The authors describe two criteria in current use for evaluating the direct effect of a treatment on brain tumors.
One of them has been made by authors following the criteria for evaluating patients with a solid tumor which was reported by Koyama and Saito. In these criteria, the effect of therapy was evaluated mainly from the results of computed tomography (CT) scan. Complete response was defined as complete resolution of all radiographic signs of intracranial tumor; partial response as a 50% or greater decrease in tumor size; no change as a decrease less than 50% and increase less than 25%; progressive disease as a 25% or greater increase in tumor size. The other criteria were described by Levin, et al. in which the effect of therapy was evaluated from results of a neurological examination, radionuclide scintiscan and CT scan. Response was defined as an improvement in at least two of the three tests while the patient was receiving a stable or decreasing dose of steroids. Progressive disease was defined as a deterioration in at least two of the three tests while the patient was receiving a stable or increasing dose of steroids. No change was defined as disease which neither progressed nor regressed as defined above.
The details of the criteria are described and their role is discussed.

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A small-sized flow probe, 8 mm in diameter, was manufactured for the continuous measurement of cerebral blood flow (CBF) by thermal diffusion. It is a modification of Carter's and incorporates a Peltier stack to create a temperature gradient between the two sensors, one cooled and the other heated, which were connected to both sides of the stack. A current supplied to the stack was adjusted to generate a temperature gradient of about 5°C in water. With this given current the temperature gradient was held constant, when the water temperature varied from 30°C to 40°C. Using 8 cats, temperature gradients were compared with CBF values by the hydrogen clearance method for quantitative assessment. It was confirmed that the correlation between the CBF values calculated from temperature gradients using the equation proposed by others and those from the hydrogen clearance has linear characteristics. Moreover, it appeared that calibration was not required for the quantitative assessment in each experiment, if the flow probe evaluated beforehand was applied to the same kind of experimental animals.
From these results, it is suggested that CBF can be monitored continuously as well as quantitatively by thermal diffusion using this type of flow probe.

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Basic aspects of hyperthermia of brain tumor were studied in in vitro experimental systems. Three rat brain tumor cell lines and three human glioblastoma cell lines were used in this study. Heat sensitivity was tested in microplate by water bath hyperthermia. Under 1 hour hyperthermia below 42°C, many of the cell lines grew rapidly, the same as control, though a few lines showed minor suppression. However, all the cell lines showed irreversible cellular damage following 1 hour hyperthermia at 46°C. In the range between 43 and 45°C each cell line demonstrated specific sensitivity. Thermotolerance induced by preheating showed again a markedly varied pattern. Three of them demonstrated apparent thermotolerance, but the others did not.
Comparison of sensitivity to heat and ACNU revealed an almost reversed correlation. For example, heat-sensitive cell lines like EB679 and T98 were moderately resistant to ACNU. In contrast ACNU sensitive cell lines like SK-MG1 and AO₂ were highly resistant to hyperthermia. These results may indicate a usefulness of the combined modality of treatment with ACNU and hyperthermia, because of their totally different mechanisms.

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Hyperthermia in conjunction with brachytherapy might allow the delivery of less toxic radiation doses while improving local control of tumors. To complement the authors' clinical study of interstitial brachytherapy of malignant brain tumors, a microwave interstitial heating system with computed data acquisition was constructed. It was evaluated in a phantom and in a series of acute and chronic experiments for heating patterns and heat toxicity in 30 normal adult canine brains. With the head fixed in a stereotaxic frame, lateral, occipital, or parietal approaches were used for placement of nylon catheters containing microwave antennas and fiberoptic thermometry probes. The antennas were operated at 915 or 2, 450 MHz using continuous-wave power sources. When a steady state was obtained, usually within 5 minutes of heating, temperatures were mapped at 1 mm intervals along the length of the antenna and radially from the antenna by moving the thermometry probes with a stereotaxic manipulator. In general it was easy to maintain a steady state for a long period. Heating patterns tended to be ellipsoidal, correlating relatively well with those predicted by phantom trials. Heat toxicity was examined by sequential quantitative computed tomography (CT) scans in chronic trials and correlated with histopathology following sacrifice at 4-8 weeks. The results suggest that 1) interstitial microwave hyperthermia is an effective means of inducing localized brain hyperthermia, 2) surgical and hyperthermia procedures are well tolerated, 3) temperature above 43°C for 30 minutes induces changes in the normal canine brain which can be measured and followed noninvasively with CT.

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Using the peripheral blood lymphocyte (PBL) interferon induction test, impaired production of gamma interferon (IFN) was investigated in patients with malignant gliomas. 10⁷ human PBLs were placed in 5 cm diameter plastic dishes containing 5 ml of RPMI-1640 medium with 10% heat-inactivated fetal calf serum (FCS) and either 5 μg/ml of OK-432 or 10 units/ml of recombinant interleukin-2 (rIL-2) for 72 hours at 37°C. The culture supernatant was then collected and used for IFN assay which was carried out in FL cells with Sindbis virus. The yields of human IFN were expressed as laboratory units; one laboratory unit corresponds to the quantity necessary to cause 50% inhibition of the viral cytopathic effect. IFN production from PBL of healthy subjects, induced by OK-432 and rIL-2, was 5, 367±525 and 344±108 units/ml, respectively. The production from patients, however, was 198±66 and less than 40 units/ml, respectively. Human lymphokineactivated killer (LAK) cells were generated by placing 2.5 × 10⁶ PBL/ml in complete medium with 10% heat-inactivated FCS and either 5 μg/ml of OK-432 or 10 units/ml of rIL-2 for 72 to 96 hours at 37°C. The antitumor cytotoxic activity was estimated in triplicate by 4 hours ⁵¹Cr release assays. The in vitro cytotoxicity of LAK cells generated from PBL of healthy subjects by rIL-2 and OK-432 against allogeneic glioma (ONS-12) cells was 75% and 50%, respectively. The LAK activity induced in patients by rIL-2 and OK-432 was between 55 and 30%, and between 30 and 7%, respectively. It was noted that very little antitumor activity (i.e. 7%) was induced by OK-432 in one patient with an initial low IFN production. The cytotoxic activity of LAK cells induced by OK-432 correlated to IFN production induced from PBL of patients with gliomas.

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Fractionated irradiation using 250 mega electron volt protons alone or in combination with ⁶⁰cobalt (Co) gamma ray was given postoperatively to 8 patients with glioma and 2 patients with meningioma. A single field was used for all patients. The irradiated field varied from 28 to 144 cm²; the irradiated depth was from 6 to 11 cm and the width of the Bragg peak was from 5 to 10 cm in the proton radiotherapy. Dose aim was approximately 74.5 Grey (Gy) over 46 days in the proton alone radiotherapy and was approximately 84.8 Gy over 56 days in the combined therapy with ⁶⁰Co gamma ray. The dose increment was from 2.5 to 5.0 Gy per fraction as treatment progressed in the proton radiotherapy. No evident increased intracranial pressure developed. Nine patients were given the planned dose of irradiation. One patient with glioblastoma multiforme deteriorated during the treatment and the planned course was not completed. The patient was reoperated. Another patient with glioblastoma multiforme deteriorated 1 month after planned irradiation of 84.2 Gy and was diagnosed as having a regrowth of the tumor. Evident and viable tumor cells were observed in the outline of the center of tumor tissue in the irradiated field. Furthermore no evident radiation effect developed in the peritumoral area showing low density on computerized tomography. Exudative dermatitis with much epilation was seen at the proton beam entrance site in all patients with complete radiotherapy. Seizure was also seen in 6 out of 9 patients. Two patients with grade III or II astrocytoma and 2 patients with meningioma were in good health 6 to 9 months after radiotherapy, but the other patients with glioblastoma multiforme died or deteriorated 1 to 5 months after radiotherapy. The issue of proton radiotherapy for brain tumor was discussed. In conclusion, it is necessary to investigate further the optimal dose and dose distribution in the tumor tissue, irradiation technique, and the combined therapy with some drug in the treatment of malignant glioma.

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Fifty children (13 years of age or under) with acute, severe head injury were analyzed, with special reference to the relations between initial computerized tomography (CT) findings, clinical severity, and outcome. Parenchymal lesions on CT were classified into five categories: normal, hemispheric swelling, hemorrhagic lesion, diffuse cerebral swelling, and low density. The severity and the outcome were evaluated using the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS), respectively, adoption of GCS scoring being restricted to patients 3 years of age or over.
Twenty-three patients (46%) showed extracerebral hematomas. The most common extracerebral hematoma was the acute subdural hematoma, which comprised 24% of the cases; epidural hematomas were found in 9 cases (18%). These figures coincided with the reported results of adult cases in severe head injury. All the epidural hematoma cases showed “normal” parenchymal lesion, and carried less clinical severity and better outcome. This might suggest that more trivial injury would cause the epidural hematoma in children than in adults. Hemispheric swelling was commonly seen in patients with acute subdural hematoma and was generally associated with low GCS scores (mean 4.8) and poor outcome (63% mortality). Compared with that in adults, hemorrhagic lesion in children was less often associated with extracerebral hematoma, and the outcome and severity of the cases with this lesion depended mainly on the multiplicity and the location of the hemorrhage. Eleven cases fulfilled the criteria of diffuse cerebral swelling, namely, slit-like ventricles and obliterated perimesencephalic cisterns, and only one had an associated subdural hematoma. Forty-two patients (84%) achieved a good recovery or a moderate disability. None were severely disabled or vegetative, and the overall mortality rate was 16%. Patients with GCS scores of 3 to 5 were uniformly poor in outcome (60% of mortality), regardless of parenchymal lesions, whereas those with GCS scores of 6 to 8 had only 8% mortality.

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Two cases of glioblastoma multiforme of the cerebellum are reported. Case 1, a 55-year-old male, was admitted in 1981 with a 3-week history of intermittent headache, vomiting, and gait instability. Case 2, a 27-year-old female suffering from von Recklinghausen's disease, was admitted in 1973 with a 6-week history of headache, vomiting, and blurred vision. On admission, cerebellar symptoms and bilateral papilledema were observed in both patients. Neuroradiological studies, including computed tomography scan and angiography, were of little help in predicting the exact nature of these tumors before surgery. At the operation, a tumor growing mainly in the right cerebellar hemisphere was found in each patient. On histological examination, hypercellularity with pleomorphism, small patches of necrosis, and vascular endothelial proliferation were noted, which appeared to be indistinguishable from those of cerebral glioblastoma. In spite of repeated operations followed by chemoradiotherapy, both patients died of tumor recurrence, 38 months and 25 months after the onset of the symptoms, respectively. Glioblastoma multiforme of the cerebellum is very rare and accounts for approximately 0.6% of all glioblastomas reported in the recent literature. Only 82 cases of the cerebellar glioblastoma have so far been reported. The biological behavior of these tumors is in all respects identical to those of the cerebral counterparts.

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Chronic subdural hematoma combined with ipsilateral arachnoid cyst in the middle cranial fossa is well known. Recently, many such cases have been reported because of introduction of X-ray computed tomography (X-CT). The authors present an unusual case of multiple chronic subdural hematomas combined with an ipsilateral arachnoid cyst in the middle cranial fossa.
A 15-year-old boy was seen because of headache, nausea and vomiting after minor head injury. Neurological abnormalities were not found except for asymmetric bulging of the left temporal region on admission. X-CT showed a high density area surrounded by a low density area in the temporal region. At the temporal region and the convexity, two avascular areas were shown by angiography. Other vascular abnormalities were very similar to typical arachnoid cyst at the middle cranial fossa. Surgery confirmed the two hematomas and arachnoid cyst.
Multiple chronic subdural hematoma is very rare. The etiological relationship between the two hematomas and the arachnoid cyst is discussed and compared with previous reports.

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Three cases of epidural hematoma are reported. They developed following craniotomy for supratentorial lesions on the contralateral side. Case 1 was a 27-year-old male. A left parietal epidural hematoma was observed after removal of a right acute subdural hematoma caused by head trauma. The epidural hematoma seemed to be induced by decompression of the injured middle meningeal artery which had been suppressed by intracranial hypertension. Case 2 was a 20-year-old female. A right frontal epidural hematoma developed following left frontal brain tumor removal. Case 3 was a 58-year-old female. She had a right parietal epidural hematoma after neck clipping of a left internal carotid-posterior communicating aneurysm. The mechanisms causing the epidural hematomas in Cases 2 and 3 were not clear. There is some possibility that development of the epidural hematoma was related to loose adhesion between the dura mater and cranium, and to the craniotomy performed by airdrill and airtome.

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Supratentorial hemangioblastoma is encountered very rarely. About 60 cases in all have been reported. The authors present a case of supratentorial hemangioblastoma and cerebellar hemangioblastoma occurring 7 years after surgery for spinal hemangioblastoma.
A 23-year-old male was admitted with severe headache and vomiting. Neurological examination showed paraplegia, left cerebellar disturbance, and horizontal nystagmus on lateral gaze to the left. Computerized tomography scans and bilateral axillar artery angiograms showed a left cerebellar cystic mass with two mural nodules. In consequent operations, two hemangioblastomas were found; one in the left cerebellar hemisphere and the other attached to the cerebellar tentorium under the left occipital lobe. The histology of these tumors revealed the well-differentiated morphology of hemangioblastomas. The authors discuss some clinical aspects of the supratentorial hemangioblastoma associated with infratentorial or spinal hemangioblastoma, and also the differential diagnosis between angioblastic meningioma and hemangioblastoma.

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A rare complication, migration of the peritoneal catheter of a ventriculo-peritoneal shunt, is reported. The patient was a 23-year-old female who had a ventriculo-peritoneal shunt installed at the age of 19 years, for her hydrocephalus secondary to tuberculous meningitis. The patient had 3 days' history of seizure and recurrent bouts of fever. A plain chest X-ray revealed the tip of the peritoneal catheter in the right hilar area with local pneumonitis. Metrizamide shuntgram revealed seepage of the contrast material into the right lower thoracic cavity. A computed tomography scan of the thorax confirmed the presence of the tip of the catheter in the right hilar area, and the site of entry into the thoracic cavity was identified as the anterior portion of the right diaphragm. The patient underwent shunt revision and the peritoneal catheter was repositioned into the peritoneal cavity.
Among various complications related to peritoneal catheters of ventriculo-peritoneal shunts, migration of a peritoneal catheter into the thoracic cavity by perforation through the diaphragm is extremely rare. The literature is reviewed regarding perforation of various viscera by peritoneal catheters of ventriculo-peritoneal shunts, and the possible causative mechanism of migration of a peritoneal catheter into the thoracic cavity is discussed. Although there is no consensus regarding the optimal length of a peritoneal catheter, unnecessarily long peritoneal catheters should be avoided.

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