Meningiomas in children and adolescents: a meta-analysis of individual patient data.

BACKGROUND: The epidemiological, prognostic, and therapeutic features of child and adolescent meningioma are poorly defined. Clinical knowledge has been drawn from small case series and extrapolation from adult studies. This study was done to pool and analyse the clinical evidence on child and adolescent meningioma. METHODS: Searches of PubMed, Medline, and Embase identified 35 case series of child and adolescent meningioma completed over the past 21 years. Individual patient data were obtained from 30 studies via direct communication with investigators. Primary outcomes were relapse-free survival (RFS) and overall survival. Prognostic variables were extent of initial surgery, use of upfront radiotherapy, age, sex, presence of neurofibromatosis, tumour location, and tumour grade. RFS and overall survival were analysed using Kaplan-Meier survival curves and multivariable Cox regression models. FINDINGS: From a total of 677 children and adolescents with meningioma, 518 were eligible for RFS analysis and 547 for overall survival analysis. Multivariable analysis showed that patients who underwent initial gross-total resection had better RFS (hazard ratio 0·16, 95% CI 0·10-0·25; p<0·0001) and overall survival (0·21, 0·11-0·39; p<0·0001) than those who had subtotal resection. No significant benefit was seen for upfront radiotherapy in terms of RFS (0·59, 0·30-1·16; p=0·128) or overall survival (1·10, 0·53-2·28; p=0·791). Patients with neurofibromatosis type 2 (NF2) had worse RFS than those without neurofibromatosis (2·36, 1·23-4·51; p=0·010). There was a significant change in overall survival with time between patients with NF2 compared with those without neurofibromatosis (1·45, 1·09-1·92; p=0·011); although overall survival was initially better for patients with NF2 than for those without neurofibromatosis, overall survival at 10 years was worse for patients with NF2. Patients with WHO grade III tumours had worse RFS than those with WHO grade I (3·90, 2·10-7·26; p<0·0001) and grade II tumours (2·49, 1·11-5·56; p=0·027). INTERPRETATION: Extent of initial surgical resection is the strongest independent prognostic factor for child and adolescent meningioma. No benefit for upfront radiotherapy was noted. Hence, aggressive surgical management, to achieve gross-total resection, is the initial treatment of choice. In the event of a subtotal resection, repeat resection is recommended to achieve maximum extirpation. Close observation is warranted for patients who have a subtotal resection or who have WHO grade III tumours. Patients without neurofibromatosis should have a minimum 10-year follow-up, whereas patients with NF2 should be considered a special risk category, necessitating life-long follow-up. FUNDING: None.

Cancer incidence in Denmark following exposure to poliovirus vaccine contaminated with simian virus 40.

BACKGROUND: Early poliovirus vaccines were accidentally contaminated with simian virus 40 (SV40). In Denmark, poliovirus vaccine was administered to most children from 1955 through 1961. SV40 DNA sequences have been detected in several human malignancies, including mesothelioma, ependymoma, choroid plexus tumors, and non-Hodgkin's lymphoma. To clarify whether SV40 infection increases risk of these cancers or of cancers arising in children, we examined cancer incidence in three Danish birth cohorts. METHODS: Population-based cancer incidence data from 1943 through 1997 were obtained from the Danish Cancer Registry. The relationship between exposure to SV40-contaminated vaccine and cancer incidence was evaluated by examining incidence in birth cohorts that differed in exposure to SV40-contaminated vaccine. In addition, cancer incidence was examined in children who were 0-4 years of age before, during, and after the period of vaccine contamination. Incidence was compared using Poisson regression, adjusting for age differences. All statistical tests were two-sided. RESULTS: After 69.5 million person-years of follow-up, individuals exposed to SV40-contaminated poliovirus vaccine as infants (i.e., born 1955-1961) or children (i.e., born 1946-1952) had lower overall cancer risk (age-adjusted relative risk [RR] = 0.86, 95% confidence interval [CI] = 0.81 to 0.91 and RR = 0.79, 95% CI = 0.75 to 0.84, respectively; P<.001 for both) than unexposed individuals (i.e., born 1964-1970, after the vaccine was cleared of SV40 contamination). Specifically, SV40 exposure was not associated with increased incidence of mesothelioma, ependymoma, choroid plexus tumor, or non-Hodgkin's lymphoma. After 19.5 million person-years of follow-up, incidence of all cancers combined, of intracranial tumors, and of leukemia among children aged 0-4 years was also not associated with SV40 exposure. Ependymoma incidence was higher during the exposed period than during the unexposed period (RR = 2.59, 95%CI = 1.36 to 4.92; P =.004 versus the period before contamination); however, incidence peaked in 1969, after the vaccine was cleared of SV40. CONCLUSION: Exposure to SV40-contaminated poliovirus vaccine in Denmark was not associated with increased cancer incidence.

Familial aggregation of intracranial aneurysms in an Inuit patient population in Kalaallit Nunaat (Greenland).

OBJECTIVE: The incidence of subarachnoid hemorrhage (SAH) and intracranial aneurysm (IA) has been reported to be higher in Greenlandic Inuits than in Caucasian Danes, but the rate of familial aggregation in Inuits is unknown. METHODS: This study retrospectively compared the rate of familial aggregation of SAH and IA (at least one first- or second-degree relative with presumed SAH and/or IA) in 120 Inuit patients from Greenland admitted to the Copenhagen University Hospital in Copenhagen, Denmark, from 1978 to 1998 with a diagnosis of ruptured IA with that in 1,037 Caucasian Danes admitted from 1978 to 1983. RESULTS: Inuit patients had a much higher rate of familial history of SAH (23.1%) and of IA (9.6%) than Danish patients (4.3 and 1.6%, respectively). In both populations, familial SAH was associated with lower age at the time of aneurysm rupture. Danish patients with familial SAH showed a higher rate of middle cerebral artery aneurysms (40 versus 26% in sporadic SAH). In Inuit patients with familial and nonfamilial SAH, 42 and 38% of the aneurysms originated from the middle cerebral artery. The overall rate of multiple aneurysms was highest among Inuits, and in both populations, it was increased in the presence of a positive family history. CONCLUSION: The rate of a positive family history of presumed SAH and IA is high among Inuits who present with SAH compared with Caucasian Danes who present with SAH. This finding, coupled with a higher rate of multiple aneurysms and younger age at presentation, suggests a potential genetic influence among Inuit families.

Long-term follow up of children with meningiomas in Denmark: 1935 to 1984.

OBJECT: Meningiomas in children are rare, infrequently described in the literature, and often associated with neurofibromatosis Type 2 (NF2). The authors report a series of 22 children treated for an intracranial meningioma in Denmark between 1935 and 1984. METHODS: Of 1542 cases of pediatric intracranial tumors in children younger than 15 years of age, 22 harbored meningiomas. Three children suffered from NF. The male/female ratio was 8:14. The mean age at the time of diagnosis was 5 years for boys and 11.5 years for girls. At the time of diagnosis all tumors were large. All patients underwent surgery. In 20 cases, the final histological diagnoses were low-grade and in two cases high-grade tumors. The follow-up period ranged from I to 45 years (mean 16 years). Two patients were lost to follow up. Four of seven boys and three of 13 girls survived. Five of 13 children in whom the tumor was completely removed survived, whereas two of seven in whom the lesion was partially removed survived. The mean survival time in children who died during follow up was 10 years. Two children with anaplastic meningioma remain alive. CONCLUSIONS: The long-term prognosis for surgically treated children with intracranial meningiomas was worse than expected. Some reasons for this may have been the late diagnosis and related large size of the tumor during a period of limited diagnostic capacity prior to the computerized tomography and magnetic resonance imaging eras, and the association of NF2 with multiple tumors of the central nervous system. Complete resection is not always possible and should be performed as an image-guided operation.

Evaluation of the lumbar and ventricular infusion test in the diagnostic strategy of pediatric hydrocephalus and the therapeutic implications.

AIM: To evaluate the infusion test as a diagnostic tool behind the choice of intervention in pediatric hydrocephalus. MATERIALS AND METHODS: Intracranial pressure (ICP) measurement and infusion test were performed intraventricularly, by lumbar route, or combined in 40 consecutive children as a part of the standard diagnostic program in 1996-1999. RESULTS: The median age was 18.5 months, ranging from 2 weeks to 13 years. In the subgroup of patients with radiological aqueductal stenosis (N=14), mean lumbar/intraventricular ICP was 13 (3-35)/10 (2-27). Mean lumbar/ventricular R(out) were 18 (4-49)/17 (6-37). For patients with radiological communication between the third and fourth ventricles (N=14), the mean lumbar/intraventricular ICP was 11 (7-17)/9 (1-16). Mean lumbar/ventricular R(out) were 8 (3-11)/8 (4-12). A total of 13 patients had a shunt insertion, 10 had an endoscopic third ventriculostomy (ETV), 5 had endoscopic fenestration of a cyst, and 12 had no surgery. Of the patients initially treated with EVT, 50% had a shunt insertion shortly after. For communicating hydrocephalus, 75% of the patients initially not operated based on normal R(out) values ended up having a shunt insertion. DISCUSSION: R(out) has doubtful value as an indicator for conducting an operation or not and in the choice between EVT and shunt in children. This should be interpreted in the light of a growing understanding of hydrocephalus on a molecular level.

[Central nervous system tumours in children. An evaluation of the completeness and validity of the Cancer Registry]. / Tumorer i centralnervesystemet hos børn. En evaluering af Cancerregisterets komplethed og validitet.

INTRODUCTION: The aim of this study was to evaluate the registration of childhood CNS tumours in the Danish Cancer Registry (CR) from 1980 to 1996, based on completeness and validity. MATERIALS AND METHODS: The completeness of the CR was estimated by examination of the Danish National Hospital Register and an independent hospital registry. To determine the validity of the CR, 640 cases of childhood CNS tumours identified in the CR were compared with the corresponding medical record, with regard to cancer morphology and date of diagnosis. RESULTS: The completeness of the CR was 98-99%. For 82% of all cases, the morphology registered in the CR was identical with that in the medical record. The validity of the morphological diagnosis was 84% for astrocytomas, 88% for ependymomas, 95% for medulloblastomas, 47% for other gliomas and 76% for miscellaneous intracranial and intraspinal neoplasms. In a further 7% of all cases, the morphological diagnosis in the CR was incorrect with respect to details but correct within these main diagnostic groups, 6% were tumours of another main diagnostic group than that registered in the CR and 5% were not tumours, were tumours outside the study criteria or were registered in the hospital journal as suspected tumours. The date of diagnosis in the CR and that in the medical records were concordant in 88% of the evaluated cases. CONCLUSION: Registration of childhood CNS tumours in the CR was highly complete, while the validity of the morphological diagnosis differed among the main diagnostic groups. The relatively low validity might be explained by the anatomic location of CNS tumours, which makes tissue sampling for histological verification and therefore diagnosis difficult.

Sub-classification of low-grade cerebellar astrocytoma: is it clinically meaningful?

OBJECTIVES: The objectives were to identify prognostic factors for the survival of children with cerebellar astrocytoma, and to evaluate the reproducibility and prognostic value of histological sub-classification and grading. METHODS: Children aged 0-14 years treated in Denmark for a cerebellar astrocytoma in the period 1960-1984 were included and followed until January 2001 or until their death. The histological specimens from each patient were reviewed for revised grading and classification according to three different classification schemes: the WHO, the Kernohan and the Daumas-Duport grading systems. RESULTS: The overall survival rate was 81% after a follow-up time of 15-40 years. The significant positive prognostic factors for survival were "surgically gross-total removal" of the tumour at surgery and location of the tumour in the cerebellum proper as opposed to location in the fourth ventricle. No difference in survival time was demonstrated when we compared pilocytic astrocytoma and fibrillary astrocytoma. Moreover, we found that the Kernohan and the WHO classification systems had no predictive value and that the Daumas-Duport system is unsuitable as a prognostic tool for low-grade posterior fossa astrocytomas. CONCLUSION: Discordant observations due to interobserver variability make histological sub-classification of low-grade cerebellar astrocytomas in children insufficient for predicting prognosis and biological behaviour. Similar survival rates in a population of paediatric low-grade cerebellar astrocytomas of grades I and II indicate that tumour grade has no prognostic significance within this group of patients. "Surgically gross-total removal", especially if the tumour is located in the fourth ventricle is of the highest importance for long-term survival. Histological sub-classification of the tumours has no predictive value.

Shunting to the cranial venous sinus using the SinuShunt.

INTRODUCTION: A new shunting principle taking advantage of the knowledge of normal CSF dynamics has been developed. EXPERIENCE AND OUTCOME: The shunt has been used in more than 150 patients. The final version has shown a stable function in 45 patients. The physiological shunting principle has an expected and immediate clinical effect. We have not seen any over-drainage and any symptoms or signs of thrombosis or occlusion of the sinus. The ventricular system decreases only slightly. The shunt has been used in children and adults and in all types of hydrocephalus. The shunt can be implanted using local anaesthesia. The implantation in the transverse sinus has proven to be simple and safe.