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Cranial operations are associated with a high risk of postoperative intracranial hemorrhage (pICH) and venous thromboembolic events, along with increased mortality and morbidity. With the use of acetylsalicylic acid (ASA) for prophylaxis becoming more prevalent, the risk of bleeding when ASA is administered preoperatively is unknown, as are the effects of discontinuation upon the occurrence of thromboembolic events, especially in societies with aging demographics. To address these questions, a retrospective analysis was performed using medical records and radiological images of 1862 patients subjected to brain tumor surgery over a decade in our department. The risk of pICH was compared in patients with metastases receiving ASA treatment versus patients not receiving ASA treatment. The occurrence of venous thromboembolic events after surgery was also evaluated. The study group consisted of 365 patients with different types of brain metastases. In total, 20 patients suffered pICH and 7 of these were associated with clinical neurological deterioration postoperatively. Of the 58 patients who took ASA preoperatively, 2 patients experienced pICH, compared with 5 patients in the non-ASA impact group ( p = 0.120). Patients who took ASA were not at significantly higher risk of pICH and therefore a worse outcome compared to the group without ASA. Therefore, these data suggest that in patients at high cardiovascular risk, ASA can be safely continued during elective brain tumor surgery.

Progesterone Receptor Membrane Component 1 (PGRMC1) is a tumour-promoting factor in several types of cancer but its role in brain tumours is poorly characterized thus far. Our study aimed to determine the effect of PGRMC1 on glioblastoma (GBM) pathophysiology using two independent cohorts of IDH wild-type GBM patients and stable knockdown GBM models. We found that high levels of PGRMC1 significantly predicted poor overall survival in both cohorts of GBM patients. PGRMC1 promoted the proliferation, anchorage-independent growth, and invasion of GBM cells. We identified Integrin beta-1 (ITGB1) and TCF 1/7 as potential members of the PGRMC1 pathway in vitro. The levels of ITGB1 and PGRMC1 also correlated in neoplastic tissues from GBM patients. High expression of PGRMC1 rendered GBM cells less susceptible to the standard GBM chemotherapeutic agent temozolomide but more susceptible to the ferroptosis inducer erastin. Finally, PGRMC1 enhanced Interleukin-8 production in GBM cells and promoted the recruitment of neutrophils. The expression of PGRMC1 significantly correlated with the numbers of tumour-infiltrating neutrophils also in tissues from GBM patients. In conclusion, PGRMC1 enhances tumour-related inflammation and promotes the progression of GBM. However, PGRMC1 might be a promising target for novel therapeutic strategies using ferroptosis inducers in this type of cancer.

This study aimed to investigate the role of Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase 2 (PLOD2) in glioblastoma (GBM) pathophysiology. To this end, PLOD2 protein expression was assessed by immunohistochemistry in two independent cohorts of patients with primary GBM (n1 = 204 and n2 = 203, respectively). Association with the outcome was tested by Kaplan−Meier, log-rank and multivariate Cox regression analysis in patients with confirmed IDH wild-type status. The biological effects and downstream mechanisms of PLOD2 were assessed in stable PLOD2 knock-down GBM cell lines. High levels of PLOD2 significantly associated with (p1 = 0.020; p2< 0.001; log-rank) and predicted (cohort 1: HR = 1.401, CI [95%] = 1.009−1.946, p1 = 0.044; cohort 2: HR = 1.493; CI [95%] = 1.042−2.140, p2 = 0.029; Cox regression) the poor overall survival of GBM patients. PLOD2 knock-down inhibited tumor proliferation, invasion and anchorage-independent growth. MT1-MMP, CD44, CD99, Catenin D1 and MMP2 were downstream of PLOD2 in GBM cells. GBM cells produced soluble factors via PLOD2, which subsequently induced neutrophils to acquire a pro-tumor phenotype characterized by prolonged survival and the release of MMP9. Importantly, GBM patients with synchronous high levels of PLOD2 and neutrophil infiltration had significantly worse overall survival (p < 0.001; log-rank) compared to the other groups of GBM patients. These findings indicate that PLOD2 promotes GBM progression and might be a useful therapeutic target in this type of cancer.

Background: The Wnt receptor Frizzled-7 (FZD7) promotes tumor progression and can be currently targeted by monoclonal antibody therapy. Here, we determined the prognostic value of FZD7 for the overall survival of glioblastoma (GBM) patients, both as individual marker and taken in combination with the previously-described markers MGMT and IDH1. Additionally, we tested whether these markers (alone or in combination) exhibited sex-specific differences., Results: High levels of FZD7 (FZD7high) associated with shorter survival in GBM patients; however, FZD7high was a significant predictor of poor survival only in male patients. Mutation of IDH1 significantly associated with longer survival in male but not female patients. Methylated MGMT promoter significantly associated with longer survival only in female patients. Combination of FZD7 with MGMT enhanced the prognostic accuracy and abrogated the sex differences observed upon single marker analysis. Combination of FZD7 with IDH1 was a significant predictor of survival in male GBM patients only., Materials and Methods: Three independent cohorts of patients with primary GBM (n=120, n=108 and n=105, respectively) were included in this study. FZD7 and IDH1 were assessed by immunohistochemistry in tissue microarrays. MGMT promoter methylation was determined by methylation-specific polymerase chain reaction. Survival analysis was performed by Kaplan-Meier estimate, log-rank test and Cox proportional hazard regression., Conclusions: Our study identifies novel individual and combination markers with prognostic and, possibly, therapeutic relevance in GBM. Furthermore, our findings substantiate the importance of sexual dimorphism in this type of cancer.

Introduction: Brain metastases (BM) commonly occur in patients with metastatic malignant melanoma (MM). Prognosis is poor even with maximal therapy. The aim of the current study was to retrospectively evaluate patients with BM of MM who were treated neurosurgically with respect to clinical presentation, recurrent disease, survival and factors affecting survival., Patients and Methods: Thirty-four patients (19f/15m) with BM of MM were treated in our hospital between 2000 and 2010. Patient data were analysed, survival was examined using Kaplan-Meier-estimates and factors affecting prognosis were evaluated using uni- and multivariate analysis., Results: Twenty-two patients (64.7%) had a single BM, whereas twelve patients (35.3%) revealed two or more lesions. Median survival for patients with a single BM was 13.0 months (95%-CI 9.3-16.7 months), this was significantly (p=0.014) better than for patients with two or more BM (median 5.0, 95%-CI 3.4-14.6 months). Nineteen patients (55.9%) developed an intracranial relapse after microsurgical resection of a first lesion. Patients with an isolated intracerebral relapse survived significantly (p=0.003) longer than those with systemic progression (median 6.0, 95%-CI 0.0-15.3 months vs median 3.0, 95%-CI 1.7-4.3 months). Similarly, patients with a high performance status showed significantly (p=0.001) prolonged survival (median 7.0, 95%-CI 0.0-19.9 months vs median 1.0, 95%-CI 0.0-2.2 months). Eleven out of nineteen patients (57.9%) underwent either another microsurgical resection (n=6) or stereotactic radiosurgery (n=5). These patients remained on a high performance status even after aggressive therapy., Discussion: Even though the prognosis for patients with BM of MM is generally poor, patients with a single BM can benefit from microsurgical resection. However, there is a high risk of intracranial relapse. In selected patients with a good performance status and recurrent intracranial disease, recurrent local therapy can be justified and useful., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Object: The aim of this observational clinical study was to analyze the impact of neurophysiological intraoperative monitoring (IOM) on the surgical procedure and to assess the benefits of such monitoring., Methods: Data for 423 patients who underwent neurophysiological IOM with somatosensory evoked potentials and brainstem auditory evoked potentials during neurosurgical procedures were collected prospectively. The patients were classified into one of five groups according to the findings of IOM, the intervention following a monitoring alarm, and the patient's postoperative neurological condition. These groups were as follows: patients with true-positive findings with intervention (42 cases, 9.9%), those with true-positive findings without intervention (42 cases, 9.9%), those with false-positive findings (nine cases, 2.1%), those with false-negative findings (16 cases, 3.8%), and those with true-negative findings (314 cases, 74.2%). Different interventions followed an event identified with monitoring. These interventions were related to dissection in 17 cases, to perfusion pressure in 11, to a limitation of the surgical procedure in five, to vessel clipping in four, to vasospasm in three, and to retraction in one case. In one case the surgical procedure was abandoned. A critical analysis and cautious estimation of the interventions revealed that IOM was helpful in preventing a postoperative deficit in 5.2% of the monitored cases. CONCLUSIONS; For critical analysis of the benefits of IOM one must evaluate not only the findings of IOM and the patient's postoperative neurological condition but also the intraoperative findings and surgical interventions following a monitoring alarm. Evidence is presented that IOM is helpful in preventing a postoperative deficit.