Hidenori Ogasawara

Intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions: Report of six cases and review of the literature

The features of intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions (GCTSPS) in six patients were investigated. GCTSPS accounted for 12.8% of all germ-cell tumors (GCT) in our brain tumor study group. In all cases, the initial symptoms were attributable to the suprasellar lesion, and symptoms due to the pineal GCT developed only after admission. Five of the six cases were histologically diagnosed as germinoma. In all cases, tumors of both regions disappeared after irradiation, resulting in no recurrence for an average of 55.3 months. Our experience and reports in the literature suggest that GCTSPS is highly sensitive to radiation in most cases, although some reports indicated that recurrence is frequent after radiation therapy alone. It is suggested that histological diagnosis in one of the GCTSPS lesions is undertaken to make a plan for the following treatment.

Hyperaemia prior to acute cerebral swelling in severe head injuries: The role of transcranial doppler monitoring

SummaryAcute cerebrovascular congestion after a closed head injury is significantly related to intracranial hypertension. As an indirect method of cerebral blood flow measurement, transcranial doppler sonography (TCD) provides a rapid and noninvasive assessment of cerebral haemodynamics, including hyperaemic conditions.TCD examinations was serially performed in 35 patients with severe head injury with intact cerebral circulation; i.e. the mean flow velocity (MFV) patterns of the middle cerebral artery (MCA) did not show signs of cerebral circulatory arrest such as systolic spike, to and fro, or no flow. The results showed that the MFV of the MCAs and ipsilateral extracranial internal carotid arteries (ICAs) in 9 of these patients increased sharply and pulsatility index (PI) decreased during 48–96 hours after the injury. This was soon followed by patterns of high intracranial resistance, consistent with elevated intracranial pressure (ICP) in monitored patients and acute brain swelling on repeated computed tomographic (CT) scans. The correlation between increased MFVs, decreased PIs, and cerebral haemodynamic changes leading to acute brain swelling is discussed.The number of patients who ended with severe disability, vegetative state, or death was 66% in this group of 9 patients, compared to only 34% for the 35 patients overall with severe head injury. Though the morbidity and mortality rates largely depend on the primary injury, the presence of acute cerebral swelling aggravate the grave course in these patients. And the ability of TCD to monitor the hyperaemic state prior to oedema should lead us to adjust the therapy in order to minimize the secondary insult related to intracranial hypertension.

Penetration of etoposide into human malignant brain tumors after intravenous and oral administration

SummaryPenetration of etoposide into the cerebrospinal fluid, brain tumor, and brain tissue after intravenous administration was investigated in patients presenting with malignant brain tumors. A relatively low dose (55–65 mg/m2) was used to compare intravenous with oral administration. High-performance liquid chromatography with fluorescence detection was used to evaluate drug levels. Plasma and cerebrospinal fluid levels of etoposide after oral administration (50–150 mg/day) were also studied so as to determine the adequate oral dose for the treatment of malignant brain tumors. The peak plasma concentration after intravenous administration ranged from 7.01 to 10.47 μg/ml, varying in proportion to the injected dose, whereas that after oral administration was lower, namely, 1.44–4.99 μg/ml, and was unstable when the oral dose was 150 mg daily. The peak cerebrospinal fluid level following either intravenous or oral administration was much lower than the plasma concentration and was influenced by the peak plasma level and the sampling site. The etoposide concentration in cerebrospinal fluid taken from the subarachnoid space and ventricle of patients displaying no tumor invasion and of those presenting with meningeal carcinomatosis and in cerebrospinal fluid taken from the dead space after tumor resection was 0.7%±0.5%, 3.4%±1.0%, and 7.2% ± 8.5%, respectively, of the plasma concentration. Serial oral administration did not result in the accumulation of etoposide in cerebrospinal fluid. The tumor concentration (1.04–4.80 μg/g) was 14.0%±2.9% of the plasma level after intravenous administration, was related to the injected dose, and was approximately twice the concentration detected in the brain tissue. Therefore, a relatively low dose of etoposide injected intravenously penetrates the brain tumor at an efficacious concentration. Our results indicate than an oral dose of 100 mg etoposide be given for malignant brain tumors, as limited penetration of the drug into the intracranial region was observed.

Intracranial metastasis from a spinal cord primitive neuroectodermal tumor: Case report

A patient with intracranial seeding from a spinal cord primitive neuroectodermal tumor with ependymal differentiation is presented. The first and second stages of intracranial dissemination were well controlled by a combination of irradiation and chemotherapy. The authors review previously published cases and discuss the possible mechanism of seeding from the spinal cord to the intracranial region.

A case of malignant teratoma developing from the septum pellucidum 7 years after removal of a mature teratoma in the pineal region

A report is presented on a case of teratoma with a malignant component arising from the septum pellucidum 7 years after total surgical removal of a mature teratoma in the pineal region. The patient was successfully treated with radiotherapy and total surgical resection of the second tumor. The case is characterized by the development of a second malignant tumor and by the long interval from complete resection of the primary tumor to the occurrence of the second tumor. Our case is not considered to be a recurrence of the mature teratoma of the pineal region but to be a multiple tumor of germ-cell tumor having multicentricity and a different temporal variety.

Combined antitumor effects of TNF and G-CSF on a human medulloblastoma xenograft line

SummaryThe antitumor effects of TNF and G-CSF on a xenograft line of human medulloblastoma were examined. (Method): 1) A human medulloblastoma xenograft line was transplanted into nude mice. Tumor bearing nude mice were divided into the following eight groups: untreated controls (C); those receiving a subcutaneous injection of G-CSF for one week (G1); for four weeks (G2); those receiving an intratumoral injection of TNF for four weeks (Tit); an intravenous injection of TNF (Tiv); those receiving a combination of G1 and Tit (G1 + Tit); a combination of G2 and Tit (G2 + Tit); and a combination of G2 and Tiv (G2 + Tiv). The relative tumor weight in each group was calculated and any antitumor effects were examined by calculating a tumor growth inhibition ratio. 2) Tumor bearing nude mice were divided into the following two groups: those receiving a subcutaneous injection of G-CSF and an intravenous injection of TNF (G + T); and only an intravenous injection of TNF (T). We evaluated the pathological findings from the tumors at 0 h, 0.5 h, 1 h, 3 h, 6 h, 12 h, 24 h and 48 h after the TNF injection. Routine H.E. staining and immunostaining using antigranulocyte and antimacrophage antibodies were performed. (Results): 1) The tumor growth inhibition ratio was 0.112, 0.190, 0.287, 0.451, 0.347, 0.635, and 0.622 at G1, G2, Tit, Tiv, G1 + Tit, G2 + Tit, G2 + Tiv group. A combined antitumor effect was clearly seen in the G2 + Tit and the G2 + Tiv groups. 2) The tumor was fragmented by the infiltration of many inflammatory cells 24 hours after TNF injection. Many more macrophages were observed in the tumors of G + T mice than in the T mice. Granulocytes were observed only in the tumors of the G + T mice.

Analysis and Distribution of Etoposide in Rat Brain Tumor Model: Intracarotid Versus Intracarotid with Angiotensin II—Induced Hypertension

The brain tissue distribution of etoposide has been investigated in 9L gliosarcoma-bearing rats with or without hypertension induced by angiotensin II (AT II). The rat brain tumor models were divided into the following two groups according to etoposide administration route: intracarotid injection (IC) group and intracarotid injection with hypertension induced by AT II (IHIC) group. Ten mg/kg of etoposide was given, and 30 min and 2, 4, 8, and 24 hr later the rats were sacrificed. The drug concentrations in the serum, tumor, and normal brain tissue were analyzed by high-pressure liquid chromatography. The etoposide concentration in the serum, tumor, and normal brain tissue peaked at 30 min in both groups. The serum concentration was similar between the two groups. The etoposide concentration in the tumor was at least 2.2 times higher in the IHIC group than in the IC group at 30 min and 2 hr. The area under drug concentration curve (AUC) in the tumor in the IHIC group was about 2.2 times higher than that in the IC group. The etoposide concentration in the normal brain on the drug injection side changed only slightly from 0.5 hr to 4 hr and was about 3 times higher in the IHIC group than in the IC group. The etoposide concentration in the contralateral normal brain was very low in both groups at 30 min and disappeared thereafter. Intracarotid injection of anticancer drugs with AT II-induced hypertension further increases the drug concentration and AUC in the tumor compared with intracarotid injection alone and can be useful in treatment of malignant brain tumors.

Medulloblastoma in infancy associated with omphalocele, malrotation of the intestine, and extrophy of the bladder

A successfully treated case of infantile medulloblastoma is presented that was associated with omphalocele, malrotation of the intestine, and extrophy of the bladder. A 5-month-old boy was admitted due to disturbance of consciousness and was diagnosed by computed tomography as having a medulloblastoma. Ventricular drainage, subduralperitoneal shunt, and removal of the tumor were performed, and postoperatively radiation therapy was administrated with 4,000 rad to the whole brain. He was discharged in good condition and no evidence of recurrence was observed at the 14th postoperative month. Medulloblastomas associated with congenital anomaly of the abdomen have been only rarely reported. The authors postulate that between the second and third month of gestation an intrinsic or extrinsic factor may have caused the development of the medulloblastoma, as well as anomalies of the abdomen such as omphalocele, malrotation of the intestine, and extrophy of the bladder.

Effect of intracarotid infusion of etoposide with angiotensin II-induced hypertension on the blood-brain barrier and the brain tissue

SummaryThis study investigated the effects of the intracarotid infusion of etoposide in combination with angiotensin 11 (AT 11)-induced hypertension on the blood-brain barrier (BBB) and brain tissue in rats. Eighty rats were divided into five groups: Group 1, intravenous infusion of AT 11 to increase arterial blood pressure; Group 2, intracarotid infusion of etoposide at 22.5 mg/m2 for 10 minutes; Group 3, intracarotid infusion of etoposide at 75.0 mg/m2 for 10 minutes; Group 4, intracarotid infusion of etoposide at 75.0 mg/m2 for 20 minutes; Group 5, intracarotid infusion of etoposide at 75.0 mg/m2 for 10 minutes with AT 11-induced hypertension. Evans blue staining of the brain was used as a monitor of BBB disruption. Mean arterial blood pressure over the experimental period in Group 1 increased from 86.3 ± 1.3 mmHg (mean ± SEM) to 139.0 ± 2.4 mmHg, and Group 5 from 85.9 ± 1.8 mmHg to 137.3 ± 2.4 mmHg. None of the animals in Group 1 and 2 showed any obvious neurological change, while all the animals in Group 3, 4 and 5 exhibited diminished activity as their sole neurological change throughout the course of the experiment. Slight evidence of BBB disruption was seen in only 25% of the animals in Group 1. Significant BBB disruption was found in the animals in Group 2, 3, 4 and 5. No histological change was observed in any animal in Group 1 and 2. Demyelination, cerebral edema, and neuronal change on the infused hemisphere were observed in half of the animals in Group 3, 4 and 5, but no marked difference was observed among the three groups.At II-induced hypertension is unlikely to have an adverse effect by itself on the BBB and brain tissue. However, intracarotid infusion of high-dose etoposide is capable of producing BBB disruption and irreversible neuronal damage by itself irrespective of infusion rate. Modification of BBB and neuropathological change in case of intracarotid infusion of etoposide with AT 11-induced hypertension primarily caused by etoposide itself and not by the AT II-induced hypertension.

Cerebral Hyperemia Prior to Acute Cerebral Swelling in Patients with Severe Brain Injuries: The Role of Transcranial Doppler Monitoring

Acute cerebrovascular congestion after a closed head injury is significantly related to intracranial hypertension. As an indirect method of cerebral blood flow measurement, transcranial doppler sonography (TCD) provides a rapid and noninvasive assessment of cerebral hemodynamic, including hyperemic condition.