Clinicopathological study of vascular endothelial growth factor (VEGF), p53, and proliferative potential in familial von Hippel-Lindau disease and sporadic hemangioblastomas.

We examined the clinical characteristics and prognosis in six patients with familial von Hippel-Lindau (VHL) disease and seven with sporadic hemangioblastomas. The expression of vascular endothelial growth factor (VEGF), p53 protein, and proliferative potential with Ki67 monoclonal antibody (MIB-1) was compared using immunohistochemical methods between sporadic and VHL disease-associated hemangioblastomas. Patients with sporadic CNS hemangioblastomas were treated by total removal of the tumors, and they had a good long-term prognosis without neurological deficits on recurrence. However, patients with familial VHL disease often had multiple hemangioblastomas in the CNS and visceral tumors. Even if total removal of CNS hemangioblastomas in patients with VHL disease was performed initially, small multiple hemangioblastomas recurred during long-term follow-up in areas remote from the primary region resected by surgery. All of the hemangioblastomas displayed extensive overexpression of VEGF protein, with moderate to marked proliferation of blood vessels. The MIB-1 indices showed low values of 0.8% as the mean, with a range of 0.03%-2.1% for all the hemangioblastomas. None of the hemangioblastomas expressed p53 protein. The hemangioblastomas in patients with VHL disease were multiple in the CNS and were combined with visceral tumors. Patients with VHL disease had a poor long-term prognosis, in contrast to those with sporadic hemangioblastomas. The immunohistochemical findings for VEGF protein, p53 protein, and MIB-1 did not differ significantly between the sporadic and VHL disease-associated hemangioblastomas.

[Significance of p53 protein expression and proliferative potential with MIB-1 on tumor recurrence of pituitary adenomas].

Total or subtotal removal on initial surgery was carried out in 103 cases of pituitary adenomas and followed up for more than 5 years in 97 cases. 22 (21%) of 103 cases had tumor recurrence after the initial surgery. The p53 protein (DO-7, Novocastra Lab.) expression and proliferative potential with MIB-1 monoclonal antibody (MBL Co.) were evaluated in the non-recurrent and recurrent pituitary adenomas. Tissue samples were embedded in paraffin after fixation in 10% formalin and 3 microns sections were activated by microwave heating before being immersed with the antibodies. The positivities of the immunostaining for p53 protein and MIB-1 were calculated as % values of tumor cell nuclei stained to 1000 tumor cell nuclei in several fields. Most of the recurrent pituitary adenomas were large macroadenomas with suprasellar extension. However, tumor recurrence was not correlated with tumor type in terms of the hormonal secretion, surgical approach, and radiotherapy. 15 cases of the non-recurrent group had values of 1.0 +/- 0.5% (mean +/- SD) for their MIB-1 positive nuclei, whereas 18 cases of the recurrent group had high values of 2.5 +/- 1.2%. A statistically significant difference was observed between the two groups. 11 of the 18 cases of recurrent pituitary adenomas revealed high values of MIB-1 in excess of 2.0%. p53 protein was not found in 21 cases of the non-recurrent group. However, 5 (28%) of the 18 cases of recurrent pituitary adenomas demonstrated p53 protein expression with positive nuclei staining at lower than 1.0%. It is concluded that evaluations of the p53 protein expression and proliferative potential with MIB-1 represent important factors in predicting tumor recurrence of pituitary adenomas.

Expression of vascular endothelial growth factor and p53 protein in association with neovascularization in human malignant gliomas.

We examined the expression of vascular endothelial growth factor (VEGF) protein, p53 protein, and the MIB-1 index in 43 patients with malignant gliomas in relation to tumor vascularization by an immunohistochemical method. Factor VIII-related antibody was employed for the evaluation of the vascularity and endothelial proliferation. Of the 42 cases of malignant gliomas, 36 (86%) demonstrated immunoreactivity for VEGF in their tumor cells, whereas 22 (52%) had VEGF in their endothelial cells. There was a tendency for the vascularity to be correlated with the immunoreactivity for VEGF (coefficient, 0.340). In addition, a marked increase in endothelial proliferation was evident in cases showing moderate to strong positivity for VEGF as compared with the others. Immunoreactivity for VEGF was found mostly in the malignant gliomas without p53 overexpression and/or with p53 overexpression. However, statistical analysis revealed a correlation between the grade of p53 overexpression and the grade of VEGF expression (coefficient, 0.507), but not between the VEGF and MIB-1 index in our series. There was a tendency for the MIB-1 indices to increase in correlation with increasing vascularity.

Ultrastructure of microvessels and tumor cell processes on central neurocytoma.

A case of central neurocytoma that was confirmed with ultrastructural and immunohistochemical studies has been reported. Ultrastructurally, thin cytoplasmic processes of tumor cells showed differentiation into neuronal cells containing parallel bundles of microtubules and abortive synapses with dense-core vesicles and/or clear vesicles. It was frequently found that the clusters of tumor cell processes were close to or around the microvessels. Microvessels were composed of endothelial cells without fenestrations and had tight junctions in the endothelial clefts. Neurosecretory granules in thin cell processes appeared close to microvessels and may have been secreted around microvessels.

Tubular bodies (Weibel-Palade bodies) in endothelial cells of glioblastomas and astrocytomas.

The mean % ratio value of the number of endothelial cells with tubular bodies for the 6 cases of the glioblastomas proved to be 32.4% in the margin, which was about two times as high as that (15.7%) in the center of the tumors, showing a tendency for tubular bodies to be increased broadly in parallel with vascularization. In the 5 cases of astrocytoma, vascularization was less marked, and the mean % ratio was lower (14.8%) in all studied locations of the astrocytoma. It is suggested that the tubular bodies in the endothelial cells of microvessels of astrocytic tumors could increase in relation to microvessel proliferation and tumor malignancy.

[P53 protein expression and proliferative potential in non-recurrent and recurrent meningiomas].

Evaluation of the p53 gene protein expression and proliferative potential with MIB-1 monoclonal antibody (MBL Co.), a new marker of cellular proliferation that binds Ki67 in paraffin sections, by immunohistochemical studies were made in 10 cases of the non-recurrent meningiomas and the 8 cases (17 samples) of the recurrent meningiomas. Tissue samples were embedded in paraffin after fixation in 10% formalin, and 3-microns sections were activated by microwave heating before being immersed with p53 protein or MIB-1 monoclonal antibody. The positivity of immunostaining for p53 protein and MIB-1 was calculated as the % values of tumor cell nuclei stained to all tumor cell nuclei examined within several fields under a light microscope. The mean % value of the proliferating cell index (PCI) stained with MIB-1 monoclonal antibody was 2.1% in the non-recurrent meningiomas, and high values of 11.9% were obtained for the recurrent meningiomas. High values of PCI exceeding 3% were indicated in most of the cases of recurrent meningiomas. p53 protein was not found in the 10 cases of non-recurrent meningiomas. However, it was positive showing values of 0.5-8.5% (mean; 3.4%) in 5 of the 8 cases of recurrent meningiomas. 2 of 4 cases of recurrent meningiomas with a benign type of histology at both initial discovery and recurrence revealed p53 protein expression in the tumor tissues. 3 of 4 cases of recurrent meningiomas, which were of the benign type at the initial operation but transformed to the malignant (atypical) type on recurrence, demonstrated positive staining for p53 protein in the tumor tissues. Although positivity for p53 protein was observed in the recurrent meningiomas with high values of PCI with MIB-1, no significant correlation between the values of PCI with MIB-1 and those for the p53 protein expression was found. The p53 gene protein may be altered on tumor recurrence and/or malignant transformation in meningiomas. It is concluded that evaluations of the p53 protein expression and proliferative potential with MIB-1 are important as additional factors for the prediction of tumor recurrence in meningiomas.

[Analysis of the proliferative potential of meningiomas with MIB-1 monoclonal antibodies].

Tumor recurrence was observed in 12 (11.3%) out of 106 cases of intracranial meningioma followed for more than 5 years. Proliferative potential was evaluated immunohistochemically with MIB-1 monoclonal antibodies in 37 cases of non-recurrent meningioma and 12 cases (21 samples) of recurrent meningioma. The proliferating cell index (PCI) was much higher in the non-recurrent meningiomas than the recurrent meningiomas (10.6 +/- 7.7 [mean +/- SD] versus 1.9 +/- 1.5). Most recurrent meningiomas had high PCI values, greater than 3%. High PCI values of more than 5% were found in 13 (62%) of the 21 samples of recurrent meningioma. However, only 4 of the 37 cases of nonrecurrent meningioma had high PCI values with MIB-1 of more than 3%. The 12 cases of recurrent meningioma were classified into 3 groups: 6 cases in which both the initial and recurrent meningiomas were benign (Group I), 5 cases in which the meningioma at the time of the initial operation was benign, but the recurrent meningioma was malignant (Group II), and one case in which malignant meningioma was diagnosed at the time of the initial operation (Group III). The PCI values with MIB-1 in most of the recurrent meningiomas were higher at the time of recurrence than at the time of the initial operation. Malignant meningiomas, such as anaplastic and atypical meningioma, and some meningotheliomatous meningiomas among the benign meningiomas recurred and had higher PCI with MIB-1 values than other meningiomas. It is concluded that PCI with MIB-1 is important as a predictive factor for the recurrence of meningiomas. Meningiomas having a PCI value with MIB-1 of more than 3% in particular should be followed carefully.

[The two familial occurrence of von Hippel-Lindau disease].

Five cases of von Hippel-Lindau disease in two families were reported. In one family there were 2 cases in a mother (55 years old) and her daughter (26 years old) which had multiple hemangioblastomas in the optic nerve, cerebellum and spinal cord in each case. Retinal angioma appeared in the case of daughter, but not in the mother. In the other family there were 3 cases in a father (28 years old), his son (11 years old) and daughter (14 years old). All of them had retinal angioma and cerebellar hemangioblastoma. Two cases out of 5 cases in the two families were associated with abdominal organ diseases which were renal cell carcinoma in a case and pancreas cyst in the other. The familial occurrence of von Hippel-Lindau disease in Japan was recognized in 21 families with 103 cases including our cases. On the study of reported cases hemangioblastoma frequently occurred in multiple region such as cerebellum, medulla oblongata and frequently presented with renal cell carcinoma, pheochromocytoma and cyst in pancreas, kidney and liver. The location of hemangioblastoma and combined disease was similar in cases in each family. The age of onset of von Hippel-Lindau disease in the second generation was younger than that of the first generation.

[Clinical study on the recurrence of meningiomas: correlating factors for the recurrence and therapeutic prognosis of meningiomas].

Authors have studied 128 cases of meningiomas which were operated on and examined histologically. 12 cases (11.3%) of 106 cases of the meningiomas followed up for more than 5 years after surgery had recurrence after the primary operation. The distribution of age and sex, the tumor location, the histological type, the extent of tumor evacuation and AgNORs counts and BrdU labeling index for the evaluation of tumor proliferation were studied comparatively in the two groups, the recurrent and nonrecurrent meningiomas. 8 cases (19.0%) of 42 cases of the meningiomas in the age-group lower than 50 years old were recurrent cases, whereas 4 cases (6.0%) of 67 cases in the age-group over 50 years old were non-recurrent. Concerning the sex distribution of the meningiomas in our cases recurrent rate was 20.5% among males and 6.0% among females. The tumor locations of the meningiomas did not correlate significantly with recurrence. The extent of tumor removal demonstrated Simpson grade I (47 cases), grade II (37 cases), grade III (17 cases), grade IV (5 cases) on primary operation. Recurrence was found in 11 cases (13.1%) of 84 cases operated on by total removal of Simpson grade I or grade II. 8 cases of 11 cases had recurrence within 5 years after the primary operation of Simpson grade I or II. Total removal of the tumor was important in order to bring about long survival after operation. But correlation between the extent of tumor removal and recurrence was not able to be recognized. Histologically, all of the malignant, atypical and papillary type of meningiomas treated in the primary operations had recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

[Turner's syndrome with pituitary hyperplasia: a case report].

Turner's syndrome, a sex-chromosome abnormality, is often accompanied by cardiovascular disorders, such as coarctation of the aorta. We encountered a case of Turner's syndrome with meningioma and pituitary hyperplasia which resulted in death from dissection of the aorta. The patient was 36-year-old female who was diagnosed as having Turner's syndrome of mosaic-type at the age of 15. She had accepted sex-hormone replacement with estrogen and progesterone over 20 years. She lost consciousness and was transferred to our institute on June 20th, 1992. She was in shock but her condition began to improve after intensive treatment. CT scan revealed a calcified mass lesion at the left frontal convexity and a markedly enhanced round mass lesion at the suprasellar region. Angiography showed tumor stain of the suprasellar region fed by the posterior ethmoidal artery. These tumors were diagnosed as multiple meningiomas. She developed dyspnea on June 24th and chest X-ray showed right pleural fluid collection and cardiomegaly. This condition was diagnosed as congestive heart failure. Her condition was getting worse and she suffered abrupt cardiac arrest on June 28th. Autopsy revealed dissection of the aorta as the cause of death. The tumor of the convexity was meningioma, and the suprasellar lesion was diagnosed as pituitary hyperplasia. It is well known that frequent excess dose injection of estrogen can induce pituitary adenoma or hyperplasia in rats. In this case, the presence of pituitary hyperplasia was thought to be the result of long-term injection of estrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

A long surviving case of recurrent medulloblastoma displaying effectiveness of ACNU/vincristine chemotherapy.

A favorable case of recurrent medulloblastoma, in which 19 years has elapsed with combination therapy due to surgery, radiation and chemotherapy since the initial operation, is reported. The case was a male of age 12 who was admitted due to medulloblastoma of the classical type. Tumor recurrences were observed 3 times within 7 years after the initial operation and radiation treatment. At the 3rd recurrence, a large tumor was found in the cerebellar vermis and left cerebellar hemisphere on CT with CSF dissemination and a high NSE level in the CSF (62 ng/ml). Only chemotherapy by intravenous administration of 2 courses of 120-150 mg ACNU (1.7-2.2 mg/kg) and 4 mg vincristine (0.06 mg/kg) with intrathecal administration of methotrexate was given at this time. The tumor image and gait disturbance with radicular pain disappeared completely and the NSE level in the CSF improved to within the normal range (5.4 ng/ml). The patient continues in complete remission, with a Karnovsky performance status of 100% at 4 years after the 3rd recurrence. We report full details of this case in which active treatments consisting mainly of chemotherapy proved to be effective for recurrent medulloblastoma, even though its prognosis is generally very unfavorable.

Pituitary adenoma combined with Rathke's cleft cyst--case report.

A rare pituitary adenoma associated with Rathke's cleft cyst was discovered incidentally in a 44-year-old male admitted after head trauma. Neurological and physiological examination found no abnormalities, except for panhypopituitarism. Computed tomography and magnetic resonance imaging demonstrated a solid mass in the sellar cavity with suprasellar extension, associated with a cystic mass extending into the third ventricle. The tumor was removed subtotally by the transcranial approach. Light microscopy demonstrated that the cyst wall was composed of ciliated columnar cells, cuboidal cells, and goblet cells, and the solid part indicated chromophobe pituitary adenoma. Immunohistochemistry demonstrated that a few adenoma cells were positive for prolactin and the cyst wall cells were positive for cytokeratin and negative for S-100 protein.

[A case of penetrating head injury caused by nail-gun].

A rare case of penetrating head injury caused by a nail-gun was described. A 24-year-old male was admitted to our hospital due to head injury. He had handled a nail-gun at a construction site. On admission the patient was fully conscious with no neurological defects. A small wound was observed at the left front-temporal region. Skull films showed a large nail embedded in the skull cavity. A computed tomographic (CT) scan, changing level of window, demonstrated intracerebral hematoma, fragment of skull bone and nail. Cerebral angiography (CAG) showed extravasation at the left frontal region. Emergency operation was performed and his recovery was uneventful. Twenty-two craniocerebral injuries caused by nail-guns have been reported in world medical literature but this was the first report in Japan. The characteristics of craniocerebral nail-gun injuries were less damage and better prognosis compared with gunshot injuries. However intracranial infection and vascular injury were possible lethal complications. In this case, preoperative examination, such as CT scan and CAG was valuable and the early operation for the sake of safety was very effective.

Histological and ultrastructural findings of benign intracranial cysts.

Since benign intracranial cysts have similar clinical and neuroradiological imaging appearances, it is difficult to distinguish between these cysts. Thus an electron microscopic study plays an important role in definite diagnosis of these non-tumorous benign cystic lesions, and also in determination of their origins. Arachnoid cysts occurring in 5 patients, epithelial cysts occurring in 2 patients, 2 cases of Rathke's cleft cysts, and one case of pineal cyst, were electron- and light-microscopically observed, and their characteristic features and differences were described. The structure of the arachnoid cyst wall was similar to that of normal arachnoid membrane. The inner surface of the arachnoid membrane. The inner surface of the arachnoid cyst wall was formed of one or several layers of arachnoid cells with slender processes, which contained large extracellular spaces, but not microvilli. As for epithelial cysts, microvilli and surface-coating material were present on the surface of epithelial cysts, and a well-developed basement membrane was continuously observed under the epithelial cells. Rathke's cleft cysts, which may basically be classified as epithelial cysts, are lined by columnar or cuboidal ciliated epithelium. The wall of the pineal cyst is composed of normal pineal tissue, and there are three layers, which have a lining of glial cells in the inner layer, a few sheets of pineal cells in the middle layer, and a fibrous capsule in the outer layer.

[Central neurocytoma--report of a case].

The authors present a case of central neurocytoma in a 23-year-old male with increased intracranial pressure syndrome. Computed tomographic (CT) scans and magnetic resonance images showed a large tumor mass with no evidence of calcification in the right lateral ventricle extending towards the third ventricle. A right transcortical-transventricular approach was performed and the tumor was totally removed. The postoperative course was uneventful and no further treatment was administered. CT shows no evidence of tumor recurrence after the six months from his surgery. Light microscopic findings suggested a diagnosis of oligodendroglioma. However, ultrastructural examinations demonstrated many dense-core or clear vesicles, microtubules and synaptic like structures within the abundant cytoplasmic processes of the tumor cells which suggested neuronal differentiation. Immunohistochemical examinations showed the tumor cells to be positive for neuron-specific enolase, sporadically positive for synaptophysin, and negative for glial fibrillary acidic protein. The final histological diagnosis was central neurocytoma. Central neurocytoma was first described by Hassoun et al, in 1982. Since then, 96 cases have been reported in the literatures. Their clinicopathological features, neuroradiological findings and prognosis are discussed.

[Ultrastructural findings of arachnoid cysts and epithelial cysts].

There may be several kinds of pathological conditions in the cystic lesion which are clinically diagnosed as benign intracranial cysts on CT scan. Light and electron microscopic studies on cyst walls were important in the differential diagnosis of benign intracranial cysts. We have studied 5 cases of intracranial arachnoid cysts and two epithelial cysts using the light and electron microscopy. Five cases of intracranial arachnoid cysts included two children and three adults (three females and two males). Three cases of them were localized in the middle cranial fossa, one case in the anterior and middle cranial fossa and one case in the lateral ventricle, giving headache and convulsion as the initial complaints. As for the epithelial cysts, one was localized at the para-collicular area complaining enlarged head and swollen anterior fontanelle and the other of four years was located in the fourth ventricle with headache and ataxic gait. On CT all of them demonstrated diffuse low density areas in both the arachnoid and the epithelial cysts without communicating findings between the cystic cavities and subarachnoid space on metrizamide CT cisternography. The arachnoid cyst walls were basically similar in structure to the normal arachnoid membrane and composed of elongated epithelial cells like the arachnoid cell and the connective tissues with lamellar collagen fiber bundles. However, 3 of the 5 cases had only fibrous tissues without epithelial cells. The inner sheath of the arachnoid cyst walls was composed of one or several layers of the arachnoid cells with flattened and relatively electron-dense cytoplasm on electron micrograph. They had a lot of elongated process and were tangled with each other, making large extracellular spaces between them. Below the electron dense arachnoid cells, compact packed cells with interdigitation partly demonstrated intercellular contacts such as numerous desmosomes and tight junctions. In those intercellular spaces collagen fibers and microfibrils were observed. The cells contained abundant cytoplasmic microfibrils and numerous organelles. They were separated from numerous collagen fibers and fibroblasts by non continuous basal lamina under the epithelial cells. Epithelial cyst wall had a layer of cuboidal or columnal epithelium in the inner layer of cyst wall. Those epithelial cells demonstrated granules having positive in PAS and mucicarmine stain in their cytoplasm. On electron microscopical study epithelial cells revealed a lot of microvilli and coating materials on the surface of them without cilia. The basement membranes were well developed under the epithelial cells separated from the connective tissues. In the intercellular clefts of the epithelial cells tight junctions and interdigitations were recognized.(ABSTRACT TRUNCATED AT 400 WORDS)

[Chemotherapy with ACNU and radiation therapy in malignant glioma in cerebral hemisphere of adult].

54 cases of malignant gliomas in adults localized in cerebral hemisphere including the location of basal ganglia and corpus callosum in 26% were survived over one month and followed more than 2 years after operation for 10 years recently. Histologically they had 40 cases of glioblastoma multiforme and 14 cases of anaplastic astrocytoma. All malignant gliomas were given an operation and radiation, classifying 4 groups due to chemotherapeutic methods; Group I (20 cases) was treated by intraarterial infusion of ACNU with 20% mannitol. The others were Group II (8 cases) treated by intraarterial infusion of ACNU only, Group III (13 cases) by intravenous infusion of ACNU only and Group IV (13 cases) by no chemotherapy. Post-operative survival rates in the malignant gliomas of Group I were that 1 year survival rate was in 16 out of 20 cases (80%), 2 years in 55%, and 5 years in 25%. In glioblastoma multiforme, 1 year survival rate of Group I was recognized in 70% and 2 years in 36%, a little better than the other treatments. 2 year survival rate of other treatments demonstrated 17% in Group II, 25% in Group III, and 11% in Group IV. CT findings of glioblastoma multiforme in Group I showed no rest tumor in 4 cases and one case of CR, and 3 cases of PR in the follow up study of 10 cases with rest tumor on CT after operation. There were no permanent complications except for temporary mild neurological deficit in 7% of Group I improving within 2 to 3 days after intraarterial infusion of ACNU and 20% mannitol. It is suggested that chemotherapy of Group I by intraarterial infusion of ACNU and 20% mannitol demonstrated a little better therapeutic efficacy than the other Groups, at least within 2 years after operation.

Intra-arterial ACNU chemotherapy employing 20% mannitol osmotic blood-brain barrier disruption for malignant brain tumors.

The clinical effects and problems of intra-arterial water-soluble antitumor nitrosourea (ACNU) therapy following osmotic blood-brain barrier modification are discussed. Twenty-one patients with malignant brain tumors were divided into two groups. Group 1 consisted of 16 patients treated by operation, irradiation, and two or more courses of intracarotid infusion of ACNU 100 mg/body (1.7-2.2 mg/kg) following 20% mannitol 200 ml (1.3-1.6 ml/sec) (7 grade 4 astrocytomas, 5 grade 3 astrocytomas, and 4 others). Group 2 consisted of five patients treated by operation, irradiation, and repeated intracarotid infusion of ACNU 100 mg/body alone (grade 4 astrocytoma). The 2-year survival rate in Group 1 was 79% (11 of 14 cases followed up for longer than 2 years) and the 3-year survival rate was 67%. Five of seven grade 4 astrocytoma patients (71%) in Group 1 survived for more than 1 year 6 months, whereas four of five grade 4 astrocytoma in Group 2 died within 1 year 6 months. The measurement of the ACNU concentration in tumor tissues and blood in 11 brain tumors, after intracarotid infusion of ACNU with blood-brain barrier disruption, showed peak values in the tumor tissues of 3.02-32.53 micrograms/gm (mean, 9.67 micrograms/gm), about three to five times as high as that in blood in most cases. This method used in Group 1 appears to be relatively safe without permanent neurological deficits and offers a potential therapeutic effect when used in combination with appropriate premedication in suitable patients.

[MCNU delivery into malignant brain tumor and normal brain tissue by intravenous or intraarterial infusion].

In 13 Fischer 344 rats transplanted intracerebrally with 9 L gliosarcoma, 13 normal Fischer 344 rats and 4 clinical cases of malignant glioma, a new water-soluble nitrosourea (MCNU) was given and the concentration was measured in blood, tumor tissues, normal brains around the tumors and normal hemispheres by intravenous or intraarterial infusion of MCNU. At 5 min. after administration of MCNU 20 mg/kg (4-5 mg/body) in 9 L gliosarcoma bearing Fischer rats, mean MCNU concentration in the blood was not different between 20 micrograms/ml intravenous and 23 micrograms/ml intraarterial administrations whereas that in the tumor tissues by intracarotid infusion of MCNU was 40 +/- 14.4 micrograms/g which was about two times as much as 22.9 +/- 8.13 micrograms/g by intravenous infusion of MCNU. Mean MCNU concentration of normal brains around tumor tissues was 2.49 micrograms/g in intravenous and 8.95 micrograms/g in intracarotid infusion. MCNU concentration of tumor tissues in 4 cases of malignant gliomas was higher by intracarotid administration than by intravenous administration compared to that in the blood. Maximum tumor/blood ratio of MCNU was 1.94 in intracarotid administration for the malignant glioma. It is suggested that intraarterial administration was more useful than intravenous infusion as an administration route for malignant brain tumors.

[Diagnostic value of neuron specific enolase (NSE) in the cerebrospinal fluid of malignant brain tumor with intrathecal metastasis].

Neuron specific enolase (NSE) in the cerebrospinal fluid (CSF) and serum of 54 cases of brain tumors, in the tumor tissues of 10 brain tumors and in the cyst fluids of 7 brain tumors was measured by radioimmunoassay with NSE measurement kit (Eiken Chemistry co.) NSE values in the cerebrospinal fluid of 35 malignant brain tumors showed abnormal increase higher than 10 ng/ml in 17 cases (about 50%) of them, whereas all of benign cases were lower than 10 ng/ml. The means and standard deviations of NSE in the cerebrospinal fluid of malignant tumors were 20.63 +/- 20.78 ng/ml in the astrocytoma grade 3 and 4, 19.73 +/- 15.5 ng/ml in the medulloblastoma and 12.4 +/- 8.9 ng/ml in the germ cell tumor. NSE values in the CSF of 12 brain tumors with intrathecal metastasis were 28.0 +/- 18.9 ng/ml (mean +/- SD) showing about three times as much as those without intrathecal metastasis. There was significant difference between these groups (p less than 0.01). All cyst fluids including in 7 cases of brain tumors demonstrated high values of NSE even if they were benign tumor and their NSE values in CSF were normal. NSE values of brain tumor tissues had no correlation with malignancy, but were higher in the periphery of the tumors than in the center. NSE values of CSF in brain tumors might be changed in relation with the improvement or deterioration on clinical state and CT. It might be suggested that the measurement of NSE in the CSF had significance as a monitor of therapeutic efficacy and prognosis for the brain tumors.