Shozaburo Uemura

Randomized comparison of intra-arterial versus intravenous infusion of ACNU for newly diagnosed patients with glioblastoma

This prospective randomized trial was performed to compare the effectiveness of intra-arterial ACNU with intravenous ACNU in newly diagnosed patients with supratentorial glioblastoma. The primary end points were overall survival and progression-free survival. Within 3 weeks after surgery, patients were randomly assigned to receive either intravenous or intra-arterial ACNU (80 mg/m2) once every 6 weeks concomitant with radiotherapy. Intra-arterial ACNU was administered for the first 3 courses followed by intravenous administration. Eighty-four patients were enrolled onto this study and among them 82 patients who passed eligibility criteria were analyzed. Patients characteristics were not different significantly between 2 treatment arms. Median survival and progression-free survival time was 59 and 24 weeks, respectively for intra-arterial arm and 56 and 45 weeks, respectively for intravenous arm. There was no significant difference respectively between two treatment arms. Among the prognostic variables including age, Karnofsky performance status, extent of surgery and treatment arm, Coxs proportional hazards model showed that age was the only significant factor for both survival and progression-free survival (P=0.003 and 0.016, respectively). With regard to toxicity, there was no significant difference between two treatment arms. Leukoencephalopathy was not observed in intra-arterial arm. In conclusion, intra-arterial ACNU when administered by the method in this study does not increase the survival and progression-free survival of newly diagnosed patients with glioblastoma over that afforded by intravenous ACNU.

A comparative immunohistochemical study of calcineurin and S-100 protein in mammalian and avian brains

SummaryThe cellular and topographic localization of calcineurin and S-100 protein was examined immunohistochemically in the mammalian and avian brain. Calcineurin immunoreactivity in both the avian and mammalian brain was located only in neuronal cells. S-100 protein was localized mainly in the glial and Schwann cells within the mammalian brain. However, in the avian brain, neuronal cells in certain regions such as the paleostriatum primitivum and the cerebellum, as well as other non-neuronal cells, exhibited S-100 protein immunoreactivity. A distinct difference was demonstrated in the macroscopic topographic distribution patterns of S-100 protein immunoreactivity between the mammalian and avian brains, while the patterns of calcineurin distribution were essentially identical. In addition, we provided calcineurin- and S-100 protein-immunocytochemical results for the turtle, frog and fish brain.

Ventriculolumbar Perfusion of 3-[(4-Amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea Hydrochloride

We report on the toxicity, intrathecal pharmacokinetics, and therapeutic effect of the ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against the subarachnoid dissemination of primary central nervous system tumors. Fifteen patients received ventriculolumbar perfusion of ACNU. One was treated with ventriculolumbar perfusion of ACNU alone, and the others underwent concomitant systemic chemotherapy; three of these patients received irradiation as well. ACNU was administered at an initial dose of 0.5 and was increased to 1.5 to 10.0 mg in six patients. Because of a lack of Level 2 or greater toxicity, the subsequent seven patients received 8.7 to 10.0 mg of ACNU dissolved in artificial cerebrospinal fluid (CSF) at a concentration of 0.1 mg/ml, from the start of the treatment. During ACNU administration, the lumbar CSF was drained at approximately the same rate as that of the infusion. Twelve patients received from 3 to 42 courses (average, 14 courses). The cumulative dose of ACNU ranged from 5 to 330.4 mg (average, 82.9 mg). One patient had a convulsion; two patients experienced transient headache, nausea, and vomiting; two others reported transient headache, nausea, vomiting, and fecal incontinence; and one experienced transient nausea, vomiting, and fecal incontinence. No side effects were noted in the other nine patients. When 9.0 to 9.5 mg of ACNU, dissolved in 90 to 95 ml of artificial CSF, was administered for 37 to 52 min, the maximum concentration of ACNU in the lumbar CSF was 9.86 to 12.79 micrograms/ml and the area under the drug concentration-time curve was 260.8 to 502.5 micrograms.min/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

MRI OF SUBARACHNOID DISSEMINATION OF MEDULLOBLASTOMA

SummaryWe report two cases with subarachnoid dissemination of medulloblastoma depicted clearly by Gadolinium-DTPA enhanced MRI. We also demonstrate the superiority of Gadolinium-DTPA enhanced MRI over nonenhanced MRI, CT, myelography and postmyelographic CT for diagnosing subarachnoid dissemination and for monitoring the response to therapy.

Epithelial Cyst of the Fourth Ventricle

A case of an epithelial cyst of the fourth ventricle is reported. A 10-month-old girl was admitted because of inactivity, developmental retardation, and enlarged head. On admission she was inactive and the head circumference measured 48.5 cm with tense fontanel and dilatation of scalp veins. Neurological examination showed a slight hyperreflexia in both lower limbs. Computerized tomography scan disclosed a large round low density area in the region of the fourth ventricle and marked dilatation of the third and lateral ventricles. Suboccipital craniectomy was performed and a 4 cm diameter cyst within the fourth ventricle was totally removed. The cyst contained watery clear fluid. On light microscopic examination, the cyst wall was composed of a single layer of columnar or cuboidal epithelial cells and thick collagenous connective tissue. Electronmicroscopic study revealed that the epithelial cells rested on a basement membrane separating them from the underlying collagenous tissue. Cilia and microvilli without coating material were occasionally present on the surface of the cells. The literature is reviewed and the origin of the cyst is discussed. The authors suggest that the cyst originated from the developing choroid plexus.

The Quantitative Analysis of Psychiatric Sequelae after Direct Surgery of Anterior Communicating Aneurysms

Follow-up study of 50 cases with directly operated anterior communicating aneurysm was made, ranging from 6 months to 5 years and 6 months. Forty six cases were alive and the condition of all these cases was evaluated through questionnaires, and 42 cases of them were examined utilizing the WAIS and Y-G test. Four patients out of 46 cases showed decreased ADL and they needed help in their daily activity. About 60% of the cases have resumed full activity of previous occupation, although 68% of the 46 cases have complained of slight headache, forgetfullness and worries about their illness being never cured. The number of cases with the above complaints decreased markedly 2 years after surgery was performed. Verbal IQrecovered sooner than Performance IQobtained on WAIS, and the profile of recovery showed quite a resemblance in the repeated WAIS. Comparing pre and post-operative cases in short term the cause of the poor IQ at present study was considered due to subarachnoid hemorrhage itself rather than to surgical intervention. Poor preoperative condition, such as grade III, IV, of Hunt and Hess, showed delay in recovery. There was no definite evidence of disturbing IQrecovery by angiospasm, ventricular dilatation, direction of aneurysm etc., as far as preoperative grade I, and II groups were concerned. The ultimate evaluation of the patient in regard to social adaptability from IQ test required a 2 year period. Symptoms of so called normal pressure hydrocephalus due to subarachnoid hemorrhage showed sometimes remarkable recovery of the mental state after shunt operation, but in other cases, shunt procedure failed to show persistent effect and several patients showed good IQ in the follow-up study, although the shunt device lost patency in early stage of follow-up. Y-G test showed interesting fact that the cases of poor IQ, especially poor Performance IQ, assumed types of passive adaptability.

Long-term survival after successful surgical treatment of a solitary brain metastasis

BackgroundWe investigated the factors associated with survival duration in 9 patients with brain metastases who survived for more than 6 years, and focused on the factors associated with long survival.MethodsOf 9 primary lesions, 5 were lung cancer, 1 was colon cancer, 1 was uterine cancer, 1 was choriocarcinoma, and 1 was renal cancer. All patients underwent total removal of a solitary brain metastasis. Of the 9 patients, 6 received chemotherapy and adjuvant radiation therapy, 1 patient received only radiation therapy, and 2 patients had no adjuvant therapy.ResultsThe factors we isolated in the 9 long-term survivors were that they were relatively young, their systemic diseases were well controlled, there was a relatively long interval between diagnosis of the primary tumor and the brain metastasis, the metastatic lesion was located in the nondominant hemisphere, and the patients were generally in good condition or had only a mild neurologic deficit.ConclusionIn some patients with controlled or absent extracranial tumor activity in whom a single brain metastatic tumor is identified after a prolonged period, surgery and local radiotherapy may provide hope for a long survival period.

Prevention of Ocular Toxicity by the Intra-carotid Perfusion of Anticancer Agents in the Treatment of Malignant Glioma

It is a problem of great concern to prevent ocular toxicity from complicating intra-carotid administration of lipophil anticancer agents. Attempts to prevent such a side effect were made during intra-carotid chemotherapy using remodeled catheter tips for epidural anesthesia. Twenty nine patients with malignant glioma received intra-carotid administration of neocarzinostatin (NCS). Six out of 17 patients (35.3%) who received intra-carotid perfusion through an original catheter without a remodeled tip, developed ocular toxicity. The catheter tip remained proximal to the ophthalmic artery in all cases. On the other hand, 12 patients with a remodeled catheter tip did not develop ocular toxicity. In the latter group the tip of the catheter was located in the internal carotid artery sufficiently distal to the ophthalmic artery, or beyond the carotid bifurcation in 3 cases. Another advantage of the remodeled catheter was that the intra-carotid perfusion was feasible for a longer period with higher doses of NCS, than treatment with the commercial catheter for superselective embolization, which was found to be easily occluded and often ejected out of the carotid artery. Prior to and during the intra-carotid perfusion selective injection of Angiografin® was performed through the catheter and the tumor was enhanced in the area of arterial supply, indicating the extent of chemotherapy and the degree of destruction of the blood-brain barrier.

Depressed Cell-Mediated Immunity in Cerebrospinal Fluid of Patients with Malignant Glioma

A great deal of study has been directed toward cerebrospinal fluid (CSF) cytology since the pioneer works of Widal et al.37 and Quincke28 in the early 20th century. Thereafter, the morphological characteristics of the CSF cells were examined in various diseases. However, the functional identification of CSF cells has remained unsolved until recent years. The increasing concern regarding the role of the immunocompetence of the central nervous system (CNS) in neurological disorders has stimulated investigation of immune mechanisms in CSF.