Microsurgery remains the treatment of first choice in CD, even though no improvement in remission rates was observed over the years, because complication or remission rates for other treatment options are comparable or worse.

Object High-grade gliomas (HGGs) and metastasis (MET) are the most common intracranial lesions in neurosurgical routine. Both of them show an invasive growth pattern extending into neural tissue beyond the margins of contrast enhancement on MRI. These “undetected” areas might be the origin of early tumor recurrence. The aim of the present study was to evaluate whether 5-aminolevulinic acid (5-ALA) fluorescence provides an additional benefit in detection of invasive tumor compared with intraoperative MRI (iMRI). Methods The authors prospectively enrolled 45 patients harboring contrast-enhancing lesions, in whom gross-total resection was intended. All patients had surgery in which iMRI and 5-ALA–guided resection were used following a specific protocol. First, a typical white light tumor resection was performed. Then, spatial location of residual fluorescence was marked. After that, an iMRI was performed and residual uptake of contrast was marked. Navigated biopsy samples were taken from all marked areas and from additional sites according to the surgeon's judgment. Cross tables and receiver operating characteristic curves were calculated, assessing performance of the imaging methods for tumor detection alone and for combined detection of infiltration zone and solid tumor (pathological tissue). Also, correlations of histopathological findings with imaging results were tested using Spearman rho. Results Thirty-four patients with HGGs and 11 with METs were enrolled. Three patients harboring a MET showed no 5-ALA enhancement and were excluded; 127 histopathological samples were harvested in the remaining patients. In HGG, sensitivity for tumor detection was significantly higher (p < 0.001) in 5-ALA (0.85) than in iMRI (0.41). Specificity was significantly lower (p < 0.001) in 5-ALA (0.43) than in iMRI (0.70). For detection of pathological tissue, 5-ALA significantly exceeded iMRI in specificity (0.80 vs 0.60) and sensitivity (0.91 vs 0.66) (p < 0.001). Imaging results of iMRI and 5-ALA did not correlate significantly; only 5-ALA showed a significant correlation with final histopathological diagnosis of the specimen and with typical histopathological features of HGGs. In METs, sensitivity and specificity for tumor detection were equal in 5-ALA and iMRI. Both techniques showed high values for sensitivity (0.75) and specificity (0.80). The odds ratio for detection of tumor tissue was 12 for both techniques. Concerning pathological tissue, no statistically significant difference was found either. Imaging results of iMRI and 5-ALA correlated significantly (p < 0.022), as with final histopathological diagnosis in METs. Conclusions In METs, due to the rate of nonenhancing lesions, the authors found no additional benefit of 5-ALA compared with iMRI. In HGG, imaging results of 5-ALA and iMRI are significantly different at the border zone; 5-ALA has a higher sensitivity and a lower specificity for tumor detection than Gd-DTPA–enhanced iMRI. For detection of infiltrating tumor at the border of the resection cavity, 5-ALA is superior to Gd-DTPA–enhanced iMRI concerning both sensitivity and specificity. Thus, use of 5-ALA in addition to iMRI might be beneficial to maximize extent of resection. Clinical synergistic effects will be evaluated in a prospective randomized trial.

BackgroundGlioblastoma multiforme (GBM), a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM.MethodsImmune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively.ResultsUsing descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA) and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival.ConclusionsDefined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0272-3) contains supplementary material, which is available to authorized users.

OBJECTIVEPlacement of a ventricular drain is one of the most common neurosurgical procedures. However, a higher rate of successful placements with this freehand procedure is desirable. The authors’ objective was to develop a compact navigational augmented reality (AR)–based tool that does not require rigid patient head fixation, to support the surgeon during the operation.METHODSSegmentation and tracking algorithms were developed. A commercially available Microsoft HoloLens AR headset in conjunction with Vuforia marker-based tracking was used to provide guidance for ventriculostomy in a custom-made 3D-printed head model. Eleven surgeons conducted a series of tests to place a total of 110 external ventricular drains under holographic guidance. The HoloLens was the sole active component; no rigid head fixation was necessary. CT was used to obtain puncture results and quantify success rates as well as precision of the suggested setup.RESULTSIn the proposed setup, the system worked reliably and performed well. The reported application showed an overall ventriculostomy success rate of 68.2%. The offset from the reference trajectory as displayed in the hologram was 5.2 ± 2.6 mm (mean ± standard deviation). A subgroup conducted a second series of punctures in which results and precision improved significantly. For most participants it was their first encounter with AR headset technology and the overall feedback was positive.CONCLUSIONSTo the authors’ knowledge, this is the first report on marker-based, AR-guided ventriculostomy. The results from this first application are encouraging. The authors would expect good acceptance of this compact navigation device in a supposed clinical implementation and assume a steep learning curve in the application of this technique. To achieve this translation, further development of the marker system and implementation of the new hardware generation are planned. Further testing to address visuospatial issues is needed prior to application in humans.

Background Dysregulation of the metabolome is a hallmark of primary brain malignancies. In this work we examined whether metabolic reprogramming through a multi-targeting approach causes enhanced anti-cancer activity in glioblastoma. Methods Preclinical testing of a combined treatment with ONC201/TIC10 and 2-Deoxyglucose was performed in established and primary-cultured glioblastoma cells. Extracellular flux analysis was used to determine real-time effects on OXPHOS and glycolysis. Respiratory chain complexes were analysed by western blotting. Biological effects on tumour formation were tested on the chorioallantoic membrane (CAM). Results ONC201/TIC10 impairs mitochondrial respiration accompanied by an increase of glycolysis. When combined with 2-Deoxyglucose, ONC201/TIC10 induces a state of energy depletion as outlined by a significant decrease in ATP levels and a hypo-phosphorylative state. As a result, synergistic anti-proliferative and anti-migratory effects were observed among a broad panel of different glioblastoma cells. In addition, this combinatorial approach significantly impaired tumour formation on the CAM. Conclusion Treatment with ONC201/TIC10 and 2-Deoxyglucose results in a dual metabolic reprogramming of glioblastoma cells resulting in a synergistic anti-neoplastic activity. Given, that both agents penetrate the blood–brain barrier and have been used in clinical trials with a good safety profile warrants further clinical evaluation of this therapeutic strategy.

By performing repeated selective adenomectomy, patients with recurrent Cushing's disease can be cured without the risk of endocrine deficits or major complications. Dynamic endocrine tests are of paramount importance for surgical decision making. Imaging and inferior petrosal sinus sampling are not helpful in locating the recurrent tumor. If normalization can not be achieved, adjuvant therapy is mandatory.

The poor prognosis of patients with glioblastoma fuels the search for more effective therapeutic compounds. We previously hypothesised that the neuroleptic olanzapine may enhance antineoplastic effects of temozolomide the standard chemotherapeutic agent used in this disease. This study tested this hypothesis. The anti-proliferative effect of olanzapine was examined by MTT assays and cell count analysis. Soft-agar assays were performed to examine colony-forming ability. In addition, the inhibitory effect of olanzapine on the migratory capacity of U87MG and A172 cells was analyzed by Transwell(®) assays. Moreover, staining for annexin V/propidium iodide or carboxyfluorescein succinimidyl ester was performed prior to flow cytometric analysis in order to better understand the subjacent cellular mechanism. Our initial hypothesis that olanzapine may enhance temozolomide's anti-tumor activity could be confirmed in U87MG and A172 glioblastoma cell lines. Moreover, treatment with olanzapine alone resulted in a marked anti-proliferative effect on U87MG, A172 and two glioma stem-like cells with IC50 values ranging from 25 to 79.9 µM. In U87MG cells, anchorage-independent growth was dose-dependently inhibited. In A172 cells, migration was also shown to be inhibited in a dose-dependent manner. In addition, olanzapine was shown to exert a cell line-dependent pleomorphism with respect to the induction of apoptosis, necrosis and/or cytostasis. Our data show that the neuroleptic olanzapine enhances the anti-tumor activity of temozolomide against glioblastoma cell lines. Moreover, this is the first study to show that olanzapine provides on its own anti-cancer activity in glioblastoma and thus may have potential for repurposing.

Intraoperative resection control in LGGs using lioUS reaches a degree of accuracy close to iMRI. Test results of lioUS are superior to cioUS. cioUS often fails to discriminate solid tumors from "normal" brain tissue during resection control. Only in lesions <10 cc cioUS does show good accuracy.