David Scheie

Glioma grading by using histogram analysis of blood volume heterogeneity from MR-derived cerebral blood volume maps.

PURPOSEnTo retrospectively compare the diagnostic accuracy of an alternative method used to grade gliomas that is based on histogram analysis of normalized cerebral blood volume (CBV) values from the entire tumor volume (obtained with the histogram method) with that of the hot-spot method, with histologic analysis as the reference standard.nnnMATERIALS AND METHODSnThe medical ethics committee approved this study, and all patients provided informed consent. Fifty-three patients (24 female, 29 male; mean age, 48 years; age range, 14-76 years) with histologically confirmed gliomas were examined with dynamic contrast material-enhanced 1.5-T magnetic resonance (MR) imaging. CBV maps were created and normalized to unaffected white matter (normalized CBV maps). Four neuroradiologists independently measured the distribution of whole-tumor normalized CBVs and analyzed this distribution by classifying the values into area-normalized bins. Glioma grading was performed by assessing the normalized peak height of the histogram distributions. Logistic regression analysis and interobserver agreement were used to compare the proposed method with a hot-spot method in which only the maximum normalized CBV was used.nnnRESULTSnFor the histogram method, diagnostic accuracy was independent of the observer. Interobserver agreement was almost perfect for the histogram method (kappa = 0.923) and moderate for the hot-spot method (kappa = 0.559). For all observers, sensitivity was higher with the histogram method (90%) than with the hot-spot method (55%-76%).nnnCONCLUSIONnGlioma grading based on histogram analysis of normalized CBV heterogeneity is an alternative to the established hot-spot method, as it offers increased diagnostic accuracy and interobserver agreement.

Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme

Helseth R, Helseth E, Johannesen TB, Langberg CW, Lote K, Rønning P, Scheie D, Vik A, Meling TR. Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme. u2028Acta Neurol Scand: 122: 159–167.u2028© 2010 The Authors Journal compilation

Incidence of intracranial meningiomas in Denmark, Finland, Norway and Sweden, 1968-1997.

It has been reported that the incidence of meningioma increased in several industrialized countries in the late 1970s and early 1980s. The aim of this study was to evaluate the time trends in incidence of meningiomas in Denmark, Finland, Norway and Sweden, with emphasis on the age distribution and sex ratio. Information about cases of meningiomas in people aged 15–84 years was obtained from the cancer registries of these Nordic countries for the years 1968–1997, and estimates of person‐years at risk were calculated from information provided by the national population registries. Age‐specific incidence rates per 100,000 and incidence rate ratios were calculated for 3‐year periods. The female:male ratios were also evaluated. The combined incidence among men increased from 1.4 to 1.9 per 100,000 during the follow‐up period, the corresponding rates for women were 2.6 and 4.5. The female:male ratio increased over time for several age groups and was as high as 3.5:1 in the group aged 40–44 years in the latest follow‐up period (1993–1997). In summary, our results provide some support for the idea that the introduction of computed tomography in the late 1970s has had an impact on the detection of cases in people aged 60 and over. The decrease in the rate or detection postmortem has affected the incidence time trend, but it also coincides with widespread use of new imaging technologies. The increasing trend shown for the female:male ratio in the group aged 35–59 years is consistent with the possibility that increasing use of hormones may affect the incidence of meningiomas in women.

Surgery for convexity meningioma: Simpson Grade I resection as the goal: clinical article.

OBJECTnRecently the relevance of Simpson resection grade as a prognostic factor for recurrence of WHO Grade I meningiomas was challenged, contradicting many previous scientific reports and traditional neurosurgical teaching. The objective of this study was to determine whether the predictive value of Simpson resection grade is outdated or remains valid with respect to meningioma recurrence and overall survival.nnnMETHODSnAll patients at least 16 years old who underwent primary craniotomies for convexity meningiomas at Oslo University-affiliated hospitals (Rikshospitalet and Ullevål University Hospitals) in the period between January 1, 1990, and January 27, 2011, were included. Overall survival and retreatment-free survival rates were correlated with patient- and surgery-specific factors.nnnRESULTSnThree hundred ninety-one consecutive patients were included in the study. The median patient age was 60.1 years (range 19-92 years). The female-to-male ratio was 2.1:1. The WHO grades were Grade I in 353 (90.3%), Grade II in 22 (5.6%), and Grade III in 16 (4.1%). The follow-up rate was 100%. Median follow-up time was 7.1 years (range 0.0-20.9 years) and total observation time was 3147 patient-years. The 1-, 5-, and 10-year overall survival rates were 96%, 89%, and 78%, respectively. Age, sex, WHO grade, and Simpson grade were significantly associated with overall survival. The 1-, 5-, and 10-year retreatment-free survival rates were 99%, 94%, and 90%, respectively. Simpson resection grade and WHO grade were significantly associated with retreatment-free survival. The hazard ratios for retreatment after combined Simpson resection Grades II+III and IV+V were 4.9- and 13.2-times higher than after Simpson Grade I resection, respectively.nnnCONCLUSIONSnSimpson Grade I resection should continue to be the goal for convexity meningiomas.

Long-Term Outcome after Resection of Benign Cerebellar Astrocytomas in Children and Young Adults (0–19 Years): Report of 110 Consecutive Cases

The objective of this retrospective study was to present long-term follow-up data for 110 consecutive children and young adults treated for a benign cerebellar astrocytoma at our institution between 1960 and 2001. Mean age at presentation was 8.9 years. The total surgical mortality was 9%, but declined from 16% in 1960–1977 to 0% in 1988–2001. At the close of the study 97/110 patients were still alive. Nine deaths were surgery related, 2 patients died of shunt-related causes and 2 patients died due to tumor recurrence. Five-, 10- and 25-year survival were 90, 89 and 85%, respectively. Multiple Cox regression analysis showed that tumor infiltration of the brain stem and the time period of surgery were the only explanatory variables significantly associated with survival. Five-year survival improved from 79% in the time period of 1960–1977 to 100% in the time period of 1988–2001. Tumor recurrence after total tumor resection was observed in 5 of 76 (7%) evaluable patients. Growth of residual tumor after subtotal tumor resection was observed in 7 of 26 (27%) evaluable patients. Recent follow- up MR revealed regression of residual tumor in 14 of 16 patients. Only 5 of these patients had received radiotherapy. Thus, spontaneous regression of residual tumor is a more frequent event than growth of residual tumor. The functional outcome was favorable in 82% of the patients [Karnofsky performance index (KPI) ≧90]. Eighteen percent of the patients had moderate to severe disabilities (KPI 50–80). Conclusions: Benign cerebellar astrocytoma is a surgical disease where the prognosis with respect to both survival and functional outcome is favorable. Spontaneous regression of residual tumor is frequently encountered, allowing for observation of residual tumors instead of performing a second resection in cases where a second resection carries a high risk of neurological sequelae.

Are melanomas averse to cerebellum? Cerebellar metastases in a surgical series

To study the propensity of different cancers to metastasize to the cerebrum and cerebellum, and to study overall survival (OS) and prognostic factors for patients after surgical resection for cerebellar metastases.

Surgical Mortality at 30 Days and Complications Leading to Recraniotomy in 2630 Consecutive Craniotomies for Intracranial Tumors

BACKGROUND:In order to weigh the risks of surgery against the presumed advantages, it is important to have specific knowledge about complication rates. OBJECTIVE:To study the surgical mortality and rate of reoperations for hematomas and infections after intracranial surgery for brain tumors in a large, contemporary, single-institution consecutive series. METHODS:All adult patients from a well-defined population of 2.7 million inhabitants who underwent craniotomies for intracranial tumors at Oslo University Hospital from 2003 to 2008 were included (n = 2630). The patients were identified from our prospectively collected database and their charts studied retrospectively. Follow-up was 100%. RESULTS:The overall surgical mortality, defined as death within 30 days of surgery, was 2.3% (n = 60). The mortality rates for high- and low-grade gliomas, meningiomas, and metastases were 2.9%, 1.0%, 0.9%, and 4.5%, respectively. Age >60 (odds ratio 1.84, P < 0.05) and biopsy compared with resection (odds ratio 4.67, P < 0.01) were significantly positively associated with increased surgical mortality. Hematomas accounted for 35% of the surgical mortality. Postoperative hematomas needing evacuation occurred in 2.1% (n = 54). Age >60 was significantly correlated to increased risk of postoperative hematomas (odds ratio 2.43, P < 0.001). A total of 39 patients (1.5%) were reoperated for postoperative infection. Meningiomas had an increased risk of infections compared with high-grade gliomas (odds ratio 4.61, P < 0.001). CONCLUSION:The surgical mortality within 30 days of surgery was 2.3%, with age >60 and biopsy vs resection being the 2 factors significantly associated with increased mortality. Postoperative hematomas caused about one third of the surgical mortality.

Histogram Analysis of MR Imaging–Derived Cerebral Blood Volume Maps: Combined Glioma Grading and Identification of Low-Grade Oligodendroglial Subtypes

BACKGROUND AND PURPOSE: Inclusion of oligodendroglial tumors may confound the utility of MR based glioma grading. Our aim was, first, to assess retrospectively whether a histogram-analysis method of MR perfusion images may both grade gliomas and differentiate between low-grade oligodendroglial tumors with or without loss of heterozygosity (LOH) on 1p/19q and, second, to assess retrospectively whether low-grade oligodendroglial subtypes can be identified in a population of patients with high-grade and low-grade astrocytic and oligodendroglial tumors. MATERIALS AND METHODS: Fifty-two patients (23 women, 29 men; mean age, 52 years; range, 19–78 years) with histologically confirmed gliomas were imaged by using dynamic susceptibility contrast MR imaging at 1.5T. Relative cerebral blood volume (rCBV) maps were created, and 4 neuroradiologists defined the glioma volumes independently. Averaged over the 4 observers, a histogram-analysis method was used to assess the normalized histogram peak height of the glioma rCBV distributions. RESULTS: Of the 52 patients, 22 had oligodendroglial tumors. The histogram method was able to differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) (Mann-Whitney U test, P < .001) and to identify low-grade oligodendroglial subtypes (P = .009). The corresponding intraclass correlation coefficients were 0.902 and 0.801, respectively. The sensitivity and specificity in terms of differentiating low-grade oligodendroglial tumors without LOH on 1p/19q from the other tumors was 100% (6/6) and 91% (42/46), respectively. CONCLUSION: With histology as a reference, our results suggest that histogram analysis of MR imaging–derived rCBV maps can differentiate HGGs from LGGs as well as low-grade oligodendroglial subtypes with high interobserver agreement. Also, the method was able to identify low-grade oligodendroglial tumors without LOH on 1p/19q in a population of patients with astrocytic and oligodendroglial tumors.

Increasing incidence and continued dismal outcome of primary central nervous system lymphoma in Norway 1989-2003 : time trends in a 15-year national survey.

The incidence of primary central nervous system lymphoma (PCNSL) appears to be increasing in some countries, whereas it is stable in others. Many reports the last decades have suggested that there have been improvements in the treatment of PCNSL. The objective of this study was to analyze time trends in the incidence, clinical features, histologic diagnosis, treatment, and outcome of nonacquired immunodeficiency syndrome (non‐AIDS) PCNSL in Norway from 1989 to 2003.

MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR

BackgroundMethylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method.MethodWe examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP) and pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR.ResultsWhen examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were found methylated by pyrosequencing. The average MGMT gene expression level was significantly lower in the group of patients with a methylated promoter independent of method used for methylation detection. Primary glioblastoma patients with a methylated MGMT promoter (as evaluated by both methylation detection methods) had approximately 5 months longer median survival compared to patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02, qMSP P = .06). One third of the analyzed samples had conflicting methylation results when comparing the data from the qMSP and pyrosequencing. The overall survival analysis shows that these patients have an intermediate prognosis between the groups with concordant MGMT promoter methylation results when comparing the two methods.ConclusionIn our opinion, MGMT promoter methylation analysis gives sufficient prognostic information to merit its inclusion in the standard management of patients with high-grade gliomas, and in this study pyrosequencing came across as the better analytical method.