Large dose fraction radiotherapy in the treatment of glioblastoma.

Twenty-four adults with glioblastoma multiforme (astrocytoma, grade 4) underwent postoperative large dose fraction radiotherapy (LDFR; 5 Gy twice weekly) with Linac X-rays. The outcome in this group was compared with that of 26 patients who received conventional fractionated radiotherapy (CFR; 2 Gy 5 times weekly). The time, dose, and fractionation (TDF) factor was about 100 in both groups. The survival rates following LDFR and CFR were, respectively, 63% vs 65% at 1 year; 36% vs 8% at 2 years; 17% vs 4% at 3 years; and 4% vs 0% at 5 years. Although the survival curve for LDFR was superior to that for CFR, the difference was not statistically significant. Autopsies of nine LDFR and 13 CFR patients showed no residual tumor in one case and no cases, respectively; small residual tumor in three cases in each group; extensive coagulation necrosis of the tumor and surrounding brain tissue in one LDFR and four CFR patients; tumor proliferation in three LDFR and four CFR cases; and mixed glioblastoma and fibrosarcoma in one LDFR and two CFR patients. These results suggest that maximum tumor removal followed by LDFR may offer a better prognosis for patients with glioblastoma than that offered by surgery plus CFR.

[Histopathologic changes and tumor cell kinetics after hyperthermia and/or radiation therapy in a rat glioma model: bromodeoxyuridine (BUdR) labelling index].

Single and combined treatment of interstitial microwave hyperthermia (HT) and radiation therapy (RT) were delivered to rat glioma models. The animal model tumors were induced by intracerebral inoculation of a small piece of G-XII glioma tissue to 6-8 week-old rats. Heating to about 44 degrees C at the surface of the inserting antenna using a 2450 MHz microwave was carried on for 30 minutes. A single dose of 800 r to the whole head was delivered by deep X-ray apparatus. In combined treatment, heating immediately preceded irradiation. Following treatment, animals were sacrificed at 1, 3, 6, 12, 24, 48, 72 and 96 hours. BUdR was administered intraperitoneally 1 hour before sacrifice. Microscopically, in HT, tumor cells became eosinophilic and separated from each other. Some of them were necrotic. Macrophage infiltration in tumor tissue was recognized after 72 hours. BUdR labelling indices were less than 1% till 24 hours had passed, then became 25% at 48 hours, nearly equal to that of the control animals. In RT, ballooning of the tumor cells was prominent, and some of the tumors became necrotic. Lymphocyte infiltration of the tumor tissue was occasionally seen. BUdR labeling indices decreased slowly; less than 10% in 24 hours, but continued until 96 hours had passed. Combined treatment of HT and RT showed addictive effect of histological changes and suppression of tumor cell growth.

Undifferentiated gliomas of the brain stem.

Undifferentiated gliomas of the brain stem were confirmed surgically in two young children. The patients were treated by aggressive irradiation of the entire neuraxis, similar to that administered for medulloblastoma. Therapy resulted in a good prognosis and there was no tumor recurrence.

[Treatment of delayed brain injury after pituitary irradiation].

Treatment for delayed brain injury after pituitary irradiation is discussed. Six cases with delayed brain injury were treated with a combination of dexamethasone or betamethasone, with heparin, glycerol, dextran 40 and some vasodilators. Two cases with temporal lobe syndrome were treated in the early stages of brain injury for a period of over 12 months were almost completely cured, another two cases with chiasma syndrome were treated in the relatively late stages, showed a partial improvement. One case which was irradiated 120 GY during 13 years did not improve. The final case treated with steroids for a short period also resulted in failure and the patient underwent an operation for the removal of the necrotic mass three years after the radiotherapy. Steroid therapy started in the early stages of brain injury after irradiation for over the 12 months is thought to be effective. Heparin therapy was also effective in one out of three cases, but in one of the cases subarachnoid hemorrhage from a traumatic aneurysm occurred during the therapy. In an acute phase, showing edematous change of the injured brain, the administration of glycerol is also thought to be useful. But the effectiveness of the other medicines containing some vasodilators was obscure or doubtful. We propose the following: (1) A meticulous observation is essential for the patients who received high doses of irradiation to diagnose brain injury in the early reversible stage. (2) Steroids should be given immediately in this reversible stage of brain injury before the irreversible "necrosis" occurs. (3) Steroids should be maintained for a long period over 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of hyperthermia in combination with radiation therapy in a rat glioma model].

Rat glioma model was used to evaluate the effect of hyperthermia with and without radiation therapy. The animal model was induced by left frontal burr hole opening and inoculation of a small piece of G-XII glioma tissue to 6- to 8-week-old rats. The therapeutical experiments were given 10-14 days after inoculation of the tumor. Interstitial heating at 44 and 45 degrees C at the surface of the inserting probe using 2450 MHz microwave was delivered for 30 minutes. Deep X-ray whole head irradiation of 800 R using Stabilipan 2 (Siemens) was given just after the hyperthermia therapy. The survival of treated animals of hyperthermia, radiation, and combination of hyperthermia and radiation was significantly superior to that of non-treated control group. There was no significant difference of survival among the treated groups, though median survival was longest in the group of combination therapy of hyperthermia and radiation. Large tumors developed at the time of death in all the control and the treated animals. Histological examination showed some tendencies of macrophage infiltration in tumor tissue of hyperthermia therapy.

Analysis of hemangiopericytic meningiomas by immunohistochemistry, electron microscopy and cell culture.

Intracranial hemangiopericytic meningiomas (HM) from seven patients were examined by immunostaining, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and cell culture. Positive staining for Factor VIII-related antigen was restricted to capillary endothelial cells. There was no reaction with anti-glial fibrillary acidic protein (GFAP) serum or anti-S-100 protein serum. In these neoplasms TEM displayed extracellular basement membrane-like material (BMLM), cytoplasmic intermediate filaments (IF) associated with a dense body, dilated rough-surfaced endoplasmic reticulum containing BMLM, a small area of interdigitation of cell membranes, and a unique intercellular punctate or linear density. By SEM these tumors had intercellular shell-like or reticular structures and irregularly branched capillaries which were compressed by ellipsoidal- or carrot-shaped tumor cells. Short-term monolayer culture showed rapid and vigorous growth of tumor cells, and the formation of pseudolumens but not of whorls. The TEM of cultured cells also showed cytoplasmic IF associated with the dense body. By SEM the cultured cells were flat and had a discoid nucleus with conspicuous nucleolar hillocks. Our results show that HM are mainly poorly specialized mesenchyme-related tumors of the meninges; some possess a potential for aggressive growth and some for differentiation into smooth muscle cells. Further study is needed to determine their histogenesis.

Diagnosis of germinal neoplasm in the thalamus and basal ganglia.

Germinal neoplasms originating in the thalamus and basal ganglia were histologically verified by stereotactic biopsies in five cases and by other methods in three cases. Immunoperoxidase staining was performed on the tumors using antibodies against human chorionic gonadotropin and placental alkaline phosphatase. The presence of human chorionic gonadotropin was demonstrated in one germinoma and two mixed tumors, but not in three germinomas. Placental alkaline phosphatase was demonstrated to be present in four germinomas and one mixed tumor. Stereotactic biopsy specimens can be studied immunohistochemically, and the placental isoenzyme of alkaline phosphatase appears to be a new tumor marker for germinoma.

Clinical pathology of primitive gliomas in the cerebrum.

To clarify the biological features of primitive gliomas in the cerebrum and clearly distinguish them from malignant or anaplastic gliomas and glioblastomas, we studied eight cases clinically and pathologically. Our evaluations included immunohistochemical and electron microscopic observations. We divided the patients into two groups, children and young adults. Most tumours appeared as ring-like, enhanced masses on computed tomography and avascular or ring-like, vascular masses on angiography. Macroscopically, the tumours were well demarcated and contained cysts. Occassionally we found tumour dissemination. Microscopically, the tumours were composed of small, round cells without remarkable structural features. Ependymal, astroglial, and oligodendroglial differentiation was evident, in varying proportions; tumours in which the differentiated areas constituted more than half of the mass were classified as poorly differentiated gliomas. By these criteria, this series comprised four undifferentiated and four poorly differentiated gliomas. Cell anaplasia and polymorphism were rare in both undifferentiated and differentiated areas of the tumours. Immunohistochemical and electron microscopic examinations also revealed glial differentiation. These primitive gliomas appear to be biologically similar, but not identical, to cerebellar medulloblastomas. In this series, five patients died because of recurrence or dissemination. Whole brain and spinal irradiation should be considered after total or subtotal surgical removal.

Intracranial granuloma caused by Aspergillus fumigatus.

A case is reported of intracranial granuloma caused by Aspergillus fumigatus involving the anterior cranial fossa and the frontal lobe. In this case, clinical symptoms developed about 5 years before the diagnosis was made. The final diagnosis was made by a craniotomy. The patient was treated with an extensive excision and chemotherapy, but finally he failed to respond to these treatments. We compile a summary of reported cases with a tabulation of pertinent information and discuss the pathogenesis, prognosis, and difficulty in treating this infection.

The incidence of delayed traumatic intracerebral hematoma with extradural hemorrhages.

After introduction of computerized tomography (CT), we experienced 22 patients with traumatic extradural and intracerebral combined hematomas, of whom 15 underwent sequential CT scans. In 14 of the 22 patients or 13 of the 15 patients whose initial CT scans were performed early, within 6 hours after injury, intracerebral hematomas developed more slowly than extradural hematomas. In ten of the 13 patients, development of intracerebral hematomas was demonstrated only after removal of extradural hematomas, and in four patients acute brain swelling was observed during surgery. Therefore it is emphasized that the incidence of post-surgical intracerebral hematoma with extradural hemorrhages is high and that acute brain swelling during surgery for extradural hematomas is largely caused by the delayed intracerebral hematomas.

Malignant melanoma of the spinal epidural space metastasized from the enucleated left eye after nine years without symptoms: report of a case.

A case of flaccid paraplegia due to a metastatic spinal epidural melanoma is reported. Symptoms occurred approximately 9 years after the enucleation of the left eye. A solid melanotic mass was removed almost totally. Three years after the operation, the patient had not regained the motility of the lower limbs. The need for long term follow-up and management of patients with such problems is discussed, and the pertinent literature is reviewed.