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Medulloblastoma with extensive nodularity (MBEN) is the only type of medulloblastoma (MB), an aggressive CNS tumour of childhood, that is connected with favourable prognosis. In patients with MBEN tumour resection and chemotherapy are sometimes sufficient. While development of other types of MB is usually connected with activation of the wingless pathway, sonic hedgehog pathway or mammalian target of rapamycin (mTor) pathway, little is known about the molecular basis of MBEN pathophysiology. In the present paper we evaluated activation of the mTor pathway and kinases upstream of mTor, mitogen-activated protein kinase (MAPK/Erk) and protein kinase B (PKB/Akt) in an MBEN sample. Using western blot technique with antibodies directed against active, phosphorylated forms of proteins, we found upregulation of mTor, Akt and Erk. Thus we postulate that the mTor pathway, often implicated in the development of CNS tumours, is also responsible for MBEN progression. Especially interesting seems implication of Erk and other kinases belonging to the same pathway: mitogen-activated protein kinase kinase (MEK-1) or phospho-ribosomal S6 kinase-1 (p90 RSK1), whose activity we usually demonstrate in more benign neoplasms. However, it remains to be clarified whether Erk pathway activation is actually prognostic for benign tumour development.

The NBN (NBS1) gene belongs to a group of double-strand break repair genes. Mutations in any of these genes cause genome instability syndromes and contribute to carcinogenesis. NBN gene mutations cause increased tumor risk in Nijmegen breakage syndrome (NBS) homozygotes as well as in NBN heterozygotes. NBS patients develop different types of malignancies; among solid tumors, medulloblastoma (MB), an embryonal tumor of the cerebellum, has been reported most frequently. The majority of medulloblastomas occur sporadically, some of them manifest within familial cancer syndromes. Several signaling pathways are known to be engaged in hereditary and sporadic MB. The aim of our study was to identify mutations in selected exons of the NBN gene and to determine the frequency of the most common NBN gene mutations in pediatric patients with different types of medulloblastoma. We screened a total of 104 patients with MB and identified 7 heterozygous carriers (6.7%) of two different germ-line mutations of NBN gene; all of them had classic MB. Our results indicate that heterozygous carriers of the germ-line NBN gene mutations (c.511A>G and c.657&#95;661del5) may exhibit increased susceptibility to developing MB. The risk of medulloblastoma is estimated to be 3.0 (for c.511A>G) and 4.86 (for c.657&#95;661del5) times higher than in the general Polish population (p<0.05). These results suggest that heterozygous NBN germ-line mutations may contribute to the etiology of medulloblastoma.

Purpose: Increasing incidence of pediatric brain tumors and improving survival rates encouraged us to assess long-term functional outcome of patients with cerebellar juvenile pilocytic astrocytoma (JPA)., Materials and Methods: Our study encompassed 105 children treated since 1980-2005 and consisted in analysis of mailed, custom-designed questionnaires., Results: Mean follow-up time was 8.3 years. Sixty out of 104 patients presented permanent neurological deficits and 47/104 presented significant behavioral disorders. Eighty-nine children continued their education at primary, secondary or high school level. Most patients and their parents were satisfied with treatment outcome. Patients' and parents' notes were usually concordant., Conclusions: Long-term functional treatment outcome of cerebellar JPA is relatively favorable, in spite of permanent neurological deficits and emotional disorders in over half of the patients. Vermian tumors are associated with worse long-term functional outcome. Neurological deficits and emotional disorders do not preclude further education and independent functioning.

Background and Purpose: The cerebellum has been associated with motor control, but more recent studies have extended its contribution to other functions, such as modulation of emotions, behavioral organization or language. The cerebellar cognitive affective syndrome was described primarily in adults. In children, cerebellar lesions are relatively frequent and some are due to neoplasm., Material and Methods: Cognitive and emotional functions were studied in 66 children who underwent surgery for cerebellar pilocytic astrocytoma at the Department of Neurosurgery of the Children Memorial Health Institute. 36 children were psychologically examined and parents of 66 children filled in a questionnaire, answering questions about children's linguistic functioning, emotion regulation and ability to initiate, organize and efficiently realize various activities., Results: The disturbances in the initiation and realization of activities were reported most often (77%). Problems in emotional regulation were noticed in 65% of children and were characterized by disinhibition, impulsivity and irritability. Language difficulties were observed in 42%. No significant differences between groups of children with different localization of tumor (vermis or cerebellar hemisphere) were observed., Conclusions: The present study confirms the psychological deficits following cerebellar lesion in children, similar to the cerebellar cognitive affective syndrome reported in adult patients.

Unlabelled: Proton MR spectroscopy (MRS) is a noninvasive chemical analysis of metabolites in brain tissue. Metabolite ratios are useful because age dependant normal values are known and differ significantly from the values obtained in various diseases of brain tissues., Aim: The aim of our study was to evaluate whether MRS correlates with magnetic resonance imaging (MRI), course of disease, pathology of resected tumours after preoperative chemotherapy and can be of prognostic value in patients with medulloblastoma (MB)., Materials and Methods: Eight patients with histologically proven MB were studied. All patients underwent MRS and MRI at diagnosis and after neoadjuvant chemotherapy consisting of VCR,VP,CTX,CBCA. Preoperative chemotherapy was followed by surgery, radiotherapy and maintenance chemotherapy. Assessment whether MRI correlates with MRS after preoperative chemotherapy was performed. Additionally MRS was correlated with the course of disease and pathology results., Results: Out of 8 patients 5 had partial remission of their tumours on MRI. Two of them had favorable reaction on MRS defined as elevation of NAA and Cr decrease in Cho,Lac/Lip. Both are alive and disease free. In 2 patients no changes, compared with MRS at diagnosis were found. Both died of the disease. One had an indistinct positive change and died. Stabilization on MRI was observed in 1 patient, who also had a good reaction on MRS. He is alive, disease free. Two patients had disease progression on MRI. Both had poor reaction on MRS, one died, one is alive with disease. It was noticed that good response on MRS correlated with chemotherapy induced tumour changes observed in pathology specimens from resected tumours. Small number of patients does not allow to draw conclusions but our results signal that MRS might be of prognostic value in brain tumours.

To evaluate the risk factors for recurrence of MB/PNET we analyzed the medical records of 157 patients treated at the Children's Memorial Health Institute between February 1981 and February 1997. The following factors were evaluated: age at diagnosis, gender, tumor size, tumor cells in the CSF, postoperative status, extent of resection and methods of treatment. We evaluated chemotherapy (CHT) doses, interval between courses, interval between surgery (S) and first course of CHT, interval between S and radiotherapy (RTX), and breaks during RTX. We divided patients into six groups: S alone, S+CHT, S+RTX, S+CHT+ RTX, S+RTX+CHT, S+CHT+RTX+ CHT. Age at diagnosis, gender, tumor size, extent of resection, postoperative status, intervals between courses of CHT, between S and the first course of CHT, and between S and RTX, and breaks during RTX had no statistical influence on relapse occurrence. Tumor cells in CSF were routinely checked for from January 1992 onward. In this group of 75 patients, 40 had tumor cells positive at surgery (28 relapsed), while in the group of 35 patients with negative tumor cells 14 relapsed (P=0.004). Out of 26 patients treated with S+RTX alone, 13 relapsed. Among 14 patients treated with S+RTX and prolonged CHT 6 relapsed. Out of 14 patients treated with S+CHT 13 relapsed; among 49 who received S+CHT+RTX 35 relapsed; and out of 51 patients treated with S+CHT+RTX+CHT 30 relapsed. In the multivariate analysis of treatment methods chemotherapy implemented after radiotherapy had a positive, though not statistically significant, influence on outcome (P=0.06). Among those receiving CHT the mean percentage of the ideal dose administered had a statistically significant influence on relapse: in the group of relapsed patients the mean dose was 76.1%, while in the group in continuous remission it was 83.7% (P=0.0013). On the basis of our data, we conclude that the presence of tumor cells in the CSF had a significant influence on the occurrence of relapse. Administration of appropriate doses of chemotherapy is extremely important for the occurrence of relapse and the final outcome of treatment. Prolonged adjuvant chemotherapy after radiotherapy seems to lower the risk of recurrence.

153 patients presenting with medulloblastoma between 1980-1992 were treated at the Department of Pediatric Neurosurgery, Child's Health Centre in Warszawa. This group was studied retrospectively and assessed for clinical presentation, histology, treatment regimen and survival. 44 cases treated between 1980 and 1986 underwent surgical resection, postoperative staging evaluation, and craniospinal irradiation, additionally patients assigned to "high risk" group received post-irradiation chemotherapy. Beginning 1986-86 patients with "standard risk" medulloblastoma were treated with preirradiation--"sandwich" chemotherapy consisting of either procarbazine, vincristine and CCNU or "eight drugs a day", followed by megavoltage irradiation, while "high risk" group received also postirradiation chemotherapy. The 5-year actuarial survival rate for all patients was 43%. There were no statistically significant differences in 5-year survival rate between the group treated with preirradiation chemotherapy--52%, and without--54%. The presented group was studied to identify variables of prognostic significance. The extent of disease at the time of diagnosis, as measured by M staging criteria was significantly associated with outcome. The extent of tumour resection, histological subtype of the tumour, postoperative complications, T-staging, and age did not influence the prognosis in the present study.