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Surgery precedes both radiotherapy and chemotherapy as the first-line therapy for glioma. However, despite multimodal treatment, most glioma patients die from local recurrence in the resection margin. Glioma surgery is inherently lesional, and the response of brain tissue to surgery includes hemostasis, angiogenesis, reactive gliosis and inflammation. Unfortunately, these processes are also associated with tumorigenic side-effects. An increasing amount of evidence indicates that the response to a surgery-related brain injury is hijacked by residual glioma cells and participates in the local regeneration of tumor tissues at the resection margin. Inducing therapeutic hypothermia in the brain has long been used to treat the secondary damage, such as neuroinflammation and edema, that are caused by accidental traumatic brain injuries. There is compelling evidence to suggest that inducing therapeutic hypothermia at the resection margin would delay the local recurrence of glioma by (i) limiting cell proliferation, (ii) disrupting the pathological connection between inflammation and glioma recurrence, and (iii) limiting the consequences of the functional heterogeneity and complexity inherent to the tumor ecosystem. While the global whole-body cooling methods that are currently used to treat stroke in clinical practice may not adequately treat the resection margin, the future lies in implantable focal microcooling devices similar to those under development for the treatment of epilepsy. Preclinical and clinical strategies to evaluate focal hypothermia must be implemented to prevent glioma recurrence in the resection margin. Placing the resection margin in a state of hibernation may potentially provide such a long-awaited therapeutic breakthrough.

Our aim was to study the association of two potential serum biomarkers glial fibrillary acidic protein (GFAP) and epidermal growth factor receptor (EGFR) with prognostic markers such as IDH1 mutation, tumor burden, and survival in patients with high-grade gliomas (HGG). Additionally, our objective was to evaluate the potential of serum EGFR as a surrogate marker for EGFR status in the tumor. Pre-operative serum samples were prospectively collected from patients with primary (n = 17) or recurrent (n = 10) HGG. Serum GFAP and EGFR levels were determined by ELISA and studied for correlation with molecular markers including EGFR amplification, tumor volume in contrast-enhanced T1-weighted MRI, and progression-free survival (PFS). Pre-operative serum GFAP level of ≥0.014 ng/ml was 86 % sensitive and 85 % specific for the diagnosis of glioblastoma. High GFAP was related to the lack of IDH1 mutation (P = 0.016), high Ki67 proliferation index (P < 0.001), and poor PFS (HR 5.9, CI 1.2-29.9, P = 0.032). Serum GFAP correlated with enhancing tumor volume in primary (r = 0.64 P = 0.005), but also in recurrent HGGs (r = 0.76 P = 0.011). In contrast, serum EGFR levels did not differ between HGG patients and 13 healthy controls, and were not related to EGFR status in the tumor. We conclude that high serum GFAP associates with IDH1 mutation-negative HGG, and poor PFS. Correlation with tumor burden in recurrent HGG implicates the potential of serum GFAP for detection of tumor recurrence. Our results suggest that circulating EGFR is not derived from glioma cells and cannot be used as a marker for EGFR status in the tumor.

The diagnosis of pediatric medulloblastoma now carries a much improved overall survival; however as outcomes advance, late mortality, from causes such as disease recurrence and subsequent malignancies, are of increasing concern for these patients. Using the Surveillance, Epidemiology, and End Results database, the causes of late mortality in long term survivors of medulloblastoma were evaluated. Patients diagnosed with a medulloblastoma between the ages of 0-19 years who survived at least 5 years after diagnosis were included. Using U.S. population data, standardized mortality ratios (SMRs) were calculated. Cumulative incidence estimates and standardized incidence ratios (SIRs) of subsequent malignancies were calculated. A total of 455 patients were included in the analysis. All patients received radiation as part of therapy. Median age at diagnosis was 7 years, and mean follow-up was 16 years. By the time of last follow-up, 20.4 % of patients had died, representing an SMR of 24.0 (95 % CI 19.3-29.4). Overall survival at 30 years was 65.5 %. Primary recurrence accounted for 59 % of late deaths, while subsequent malignancy accounted for 11.8 %. SIR for subsequent malignancy in these patients was 10.4 (95 % CI 6.9-15.1). The most common secondary tumor was another brain tumor (32 %), followed by thyroid cancer (21 %). These data demonstrate that late mortality remains a significant problem in these patients. The causes of death are largely attributable to disease recurrence and secondary malignancies. Efforts to improve risk stratification and tailor therapy will help in reducing late mortality in this population.

Novel therapeutic options for patients with recurrent primary central nervous system lymphoma (RPCNSL) are needed. Bendamustine, a bifunctional purine analog/alkylating agent, is approved for use in patients with progressive systemic indolent non-Hodgkin's B-cell lymphomas. Limited data suggests that bendamustine may partition into the brain in the setting of a disrupted blood-brain barrier. This report describes the first known experience of patients with RPCNSL treated with bendamustine. Therapy was well-tolerated and best response was noted as stable disease after eight cycles of bendamustine followed by a subsequent local systemic recurrence found at five months follow-up. CNS involvement in this patient remained stable 20 + months post-bendamustine treatment. Based on our observations, further neuropharmacokinetic and efficacy studies with bendamustine may be warranted in this patient population.

The authors report the clinical features of and imaging studies on a rare case of pediatric malignant prolactinoma. A 12-year-old boy presented with ataxia, blurred vision, and consciousness disturbance. He had received transcranial surgery and adjuvant radiotherapy. However, the tumor regrew with craniospinal metastasis 16 months after the operation. The relevant literature was reviewed regarding the clinical presentation, pathogenesis, treatment approaches, and prognosis of malignant prolactinoma.

The purpose of the study was to assess health-related quality of life (HQL) in patients with high-grade malignant glioma of the brain. The EORTC core Quality of Life Questionnaire (QLQ-C30) and a Brain Cancer Module (BCM20) were administered at baseline and several weeks later (follow-up) to 105 patients with either recently-diagnosed (n = 41) or recurrent (n = 64) malignant glioma. In addition, the attending neurologists completed a standard neurological examination, a modified Barthel Activities of Daily Living Index (BADLI) and the Karnofsky Performance Scale (KPS). In a preliminary step, the QLQ-C30 was found to have acceptable reliability (internal consistency and test-retest reliability). Newly-diagnosed patients and those with a KPS of 80-100 had significantly better physical, role and cognitive functioning and global quality of life with less fatigue, visual disorder, motor dysfunction, communication deficit, weakness of both legs and trouble controlling the bladder than did those with recurrent disease and those with a KPS of 50-70. Similarly, those capable of independent activities of daily living, as reported on the BADLI, had higher functioning scores and less fatigue than did those who were not independent. Patients with dysphasia, mental confusion or motor deficit on neurological examination reported significantly lower levels of physical, role, cognitive, emotional and social functioning and global quality of life than did patients not having these difficulties. They also had significantly more symptoms. In patients with deteriorating neurological status between baseline and follow-up, there was a marked decline in cognitive, physical, role, emotional and social functioning and global quality of life and an increase in fatigue. Thus, there are significant differences in HQL between patients with newly-diagnosed and recurrent brain cancer and between patients with differing KPS and BADLI scores. In addition, the HQL scores provide details not provided by the KPS and the BADLI. Deterioration in neurological function is accompanied by significant deterioration in a range of HQL domains and in global quality of life.

Experimental brain tumors were excised from rats for sequential observation of changes in local capillary permeability during the postsurgical period. Experimental brain tumor-bearing rats were prepared by stereotaxic transplantation of cultured tumor cells and the resultant tumor was delineated by administration of a dye. Following excision of the stained tumor by craniotomy, sequential changes in local capillary permeability were quantitatively followed-up by autoradiography, using 14C-amino-isobutyric acid as a tracer. Capillary permeability was enhanced following surgery, reaching a maximum both in the extent and degree on the third day. After undergoing a gradual reduction, it showed a marked increase for the second time in a very small area on the 10th postoperative day. A recurrence of the tumor was responsible for this late but marked increase. For a control group, the caudate nucleus was excised from normal rats, followed by observation of the sequential changes in the local capillary permeability. Due to surgical procedure, capillary permeability reached a maximum both in the extent and degree on the 5th postoperative day (slightly later than in the tumor group). This change in capillary permeability was less pronounced than in the tumor group. The difference in the conditions of surgery--tumor excision and partial excision of a normal brain tissue--appeared to explain this difference. The results of this study indicated that it is more desirable to give water-soluble antineoplastic agents early during the postoperative period for chemotherapy of a malignant brain tumor after surgery.

A literature review of pregnancy-related vertebral haemangiomas, pregnancy-related haemangiomas outside the nervous system and its coverings, and pregnancy-related meningiomas was performed. All three conditions tended to occur during the first pregnancy, the second or third trimester, to ameliorate postpartum, and to recur during a subsequent pregnancy. These results suggested a hormonal influence on the clinical expression of haemangiomas and meningiomas. To test whether a hormonal factor is also operative in the (not pregnancy related) symptomatic and asymptomatic counterparts of these conditions we also reviewed the literature concerning the symptomatic and asymptomatic haemangiomas and meningiomas for the following: frequency, sex and age distribution. No arguments were found to suggest that steroid hormones are strong factors in the development of asymptomatic and symptomatic lesions. The pregnancy-related counterparts have to be considered as subsets with their own behaviour.