A lateral ventricular gliosarcoma arising in an ependymoma.

OBJECTIVE: We describe a 29-year-old man with gliosarcoma in the lateral ventricle. CASE: The patient presented with headache and impairment of consciousness. Computed tomography and magnetic resonance imaging localized the tumor to the right lateral ventricle and showed heterogeneous enhancement with administration of contrast agents. The tumor was partially removed via a transcallosal approach. Histologic examination disclosed gliosarcoma arising by malignant transformation of an ependymoma. POST-OPERATIVE COURSE: The patient died of tumor progression 78 days after admission, despite intensive radiotherapy and chemotherapy.

Primary Ki-1 lymphoma in the central nervous system.

Large cell anaplastic malignant lymphoma with Ki-1 (CD30) antigen is a new entity among human non-Hodgkin's malignant lymphomas according Updated Kiel Classification and is also a very rare subtype in primary central nervous system (CNS) malignant lymphomas. The precise clinical characteristics and the significance of Ki-1 antigen have yet to be clarified. The authors herein report a case of Ki-1 positive primary T-cell CNS malignant lymphoma. A 49-year-old man presented with multiple mass lesions in the brain on MRI. Immunohistochemical investigations of biopsy specimens from the superior medullary velum revealed a large cell anaplastic T-cell lymphoma positive for Ki-1 antigen. After administering extensive chemo-radiotherapy, the patient has survived for more than 42 months after the onset of symptoms.

Vascular endothelial growth factor in chronic subdural haematomas.

OBJECTIVE: To elucidate molecular aspects of the mechanisms of expansion of chronic subdural haematomas (CSH), we examined the expression of two representative angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in CSH. METHODS: We quantified VEGF and bFGF in haematoma fluid and serum of 20 patients with CSH using an enzyme-linked immunosorbent assay. Mean concentrations of VEGF in the haematoma fluid (10277 pg/ml) and in serum, (355 pg/ml) were much greater than those of bFGF (haematoma, 3.04 pg/ml; serum, 4.74 pg/ml). Surgical specimens, including dura and the outer membrane of the CSH were analysed by in situ hybridisation to detect VEGF mRNA. Macrophages and vascular endothelial cells in the outer membrane over expressed VEGF mRNA. CONCLUSIONS: Enhanced production of VEGF by macrophages and vascular endothelial cells in the outer membrane is thought to be pathogenetically important in CSH.

Efficacy of single-bolus vs. frequent low-dose treatment with nitrosourea in experimental gliomas.

BACKGROUND: Malignant glioma remains a fatal disease. Continuous or frequent low-dose (FLD) chemotherapy with nitrosoureas reportedly causes fewer side-effects than single-bolus therapy without decreasing the antitumour effects. MATERIALS AND METHODS: To study the effect of FLD treatment with nimustine (ACNU) in rats with glioma, we intracerebrally inoculated with C6 glioma cells. We began the ACNU treatment 5 or 8 days later (total dose, 25 or 40 mg/kg) i.p. as either one bolus or smaller doses spread over 5 days week. RESULTS: At a total dose of 25 mg/kg beginning at day 8, survival duration did not differ between untreated controls and the FLD group, while the bolus significantly prolonged survival; the FLD group showed some improvement beyond control survival at 40 mg/kg (each p <0.001). Beginning treatment after 5 rather than 8 days prolonged survival somewhat further. CONCLUSION: FLD treatment with ACNU is less effective against experimental glioma in rats than bolus treatment.

[A case showing effective radiotherapy for a radiation-induced glioblastoma].

Radiation-induced glioblastoma is usually resistant to all treatments. We report a case with radiation-induced glioblastoma, in which radiotherapy was remarkably effective. A 14-year-old female with a history of acute lymphoblastic leukemia, at the age of 7, underwent 15 Gy of radiotherapy to the whole brain. She was admitted to our department due to the development of headache and nausea. Magnetic resonance imaging showed an irregularly enhanced mass in the left frontal lobe. Partial removal of the mass was performed and histological examination showed it to be glioblastoma with a high MIB-1 index. The patient underwent 40 Gy of local radiotherapy and chemotherapy with ACNU and Interferon-beta for 2 years. The residual tumor disappeared after the radiotherapy, and her status is still "complete remission", 29 months after the onset.

[Acute hepatitis B virus after chemotherapy for a case with germinoma].

A 28-year old man with HCG-producing germinoma had undergone chemotherapy and radiotherapy. On admission for the fifth session of maintenance chemotherapy, he was found to be positive for hepatitis B (HB)s antigen, but negative for HBs antibody. HBs antigen had been negative during previous admissions. Since liver function was normal, the patient underwent chemotherapy. During myelosuppression after chemotherapy, liver dysfunction developed and acute HB was diagnosed. He fortunately showed seroconversion 2 months after onset. Serum immunological examinations are required for patients receiving chemotherapy.

[Educational level of patients with germ cell tumor radiated in childhood].

In order to estimate the influence of radiotherapy on the intellectual development of children with brain tumor, we investigated the educational level of 21 patients with germ cell tumor who had undergone radiotherapy. They were divided into three groups in accordance with their age at the time of radiation; under school age group (under 6 years of age), elementary school age group (from 7 to 12 years of age), and junior high and high school age group (from 13 to 18 years of age). There were 2 cases in the under school age group, one of them graduated from high school and the other is presently a junior high school student. There were 5 cases in the elementary school age group. 3 of these graduated from university, 1 is presently a university student and 1 is a high school student. There were 14 cases in the junior high and high school age group. 2 of these are university students, 7 graduated from high school, 1 is presently a junior high school student, and 4 died because of tumor progression. The mean period of hospitalization of the patients who have been admitted to university was 63.0 days, and that of patients who have not been admitted university was 135 days. There is a statistical difference (p < 0.05). It could be concluded that the period of hospitalization rather than radiotherapy seemed to influence the educational status of children with brain tumor.

Transcerebellomedullary fissure approach with special reference to methods of dissecting the fissure.

OBJECT: The purpose of the present study was to refine the transcerebellomedullary fissure approach to the fourth ventricle and to clarify the optimal method of dissecting the fissure to obtain an appropriate operative view without splitting the inferior vermis. METHODS: The authors studied the microsurgical anatomy by using formalin-fixed specimens to determine the most appropriate method of dissecting the cerebellomedullary fissure. While dissecting the spaces around the tonsils and making incisions in the ventricle roof, the procedures used to expose each ventricle wall were studied. Based on their findings, the authors adopted the best approach for use in 19 cases of fourth ventricle tumor. The fissure was further separated into two slit spaces on each side: namely the uvulotonsillar and medullotonsillar spaces. The floor of the fissure was composed of the tela choroidea, inferior medullary velum, and lateral recess, which form the ventricle roof. In this approach, the authors first dissected the spaces around the tonsils and then incised the taenia with or without the posterior margin of the lateral recess. These precise dissections allowed for easy retraction of the tonsil(s) and uvula and provided a sufficient view of the ventricle wall such that the deep aqueductal region and the lateral region around the lateral recess could be seen without splitting the vermis. The dissecting method could be divided into three different types, including extensive (aqueduct), lateral wall, and lateral recess, depending on the location of the ventricle wall and the extent of surgical exposure required. CONCLUSIONS: When the fissure is appropriately and completely opened, the approach provides a sufficient operative view without splitting the vermis. Two key principles of this opening method are sufficient dissection of the spaces around the tonsil(s) and an incision of the appropriate portions of the ventricle roof. The taenia(e) with or without the posterior margin of the lateral recess(es) should be incised.

Involvement of the multidrug resistance protein 3 in drug sensitivity and its expression in human glioma.

The multidrug resistance protein (MRP) family belongs to the ATP-binding cassette superfamily (ABC) of transporters, which are involved in ATP-dependent transport of hydrophobic compounds. One of the MRP family, MRP1, is partially associated with the multidrug resistance phenotype in brain tumors. In this study, we asked whether another MRP family gene, MRP3, could affect drug sensitivity to anticancer agents in human glioma cell lines and clinical glioma specimens. We first produced two antisense transfectants by introduction of antisense MRP3 cDNA into the glioma cell line NHG2, which endogenously expresses MRP3. The two MRP3 antisense transfectants showed 2- to 5-fold increases in drug sensitivity to etoposide and cisplatin compared with NHG2 cells, but their sensitivity to vincristine or nitrosourea was not changed. Two MRP3 cDNA sense transfectants of pig kidney cell lines showed 4- to 6-fold drug resistance to etoposide, but only 1.4- to 1.5-fold to cisplatin. We next compared the mRNA levels of four ABC transporters, multidrug resistance 1 (MDR1), MRP1, MRP2 and MRP3 in clinical samples, including 34 patients with gliomas, by quantitative RT-PCR analysis. In some of the clinical samples, increased expression of MRP1 and MRP3 was apparent in malignant gliomas. In situ hybridization revealed that glioma cells were stained with MRP3 probe. MRP3 may modulate drug sensitivity to certain anticancer agents in human gliomas.

[Clinical trial of bradykinin-enhancing chemotherapy for a recurrent malignant glioma: a case report].

Patients with malignant glioma undergo a combined treatment with surgical resection, radiotherapy, and chemotherapy. Although those treatments usually show some restraining effects on the tumor, a relapse occurs in most of the patients within a few years. We have investigated the feasibility and safety of intra-arterial chemotherapy for malignant brain tumors by enhancing vascular permeability using intra-arterial bradykinin infusion. In 2001, The Committee of Ethics in Kyushu University approved our clinical trial of the bradykinin-enhancing chemotherapy for recurrent malignant gliomas. We here report the first case of our clinical trial. A 31-year-old man, who had undergone surgical resection followed by chemotherapy and irradiation for malignant progression of the left frontal astrocytoma over a period of 2 years, had a relapse of the tumor in the bilateral frontal lobes. After obtaining informed consent, bradykinin and carboplatin were infused through a microcatheter at the left A1 portion under general anesthesia. By dose escalation of bradykinin, the enhanced lesion in the bilateral frontal lobes diminished on magnetic resonance imaging after 3 trials with 3-week intervals, regardless of new lesions outside of the treated area. No neurological or physiological complication including myelosuppression was noted. Bradykinin-enhancing chemotherapy appeared to be effective and safe for malignant glioma. Because it was able to increase drug delivery to the tumor, it was possible to reduce the size of the dose of chemotherapeutic agent, which resulted in minimum complication.

Different responses of benign and atypical meningiomas to gamma-knife radiosurgery: report of two cases with immunohistochemical analysis.

Recent reports have shown that gamma-knife radiosurgery provides a safe and effective strategy for the management of brain tumors. To evaluate the role of stereotactic radiosurgery in the management of meningiomas, we investigated the histopathology of two patients. The patients, a 37-year-old man and a 54-year-old woman, presented with visual field disturbance or headache. Imaging studies demonstrated intracranial meningiomas--tentorial and sphenoid ridge, respectively. Each patient undewent subtotal surgical resection (more than 90% in both patients), followed by gamma-knife radiosurgery of the remnant tumor marginal doses of 15 Gy. Pathological examination of the original tumors revealed a meningothelial meningioma and an atypical meningioma, respectively. Enlargement of the remnant tumors 4 months after radiosurgery resulted in total surgical resection in both patients. Thirteen months later, the patient with the atypical meningioma underwent a third operation for early recurrence of the tumor. Histopathology was investigated, and MIB-1, p53, and bcl-2 labeling indexes (LI) were analyzed immunohistochemically. Histopathologically, the specimens showed necrosis and intratumoral vessel obliteration after radiosurgery in both cases. However, more remnant tumor cells survived in the atypical meningioma. Immunohistochemically, increased wild-type p53, decreased bcl-2 expression, and decreased MIB-1 LI were observed in the benign meningioma. In the atypical meningioma, on the contrary, MIB-1 LI was decreased and mutant-type p53 and bcl-2 expression were unchanged. The specimen from the third operation revealed an anaplastic meningioma, and MIB-1 LI was markedly increased. These findings suggest that the efficacy of radiosurgery may differ between benign and atypical meningiomas.

The specific expression of three novel splice variant forms of human metalloprotease-like disintegrin-like cysteine-rich protein 2 gene inBrain tissues and gliomas.

We have previously identified 67 exons on a yeast artificial chromosome contig spanning 1.5 Mb around the multidrug resistance 1 gene region of human chromosome 7q21.1. In this study, we identified three novel cytoplasmic variants (MDC2-gamma, MDC2-delta, and MDC2-epsilon) of the human metalloprotease-like disintegrin-like cysteine-rich protein 2 (MDC2) among these exons by screening a human brain cDNA library and also by using a reverse transcription polymerase chain reaction. Genomic sequence analysis strongly supported the idea that the variations in the cytoplasmic domain were generated by alternative splicing. The expression of MDC2 variant forms in human brain tissue and gliomas was examined by reverse transcription polymerase chain reaction and RNase protection assay. MDC2-epsilon was expressed only in the cortical and hippocampal regions in human brain, but not in gliomas. In contrast, MDC2-gamma was a major form expressed in human gliomas. Specific expression of these cytoplasmic variants of MDC2 in human brain and its malignancies is discussed.

Ultrasonic surgical system (SONOPET) for microsurgical removal of brain tumors.

We use the ultrasonic surgical system in the treatment of brain tumors such as meningioma, neurinoma, glioma, etc. SONOPET is a useful and safe ultrasonic surgical system for microsurgery. The outer diameter of the tip of ultrasonic surgical systems is usually 2.5 mm and the inner diameter 2.0 mm. However, the outer diameter of the SONOPET is 1.9 mm and the inner diameter 1.5 mm. Even in a deep site, because of the small diameter tip, the operation can be done easily. Further, the very thin outer diameter of the tip flue, 5 mm, makes it easy to operate in the deep site. The maximum amplitude of the distal end tip, which can be an important factor in tissue fragmentation, is 240 microns. It is said that the thinner tip breaks down easily, but by reducing metal fatigue the lifetime of the tip is longer and a larger amplitude can be obtained. As a result, hard tissue fragmentation becomes available even with a thinner tip. The handpiece is very light in weight, approximately 110 g, helping to reduce operator fatigue when in long term use. The weight is approximately one-half of conventional types. Because of the high efficiency of the electricity/vibration energy conversion rate, the handpiece does not heat up during the operation. Also, since water cooling is not necessary, the procedures before and after use are simple. Changing the handpiece during the operation is also easy.

Rational approach to treatment of moyamoya disease in childhood.

Early diagnosis and treatment of moyamoya disease in children is essential to minimize residual mental and physiologic deficits. Current treatment of childhood moyamoya disease in Japan, preoperative evaluation of perfusion reserve as a surgical indication, and the role of noninvasive follow-up by magnetic resonance angiography are reported. Approximately 20% of children with definite moyamoya disease were observed or treated medically. Among surgical procedures, single indirect bypass surgery was used in approximately 30% of all patients; combinations of direct and indirect bypass surgery, 20%; and multiple-indirect bypass surgery, 18%. Both adequate understanding of the primary condition and determination of optimal treatment, including specific operative procedures, required evaluation of cerebral circulation and metabolism. Surgical indications included reduced perfusion reserve in affected brain by positron emission tomography or single photon emission tomography with administration of acetazolamide or a CO2 load. Postoperative improvements of cerebral perfusion reserve show better correlation with disappearance of ischemic attacks than does angiographically demonstrated collateral formation. Follow-up evaluation with magnetic resonance angiography has advantages over conventional angiography because it is noninvasive and avoids general anesthesia.

Origin and evolution of the Department of Neurosurgery, Neurological Institute, Faculty of Medicine, Kyushu University.

The Department of Neurosurgery at Kyushu University had its origins within the First Department of Surgery and was established as a subspecialty at the Neurological Institute more than 30 years ago under the leadership of Katsutoshi Kitamura. Further development of the neurosurgical department has proceeded during the chairmanship of Masashi Fukui. These leaders and many other dedicated physicians and surgeons, nurses, investigators from other countries, and staff members have contributed to the creation of a research-oriented neurosurgical environment that interacts fruitfully with the other components of the Neurological Institute. This article describes the development of neurosurgery within Kyushu, which has been a highly cosmopolitan area throughout its long history. More specifically, this account outlines the origin and growth of the Department of Neurosurgery at Kyushu University.

A comparative study of apoptosis and proliferation in germinoma and glioblastoma.

Intracranial germinoma has a relatively good prognosis when treated with radiotherapy and chemotherapy, whereas glioblastoma has a poor prognosis irrespective of these treatments. Cell proliferation and cell death are opposing processes in tumor growth, with tumor progression reflecting the balance between proliferating and apoptotic cells. We investigated cell proliferation and cell death using MIB-1 staining and nick-end labeling in 13 germinomas in comparison with 11 glioblastomas. Expression of BAX and Bcl-2, which regulate apoptosis, were studied by immunohistochemistry. Although germinomas showed strong MIB-1 immunostaining similar to that seen in glioblastomas, germinomas included significantly more apoptotic cells. The ratio of apoptotic ratio to MIB-1 labeling index for germinomas was 72.9 +/- 36.9 (mean +/- SD), a higher, statistically significant ratio as compared with glioblastomas (14.5 +/- 11.2; P < 0.01). Furthermore, germinomas showed greater expression of BAX than did glioblastomas, while the expression of Bcl-2 was weak in both tumor types. A comparison of these apoptotic-related proteins showed that immunoreactivity for BAX was relatively higher in germinomas than in glioblastomas (P < 0.01), corresponding well to numerous apoptotic cells identified in germinoma tissues. These findings may account for the prognostic difference between germinoma and glioblastoma in the face of a similar proliferation potential according to MIB-1 immunostaining. The balance between cell proliferation and death should be considered when predicting outcomes in patients with intracranial tumors.

[A case of effective urgent irradiation therapy for metastatic spine tumor].

A 74-year-old man noticed weakness in bilateral lower limbs 2 months prior to admission. The weakness had rapidly progressed and he could not stand by himself on admission. All thoracic vertebral bodies showed mosaic pattern on T 2 weighted-image. At Th 10 and Th 11, two enhanced masses compressed spinal cord posteriorly. Basal-serum tumor markers, such as LDH, ALP, total-acid phosphatase and prostatic acid phosphatase were elevated, metastatic spine tumor from prostatic carcinoma was suspected. Biopsy specimen from its prostate revealed low differentiated adenocarcinoma. Because sphincter dysfunction progressed rapidly after admission, we started 3 Gy/day irradiation within 24 hr from its appearance targeting both Th 10 to L 1 vertebral bodies and the prostate in total 30 Gy. The clinical symptoms started to resolve immediately, and the disappearance completely within 7 months. This case illustrated that urgent irradiation was effective for broad metastatic spinal tumor with rapidly progressive neurological deficits.

Linkage of familial moyamoya disease (spontaneous occlusion of the circle of Willis) to chromosome 17q25.

BACKGROUND AND PURPOSE: Moyamoya disease is a cerebrovascular disease of unknown cause that mainly affects Japanese children. The incidence of familial occurrence accounts for 9% of cases. The characteristic lesions of moyamoya disease are occasionally seen in neurofibromatosis type 1, of which the causative gene (NF1) has been assigned to chromosome 17q11.2. METHODS: To determine whether a gene related to moyamoya disease is located on chromosome 17, we conducted microsatellite linkage analyses on 24 families containing 56 patients with moyamoya disease. Leukocyte DNA extracted from the family members was subjected to polymerase chain reaction for a total of 22 microsatellite markers on chromosome 17. The amplified polymerase chain reaction fragments were analyzed with GeneScan on an automated sequencer. RESULTS: Two-point linkage analysis gave a maximum log(10) odds (LOD) score of 3.11 at the recombination fraction of 0.00 for the marker at locus D17S939. The affected pedigree member method also showed a significantly low P value (<1. 0x10(-5)) for the 5 adjacent markers at 17q25. Multipoint linkage analysis also indicated that the disease gene is contained within the 9-cM region of D17S785 to D17S836, with a maximum LOD score of 4. 58. CONCLUSIONS: A gene for familial moyamoya disease is located on chromosome 17q25.

Effect of intracarotid bradykinin infusion on cerebral blood flow in dogs.

We examined whether intracarotid infusion of bradykinin altered circulation in the normal canine brain. Twenty-four anesthetized dogs were divided into four groups receiving different doses of bradykinin (1, 2.5, 5, and 10 micrograms kg-1 min-1). Regional cerebral blood flow (rCBF) was measured continuously using laser Doppler flowmetry through a burr hole in the frontal bone. Systemic blood pressure (SBP) and heart rate (HR) were monitored simultaneously. Higher doses of bradykinin significantly but temporarily decreased rCBF and SBP immediately after the start of infusion; these parameters rapidly recovered and then were stable through the rest of the infusion. During this period, percent change in rCBF and SBP was small, and differences between groups were not significant. On the other hand, HR increased during infusion and remained high. SBP, rCBF, and HR returned to pre-infusion levels after bradykinin was stopped. The results suggest that intracarotid infusion of bradykinin for treatment of brain tumors would be safe in terms of circulation to the uninvolved brain.