The frequency and characteristic features of patients with metastatic brain tumors are summarized in this paper, which was mainly excerpted or re-estimated from the Brain Tumor Registry of Japan. Essence of this paper was as follows, 1)The number of cancer patients who may suffer from metastatic brain tumors was estimated as over 60,000 per year in Japan,calculated by using the data from National Surveillance study in 2000. 2)The recent frequency trend for metastatic brain tumors by primary site are : Increasing : lung cancer, rectal cancer, and renal cancer,Increasing but in small amount : hepatoma,Decreasing : breast cancer, uterus cancer. 3) Metastatic brain tumors with hemorrhagic tendency are : hepatoma, choriocarcinoma, renal cell carcinoma, and melanoma. 4) Frequency of meningeal carcinomatosis from solid cancers by site : Gastric cancer : 35-55%, lung cancer : 25-30%, breast cancer : 10-35%. 5) Cancer patients with metastatic brain tumors died mainly of uncontrolled metastates in other organs in about 70% of all metastatic brain tumors. 6) The prognosis for patients with metastatic brain tumors (2-year survival rates) : Relatively good : head and neck cancer/uterus cancer (40-45%), Fair : renal cell cancer/breast cancer (30%), poor : lung cancer/gastric or colo-intestinal cancer (15-20%)

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Stereotactic irradiation is widely applied for treating brain tumors, AVM and so on. Stereotactic irradiation therapy is divided into stereotactic radiosurgery (SRS) and Stereotactic radiotherapy (SRT). SRS is radiotherapy utilizing a large dose with a single fraction, and SRT is hypofractionated radiotherapy. The Gamma Knife, liniac surgery systems and CyberKnife are all used for SRS. The Gamma Knife contains 201 small Co-60 sources. A metal frame and helmet are used to fix the patient's head and to deliver the precise dose to the target. Patients are usually treated with multi-isocentric planning to obtain the correct homogenous dose distribution. The Gamma Knife can only be applied for use in the brain region, and not for the neck region because of the metal frame and helmet. Several defferent linac surgery systems are commercially available. Patients are usually fixed to a linac couch with a metal frame. Multiple arcs with small sized cones are usually used to obtain the proper spherical dose distribution. Multiple isocentric planning is applied for non-spherical targets. A micro-multileaf system is also used. It is easy to obtain an arbitrary field adjusted to the shape of the target using the micro-multileaf. Multiple non-coplanar beams are used for this micro-multileaf treatment. The CyberKnife is a linear accelerator mounted on an industrial robot. It contains a target locating system (TLS). If there is any movement of the patient during treatment, the CyberKnife evaluates the movement and the robot maintains its possition on the target. Because of the TLS, an invasive metal frame is not needed. Non-isocentric treatment can be performed with the CyberKnife, and the target can be treated with conformal shape planning. Stereotactic radiotherapy is also applicable for tumors in the body, especially of the lung and liver. There are several systems to adjust the movement of the tumor due to patient's respiration. A body frame is also commercially available. The FOCAL system is a combination of CT and liniac. The location of the tumor is evaluated with CT before treatment and liniac therapy is done on the same table as the CT. RTRT is a combination of fluoroscopy and liniac. Tumor is continuously monitored with fluoroscopy, and a linac X-ray beam is delivered when the tumor is inside the treatment area. The CyberKnife also can be applied for tumors in the body. A robot evaluates the tumor location and the robot according to the movement of the tumor. The linac X-ray beam can be delivered continuously. Every hospital must choose the best system according to the number of patients and distribution of the disease

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For the treatment of pituitary adenomas, transsphenoidal surgery is established as a first choice of treatment. However, pituitary adenomas are occasionally not curable by surgery alone, when they extend into the cavernous sinus or are found in the patients with poor physical conditions. Here we present our experience with stereotactic radiosurgery using a gamma knife in the treatment of 34 pituitary adenomas. There were 3 non-functioning adenomas and 31 functioning; 17 growth hormone (GH) and 14 adrenocorticotropic hormone (ACTH) adenomas. The mean radiation dose delivered to the tumor margin was 16 Gy and 32.1 Gy for non-functioning tumors and functioning tumors, respectively, while keeping the dose to the optic pathway below 10 Gy. With a median follow-up of 3 years, tumor growth control was achieved in all cases. In GH producing tumors, 8 of 16 evaluated cases were endocrinologically improved : serum GH<5 ng/ml, the insulin like growth factor-1 (IGF-1) <450 ng/ml, and the remaining 5 cases also showed a steady decrease of the GH and IGF-1 level. In ACTH producing tumors, 7 of 11 cases were endocrinologjcally normalized (<90/ig/day 24 hour-urinary free cortisol). One patient showed permanent hypopituitarism, and another one presented with abducens nerve palsy more than 5 years after radiosurgery. Gamma knife radiosurgery is a safe treatment modality for pituitary adenomas, with an effectiveness equivalent to conventional radiation therapy but with much less risk of radiation injury to the surrounding structures. Longer follow-up data with a further accumulation of cases is essential, but our experience reported here will contrbute to establish a radiosurgical protocol for these tumors.

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Our current strategy for the treatment of metastatic brain lesions is as follows ; 1) Lesions less than 3 cm in mean diameter, whether single or multiple (less than 4 lesions), are treated by radiosurgery. 2) Multiple lesions (5 or more lesions) are treated by whole brain radiation therapy (WBRT). 3) Large single lesions (3 cm or larger), if the lesion is surgically accessible, are treated by surgical resection in the case of patients with controlled systemic disease. After tumor resection, adjuvant therapy is performed by radiosurgery for the surrounding area of the brain after removal instead of WBRT. In addition to these cases, we have treated large cystic lesions using stereotactic aspiration and subsequent radiosurgery. Using this less invasive strategy, the control of brain metastases has improved for patients with a limited survival period.

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The core technology of advanced medicines provided us opportunities of gene therapy for cancer patients and there are a rapidly growing number of cancer gene therapies worldwide. For malignant brain tumors, a suicide gene therapy using herpes simplex virus thymidine kinase gene and ganciclovir was opened in USA in 1992. Recently, we made a gene therapy protocol of our own, which used cationic multilamellar liposomes entrapped with inter-feron-β(IFN-β)gene as a vector. In April 2000, we started clinical trial of IFN-βgene therapy for the patients with malignant glioma. Until now, 5 patients received the treatment and then they are under evaluation on safety and usefulness. Here we introduce history, present, and prospect of gene therapy for malignant brain tumors.

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The progression and rupture of atherosclerotic plaques appear to play key rotes in the pathogenesis of ischemic coronary heart disease and ischemic stroke in humans. Recent research has suggested the importance of oxidative modification of low density lipoprotein (LDL). Oxidized LDL elicits lipid accumulation, as well as proin-flammatory changes, in arterial walls. Interactions between oxidized LDL and its receptors, such as scavenger receptor class A (SR-A), CD36, lectin-like oxidized LDL receptor-1 (LOX-1), and scavenger receptor for phos phatidylserine and oxidized lipoprotein (SR-PSOX), appear to play important roles in this process. In addition, the HDL-mediated efflux of cholesterol acts as protection against the oxidized LDL-induced atherogenesis. On the other hand, restenosis after angioplasty or surgery may depend more upon smooth muscle proliferation and extra-cellular matri production.

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There are 2 important aspects in the medical treatment of carotid artery disease. One is antiatherosderotic and the other is antithrombotic therapy. Evidence from recent trials show that stroke risk is reduced by statins or ACE inhibitors. Aspirin is effective for the secondary prevention of ischemic stroke. However, there is no defini tive evidence that supports the use of anticoagulants in the treatment of noncardiogenic ischemic stroke.

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The effects of gamma radiosurgery on 106 out of 150 cases of skull base meningiomas which had been treated by gamma knife and followed-up for more than 3 years (mean of 48.2 months) have been evaluated. Overall results showed that partial resonse (PR) was found in 44 cases, minor response (MR) in 9, no change (NC) in 42 and progression (PG) in 11. Another words, response rate was 41.5%, control rate was 89,6% and progression rate was 10.4%. There found differences of the response among different locations; the response rate of C-P angle and CS-parasellar meningiomas showed higher than others, but control rate was higher in C-P angle and tentorial meningioma. Progression was found only in CS-parasellar and petroclival meningioma. The progression rate has changed from 0% at less than 3 years of follow-up, 10.4% at more than 3 years and 18.2% at more than 5 years. The factors related to the progression are the tumor size, the radiation dosis, the locations and the tumor pathology. Side effects were found in 4 cases (4.6 %)-that is radiation induced edema in one, hearing deterioration in two and visual deterioration in one case within 2 years of treatment.

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We report a case of delayed encephalocele that occurred 4 years after a head injury. A 22-year-old man was transported to our hospital because of a syncopal attack. He had a past history of head injury from a traffic accident 4 years before. At that time pneumocephalus was diagnosed by plain head CT and he had stayed at a hospital for a month till the pneumocephalus disappeared. On this admission, we found a craniodural defect at the posterior wall of the frontal sinus and brain tissue herniated into the frontal sinus. We removed the hemiated brain tissue by surgery and repaired the anterior skull base. It is thought that the craniodural defect at the skull base was formed by the pulsating leptomeningeal cyst and the frontal sinusitis. We often experience head injuries with pneumocephalus. Most of them are naturally healed with conservative therapy and require no further examination. Although it is extremely rare, posttraumatic encephalocele should be kept in mind when treating head injury patients with neumocephalus.

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