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We report our remarks on 22 patients, 80 years of age and older, who were treated for glioblastoma multiforme. The 16 patients who underwent a multimodality treatment (surgery + radiotherapy + chemotherapy) had an average survival of 16.7 months versus the 5.8 months of the 8 patients treated with biopsy followed by radiotherapy and/or chemotherapy (log-rank test, P < 0.001). Moreover, we point out the importance of MGMT hypermethylation as a significant prognostic factor: the 9 patients with nonmethylated MGMT had a mean survival of 7.7 months vs. 17.9 months of the 13 patients with the MGMT promoter methylated (log-rank test, P = 0.0006). Several studies have pointed out age as an important negative factor for the outcome of elderly patients affected by glioblastoma multiforme. Elderly patients with a diagnosis of glioblastoma multiforme are thus generally excluded from clinical trials of treatment for the neoplasm, because it is a common opinion that the prognosis for such patients is particularly poor. On the contrary, according to our clinical and surgical experience, we firmly believe that patients older than 80 years with a histologically proven diagnosis of glioblastoma multiforme and in good health conditions (Karnofsky performance status >60) should be treated in the same way as younger patients.

Brain metastases from renal carcinoma may appear even a long time after surgical treatment of the primary tumor. The authors present 2 series of patients, one of which has already been published and the other new, for a total of 4 cases of brain metastasis from renal carcinoma with late onset, which occurred 13, 17, 26 and 12 years after primary surgical treatment. The other cases described in the literature were also critically reviewed.

Background: Continuous research into new strategies and chemotherapy agents for the treatment of malignant high-grade gliomas have led to the synthesis of a new chemotherapy drug, temozolomide (TMZ), with a lower toxicity profile compared to conventional chemotherapy agents, such as nitrosoureas. Temozolomide is an oral alkylating chemotherapy agent licensed for the treatment of recurrent high-grade gliomas, anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Because of its favorable pharmacokinetic and pharmacodynamic properties and improved tolerability, TMZ is now under investigation for concomitant use with radiotherapy in patients with newly-diagnosed GBM. We present a phase II clinical trial investigating the efficacy and safety of radio-chemotherapy combined treatment using TMZ, followed by six cycles of adjuvant chemotherapy with TMZ, in patients with newly-diagnosed GBM who have undergone debulking surgery or biopsy only., Patients and Methods: Twenty-one patients with newly histologically-diagnosed GBM were enrolled into this phase II clinical trial. In phase I of the study, TMZ (75 mg/m2/day per 7 days/wk for 6 weeks) was orally administered to patients concomitantly with radiotherapy (RT) (2 Gy per fraction once daily, per 5 days/wk for 6 weeks). In phase II of the study, four weeks after completion of RT, a monochemotherapy using TMZ was administered at the dosage of 200 mg/m2/day per 5 days every 28 days for 6 cycles. Primary end-points were the safety and tolerability profile of this two-phase combined treatment and secondary end-points were the objective response and survival rates at twelve months and eighteen months from study entry., Results: The one-year survival rate of patients treated with the investigated multimodality treatment was 58% and median survival time was 15.7 months. Concomitant RT plus TMZ (phase I) followed by adjuvant TMZ (phase 2) were well-tolerated; indeed, nonhematological adverse events were rare and mild to moderate in severity; grade 3 and 4 neutropenia and thrombocytopenia were the major-related hematological side-effects observed in only 2 and 3 of all patients in phase I and 4 patients in phase II. We found that the combination of radio- and chemo-therapy, in phase I of the study did not significantly increase the incidence and severity of hematological toxicity caused by the adjuvant TMZ-based chemotherapy administered in phase II of the study., Conclusion: The investigated multimodality treatment regimen was well-tolerated and prolonged survival while improving patients' quality of life.

Brain metastasis from hepatocarcinoma are a decidedly rare occurrence in countries where this pathology is most frequent. The authors describe a case of metastases from hepatocellular carcinoma in a patient suffering from post-HBV hepatic cirrhosis with hemorrhagic onset. The "stroke-like" presentation of the cerebral localization of the disease can be explained by both the important vascularization of the tumor and the frequent hemocoagulative alterations caused by the cirrhosis. The importance of diagnostic neuroradiology is briefly addressed, with reference to the fundamental role played by MRI. Surgery of these lesions does not present any particular technical problems as long as they are located in accessible areas and the patient's general and neurological conditions allow it. Postoperative radiotherapy seems to improve the quality and quantity of residual life, although the number of patients described in the literature is too small to draw any definite conclusion. Promising molecular biology studies are under way to evaluate the role of oncosuppresor gene expression in hepatocarcinogenesis and in the way the disease spreads.

Purpose: EGR-1 is an immediate early gene with diverse functions that include the suppression of growth. EGR-1 is down-regulated many cancer cell types, suggesting a tumor suppressor role, and may critically involve the p53 pathway. The aim of this work was to measure the expression of EGR-1 and the p16/INK4a/ARF-Mdm2-p53 pathway status in fresh human gliomas., Experimental Design: Thirty-one human gliomas with different grades of malignancy were investigated for Egr-1 mRNA and the protein expression, frequency, and spectrum of p53 gene mutations, mdm2 gene amplification, and p16/INK4a/ARF allele loss., Results: The amplification of Mdm2 and the deletion of the p16/INK4a gene was found in 3 and 5 cases, respectively, whereas mutations of p53, including two novel mutations, were observed in 10 other cases. The three types of changes occurred strictly mutually exclusively, emphasizing that these genes operate in a common pathway critical to glioma progression. EGR-1 mRNA was significantly down-regulated in astrocytomas (14.7 +/- 5.1%) and in glioblastomas (33.6 +/- 10.0%) versus normal brain. Overall, EGR-1 mRNA was strongly suppressed (average, 15.2 +/- 13.9%) in 27 of 31 cases (87%), independent of changes in p16/INK4a/ARF and Mdm2; whereas 4 of 31 cases with residual EGR-1 expression as well as the highest EGR-1 variance segregated with p53 mutations. Immunohistochemical analyses confirmed the suppression of EGR-1 protein., Conclusions: These results indicate that EGR-1 is commonly suppressed in gliomas independent of p16/INK4a/ARF and Mdm2 and that suppression is less crucial in tumors bearing p53 mutations, and these results implicate an EGR-1 growth regulatory mechanism as a target of inactivation during tumor progression.

The presence and variant distribution of human herpesvirus 6 (HHV-6) was investigated by a nested polymerase chain reaction (PCR) in 118 biopsies from patients affected by nervous tissue tumor (115 primary tumors and 3 metastasis) and in 31 autopsy samples from the brain of healthy individuals. HHV-6 DNA sequences were detected in normal and neoplastic nervous tissue at a frequency of 32% and 37%, respectively. In both tissues, variant A was three times more frequent than the variant B. Peripheral blood lymphocytes (PBLs) derived from seven tumor affected patients contained the same variant as their respective brain sample, as judged by PCR. The expression of HHV-6 encoded immediate early protein p41 was detected by immunohistochemistry in neoplastic but not in normal brain. This may reflect viral reactivation from latency in immunocompromised patients. The seroepidemiological data indicated a frequency distribution of anti-HHV-6 antibodies in patients with brain tumors similar to that found in healthy donors.

Brain metastases from thyroid carcinoma is unusual, with a frequency of 1%. We report twelve patients, with single brain metastases and with a karnofsky performance scale score >60 at admission. No metastasis was seen during the uptake of iodine-131, even in the cases from differentiated thyroid carcinoma, suggesting absence of differentiation between primary and metastasic disease. The histopathology of thyroid carcinomas was anaplastic in five cases, differentiated in six, and medullary in one. Only in four patients, brain was the unique site of metastatic spread; in others, bones and lungs were also involved. All metastases were surgically removed, and all patients were treated with radiotherapy (45 Gy) in the postoperative course. The survival average was 19.8 months, and the quality of life was satisfactory in all patients. One patient remained alive till 5 years. Anaplastic histopathology and size of the primitive, and also bone involvement of thyroid disease were significant risk factors in our cases (p < 0.05). According to the literature, surgery is the best therapeutical choice. Alternative strategies in the management of brain metastasis, such as iodine-131 therapy, are discussed, paying particular attention to the relevant side effects.

Systemic metastases from ovarian carcinoma are frequent, but they rarely affect the central nervous system. The treatment of this type of metastases in not clear. Two cases of solitary cerebral metastasis from ovarian carcinoma are reported. Two patients, submitted to therapeutic protocol established for ovarian carcinoma, presented after 17 and 25 months respectively the appearance of symptoms from brain solitary metastasis without other metastases. They underwent surgery, radiotherapy and chemotherapy for solitary cerebral metastasis. Treatment of the brain lesion resulted in KPS improvement (KPS = 90) and survival was 16 and 30 months, respectively. From the 2 cases presented and the review of the literature, it appears that a better outcome may be obtained by a combined treatment of metastases, including surgery, radiotherapy and chemotherapy.

Methods: We report on 15 patients surgically treated for intraparenchymal brain metastases from sarcoma, including six osteosarcomas, five leiomyosarcomas, two malignant fibrous histiocytomas, and two alveolar soft-part sarcomas (ASPS)., Result: Median survival after craniotomy was 9.3 months. Patients with a preoperative Karnofsky performance score of > 70 survived for 12.8 versus 5.3 months for those with a Karnofsky performance score < 70 (p=0.03). Patients with evidence of only lung metastases at the time of surgery (nine cases) survived 8.6 months, which was similar to the 10.4-month survival for patients with disease limited to the brain (p=0.1). The two patients with alveolar soft-part sarcomas are alive at 15 and 20 months after surgery., Conclusion: We conclude that surgery is effective in treating selected patients with sarcoma metastatic to the brain and that patients with metastasis from ASPS may have a relatively good prognosis if they are surgically treated. The complete removal of all brain metastases and a Karnofsky performance score > 70 are associated with a favorable prognosis; the presence of concurrent lung metastases is not a contraindication to surgery.

A case of intraparenchymal schwannoma is presented. A 61-year-old woman, with stigmata of von Recklinghausen's neurofibromatosis (NF-2), presented with a history of weakness of the right lower limb for 2 months. She was investigated by MR which showed a circular mass with a maximum diameter of 5 cm in the right parieto-occipital lobe. The tumor was removed in toto via a left parieto-occipital craniotomy. The patient was discharged two weeks after the operation and remains well now 2 years later. The clinical and neuroradiological findings of reported intraparenchymal schwannomas, including the case reported here, are discussed.

Forty patients with multifocal and multicentric cerebral tumours were retrospectively studied. The patients were divided into two groups: ten patients with multicentric tumours (group A), and 30 patients with multifocal tumours. As far as their preoperative clinical history and the incidence of the various symptoms and signs are concerned, there were no significant differences between the two groups. CT permitted a correct diagnosis in 90% of the cases. All of the patients underwent the removal of the tumour(s) and received radiotherapy; 30 patients also received chemotherapy. In group A, nine patients died and one was lost to follow-up one year after treatment; the average survival was ten months from the appearance of the multicentric tumour. In group B, 29 patients died and one is still alive two years after treatment; the average survival was six months. We consider the problems of diagnosis and the long-term follow-up of patients.

The authors report 19 cases of solitary cerebral metastases from malignant melanoma. In 15 patients, the primary lesion was known at the time the metastasis was diagnosed; deltoid-scapular in 4 cases, thoracic in 5, inguinal in 4 and neck in 2. The primary location was unknown in 4 patients. Presenting symptoms were: epileptic seizures in 9 cases, headache in 8, strength deficit of the limbs in 2. In 3 patients (16%) neurological symptoms were the first clinical sign of the systemic tumor; in 16 cases (84%) there was a long interval between treatment of the primary and appearance of the cerebral metastasis (average 3.8 years; median 3.4 years). All patients were submitted to surgery and radiotherapy (whole-brain in 14 and radiosurgery in 5). In 10 cases the lesion was removed 'en bloc' (no internal touch technique). Average survival was 9 months (median 8 months) and was influenced by 'en bloc' resection and whole-brain irradiation. None of the patients operated by the 'no touch technique' presented a recurrence.

Two cases of intradural cavernous angioma of the cauda equina are reported, one of which presented with symptoms of subarachnoid hemorrhage. The clinical and therapeutic aspects of intradural angiomas, in particular those of the cauda equina, are discussed.

We report one case of haemangiopericytoma and two cases of meningioma whose presenting symptom was subarachnoid haemorrhage. We discuss the etiopathogenetic factors involved in this rare mode of onset in the light of the published work.

Twenty-nine cases of single cerebral metastases from renal carcinoma were the object of a retrospective and prospective study covering a period of 15 years (1975-1988). The best diagnostic means were NMR imaging with paramagnetic contrast medium and CAT scans after intravenous injection of a double dose of contrast medium. All patients underwent total surgical removal of the cerebral lesion. Radiotherapy was useful but had less influence on further reproduction than in metastases from tumors of other sites. The median survival was 28.1 months in patients who received radiotherapy and 23 months in the others. No significant difference in survival was found between the group of patients with unknown primary tumors and the other group with diagnosed primary neoplastic disease.

Thirty-four breast cancer patients with single brain metastases were reviewed: 9 underwent surgical removal only and 25 surgical removal and radiotherapy. A longer survival was seen in patients who underwent surgical removal and radiotherapy, with a mean survival of 28 months. In the 9 patients who did not receive whole brain radiotherapy, the mean survival was 15 months and there was an higher frequency of brain relapse.

Clinical features and surgical outcome of 16 patients with dermoid or epidermoid cysts on the midline of the posterior cranial fossa are compared. Salient points in the comparison are the younger age, presence of associated malformations and better prognosis of dermoid cyst.

Solitary cerebral metastases from lung cancer are not uncommon clinical events. Whatever treatment is adopted, long-term survival is rare. Very rare indeed are reports of patients surviving the discovery of lung cancer and brain metastasis for 10 years or more. Indeed, only 16 cases have been reported to our knowledge. We report two further cases, stressing the importance of correct clinicopathological staging so that treatment may be conducted in the way most likely to ensure longer and better survival and, pending a therapeutic breakthrough, to increase the number of long-term survivors.

A case of multiformis glioblastoma with a parieto-temporal and brainstem localization is presented. Multicentric gliomas are unfrequently reported in the literature, and very often rise diagnostic problems with other multiple lesions of the Central Nervous System, either of neoplastic nature or not. After briefly reviewing the pathogenetic hypothesis concerning this lesion, indication and limits of clinical and radiological investigations are discussed.

The authors report on the clinical data, operating technique, postoperative complications, and late results in a series of 31 epidermoid and 21 dermoid cysts of the central nervous system.

The authors report on the results obtained on a series of 325 patients operated on for single brain metastasis at the Institute of Neurosurgery of the University of Rome during the period 1951-1979. After analyzing the results vis-à-vis the site of the brain metastasis, the site of the primitive tumour and the surgical treatment administered; emphasis is given to the importance of the advent of the CT scan which has permitted a more accurate selection of the patients resulting in improvement in operative mortality and average survival time which at present is one year.