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Kazunari Yoshida, Shigeo Toya, Mitsuhiro Ohtani, Shunichi Okui, Nobuo Takenaka and Kenichi Harigaya

✓ A case of pineal germ-cell tumor producing human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) is reported in a 23-year-old man. Extraneural metastasis developed during a course of combined chemotherapy after radiation therapy. Postmortem examination revealed that the metastatic pulmonary tumor was a choriocarcinoma, producing only HCG.

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Kazunari Yoshida and Takeshi Kawase

Object. Since 1974, 27 patients with trigeminal neurinomas (TNs) have been treated at Keio University Hospital and ancillary institutes. In the present study the clinical features and developmental patterns of these 27 cases are analyzed, and the clinical features of 402 cases reported in the literature are reviewed. Based on the analysis of the developmental patterns of the TNs, the surgical strategy for a one-stage removal of TNs involving multiple fossae is described.

Methods. Trigeminal neurinomas are classified into six types according to tumor location. Types M, P, and E are tumors involving a single compartment, that is, the middle fossa, posterior fossa, or extracranial space, respectively. Types MP (middle and posterior fossae), ME (middle fossa and extracranial space), or MPE (middle and posterior fossae and extracranial space) are tumors involving multiple compartments. Advances in neuroimaging technologies, such as magnetic resonance imaging, have revealed a high incidence of TNs extending into multiple fossae, namely 36.2% in cases reported since 1983 and 59% in the authors' series. All but one of the most recent 19 patients in this series underwent skull base surgery, whereas the remaining nine patients were surgically treated via the conventional subdural approach. The rate of total tumor removal and the clinical outcome were significantly better in those patients treated by skull base surgery than those treated by conventional surgery.

Conclusions. The TNs extending into multiple fossae can be totally removed using the following single-stage surgical techniques: Type MP by the anterior transpetrosal approach; Type ME by the zygomatic or orbitozygomatic infratemporal approach; and Type MPE by the zygomatic transpetrosal approach. In 12 of 13 cases involving multiple fossae in this series, total tumor removal was achieved using single-stage skull base surgery.

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Shigeo Ohba, Kazunari Yoshida, Yuichi Hirose, Eiji Ikeda, Yoichi Nakazato and Takeshi Kawase

This 32-year-old woman, 27 weeks pregnant, harbored a cystic mass with a solid component in the left frontal lobe. Histologically, the lesion was hypercellular and contained a diffuse sheet of eosinophilic cells of various sizes. The cells were almost round and had a few prominent, eccentrically placed, hyperchromatic nuclei of various sizes. Immunohistochemically, the tumor was reactive for vimentin, epithelial membrane antigen, cytokeratin AE1/AE3, smooth muscle actin, and BAF47/INI-1, and negative for glial fibrillary acidic protein, neurofilament protein, S100 protein, CK7, CK20, HMB-45, MIC2, and Bcl-2. The Ki 67 labeling index was 4.2%. Comparative genomic hybridization analysis revealed aberrations of the chromosomal copy number of +7 and −10. This tumor could not be categorized according to the present World Health Organization classification. Results of staining with glial fibrillary acidic protein were not consistent with a glioma, and staining with INI-1 was inconsistent with atypical teratoid/rhabdoid tumor. The tumor was therefore designated as a “cerebral tumor with extensive rhabdoid features.”

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Kazuhide Adachi, Takeshi Kawase, Kazunari Yoshida, Takahito Yazaki and Satoshi Onozuka

Object

Surgery for skull base meningiomas (SBMs) can lead to complications because these lesions are difficult to approach and can involve cranial nerves and arteries. The authors propose a scoring system to evaluate the relative risks and benefits of surgical treatment of SBMs.

Methods

The authors used a 2-step process to construct their scale. First, they derived significant predictive variables from retrospective data on 132 SBM cases treated surgically (primary surgeries only) between May 2000 and December 2005. Next, they validated the predictive accuracy of their scoring system in 60 consecutive cases treated surgically between January 1995 and April 2000, including both primary and repeated surgeries. Finally, they investigated the effect of the surgery on the patients' preoperative symptoms for consecutive cases treated surgically between January 1995 and December 2005, including both primary surgeries and retreatments.

Results

Five items that predicted surgical risk were identified: 1) tumor attachment size; 2) arterial involvement; 3) brainstem contact; 4) central cavity location; and 5) cranial nerve group involvement. The authors named their scoring system the ABC Surgical Risk Scale, after the initial letters of these items. Each factor was assigned a score of 0–2 points, and an additional point was added for previous surgical treatment or for radiation, giving a possible total score of 12 points. On average, the scoring system allocated 2 points for gross-total resections, 6.1 points for near-total resections, and 9 points for subtotal resections, with significant differences between groups. For cases scoring ≥ 8 points, the percentage of cases showing neurological deterioration postoperatively exceeded the percentage showing improvement.

Conclusions

The authors conclude that this scoring system can be used to predict the extent of tumor removal and that the scores reflect the surgical risk.

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Raita Fukaya, Kazunari Yoshida, Takenori Akiyama and Takeshi Kawase

The origin of moyamoya disease remains unknown. The onset of the angiographically apparent changes of typical moyamoya disease occurs in childhood, but de novo development of the disease has not been confirmed angiographically. The authors report on a case of de novo development of moyamoya disease in a middle-aged female whose cerebral angiography demonstrated no abnormal findings 5 years previously. To the best of the authors' knowledge, this case is the first reported instance of de novo development of definite moyamoya disease verified angiographically. This case demonstrates that the de novo development of moyamoya disease in a middle-aged adult did in fact occur, and angiographically visible features of the disease took < 5 years to complete.

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Shigeo Ohba, Yuichi Hirose, Kazunari Yoshida, Takahito Yazaki and Takeshi Kawase

Object

The introduction of temozolomide (TMZ) has advanced chemotherapy for malignant gliomas. A considerable number of glioblastoma cases are refractory to TMZ, however, and the development of novel chemotherapeutic regimens is needed. The authors of previous studies have revealed that hsp90 is expressed at higher levels in human neoplastic tissues, including gliomas, than in normal tissues. Heat shock protein 90 is involved in a cytoprotective mechanism against cellular stressors such as DNA damage, and the authors hypothesized that hsp90 inhibitors might act as antitumor agents against gliomas and potentiate the cytotoxicity of DNA-damaging agents.

Methods

The authors examined the cytotoxicity of an hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), both alone and in combination with 1 of 3 DNA-damaging agents (cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea, and TMZ) in human glioma cell lines. The cytotoxicity of these agents to glioma cells was measured using a colony formation assay. The cell cycle phase distribution, protein expression, and number of apoptotic cells were measured using a fluorescence-activated cell sorting assay, immunoblot assays, and double staining with annexin V and propidium iodide. In an in vivo experiment, 17-AAG, cisplatin, or 17-AAG and cisplatin were administered intraperitoneally to mice with xenografted U87MG cells, and the resulting tumor volumes were measured.

Results

The authors found that 17-AAG reduced the clonogenicity of U87MG cells, and at a low concentration (< 100 nM) potentiated the cytotoxicity of the DNA-crosslinking agents cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea, but not that of the DNA-methylating agent TMZ. This 17-AAG–induced potentiation of DNA crosslinking agent–induced cytotoxicity was a consequence of prolonged G2-M arrest accompanied by the suppression of cdc2 and cdc25C and of increased apoptotic cell death accompanied by the degradation of the antiapoptosis proteins Akt and survivin. Similar effects were observed when cells were treated with radicicol, another hsp90 inhibitor. The 17-AAG–induced enhancement of DNA crosslinking agent–induced cytotoxicity was also observed in other cell lines. In addition, 17-AAG sensitized xenografted U87MG cells to cisplatin in nude mice.

Conclusions

Heat shock protein 90–targeted therapy may be an effective strategy for potentiating chemotherapy using DNA-crosslinking agents for TMZ-refractory gliomas.

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Shigeo Ohba, Masahito Kobayashi, Takashi Horiguchi, Satoshi Onozuka, Kazunari Yoshida, Takayuki Ohira and Takeshi Kawase

Object

Although gross-total resection (GTR) is a preferable treatment for skull base meningiomas, subtotal resection (STR) with or without radiation therapy can be considered as an alternative treatment for patients at considerable surgical risk. The long-term prognosis of such patients might be related to the biological activity of the tumor. This study examined predictors of progression-free survival (PFS) and sought to determine the optimal treatment strategies, focusing on the pathobiological findings of skull base meningiomas.

Methods

This study included 281 patients with skull base meningiomas (mean follow-up period 88.4 months). Risk factors for tumor progression were examined using a multivariate analysis. The PFS and overall survival (OS) rates were evaluated using the Kaplan-Meier method. The functional outcomes of the patients were measured using the Karnofsky Performance Scale (KPS).

Results

The 10-year PFS and OS rates were 66.4% and 97.4%, respectively. Overall, 83.3% of patients achieved a favorable outcome, that is, an improved or unchanged KPS score. The extent of resection, additional radiotherapy, histological grade, MIB-1 index, and p53-positive rate were significantly associated with PFS. The PFS of patients undergoing STR without radiation therapy was significantly shorter than that of either those undergoing STR with radiation therapy or GTR, while no statistical difference was observed between the latter 2 groups. Among the patients undergoing STR with pathobiological risk factors (histological grade, MIB-1 index, and p53-positive rate), the PFS of the patients who received radiation therapy was better than that of those who did not receive radiation therapy. Among the patients undergoing STR without such risk factors, the PFS was not significantly different between patients who received radiation therapy and those who did not.

Conclusions

For patients with skull base meningiomas, a GTR is desirable and additional radiation therapy after STR may contribute to a longer PFS. Additional radiation therapy should be recommended, especially for patients with pathobiological risk factors, but not necessarily for those without such risks.

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Yohei Kitamura, Takenori Akiyama, Hikaru Sasaki, Yuichiro Hayashi and Kazunari Yoshida

Meningiomas rarely cause CSF dissemination, and CSF seeding to the optic nerve (ON) is extremely rare. This is the first report of 2 cases of atypical meningioma with subacute visual loss due to ON seeding. The authors present the genetic characteristics of these atypical meningiomas with CSF dissemination. The patient in Case 1 was a 36-year-old woman with a 1.5-cm mass within the left ON, and the patient in Case 2 was a 70-year-old woman with a 0.9-cm mass around the right ON. Both individuals had undergone multiple surgeries for primary lesions and local recurrent lesions. They presented with subacute visual loss, and both tumors were completely resected. The pathological diagnosis was atypical meningioma with high MIB-1 indices and p53-positive cell ratios in each case. Comparative genomic hybridization showed significant chromosomal copy number alterations similar to the results of previous surgeries, confirming that the tumors were disseminated lesions. The present findings suggest that genetic characteristics, such as 1p and 10qcen-23 losses and 17q and 20 gains, shared by the 2 cases might be associated with CSF dissemination of meningiomas.

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Ryosuke Tomio, Masahiro Toda, Kazunari Yoshida and Hamid Borghei-Razavi

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Ryosuke Tomio, Masahiro Toda, Agung Budi Sutiono, Takashi Horiguchi, Sadakazu Aiso and Kazunari Yoshida

OBJECT

Extended endoscopic transnasal surgeries for skull base lesions have recently been performed. Some expert surgeons have attempted to remove tumors such as chordomas, meningiomas, and pituitary adenomas in the clival region using the transnasal approach and have reported abducens nerve injury as a common complication. There have been many microsurgical anatomical studies of the abducens nerve, but none of these studies has described an anatomical landmark of the abducens nerve in the transnasal approach. In this study the authors used cadaver dissections to describe Grüber's ligament as the most reliable landmark of the abducens nerve in the transnasal transclival view.

METHODS

The petroclival segment of the abducens nerve was dissected in the interdural space—which is also called Dorello's canal, the petroclival venous gulf, or the sphenopetroclival venous confluence—using the transnasal approach in 20 specimens obtained from 10 adult cadaveric heads.

RESULTS

The petroclival segment of the abducens nerve clearly crossed and attached to Grüber's ligament in the interdural space, as noted in the transnasal view. The average length of the dural porus to the intersection on the abducens nerve was 5.2 ± 1.0 mm. The length of the posterior clinoid process (PCP) to the intersection on Grüber's ligament was 6.4 ± 2.6 mm. The average width of Grüber's ligament at the midsection was 1.6 ± 0.5 mm.

CONCLUSIONS

Grüber's ligament is considered a useful landmark, and it is visible in most adults. Thus, surgeons can find the abducens nerve safely by visualizing inferolaterally along Grüber's ligament from the PCP.