Utility of a prognostic assessment tool to predict survival following surgery for brain metastases.

Background: Brain metastases account for more than 50% of all intracranial tumors and are associated with poor outcomes. Treatment decisions in this highly heterogenous cohort remain controversial due to the myriad of treatment options available, and there is no clearly defined standard of care. The prognosis in brain metastasis patients varies widely with tumor type, extracranial disease burden and patient performance status. Decision-making regarding treatment is, therefore, tailored to each patient and their disease. Methods: This is a retrospective cohort study assessing survival outcomes following surgery for brain metastases over a 50-month period (April 1, 2014-June 30, 2018). We compared predicted survival using the diagnosis-specific Graded Prognostic Assessment (ds-GPA) with actual survival. Results: A total of 186 patients were included in our cohort. Regression analysis demonstrated no significant correlation between actual and predicted outcome. The most common reason for exclusion was insufficient information being available to the neuro-oncology multidisciplinary team (MDT) meeting to allow GPA calculation. Conclusions: In this study, we demonstrate that "predicted survival" using the ds-GPA does not correlate with "actual survival" in our operated patient cohort. We also identify a shortcoming in the amount of information available at MDT in order to implement the GPA appropriately. Patient selection for aggressive therapies is crucial, and this study emphasizes the need for treatment decisions to be individualized based on patient and cancer clinical characteristics.

Intra-cranial hypertension and vision-threatening papilloedema caused by intradural spinal tumours: a case series of three.

Spinal tumours infrequently cause hydrocephalus, on rare occasions, they can also cause papilloedema, in the absence of ventriculomegaly. When the latter occurs, they can be a diagnostic challenge for physicians. In the absence of limb neurology, much of the initial diagnostic effort is focused solely on intra-cranial causes. This can result in diagnostic delay, misdiagnosis and mistreatment.We describe three cases of intradural spinal tumours that presented with isolated vision-threatening papilloedema. We compare and contrast these patients who had similar presentations, but different management strategies. The different operative management of their spinal tumours, as well as the acuity of visual deterioration determined their respective clinical course and patient journeys. We emphasise the need to preserve vision as a priority, through emergency cerebrospinal fluid (CSF) diversion if necessary. We remind our readers to 'think outside the box' in cases of unexplained papilloedema, and recognise spinal pathology as a possibility amongst the differentials.

Chiari Malformation Type 1 in Adults.

The term Chiari malformation refers to a heterogeneous group of anatomical abnormalities at the craniovertebral junction. Chiari malformation type 1 (CM1) refers to the abnormal protrusion of cerebellar tonsils through the foramen magnum and is by far the commonest type. Its prevalence is estimated approximately 1%; it is more common in women and is associated with syringomyelia in 25-70% of cases. The prevalent pathophysiological theory proposes a morphological mismatch between a small posterior cranial fossa and a normally developed hindbrain that results in ectopia of the tonsils.In most people, CM1 is asymptomatic and diagnosed incidentally. In symptomatic cases, headache is the cardinal symptom. The typical headache is induced by Valsalva-like maneuvers. Many of the other symptoms are nonspecific, and in the absence of syringomyelia, the natural history is benign. Syringomyelia manifests with spinal cord dysfunction of varying severity. The approach to patients with CM1 should be multidisciplinary, and the first step in the management is phenotyping the symptoms, because they may be due to other pathologies, like a primary headache syndrome. Magnetic resonance imaging, which shows cerebellar tonsillar decent 5 mm or more below the foramen magnum, is the gold standard investigative modality. The diagnostic workup may include dynamic imaging of the craniocervical junction and intracranial pressure monitoring.The management of CM1 is variable and sometimes controversial. Surgery is usually reserved for patients with disabling headaches or neurological deficits from the syrinx. Surgical decompression of the craniocervical junction is the most widely used procedure. Several surgical techniques have been proposed, but there is no consensus on the best treatment strategy, mainly due to lack of high-quality evidence. The management of the condition during pregnancy, restriction to lifestyle related to athletic activities, and the coexistence of hypermobility require special considerations.

Reconfiguration from emergency to urgent elective neurosurgery for glioblastoma patients improves length of stay, surgical adjunct use, and extent of resective surgery.

Background: Glioblastoma (GB) is the most common intrinsic brain cancer and is notorious for its aggressive nature. Despite widespread research and optimization of clinical management, the improvement in overall survival has been limited. The aim of this study was to characterize the impact of service reconfiguration on GB outcomes in a single centre. Methods: Patients with a histopathological confirmation of a diagnosis of GB between 01/01/2014 and 31/12/2019 were retrospectively identified. Demographic and tumour characteristics, survival, treatment (surgical and oncological), admission status, use of surgical adjunct (5-aminolevulinic acid, intra-operative neuro-monitoring), the length of stay, extent of resection, and surgical complications were recorded from the hospital databases. Results: From August 2018 the neurosurgical oncology service was reconfigured to manage high-grade tumours on an urgent outpatient basis by surgeons specializing in oncology. We demonstrate that these changes resulted in an increase in elective admissions, greater use of intra-operative adjuncts resulting in the improved extent of tumour resection, and a reduction in median length of stay and associated cost-savings. Conclusions: Optimizing neuro-oncology patient management through service reconfiguration resulted in increased use of intra-operative adjuncts, improved surgical outcomes, and reduced hospital costs. These changes also have the potential to improve survival and disease-free progression for patients with GB.

Is there a limited value of cytoreductive surgery in elderly patients with malignant gliomas?

Background: Glioblastoma (GB) is well known for being the most aggressive primary cerebral malignancy. The peak incidence is at 60-70 years of age, with over half of patients aged over 65 years at diagnosis. Methods: Patients with a confirmed histological diagnosis of GB between January 2009 and June 2016 at a single center were retrospectively identified. The inclusion criteria for the study were age over 65 years at diagnosis, and surgical management with either a burr hole biopsy or craniotomy. Results: A total of n = 289 patients underwent surgery for GB, with a median age at diagnosis of 71 years, and of whom 64% were male. Craniotomies were performed in 71%, with burr hole biopsies performed in the remainder (29%). Patient survival differed significantly with treatment modality (P < 0.001), ranging from a median of 382 days in those treated with a combination of craniotomy, radiotherapy (RT), and temozolomide (TZM), to 43 days in those only receiving a burr hole biopsy with no further treatment. On multivariable analysis, treatment with RT + TZM was significantly independently associated with longer patient survival (P < 0.001). Craniotomy was associated with a significant improvement in performance status, compared to burr hole biopsy (P = 0.006). For the subgroup of patients receiving TZM, those with a methylated O6-methylguanine-DNA-methyltransferase (MGMT) status had significantly longer overall survival than those with unmethylated MGMT (median: 407 vs. 341 days, P = 0.039). Conclusion: Our retrospective data demonstrate that the elderly population with GB benefit from aggressive chemo-RT, regardless of surgical intervention.

An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma.

Background Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery. Methods We conducted a multicentre feasibility study of 5-ALA with BCNU wafers followed by standard-of-care chemoradiotherapy (chemoRT) in patients with suspected GBM. Patients judged suitable for radical resection were administered 5-ALA pre-operatively and BCNU wafers at the end resection. Post-operative treatment continued as per routine clinical practice. The primary objective was to establish if combining 5-ALA and BCNU wafers is safe without compromising patients from receiving standard chemoRT. Results Seventy-two patients were recruited, sixty-four (88.9%) received BCNU wafer implants, and fifty-nine (81.9%) patients remained eligible following formal histological diagnosis. Seven (11.9%) eligible patients suffered surgical complications but only two (3.4%) were not able to begin chemoRT, four (6.8%) additional patients did not begin chemoRT within 6 weeks of surgery due to surgical complications. Eleven (18.6%) patients did not begin chemoRT for other reasons (other toxicity (n = 3), death (n = 3), lost to follow-up/withdrew (n = 3), clinical decision (n = 1), poor performance status (n = 1)). Median progression-free survival was 8.7 months (95% CI: 6.4-9.8) and median overall survival was 14.7 months (95% CI: 11.7-16.8). Conclusions Combining BCNU wafers with 5-ALA-guided surgery in newly diagnosed GBM patients is both feasible and tolerable in terms of surgical morbidity and overall toxicity. Any potential therapeutic benefit for the sequential use of 5-ALA and BCNU with chemoRT requires further investigation with improved local delivery technologies.

Importance and Evidence of Extent of Resection in Glioblastoma.

Maximal safe resection is an essential part of the multidisciplinary care of patients with glioblastoma. A growing body of data shows that gross total resection is an independent prognostic factor associated with improved clinical outcome. The relationship between extent of glioblastoma (GB) resection and clinical benefit depends critically on the balance between cytoreduction and avoiding neurologic morbidity. The definition of the extent of tumor resection, how this is best measured pre- and postoperatively, and its relation to volume of residual tumor is still discussed. We review the literature supporting extent of resection in GB, highlighting the importance of a standardized definition and measurement of extent of resection to allow greater collaboration in research projects and trials. Recent developments in neurosurgical techniques and technologies focused on maximizing extent of resection and safety are discussed.

Challenges to Neurosurgery During the Coronavirus Disease 2019 (COVID-19) Pandemic.

The coronavirus disease 2019 pandemic has presented a massive burden to most health care systems across the globe. The demand for intensive care unit capacity in particular has increased significantly, and hospitals in most affected regions have struggled to cope. The focus of health care activity has shifted to the pandemic, with a negative impact on the management of other conditions. Neurosurgery, like most specialties, has been drastically affected but, arguably, warrants special considerations because many of the treatments required are time-critical. Lack or delay of appropriate intervention may lead, for an individual patient, to permanent neurologic injury and a significant decline in function and quality of life, or even death. In this report, we consider the challenges that neurosurgeons currently face in relation to the pandemic and are likely to face in the foreseeable future. The challenges are multifaceted with practical, ethical, legal, and other implications. These include re-deployment of staff to areas outside neurosurgery, treatment priority setting, ethical decision-making and risk of moral injury, as well as medicolegal risks, financial uncertainties and implications for training, research, and global health work. As well as patients, these challenges will affect neurosurgeons as doctors and as humans. The international neurosurgical community has a moral duty to contribute to the global response to the COVID-19 crisis, but also to retain a duty to care for individual patients.

Traumatic dural venous sinus thrombosis; a challenge in management of head injury patients.

Venous sinus thrombosis secondary to traumatic brain injury and head trauma is increasingly detected following contrast enhanced cranial imaging in acute trauma. The presence of sinus thrombosis poses further challenges in the management of traumatic brain injury patients with cerebral contusions, intraparenchymal haemorrhages or subdural/extradural haemorrhages. The decision to anti-coagulate such trauma induced venous sinus thrombosis is controversial and requires further attention and research to delineate risks versus benefits of treatment. In this article we report 4 cases of venous sinus thrombosis following head trauma and review the literature on management of such patients.

Cranial Focal Nodular Haematopoietic Hyperplasia: A case report and literature review.

Focal Nodular Haematopoietic Hyperplasia (FNHH) is an uncommon, benign, osteolytic lesion and so far, has not been reported cranially. Here, we report the first cranial case of a patient with right frontal bone FNHH and describe the clinical history, management and follow up with review of the literature of this rare pathology.

Effect of Subthalamic Nucleus Stimulation on Pedunculopontine Nucleus Neural Activity.

BACKGROUND: The pedunculopontine nucleus has recently been proposed as an alternative target for deep brain stimulation for the treatment of medically intractable Parkinson's disease. The suggested indication for pedunculopontine nucleus deep brain stimulation is severe and medically intractable axial symptoms such as gait and postural impairment. OBJECTIVE: Our goal in this study was to describe the effects of subthalamic nucleus stimulation on pedunculopontine nucleus electrophysiological activity. METHODS: Fourteen male Wistar rats were divided into a sham stimulation group and an experimental group. In both groups, electrodes were implanted bilaterally into the subthalamic nucleus and into the right pedunculopontine nucleus. Microelectrode recordings were carried out in both groups prior to and during subthalamic nucleus stimulation. RESULTS: Subthalamic nucleus stimulation produced no clear inhibition of neuronal firing in the pedunculopontine nucleus. However, we found that stimulation of the subthalamic nucleus at 60 Hz produces some entrainment of pedunculopontine nucleus neuronal firing and a shift of subthalamic nucleus firing patterns to more tonic and random patterns. These results are consistent with the effects of deep brain stimulation on neuronal activity in the subthalamic nucleus and globus pallidus internus. CONCLUSION: The result of this study provides additional evidence to improve our understanding of the mechanism of subthalamic nucleus-deep brain stimulation, and its physiological consequences.

Complex interactions between the components of the PI3K/AKT/mTOR pathway, and with components of MAPK, JAK/STAT and Notch-1 pathways, indicate their involvement in meningioma development.

We investigated the significance of PI3K/AKT/mTOR pathway and its interactions with MAPK, JAK/STAT and Notch pathways in meningioma progression. Paraffin-embedded tissue from 108 meningioma patients was analysed for the presence of mutations in PIK3CA and AKT1. These were correlated with the expression status of components of the PI3K/AKT/mTOR pathway, including p85α and p110γ subunits of PI3K, phosphorylated (p)-AKT, p-mTOR, p-p70S6K and p-4E-BP1, as well as of p-ERK1/2, p-STAT3 and Notch-1, clinicopathological data and patient survival. A mutation in PIK3CA or AKT1 was found in around 9 % of the cases. Higher grade meningiomas displayed higher nuclear expression of p-p70S6K; higher nuclear and cytoplasmic expression of p-4E-BP1 and of Notch-1; lower cytoplasmic expression of p85αPI3K, p-p70S6K and p-ERK1/2; and lower PTEN Histo-scores (H-scores). PTEN H-score was inversely correlated with recurrence probability. In univariate survival analysis, nuclear expression of p-4E-BP1 and absence of p-ERK1/2 expression portended adverse prognosis, whereas in multivariate survival analysis, p-ERK1/2 expression emerged as an independent favourable prognostic factor. Treatment of the human meningioma cell line HBL-52 with the PI3K inhibitor LY294002 resulted in reduction of p-AKT, p-p70S6K and p-ERK1/2 protein levels. The complex interactions established between components of the PI3K/AKT/mTOR pathway, or with components of the MAPK, JAK/STAT and Notch-1 pathways, appear to be essential for facilitating and fuelling meningioma progression.

Fall-related emergency department admission: fall environment and settings and related injury patterns in 6357 patients with special emphasis on the elderly.

PRINCIPALS: Throughout the world, falls are a major public health problem and a socioeconomic burden. Nevertheless there is little knowledge about how the injury types may be related to the aetiology and setting of the fall, especially in the elderly. We have therefore analysed all patients presenting with a fall to our Emergency Department (ED) over the past five years. METHODS: Our retrospective data analysis comprised adult patients admitted to our Emergency Department between January 1, 2006, and December 31, 2010, in relation to a fall. RESULTS: Of a total of 6357 patients 78% (n = 4957) patients were younger than 75 years. The main setting for falls was patients home (n = 2239, 35.3%). In contrast to the younger patients, the older population was predominantly female (56.3% versus 38.6%; P < 0.0001). Older patients were more likely to fall at home and suffer from medical conditions (all P < 0.0001). Injuries to the head (P < 0.0001) and to the lower extremity (P < 0.019) occurred predominantly in the older population. Age was the sole predictor for recurrent falls (OR 1.2, P < 0.0001). CONCLUSION: Falls at home are the main class of falls for all age groups, particularly in the elderly. Fall prevention strategies must therefore target activities of daily living. Even though falls related to sports mostly take place in the younger cohort, a significant percentage of elderly patients present with falls related to sporting activity. Falls due to medical conditions were most likely to result in mild traumatic brain injury.

What is New and Innovative in Emergency Neurosurgery? Emerging Diagnostic Technologies Provide Better Care and Influence Outcome: A Specialist Review.

The development of emergency medical services and especially neurosurgical emergencies during recent decades has necessitated the development of novel tools. Although the gadgets that the neurosurgeon uses today in emergencies give him important help in diagnosis and treatment, we still need new technology, which has rapidly developed. This review presents the latest diagnostic tools, which offer precious help in everyday emergency neurosurgery practice. New ultrasound devices make the diagnosis of haematomas easier. In stroke, the introduction of noninvasive new gadgets aims to provide better treatment to the patient. Finally, the entire development of computed tomography and progress in radiology have resulted in innovative CT scans and angiographic devices that advance the diagnosis, treatment, and outcome of the patent. The pressure on physicians to be quick and effective and to avoid any misjudgement of the patient has been transferred to the technology, with the emphasis on developing new systems that will provide our patients with a better outcome and quality of life.

Expression of interleukin-8 receptor CXCR2 and suppressor of cytokine signaling-3 in astrocytic tumors.

The aim was to expand recently published information regarding the significance of the interleukin (IL)-8/p-STAT-3 (signal transducer and activator of transcription) pathway in astrocytomas, focusing on the IL-8 receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and the STAT-3 inhibitor SOCS-3 (suppressors of cytokine signaling). A total of 91 paraffin-embedded human astrocytoma tissues (grades II-IV) were investigated for the association of SOCS-3 and CXCR2 expression with clinicopathologic and morphometric microvascular characteristics, vascular endothelial growth factor (VEGF), IL-8 and p-STAT-3 expression and patient survival. Peripheral IL-8 secretion levels were assessed by enzyme-linked immunosorbent spot (ELISPOT). SOCS-3, p-STAT-3 and CXCR2 protein levels were also quantified by Western immunoblotting in six cases, and the protein levels of SOCS-3 and CXCR2 were correlated with the immunohistochemical expression of the respective proteins. All CXCR2-positive cases by Western immunoblotting displayed increased peripheral IL-8 secretion levels. Treatment of primary glioblastoma cell cultures with exogenous IL-8 enhanced proliferation, and this effect was inhibited by treatment with a neutralizing anti-CXCR2 antibody. SOCS-3 and CXCR2 were expressed by neoplastic astrocytes in 92.4% and 48.78% of cases, respectively, with their levels increasing with histological grade and extent of necrosis. VEGF expression and microvessel density, CXCR2 and IL-8 levels were interrelated. SOCS-3 and p-STAT-3 were co-expressed in 85.7% of cases, although they were not interrelated. In univariate survival analysis, increased SOCS-3 expression and the presence of CXCR2 adversely affected survival, whereas in multivariate analysis, only CXCR2 remained significant. The prognostic significance of CXCR2 was validated in an independent set of 63 patients. Our data implicate IL-8/CXCR2 signaling pathway in the progression and regulation of angiogenesis in astrocytomas and provide a rationale for CXCR2 therapeutic exploitation in these tumors.

Cell-type-dependent thyroid hormone effects on glioma tumor cell lines.

Purpose. The present study investigated the potential effects of long-term T3 treatment on glioma tumor cell lines. Thyroid hormone action on cell growth, differentiation and survival during development may be of therapeutic relevance Methods and Results 1321N1 cell line, an astrocytoma grade II, and U87MG, a glioblastoma grade IV, were exposed for 2 and 4 days in medium deprived of T3 and in medium containing 1 nM T3. T3 promoted re-differentiation in both cell lines. However, T3 increased cell proliferation in 1321N1 (2 days) which declined thereafter (4 days) while in U87MG resulted in suppression of cell proliferation. At the molecular level, a 2.9 fold increase in the expression of TRα1 receptor was observed in U87MG versus 1321N1, P < 0.05. TRß1 receptor was undetectable. These changes corresponded to a distinct pattern of T3-induced kinase signaling activation; T3 had no effect on ERK activation in both cell lines but significantly increased phospho-Akt levels in 1321N1. Conclusion. In conclusion, T3 can re-differentiate glioma tumor cells, whereas its effect on cell proliferation appears to be dependent on the type of tumor cell line with aggressive tumors being more sensitive to T3. TRα1 receptor may, at least in part, be implicated in this response.

Analysis of interleukin (IL)-8 expression in human astrocytomas: associations with IL-6, cyclooxygenase-2, vascular endothelial growth factor, and microvessel morphometry.

Malignant astrocytomas are highly vascular neoplasms with potent angiogenic activity. The present study aimed to investigate peripheral and local expression of interleukin (IL)-8 in astrocytomas with possible associations to IL-6, cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) expression, and microvessel morphometry. IL-6- and IL-8-secreting peripheral blood monocytes (PBMCs) were evaluated in 17 glioblastoma (WHO grade IV), 5 anaplastic astrocytoma (WHO grade III), and 6 diffuse astrocytoma patients (WHO grade II), in parallel with 23 healthy controls using enzyme-linked immunosorbent spot (ELISPOT) assay. The IL-8 expression was assessed immunohistochemically in patients' tumor tissue sections and correlated with the expression of COX-2, VEGF, IL-6, and microvessel morphometry (assessed using CD34 antibody). Eighteen cases were also stained for CD31 and used as an additional vessel marker to validate our results regarding microvessel morphometry. IL-6 and IL-8 were highly secreted in the PBMCs of glioma patients compared with controls (p = 0.0001, p < 0.0001, respectively), with a positive correlation between IL-8 expression and secretion levels (p = 0.001). IL-8 immunoreactivity was detected in malignant cells or macrophages in perivascular areas and in pseudopalisading cells around necrosis and was positively correlated with histological grade (p = 0.0175) and tumor necrosis (p = 0.0793). IL-6 and IL-8 expression levels were positively correlated (p = 0.0036) and associated with COX-2 and VEGF expression (IL-6: p = 0.0133, p = 0.065; IL-8: p = 0.0139, p = 0.0101), but not with microvessel morphometry, by either CD31 or CD34. The coordinate expression and topographical relationship of IL-6, IL-8, COX-2, and VEGF in the same tumor areas (e.g., perinecrotic areas) attest to their intimate liaison in terms of cancer-induced angiogenesis, which is probably secondary to the induction of multiple interdependent molecular pathways. Moreover, our study seems to be the first attempt to link IL-8 expression by tumor cells with histological grade, implicating its potent role in gliomagenesis.

Comparative analysis of peripheral and localised cytokine secretion in glioblastoma patients.

BACKGROUND: Malignant gliomas are the most common primary brain tumours of both children and adults. The unique aspects of their biology and anatomic site render them refractory to conventional therapeutic strategies such as surgery and chemotherapy. Significant attention has been given, recently, to immunotherapy which, although promising in preclinical studies, has not yet enhanced the survival of patients with glioblastomas. METHODS: To further understand the immunobiology of glioblastomas in clinical settings, we examined the secretion of four main cytokines in the peripheral blood and in primary cell cultures of 33 human glioblastoma patients. An ELISPOT methodology was used for the first time to examine Th1, and Th2 cytokine secretion from both peripheral lymphocytes and glioma tumour cells. RESULTS: Th1 cytokines (tumour necrosis factor (TNF-alpha), interferon (IFN-gamma) were markedly reduced compared to control levels (P=0.01 and P<0.001, respectively), whereas in contrast, Th2 (interleukin (IL)-4 and IL-10) were strongly expressed in both peripheral lymphocytes and glioma cell cultures (P=0.05 and P<0.001, respectively). CONCLUSION: This pattern indicates an 'immunosuppressive status' in glioblastomas which is related to their origination and the evasion of glioma cells from immune surveillance and could account for the failure of immunotherapy in such tumours. Furthermore, ELISPOT methodology can be used for monitoring of cytokine secretion from tumour cells, in addition to the well-established peripheral cytokine secretion.

Application of the ELISPOT method for comparative analysis of interleukin (IL)-6 and IL-10 secretion in peripheral blood of patients with astroglial tumors.

Glioblastoma, (grade IV astrocytoma), is characterized by rapid growth and resistance to treatment. Identification of markers of aggressiveness in this tumor could represent new therapeutic targets. Interleukins (IL)-6 and IL-10 may be considered as possible candidates, regulating cell growth, resistance to chemotherapy and angiogenesis. ELISPOT method provides a useful tool for the determination of the exact cell number of peripheral lymphocytes secreting a specific cytokine. IL-6 and IL-10 secretion levels were determined using ELISPOT methodology in peripheral blood mononuclear cells of 18 patients with astrocytic neoplasms (3 grade II and 15 grade IV), in parallel with 18 healthy controls. Additionally, immunohistochemical expression of these two cytokines was performed in paraffin-embedded neoplastic tissue in 12 of these patients. The secretion of IL-6 from peripheral monocytes was significantly higher in glioma patients compared to controls (P = 0.0003). In addition, IL-10 secretion from peripheral mononuclear and tumor cells of glioma patients was also higher as compared to healthy controls (P = 0.0002). Based on immunohistochemical staining, IL-6 expression was localized in tumor cells and macrophages as well as in areas of large ischemic necrosis, while the major source of IL-10 expression in glioblastomas was the microglia/macrophage cells. It is suggested that IL-10 contributes to the progression of astrocytomas by suppressing the patient's immune response, whereas IL-6 provides an additional growth advantage. This study demonstrates for the first time the usefulness of ELISPOT in estimating the secretion of IL-6 and IL-10 from peripheral blood and the correlation of their expression in neoplastic cells.