廣瀬 雄一

FLOW 800 is software for analytical colour visualisation and objective evaluation of fluorescence video obtained by microscope-integrated intraoperative indocyanine green fluorescence angiography. A 56-year-old male underwent surgical excision of a large complex arteriovenous malformation (AVM) of the right parietal region. FLOW 800 software was used to identify feeding arteries, arterialised veins and passing vessels. Complete excision of the AVM was achieved, confirmed by FLOW 800 and postoperative digital subtraction angiography. The role of FLOW 800, its applications and limitations in AVM surgery are discussed. (C) 2011 Elsevier Ltd. All rights reserved.

This study compared digital measurement of aneurysm volume by 3D rotational angiography (3D-RA) with an approximation technique using three diameters of an aneurysm to re-interpret previously reported optimal packing densities (volume embolization ratio, VER) in coil embolization of intracranial aneurysms. Estimation of the volume of saccular aneurysms is important for calculation of the V ER, which is in turn reported to be useful for prediction of coil compaction. The conventional formula for the volume estimation is V=4/3 pi(A/2) (B/2) (C/2), where A, B, and C are the aneurysmal height, length, and width measured on 3D-RA image respectively. Using 3D rotational angiography data from 74 aneurysms, the approximated volume generated using the conventional formula was directly compared with the digitally measured volume. The digitally measured volume varied from 0.003 ml to 7.935 ml, and the dome-to-neck ratio (D/N) from 0.79 up to 4.62. We found that the conventional formula almost systematically underestimated the volume by up to 50 %, particularly when the neck was large relative to the dome (D/N<2). On average, digitally measured volume was 1.26 similar to 1.29 times larger than the approximated volume obtained using the conventional formula. Conventional 2D angiography based aneurysm volume calculation tends to underestimate an aneurysm volume, so the so-called VER (volume embolization ratio) could be overestimated.

Rhabdoid tumor (RT) of the central nervous system is an uncommon and aggressive neoplasm that usually affects pediatric patients. Currently, these tumors are classified as malignant RT or atypical teratoid/RT. Another entity of intraparenchymal brain tumor with a rhabdoid component is the extremely rare rhabdoid glioblastoma. A 23-year-old woman presented with a malignant RT in the right thalamus. The tumor was adjacent to the right lateral ventricle and was partially resected. Histological examination revealed prominent proliferation of rhabdoid cells, which is consistent with a diagnosis of malignant RT; the typical features of glioblastoma were not observed. The tumor cells stained positively for integrase interactor-1 and glial fibrillary acidic protein. Therefore, the tumor may have originated from glial components. Genetic analysis using comparative genomic hybridization showed a deoxyribonucleic acid copy-number gain on chromosome 7 but not on chromosome 22. The tumor did not respond to chemotherapy or radiotherapy, and the patient survived for only 4 months after surgery. The present case of malignant RTs shows certain similarities with those of rhabdoid glioblastoma. Further accumulation and analysis of data, including data from genetic analyses, may lead to the identification of a new type of malignant RT.

The introduction of 320-row area detector CT (ADCT) has led to a new era in CT. ADCT should not be thought of as conventional CT scanning with a larger number of detector rows. Since the overall width of the detector is greatly expanded, the brain can be scanned in a single rotation. This makes it possible to perform non-contrast CT scanning in a single rotation. ADCT also permits volume data to be acquired along the temporal axis by continuous scanning (4D data). Since scanning can be completed in a single rotation, sedation is not required even in patients who may be difficult to examine, such as pediatric patients and patients with impaired consciousness. Scanning can also be completed in approximately 1 second in routine 3D-CTA studies, permitting the amount of contrast medium to be reduced. In addition, volume data from the arterial phase to the venous phase (4D data) can be acquired by sequential scanning (continuous or intermittent scanning). In particular, since ADCT is superior to DSA in terms of tissue contrast, especially in the venous phase, visualization is improved and three-dimensional assessment can be performed more easily. In addition, ECG-gated continuous volume scanning allows an extensive range from the head through the carotid arteries to the heart (coronary arteries) to be examined in a single scan. Given the strong association between carotid artery stenosis and coronary artery stenosis, the ability to assess both in a single study is of great clinical value. ADCT also supports 160-row helical scanning, which permits the range from the head to the inguinal region to be scanned in approximately 6 seconds. Moreover, since ADCT allows the arteries of the entire body to be examined with no increase in the amount of contrast medium, the range from the location where the sheath is to be introduced to the lesion can be confirmed before neuroendovascular therapy. As discussed above, ADCT has many advantages. However, ADCT studies can generate a huge number of reconstructed images, sometimes reaching several thousand. It is impossible to interpret all of these images individually. In addition, sequential scanning is associated with higher X-ray exposure. It is therefore essential to select the ideal scanning method for the clinical objective, to set the optimal exposure dose, and to perform reconstruction and analysis appropriately.

61歳男。運転中に突然のめまい感を自覚し持続したため近医を受診した。脳梗塞の診断で抗血小板薬を内服し軽快したが、退院後2ヵ月に同様のめまいを自覚したため紹介入院となった。MRI拡散強調像で右小脳半球と左後頭葉領域に高信号を認め、3次元CT撮像で、右内頸動脈から分岐し、脳底動脈を形成する遺残動脈を認めた。遺残動脈は舌下神経管を通過し脳底動脈に合流しており、Persistent primitive hypoglossal artery(PPHA)と考えられた。両側椎骨動脈は低形成でPPHA分岐部近傍に高度狭窄を認め、多発性閉塞症を生じたと判断した。小径のバルーンカテーテルでPTAを施行したが拡張が得られず、径を大きくして再PTAを行ったが、短時間でrecoilを認めたためステントを留置後に拡張を行った。術後CTで良好な拡張と内腔の開存を確認し、MRIで塞栓症は認めず経過良好で退院し、6ヵ月後のDSA、CTでも再狭窄は認めていない。

Although brain metastases are one of the most frequently diagnosed sequelae of systemic malignancy, their optimal management still is not well defined. In that respect, the different diagnostic and therapeutic approaches of BMs patients is an issue for serious discussions. The treatment options include surgical excision, WBRT, radiosurgery, chemotherapy, immunotherapy, etc. Nowadays, the aforementioned treatment modalities are usually combined in different treatment schemes. More than one option is used for the same patient and combining these treatment modalities gives better results than when separately use them. The value of surgical excision of progressing brain metastases treated with gamma knife surgery (GKS) is not well investigated.With the present study, we aim to investigate the value of surgical excision of symptomatic brain lesions that have been previously treated with GKS.

37歳女。Ehlers-Danlos症候群の遺伝子診断中に突然の左耳鳴が出現した。頭部MRI、MRA上CCFを指摘され紹介受診した。3DCTAを施行し左ICA近傍からのdirectCCFを確認した。頸動静脈の間欠的用手圧迫による保存的療法にて症状は一時的に改善するも、再び増悪した。頭蓋内への著明なcortical refluxに伴う高次機能障害出現のため、全身麻酔下にSOVからのアプローチにて経静脈的塞栓術を施行した。術後失語、耳鳴は2週間ほどで完全に消失し、mRS0にて退院した。術後の評価はMRDSAにて行い、増悪は認めていない。

【目的】近赤外線スペクトロスコピー（NIRS）による術中モニタリング下で急性期にcarotid artery stenting（CAS）を施行した頚部頚動脈狭窄症による脳梗塞の１例を報告する．【症例】右片麻痺および失語にて発症した76歳男性．頭部CTでは明らかな虚血性変化を認めなかったが，CT潅流画像では左中大脳動脈領域に広範囲にpenumbra領域を認めた．3D-CTAでは左内頚動脈起始部に高度狭窄を認めた．治療前はNIRSにて局所酸素飽和度の著明な左右差を認めた．前拡張後，ステントを留置した．ステント留置直後に左側の局所酸素飽和度が10%上昇したため，後拡張は施行せず手技を終了した．術後経過は順調であった．【結論】急性期CASではNIRSの所見が術中の拡張手技のdecision makingに有用である．

Despite recent advances in various therapeutic modalities for treating malignant gliomas, these tumors are still hardly curable, and the development of the new therapies is warranted in the field of chemotherapy and radiotherapy. In this context, many therapeutic compounds have been investigated, and, especially, drug treatment using molecular targeting compounds has attracted considerable attention amongst neuro-oncologists. Since previous studies have elucidated that malignant gliomas show an up-regulation of various growth factor receptor-related activities, many clinical studies using compounds targeting those receptors have been conducted. However, the development of effective molecular targeting therapy for malignant gliomas is limited by a relative lack of understanding of the biology of glioma cells. Thus, laboratory investigation including an animal tumor model is indispensible in designing a better therapeutic approach for these tumors. On the other hand, genetic analysis of gliomas has led to the discovery of prognostic markers. Recent clinical studies focusing on genetic markers has revealed the importance of the methylation status of the O6-methylguanine-DNA methyltransferase promoter and mutational status of isocitrate dehydrogenase 1 as prognostic factors of gliomas, leading to the idea that genetic analysis could help in selecting cases with a favorable treatment response and, possibly, individualization of the treatment. In this text, recent advances in glioma biology are reviewed to help better understand the problems and future prospects in the treatment of these tumors.

OBJECTIVE AND BACKGROUND: We evaluated the feasibility and effectiveness of transsphenoidal surgery for large and giant pituitary adenomas with suprasellar extensions as these tumors have been therapeutic challenge. SUBJECTS AND METHODS: We retrospectively analyzed 50 cases with 56 surgeries in patients with pituitary adenomas that were surgically treated between January 2005 and January 2010 at Fujita Health University. Among those cases, 39 cases were large or giant pituitary adenomas including 11 cases of giant adenomas. RESULTS: 37 cases 41 approaches were transsphenoidal, 2 approaches were transcranial, and in 1 case transcranial approach following transsphenoidal surgery was performed. The most frequent preoperative symptoms were visual impairment and visual field defect (28 cases, 75.6%), and improvement of visual function after surgery was observed in 18 cases, 64%. As endocrinological results, among the 11 cases of functioning adenomas, improvement of endocrinological examination was observed in 10 cases, and normalization of the hormonal examination and complete remission was seen in 7 cases which was 64%. CONCLUSIONS: Transsphenoidal approach is safe and effective procedure even in large or giant pituitary adenomas, because it allows rapid and appropriate decompression of the optic nerves and chiasm with low morbidity rates. Transcranial approaches were indicated only in irregular shaped adenomas or eccentric extensions that could not be reached through the transsphenoidal route.

Supratentorial primitive neuroectodermal tumors (sPNET) occurring in adults are rare. Only 56 such cases have been previously reported. This report documents a 56-year-old male who presented with the chief complaint of right facial palsy. Magnetic resonance imaging (MRI) revealed left frontal and bilateral periventricular lesions. Surgery was performed for the frontal mass, which was histologically diagnosed to be sPNET. An immunohistochemistry assay for CD99, and a fluorescence in situ hybridization (FISH) assay for t(11;22) translocation revealed this PNET to be a central PNET. This case was the first case to detect a central PNET using both immunohistochemistry and the FISH assay in adult sPNET. Though radiation therapy was performed, an MRI performed 2.5 months after the surgery revealed a regrowth of the tumor. The patient died 5 months after surgery. This case report is accompanied by a review of 57 cases of adult sPNET.

OLIG2 is a basic helix-loop-helix transcription factor regulating the generation of oligodendrocytes from neural progenitor cells, and the function of OLIG2 is inhibited posttranslationally through the interaction with ID2. This study aims to examine if the analysis of OLIG2 and ID2 expression in glioma tissues helps the differential diagnosis of chemosensitive oligodendroglial tumors from astrocytic tumors. Expression levels of OLIG2 and ID2 in 11 oligodendroglial and 27 astrocytic tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR, and immunohistochemistry. The mean expression level of OLIG2 was higher in oligodendroglial tumors than astrocytic tumors, but some astrocytic tumors showed high OLIG2 expression, indicating that OLIG2 cannot be an independent marker of oligodendroglial tumors. No significant difference was observed between ID2 expression in oligodendroglial tumors and astrocytic tumors. It was notable that OLIG2 expression was predominant over ID2 expression in oligodendroglial tumors, while ID2 expression was predominant over OLIG2 expression in astrocytic tumors. Comparative genomic hybridization revealed that gliomas with loss on chromosome 1p, which is closely associated with chemosensitivity, also showed the predominant expression of OLIG2 over ID2. These results indicate that the immunohistochemical study on the relative expression level of OLIG2 to ID2 can be a useful screening for oligodendroglial tumors.

The authors describe the case of a patient with a glioblastoma multiforme who showed remarkably good response to chemotherapy. A genetic analysis using comparative genomic hybridization (CGH) revealed that the tumor had a gain on the q arm of chromosome 1 (1q). Using CGH for a series of genetic analyses of more than 180 patients with gliomas, six were found to have a demonstrated 1q gain. Although the tumors in all six of these cases were histopathologically diagnosed as high-grade gliomas, compared with other malignant gliomas they demonstrated a good prognosis because of their favorable chemotherapeutic sensitivity. In immunohistochemical tests, most of the tumor cells in these cases were negative for O-6-methylguanine-DNA methyltransferase, which antagonizes the effect of DNA-alkylating chemotherapeutic agents. The authors believed that a gain of 1q could be produced through the genetic events that cause loss of 1p, because these chromosomal aberrations have an imbalance of DNA copy number in common (1p < 1q). A gain of 1q is an infrequent chromosomal aberration and its clinical importance should be investigated in a larger study; however, patients with malignant gliomas demonstrating a 1q gain possibly show longer survival and good response to chemotherapy similar to patients with tumors demonstrating 1p loss. The importance of using genetic analysis for gliomas is emphasized in this report because it may help in selecting cases responsive to chemotherapy and because appropriate treatment for these patients will lead to progress in the treatment of malignant gliomas.

Although second-generation replication-conditional herpes simplex virus type 1 (HSV-1) vectors defective for both ribonucleotide reductase (RR) and the virulence factor gamma(1)34.5 have been proven safe through a number of animal experiments and clinical trials, their therapeutic efficacy was also markedly reduced. To overcome this situation, we concentrated on the use of a tumor-specific promoter in this study, to express ICP34.5 selectively in malignant glioma cells. As a molecular marker for malignant glioma, we focused on the neural RNA-binding protein, Musashi1. On the basis of the results of defective vector dvM345, as reported previously, we created, via homologous recombination, a novel HSV-1 vector termed KeM34.5, which expresses ICP34.5 under the transcriptional control of the musashi1 gene promoter (P/musashi1). Cytotoxicity mediated by KeM34.5 was significantly enhanced in human glioma cell lines (U87MG, U87MG-E6, U251, and T98G), resulting in an approximately 2-log increase in viral yield, compared with its parental vector G207. This virus also showed much higher therapeutic efficacy in the in vivo glioma model, while maintaining the desirable neuroattenuated phenotype. These results suggest that oncolytic HSV-1 expressing ICP34.5 under the transcriptional control of the musashil gene promoter could be a promising therapeutic agent for the treatment of malignant glioma.

Gliomas are the most common primary brain tumor, and are histopathologically classified according to their cell type and the degree of malignancy. However, sometimes diagnosis can be controversial, and tumors of the same entity possibly have a wide range of survival. Genetic analysis of these tumors is considered to have great importance in terms that it can provide clinically relevant classification of the tumors and compensate for the limitation of the histological classification. Previous studies using comparative genomic hybridization (CGH) demonstrated that copy number aberrations (CNAs) were frequently recognized in these tumors, and revealed that a gain on chromosomal arm 7q was the most common CNA in diffuse astrocytomas, whereas a small population of the tumor showed losses on 1p/19q which characterizes oligodendrogliomas with good responsiveness to chemotherapeutic regime using procarbazine, nitrosourea and vincristine. High grade (malignant) gliomas (i.e. anaplastic astrocytomas, anaplastic oligodendrogliomas and glioblastomas) have been reported to have a gain on 7p and losses on 9p and 10q. In case of ependymomas, frequent chromosomal aberrations in intracranial tumors were a gain on 1q and losses on 6q, and, on the other hand, a gain on chromosome 7 was recognized almost exclusively in spinal cord tumors. These data suggest that intracranial and spinal cord ependymomas are different genetic diseases and comprise different subgroups within one histological entity. In conclusion, genetic analysis of gliomas may help to classify these tumors and provide leads concerning their initiation and progression. The relationship of these aberrations to patient outcome needs to be addressed.

Pharmacologic inhibition of the DNA signal transducers Chk1 and p38 blocks G(2) arrest and sensitizes glioblastoma cells to chemotherapeutic methylating agent-induced cytotoxicity. Because Akt pathway activation has been suggested to also block G(2) arrest induced by DNA-damaging agents and because glioma cells frequently have high levels of Akt activation, we examined the contribution of the Akt pathway to methylating agent-induced G(2) arrest and toxicity. U87MG human glioma cells containing an inducible Akt expression construct were incubated with inducing agent or vehicle, after which the cells were exposed to temozolomide and assayed for activation of the components of the G(2) arrest pathway and survival. Temozolomide-treated control cells activated the DNA damage signal transducers Chk1, Chk2, and p38, leading to Cdc25C and Cdc2 inactivation, prolonged G(2) arrest, and loss of clonagenicity by a combination of senescence and mitotic catastrophe. Temozolomide-treated cells induced to overexpress Akt, however, exhibited significantly less drug-induced Cdc25C/Cdc2 inactivation and less G(2) arrest. Akt-mediated suppression of G(2) arrest was associated not with alterations in Chk1 or p38 activation but rather with suppression of Chk2 activation and reduced recruitment of Chk2 to sites of damage in chromatin. Unlike bypass of the G(2) checkpoint induced by pharmacologic inhibitors of Chk1 or p38, however, Akt-induced bypass of G(2) arrest suppressed, rather than enhanced, temozolomide-induced senescence and mitotic catastrophe. These results show that whereas Akt activation suppresses temozolomide-induced Chk2 activation and G(2) arrest, the overriding effect is protection from temozolomide-induced cytotoxicity. The Akt pathway therefore represents a new target for the sensitization of gliomas to chemotherapeutic methylating agents such as temozolomide.