Expertise in surgical neuro-oncology. Results of a survey by the EANS neuro-oncology section.

Introduction: Technical advances and the increasing role of interdisciplinary decision-making may warrant formal definitions of expertise in surgical neuro-oncology. Research question: The EANS Neuro-oncology Section felt that a survey detailing the European neurosurgical perspective on the concept of expertise in surgical neuro-oncology might be helpful. Material and methods: The EANS Neuro-oncology Section panel developed an online survey asking questions regarding criteria for expertise in neuro-oncological surgery and sent it to all individual EANS members. Results: Our questionnaire was completed by 251 respondents (consultants: 80.1%) from 42 countries. 67.7% would accept a lifetime caseload of >200 cases and 86.7% an annual caseload of >50 as evidence of neuro-oncological surgical expertise. A majority felt that surgeons who do not treat children (56.2%), do not have experience with spinal fusion (78.1%) or peripheral nerve tumors (71.7%) may still be considered experts. Majorities believed that expertise requires the use of skull-base approaches (85.8%), intraoperative monitoring (83.4%), awake craniotomies (77.3%), and neuro-endoscopy (75.5%) as well as continuing education of at least 1/year (100.0%), a research background (80.0%) and teaching activities (78.7%), and formal interdisciplinary collaborations (e.g., tumor board: 93.0%). Academic vs. non-academic affiliation, career position, years of neurosurgical experience, country of practice, and primary clinical interest had a minor influence on the respondents' opinions. Discussion and conclusion: Opinions among neurosurgeons regarding the characteristics and features of expertise in neuro-oncology vary surprisingly little. Large majorities favoring certain thresholds and qualitative criteria suggest a consensus definition might be possible.

Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222.

BACKGROUND: Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma. METHODS: To comprehensively evaluate the impact of variation in TP53 on risk, we analysed 23 tagSNPs and imputed 2377 unobserved genotypes in four series totaling 4147 glioma cases and 7435 controls. RESULTS: The strongest validated association signal was shown by the imputed single-nucleotide polymorphism (SNP) rs78378222 (P=6.86 × 10(-24), minor allele frequency ~0.013). Confirmatory genotyping confirmed the high quality of the imputation. The association between rs78378222 and risk was seen for both glioblastoma multiforme (GBM) and non-GBM tumours. We comprehensively examined the relationship between rs78378222 and overall survival in two of the case series totaling 1699 individuals. Despite employing statistical tests sensitive to the detection of differences in early survival, no association was shown. CONCLUSION: Our data provided strong validation of rs78378222 as a risk factor for glioma but do not support the tenet that the polymorphism being a clinically useful prognostic marker. Acquired TP53 inactivation is a common feature of glioma. As rs78378222 changes the polyadenylation signal of TP53 leading to impaired 3'-end processing of TP53 mRNA, the SNP has strong plausibility for being directly functional contributing to the aetiological basis of glioma.

Nuclear karyopherin a2: a novel biomarker for infiltrative astrocytomas.

The karyopherin (KPNA) protein family is involved in nucleocytoplasmic trafficking. Increased KPNA levels have been found to predict poor prognosis for a variety of solid tumors, including breast, ovarian, cervical, and prostate cancer, and melanoma. The purpose of this study was to evaluate karyopherin a2 as novel biomarker for astrocytic gliomas of WHO grades II-IV. We semiquantitatively measured nuclear expression of karyopherin a2 and the MIB1 labeling index, by immunohistochemical analysis, for 94 primary (23 astrocytomas WHO grade II, 24 astrocytomas WHO grade III, 47 glioblastomas) and 12 recurrent gliomas. In addition, IDH1 mutation status and Nijmegen breakage syndrome 1 protein expression were assessed, by immunohistochemical analysis, for all 71 malignant (WHO grade III and IV) and all 94 primary gliomas, respectively. Statistical analysis was performed by use of standard techniques. Karyopherin a2 expression correlated significantly with histological grade (p < 0.001), with proliferative activity as assessed by the MIB1 index (p < 0.001), with IDH1 mutation status (p = 0.032), and with Nijmegen breakage syndrome 1 protein expression (p = 0.001). Recurrent tumors expressed significantly higher levels of karyopherin a2 (p = 0.045) than primary growths. Multivariate analysis of the overall series identified low karyopherin a2 expression (defined as less than 5 %) as an independent prognostic predictor of overall (p = 0.041) and progression-free survival (p = 0.004). Survival of glioblastoma patients >5 years was seen only in those with KPNA2 expression levels ≤1 % (p = 0.014). KPNA2 expression may have potential as a novel diagnostic and prognostic biomarker for astrocytic gliomas.

Frequent abnormalities of the immune system in gliomas and correlation with the WHO grading system of malignancy.

AIM: To investigate the cellular and humoral immunity status of gliomas, and their association with the WHO grading system. MATERIAL AND METHODS: We have conducted a case-control study of 49 patients with gliomas and 30 healthy controls. We used ELISA assays, radial immunodiffusion, indirect immunofluorescence, latex test and flow cytometry assays to estimate preoperative in serum the immunological profile. RESULTS: Patients with glioma had significantly reduced amounts of IL2 (p=0.000), TNF-a (p=0.033), IgG (p=0.011), IgA (p=0.027),C4 (p=0.026) ,CD3+ (p=0.001), CD4+ (p=0.000), CD8+ (p=0.002), ratio CD4/CD8 (p=0.000), CD19+ (p=0.04) and elevated IL10 (p=0.05) compared with healthy controls. No statistically significant differences were observed concerning viral agents, total NK cells, IgM, IgE, IL16, granzyme-b, RF, ANA, ENA, anti-dsDNA and anti-cardiolipin antibodies. A higher WHO grade, after controlling for age and gender, was associated with decreased number of CD3+ (p=0.011), CD4+ (p=0.015), CD8+ (p=0.048) and ratio CD4/CD8 (p=0.027), as well as with decreased IL2 (p=0.018), C4 (p=0.02), and IgG (p=0.05). IL2 and CD4+ counts were significant predictors of grade. CONCLUSIONS: A shift from Th1 to Th2, a CD3+ and CD19+ lymphocytopenia, a diminished fraction CD4/CD8 and a reduced amount of immunoglobulins and complement were observed in the patients with gliomas. A higher WHO grade of the tumor was associated with greater impairments of immunity. Since defects of both humoral and cellular immunity were equally observed and significant predictors of grade were assessed, a preoperative evaluation of the immune system of patients with gliomas is being proposed.

Descriptive epidemiology of cerebral gliomas in northwest Greece and study of potential predisposing factors, 2005-2007.

BACKGROUND: To investigate the epidemiologic and clinical characteristics (age, sex, tumor location, socioeconomic status) and potential predisposing factors (alcohol, tobacco, mobile phone use, severe head trauma) of cerebral gliomas in a defined area of Northwest Greece. METHODS: The prospective study was conducted in patients with gliomas referred to all 7 hospitals of a study area with a population of 488,435 inhabitants, from June 1, 2005, to May 31, 2007. Incidence rates (IR) were calculated as new cases diagnosed among residents of the study area during the study period per 100,000 inhabitants. A case-control study was carried out in order to study the possible association of the risk of glioma with smoking, alcohol, use of mobile phone, and severe cranial trauma. RESULTS: A total of 56 glioma incident cases were identified with IRs of glioma and glioblastoma (GBM) at 5.73/10(5)/year and 3.69/10(5)/year, respectively. A male to female ratio of 1.25 was obtained in the GBM group. IRs of glioma and GBM for both males and females were higher in the age group 60-79. The most frequent anatomic location was the frontal lobe. 46.5% of the patients originated from the low, 25% from the middle and 28.5% from the high socioeconomic class. There was no significant association between glioma and alcohol consumption, smoking and mobile phone use. A trend for a positive association between the risk of glioma and a history of severe cranial trauma was observed, but this association was not statistically significant. CONCLUSION: The estimated IR of glioma and GBM in this study was higher compared with data from other studies carried out on European, Asian and US populations. Further studies may be needed to assess the possible association of genetic, environmental and lifestyle factors with the high occurrence of gliomas observed in this study.

Solitary plasmacytoma of the upper cervical spine: therapeutic considerations.

Solitary plasmacytomas are localized plasma cell malignancies involving bone marrow (solitary bone plasmacytoma, SBP) or extramedullary tissues (solitary extramedullary plasmacytoma, SEP). The upper cervical spine involvement by SBP is a rare and more challenging condition. The authors describe a patient with solitary plasmacytoma involving all the elements of C2 vertebra. Severe neck pain was the only manifestation of disease. The patient underwent an occipito-cervical stabilization with a partial decompression through a single posterior approach. The authors stress the importance of early diagnosis followed by appropriate multidisciplinary treatment strategies, including surgery and discuss the management dilemmas concerning the timing and management consequence, in scope to prevent a major neurological damage and allow the patient to be ambulatory.

Resection of giant meningiomas of the anterior cranial fossa using orbital osteotomies.

AIM: The challenge in large cranial base meningiomas is total resection of the tumor with the least possible mortality and morbidity. During the last two decades the technical approaches for anterior skull base tumors have shown a considerable progress, providing a wide exposure with minimal brain retraction. The purpose of this study is to present our experience with these approaches for treatment of giant anterior cranial fossa meningiomas. METHODS: A retrospective analysis was performed in 20 patients with giant meningiomas (diameter >4.5 cm) of the anterior cranial fossa, which were treated surgically in our department, between January 1992 and January 2002. There were 5 men and 15 women with an average age of 48,3 years. Mental and visual disturbances were the most common presenting symptoms. We used the extended subfrontal approach for 16 patients and the fronto-orbito-zygomatic approach for 4 patients. The follow-up period ranged from 3 to 10 years. RESULTS: In all patients, total resection of the tumor (Simpson grade I, 12 patients, Simpson grade II, 8 patients) was accomplished. Significant improvement occurred by the time of follow-up examination in all but three patients. No evidence of recurrence was observed in 19 of the 20 patients. CONCLUSIONS: The extended anterior skull base approaches, using orbital osteotomies, for giant meningiomas of the anterior cranial fossa have improved the extent of radical tumor removal with minimal neurological morbidity. Furthermore a long term prevention of recurrence was achieved.