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BackgroundMethylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome.MethodsThe methylation status of MGMT, CD81, GATA6, DR4, and CASP8 in 76 patients with primary glioblastomas was investigated. Methylation-specific PCR reaction was performed using bisulfite treated DNA. Evaluating glioblastoma patient survival time after operation, patient data and gene methylation effect on survival was estimated using survival analysis.ResultsThe overwhelming majority (97.3%) of tumors were methylated in at least one of five genes tested. In glioblastoma specimens gene methylation was observed as follows: MGMT in 51.3%, GATA6 in 68.4%, CD81 in 46.1%, DR4 in 41.3% and CASP8 in 56.8% of tumors. Methylation of MGMT was associated with younger patient age (p < 0.05), while CASP8 with older (p < 0.01). MGMT methylation was significantly more frequent event in patient group who survived longer than 36 months after operation (p < 0.05), while methylation of CASP8 was more frequent in patients who survived shorter than 36 months (p < 0.05). Cox regression analysis showed patient age, treatment, MGMT, GATA6 and CASP8 as independent predictors for glioblastoma patient outcome (p < 0.05). MGMT and GATA6 were independent predictors for patient survival in younger patients’ group, while there were no significant associations observed in older patients’ group when adjusted for therapy.ConclusionsHigh methylation frequency of tested genes shows heterogeneity of glioblastoma epigenome and the importance of MGMT, GATA6 and CASP8 genes methylation in glioblastoma patient outcome.

Objectives. The aim of the study was to evaluate the frequency and the causes of the intra- and postoperative cerebrospinal fluid (CSF) leaks and to discuss the sella closure methods. Methods. During the period from 1995 to 2005, 313 patients underwent 356 transsphenoidal operations for pituitary adenoma. Microadenoma was found in 80 (22.5%) cases, and in 276 (77.5%) cases, macroadenoma was removed. Two different methods to close the sella were used. The first one consisted packing the sella turcica and sphenoidal sinus with autologous fat and restoring the defect of sella turcica with autologous bone. In more resent practice, the regenerated oxidized cellulose (Surgicel®) and collagen sponge with human fibrin (TachoSil®) were used to cover the sella membrane defect, followed by packing the sella with autologous fat and covering the dural defect with Surgicel® and TachoSil®. Results. Adenoma was totally removed in 198 (55.6%) cases out of 356. Microadenoma was totally removed in 91.3% and macroadenoma in 45.3% of cases, respectively. Postoperative complications were noted in 40 (11.2%) patients. Two (0.6%) patients died after surgery. Intraoperative CSF leakage was observed in 58 (16.3%) cases. Postoperative CSF leakages were observed in 3 cases, when the method of packing the sella with just autologous fat was used, whereas in 29 cases when the sella fat packing was used together with Surgicel® and TachoSil® to cover the sella membrane and dural defects, no postoperative CSF leakages were observed. Conclusions. The technique of covering the sella membrane and dural defects with Surgicel® and TachoSil® in the presence of intraoperative CSF leakage appeared to be the most reliable one, as no postoperative CSF leakage applying this technique has been observed.

Consciousness and emotional stability should be considered important personality-related determinants of HRQoL in BT patients. Psychological distress, functional disability, and cognitive impairment are also important predictors of HRQoL.