Glioblastoma microenvironment: The stromal interactions.

Glioblastomas (GBMs) are the most common primary brain tumors with poor prognosis due to their aggressive growth accompanied by invasive behavior and therapy-resistance. These features promote a high rate of recurrence; therefore, they are largely incurable. One major cause of the incurability is brought about by the intimate relationship of GBM cells with the microenvironment, which supports the tumor growth in various ways by providing a permissive neighborhood. In the tumor microenvironment are glioma stem cells (GSC); endothelial cells (EC) and hypoxic regions; immune cells and immune modulatory cues; astrocytes; neural stem/precursor cells (NPC) and mesenchymal stem cells (MSC). Each cell type contributes to GBM pathology in unique ways; therefore, it is necessary to understand such interactions between GBM cells and the stromal cells in order to establish a through understanding of the GBM pathology. By explaining the contribution of each stromal entity to GBM pathology we aim to draw an interaction map for GBMs and promote awareness of the complexity of the GBM microenvironment.

Mortality Outcomes of Endovascular Treatment and Surgical Clipping in Patients with Cerebral Aneurysms: A Single-Center Study.

AIM: To compare endovascular and surgical treatment methods for cerebral aneurysms focusing on mortality. MATERIAL AND METHODS: The study included 187 patients who had undergone aneurysm treatment. The patients were divided into four groups according to their treatment modality and subarachnoid hemorrhage status: patients with endovascular treatment and bleeding aneurysms (EVG-b), patients with endovascular treatment and non-bleeding aneurysms (EVG-nb), patients with surgical clipping and bleeding aneurysms (SCG-b), and patients with surgical clipping and non-bleeding aneurysms (SCG-nb). The Hunt?Hess scores, Fisher grade, aneurysm morphology, and length of stay (LOS) were compared between groups. RESULTS: There was no significant difference in the mortality rate between EVG-b and SCG-b at the end of the first year (23.5% and 39.7%, respectively; p > 0.05). A significantly shorter LOS was observed in EVG-b than in SCG-b (11.5 days and 15 days, respectively; p=0.027). Fusiform aneurysms were associated with higher patient mortality, whereas saccular aneurysms were associated with a 1.9-fold higher survival (p=0.037; 95% confidence interval: 0.83?4.74). The rate of closure of non-bleeding aneurysms was 93.4%. Complete embolization was verified in all bleeding aneurysms. In EVG-nb, the morbidity rate was 5%, the mortality rate was 3%, and the mean LOS was 2.86 days. CONCLUSION: Both treatment methods showed similar mortality rates, but hospital stays were shorter after endovascular treatment.

Comparing Tumor Cell Invasion and Myeloid Cell Composition in Compatible Primary and Relapsing Glioblastoma.

Glioblastoma (GBM) recurrence after treatment is almost inevitable but addressing this issue with adequate preclinical models has remained challenging. Here, we introduce a GBM mouse model allowing non-invasive and scalable de-bulking of a tumor mass located deeply in the brain, which can be combined with conventional therapeutic approaches. Strong reduction of the GBM volume is achieved after pharmacologically inducing a tumor-specific cell death mechanism. This is followed by GBM re-growth over a predictable timeframe. Pharmacological de-bulking followed by tumor relapse was accomplished with an orthotopic mouse glioma model. Relapsing experimental tumors recapitulated pathological features often observed in recurrent human GBM, like increased invasiveness or altered immune cell composition. Orthotopic implantation of GBM cells originating from biopsies of one patient at initial or follow-up treatment reproduced these findings. Interestingly, relapsing GBM of both models contained a much higher ratio of monocyte-derived macrophages (MDM) versus microglia than primary GBM. This was not altered when combining pharmacological de-bulking with invasive surgery. We interpret that factors released from viable primary GBM cells preferentially attract microglia whereas relapsing tumors preponderantly release chemoattractants for MDM. All in all, this relapse model has the capacity to provide novel insights into clinically highly relevant aspects of GBM treatment.

Development of a Giant Cornu Cutaneum in a Patient with a Coincidental Foreknown Intracranial Meningioma.

The diagnostic spectrum for scalp lesions is extensive and comprises either benign or malignant features. Cornu cutaneum (CC) is a well-recognized condition; however, its origin and natural course are not always obvious. We present the case of a 78-year-old male patient who was diagnosed with intracranial meningioma in 2014 and who subsequently refused treatment. He presented a new scalp lesion, resembling a horn, in the vertex region 1.5 years after his last follow-up. The lesion was excised, and the patient was histopathologically diagnosed as having CC caused by squamous cell carcinoma. CC can be easily recognized when it resembles animal horn; however, it can assume different shapes that require a physician to be vigilant. Moreover, a lesion’s benign or malignant nature is not obvious in all cases. Hard, protruding scalp lesions should be examined for CC, and a histopathological evaluation should be performed to make a definitive diagnosis.

Initial Results of Using Blood Beta 2 Transferrin as a Marker of the Functional Status of a Shunt.

OBJECTIVE: Ventriculoperitoneal shunt is the most common cerebrospinal fluid diversion procedure to treat hydrocephalus. With the change of physiologic cerebrospinal fluid absorption site from arachnoid granulations to the peritoneum, beta 2 transferrin enters the systemic circulation. Therefore, the detection of beta 2 transferrin in the blood can possibly be used as a noninvasive method to assess the functional status of the shunt. The objective of this study was to study the presence of beta 2 transferrin in patients with functional shunts and in shunts suspected of being malfunctional. METHODS: Blood samples were obtained from a group of 20 patients with functional ventriculoperitoneal shunts, from a control group of 10 age-matched healthy volunteers, and from 8 patients with suspected shunt malfunction (6 ventriculoperitoneal, 2 lumboperitoneal). Blood serum beta 2 transferrin levels were measured by enzyme-linked immunosorbent assay with specific anti-beta 2 transferrin antibodies. RESULTS: The mean age in the ventriculoperitoneal shunt group was 36.5 years (range, 24-50 years). The mean age in the control group was 39.5 years (range, 32-48). There was no statistical difference in age between the groups. Beta 2 transferrin levels were 1.99 ± 1.02 ng/mL in the ventriculoperitoneal shunt group and 0.05 ± 0.02 ng/mL in the control group; the statistical difference was strongly significant (P < 0.001). Patients presenting with suspected shunt malfunction had preoperative low beta 2 transferrin levels (0.10 ± 0.12). Postoperatively, their beta 2 transferrin levels increased to 1.75 ± 0.46 ng/mL, and the difference was statistically significant (P = 0.012). CONCLUSION: Blood beta 2 transferrin can be used as a noninvasive test to assess the functional status of a shunt.

The Acute and Delayed Effects of Vagal Nerve Stimulation on an Absence Epilepsy Model in WAG/Rij.

AIM: Vagal nerve stimulation (VNS) is an effective method of treatment for epilepsy patients either unresponsive to medical therapy or not suitable for resective surgeries. We designed an experimental study on Wistar Albino Glaxo rats from Rijswijk (WAGRij) to investigate the effects of VNS on a non-convulsive epilepsy model. MATERIAL AND METHODS: The experiment was performed on six WAG/Rij rats, a validated strain for genetic absence seizures. The animals were underwent VNS and the effects were investigated on electroencephalography (EEG) recordings at 22, 24, 26 hours of stimulation and 15 days after the cessation, for duration of spike and wave complexes (SWC), the numbers, mean duration of SWC and frequencies in an hour. RESULTS: EEG recordings demonstrated that the mean duration of SWC was 353.1 seconds and the number of activity per hour was 62 at the baseline. There were statistically significant decreases in the total duration of SWC and the number of activities (61.8% and 78% decrease, respectively). There were no significant decreases in the mean duration of SWC and the frequencies. CONCLUSION: The acute stimulation of the vagal nerve caused a statistically significant decrease both in overall duration of SWC and the number of complexes in an hour. Moreover, the positive effects seemed to last even 15 days after the cessation of the stimulation. Further studies focusing on different stimulation parameters and delayed effects of the VNS on human absence seizures are warranted.