma patients. In this observational study, the concentrations of D- and L- 2-HG were determined in 57 tumor tissue samples of glioma patients (n=57) WHO grade I through IV (astrocytoma, oligodendroglioma, secondary glioblastoma, and glioblastoma multiforme) in vitro. Also, genetic mutation status on isocitrate dehydrogenase 1 and 2 (IDH 1/2) was determined from these samples. The objective of this study was to confirm or to reject the hypothesis of the direct correlation of 2-HG concentration in tumor tissue and the results from IDH 1/IDH 2 point mutation analyses. The concentrations of 2-HG were quantified using high sensitive HPLC and Q-TOF HRMS spectrometer setup. Concurrently, the genetic mutation analyses of both IDH 1 (cytosolic) and IDH 2 (mitochondrial) were performed by the isolation of tumor tissue DNA, PCR amplification, and subsequent Sanger forward sequencing. Our results indicate that there is no definite correlation between the two as we identified cases of glioma tumors with significantly increased concentration of one or both L- and D- 2-HG but no IDH 1/2 mutations (44% 2-HG positive cases).

Is there an impact of subdural drainage duration and the number of burr holes on the recurrence rate of unilateral chronic subdural haematoma?

INTRODUCTION: Purpose of the study is to evaluate a possible influence of subdural drainage duration and burr hole quantity on a relapse of a unilateral chronic subdural haematoma (CHSH). METHODS: Sixty - five patients who underwent evacuation of unilateral CHSH via 1 or 2 burr holes and subdural drainage during a period from January 2014 to December 2018 were retrospectively analyzed. Duration of the subdural drainage and the number of burr holes used were assessed in relation to an incidence of CHSH recurrence. According to the subdural drainage duration, we divided the patient cohort into two subgroups: with the subdural drainage duration of 1-3 days and 4-5 days. We also evaluated a possible influence of the subdural drainage duration on risk of postoperative infection. RESULTS: An overall incidence of CHSH recurrence was 18.5%. In 45 patients treated by means of a single burr hole the haematoma recurrence was observed in 10 patients (22.2%), in 22 patients with two burr holes recurrence occurred in 2 of them (9.1%). The difference was however, not statistically significant (p=0.3214). We did not observe any significant influence of age, gender and subdural drainage duration on the incidence of CHSH recurrence. The duration of subdural drainage had not significant impact on postoperative infection rate (p=0.0950). CONCLUSION: The number of burr holes used does not affect the rate of unilateral CHSH recurrence. Similarly the duration of subdural drainage affects neither the unilateral CHSH recurrence rate nor the incidence of postoperative infection.

Dysphagia after anterior cervical discectomy and interbody fusion - prospective study with 1-year follow-up.

INTRODUCTION: Dysphagia is a common finding after anterior cervical discectomy. The incidence and severity of swallowing disorders are variable and depend on many factors. METHODS: 73 patients after 1- or 2-level anterior cervical discectomy and fusion /ACDF/ were enrolled in prospective, single-center study. The severity of dysphagia was evaluated by the Bazaz-Yoo dysphagia score before surgery and 6 weeks, 3, 6 and 12 months after surgery. The impact of factors such as sex, age, number of operated segments, smoking, gastroesophageal reflux disease, hypertension, duration of surgery and pre-existing dysphagia on the incidence of dysphagia after surgery was verified. The correlation between the duration of surgery and severity of postoperative dysphagia, and similarly between the age and severity of preoperative and postoperative dysphagia was studied. RESULTS: Dysphagia was present in 22% patients within 12 months after surgery. No patient reported severe dysphagia. No significant relationship was demonstrated between sex, age, number of operated segments, pre-existing dysphagia, gastroesophageal reflux disease, hypertension and the incidence of dysphagia after surgery. Smokers showed a significantly lower incidence of dysphagia before surgery and within 12 months after ACDF (p.

[The role of contrast-enhanced pulse inversion harmonic imaging (CEUS) and contrast-enhanced computed tomography (CECT) in the preoperative diagnosis of renal lesions]. / Die Rolle von kontrastmittelverstärktem "pulse inversion harmonic imaging" (CEUS) und kontrastmittelverstärkter Computertomographie (CECT) bei der präoperativen Diagnose von renalen Raumforderungen.

OBJECTIVE: The preoperative assessment of structural and functional changes in renal tumors using contrast-enhanced pulse inversion harmonic imaging (CEUS) and contrast-enhanced computed tomography (CECT). MATERIALS AND METHODS: All consecutive patients referred to two tertiary hospitals for surgery on suspicion of a malignant renal lesion, who had been examined under the predefined study protocol using CEUS and CECT, were prospectively included in the study. All renal lesions suspected of being malignant were subjected to histopathological examination. Lesions expected to be benign were followed up according to the study protocol. The accuracy of CEUS and CECT with the final histology or follow-up results and the statistically significant difference between the two imaging techniques was calculated. RESULTS: Over a period of 3 years (2008-2011), 68 of 93 patients examined met the study criteria. The prevalence of malignant tumors in the study was 72%. Fifty four (79%) patients underwent surgery and had a histologically confirmed renal tumor (clear cell carcinoma 45, urothelial papillocarcinoma 4, angiomyolipoma 1, oncytoma 3, xanthogranulomatous pyelonephritis 1) and 14 (21%) patients underwent regular follow-up. Specificity, sensitivity and area under the curve (AUC) reached 57.9%, 98% and 0.779 for CEUS and 52.6%, 98% and 0.753 for CECT. CONCLUSION: The results show that both imaging methods can reliably rule out malignant disease due to absence of enhancement. Taking into consideration that CEUS can be carried out without severe risk or discomfort, it is time to reconsider CEUS as the method of choice for diagnosis, while CECT should be reserved for staging.

Surgical site infections after degenerative lumbar spine surgery.

Degenerative lumbar spine disease is nowadays considered as a serious health condition, because the number of patients requiring a surgical intervention is in last decades rapidly increasing. At the time of surgery indication, it is important to assess the risk of complications incidence, especially surgical ones, because when they occur, they usually lead to reoperation, prolonged hospitalisation and drug use, economic consequences and a compromised postoperative outcome and benefits. Postoperative infectious complications may occur, even after following aseptic and hygienic epidemiological rules. This article contains an interdisciplinary review of diagnosis, treatment and prevention of postoperative surgical site infections after degenerative lumbar spine surgery. Key words: postoperative complications lumbar spine surgical treatmens - spondylodiscitis.

[Screening of celiac disease in patients with osteoporosis and osteopenia]. / Screening celiakie a pacientu s osteoporózou a osteopenií.

The celiac disease is traditionally viewed as the children's disease with a typical form accompanied mainly by intestinal symptoms and malabsorption. This opinion is still generally accepted by the medical community. Findings based on the area-wide screening show that the prevalence has risen from the original 1 : 1 000-1 500 to 1 : 70-550. The average prevalence in the western countries is nearly 1 : 100. The prevalence of the celiac disease in the Czech republic is estimated to be approximately 1 : 200-250. It means that the number of people in the Czech republic who are likely to be affected is about 40,000-50,000 people. Currently only 10-15% of the total number of the ill people are diagnosed and monitored. Adult patients represent the main diagnostic problem because their clinical pictures are individual and the main symptoms are atypical (nonenteral). These are anaemia (mainly sideropnic), early/premature osteoporosis, herpetiformic (Duhring) dermatitis, polyneurititis, ataxia, depression, behavioural disorders, menstrual cycle disorders and infertility. Therefore our attention is currently focused on the screening of these groups of subjects. The purpose of our study was to check the frequency of the celiac disease with patients with diagnosed osteoporosis and osteopenia. In our study we have confirmed the assumption that the prevalence ofthe celiac disease in the group of subjects was 1 : 50, which means that 2.2% of patients with osteoporosis and osteopenia are affected by celiac sprue and therefore screening examination of these patients with the subsequent causal treatment (gluten-free diet) is recommended.