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Masakazu Takayasu, Masahito Hara, Katsuaki Yamauchi, Mitsuhiro Yoshida and Jun Yoshida

✓ Although atlantoaxial transarticular screw fixation is technically demanding and there is a significant risk of vertebral artery (VA) injury, transarticular screw insertion in the middle and lower cervical spine is simple and can be performed safely with the aid of lateral fluoroscopic guidance. The authors describe the surgical techniques and outcome of transarticular screw fixation in the middle and lower cervical spine.

Transarticular screw insertion into C2–3 or caudal cervical joints was performed from the articular pillar, directing the screw anterocaudally to penetrate the facet joint and the anterior cortex of the articular pillar, parallel to the sagittal plane. Because the VA and the nerve roots are anterior to the articular pillar at these levels, the screw can be placed safely with the assistance of lateral fluoroscopic guidance. Twenty-five patients ranging in age from 15 to 84 years underwent transarticular screw fixation, with a total of 81 screws. The transarticular screw was used as an anchor screw in combination with posterior cervical instrumentation in 19 patients and for facet screw fixation itself in six patients. Screw placement was successful and uncomplicated in all cases. The follow-up period ranged from 3 months to 5 years. No instance of screw backout or loosening was identified radiographically; fusion was achieved in all patients. Biomechanical strength is maintained by penetrating four cortical layers. When performed appropriately, this method is safe and reliable and deserves more widespread use.

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Goro Otsuka, Kiyoshi Saito, Tazuka Yoshida, Yoshio Suzuki and Jun Yoshida

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Goro Otsuka, Kiyoshi Saito, Tetsuya Nagatani and Jun Yoshida

Object. Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2.

Methods. From among 283 patients with neurofibromatosis who had been registered in a nationwide study in Japan between 1986 and 1987, 74 patients with bilateral vestibular schwannomas were analyzed. The mean duration of follow up after diagnosis was 121 months (range 2–287 months). Results of a Kaplan—Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. Patients with small vestibular schwannomas at diagnosis (< 2 cm in diameter) had better rates of survival. Other variables such as sex, additional tumors in the CNS, or dermal abnormalities did not significantly affect survival.

Conclusions. This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

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Symptomatic Rathke's cleft cyst

Morphological study with light and electron microscopy and tissue culture

Jun Yoshida, Tatsuya Kobayashi, Naoki Kageyama and Masaki Kanzaki

✓ A rare case is reported in which a symptomatic Rathke's cleft cyst was studied by light and electron microscopy and tissue culture. The findings are compared with those of a craniopharyngioma studied in the same way. The patient was a 26-year-old woman presenting with headache, chiasmatic syndrome, and hypopituitarism. A cyst containing a mural nodule was partially removed and an Ommaya reservoir placed in the operative site for further treatment. The cyst wall was composed of connective tissue and three kinds of epithelial cells: non-ciliated squamous, ciliated columnar, and mucous-secreting cells. The morphology of these cells in vitro was similar to prickle cells seen in craniopharyngioma and the epidermis. It is concluded that both Rathke's left cyst and craniopharyngioma originate in remnants of Rathke's pouch, but at times may show some histological differences.

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Masaaki Mizuno, Jun Yoshida, Toru Takaoka and Kenichiro Sugita

✓ The authors evaluated the effect of liposomal transfection of human γ-interferon (HuIFN-γ) gene into human glioma cells and lymphokine-activated killer (LAK) cells, alone and in combination. An HuIFN-γ; gene inserted in a eukaryotic expression vector was entrapped in liposomes bearing positive surface charges. Liposomal gene transfection induced production of HuIFN-γ and its secretion in culture medium of human glioma cell lines (SK-MG-1 and U-251 MG). At 4 days after transfection, the cells produced 10 to 50 U/ml of HuIFN-γ in the medium, whereby the major histocompatibility complex (MHC) class I and II antigens, as well as intercellular adhesion molecule-1 (ICAM-1), were induced on the glioma cell surface. The growth-inhibiting effect of transfection-induced HuIFN-γ; was much stronger in comparison with control cultures exposed to 500 U/ml of exogenously added HuIFN-γ;. In addition, 20% to 40% growth inhibition was obtained in the glioma cells when they were treated with LAK cells alone at a 5:1 ratio of effector to target cells. Liposomal transfection of HulFN-γ; gene into human glioma cells combined with immunotherapy using LAK cells was more effective than either technique alone. The reinforcement of growth inhibition in the case of combined therapy was quenched by anti-ICAM-I monoclonal antibody, but not by anti-MHC class I or II monoclonal antibodies. These results suggest that the combined effect of liposomal transfection of HuIFN-γ; gene plus LAK cells into human glioma cells is a potentially useful therapy for malignant glioma, and that the mechanisms of the reinforcement of growth inhibition are closely related to the expression of ICAM-I on the glioma cell surface.

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Eiji Tachibana, Kiyoshi Saito, Keizo Fukuta and Jun Yoshida

Object. This study was undertaken to investigate the healing process and to delineate factors important for the survival of free fascial grafts used for dural repair.

Methods. A dural defect was created in guinea pigs and then reconstructed using either a free fascial graft or an expanded polytetrafluoroethylene (ePTFE) sheet. The fascial graft was covered directly by subcutaneous tissue (Group I) or by a silicone sheet to prevent tissue ingrowth from the subcutaneous tissue (Group II). The ePTFE sheet was covered with a silicone sheet (Group III). One or 2 weeks postoperatively, the strength of the dural repair was evaluated by determining the pressure at which cerebrospinal fluid (CSF) leaked through the wound margins. The dural repair was also histologically examined. In addition, using a rat model, specimens obtained from similar reconstruction sites were immunohistochemically stained with antibodies against basic fibroblast growth factor (bFGF), epidermal growth factor, or transforming growth factor—β.

The pressures at which CSF leaked after 1 and 2 weeks, respectively, were 50 ± 14 mm Hg and 126 ± 20 mm Hg in Group I, 70 ± 16 mm Hg and 101 ± 38 mm Hg in Group II, and 0 mm Hg and 8 ± 8 mm Hg in Group III. Failure of repairs made in Group III occurred at significantly lower pressures when compared with Groups I and II. In Groups I and II, a thick fibrous tissue formed around the fascial graft. This tissue tightly adhered to adjacent dura mater. The fibrous tissue displayed a positive reaction for the presence of bFGF. In Group III, only a thin fibrous membrane surrounded the ePTFE sheet.

Conclusions. Fascial grafts tolerated extraordinary intracranial pressures at 1 week postoperatively. Free fascial grafts can heal with durable fibrous tissue without the presence of a blood supply from an overlying vascularized flap.

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Takashi Tashiro, Jun Yoshida, Masaaki Mizuno and Kenichiro Sugita

✓ Lymphokine-activated killer (LAK) cells generated from peripheral blood lymphocytes incubated with recombinant interleukin-2 were transfected with the human tumor necrosis factor (TNF)-α gene by means of novel liposomes with a positive change on their surface. The cells secreted significant amounts of TNF-α into the culture medium and exhibited reinforcement of cytotoxicity toward a human glioma cell line (U251-SP), being three times more cytotoxic than nontransfected LAK cells. The mechanism for the reinforcement of cytotoxicity is considered to involve not only an increase in TNF-α secretion from LAK cells but also its expression on their surface. Intratumoral or intrathecal injection of LAK cells transfected with the TNF-α gene may be useful for the treatment of patients with malignant gliomas.

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Manabu Hatano, Masaaki Mizuno and Jun Yoshida

Object. Many human glioma cells are resistant to ceramide. In this study the authors investigated the mechanisms of that resistance and considered ways to overcome it.

Methods. The authors first administered C2-ceramide (N-acetylsphingosine) to human glioma cells from rare cell lines susceptible to C2-ceramide (SKMG1 and U87MG) and other cell lines resistant to it (U251SP, T98G, SKAO2, and U251MG). Following this, the authors analyzed the statuses of transduction signals such as cell viability, morphological changes, caspases, mitochondrial membrane potential, apoptosis-inducing factor, oligonucleosomal DNA fragmentation, and the inhibitor of apoptosis protein (IAP) family.

Conclusions. Ceramide resistance was found to arise from the inhibition of caspase-7 induced by IAPs, especially X chromosome—linked IAP (XIAP). Small interfering RNA (siRNA) on XIAP quenched that resistance in ceramide-resistant human glioma cells (U251SP, T98G, SKAO2, U251MG), indicating that a siRNA for XIAP may be a useful tool for overcoming the resistance to ceramide in human glioma cells.

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Kiyoshi Saito, Keizo Fukuta, Masakatsu Takahashi, Yukio Seki and Jun Yoshida

✓ The authors report two patients with benign fibroosseous lesions involving the center of the skull base: a 15-year-old boy with repetitive meningitis and pneumocephalus and a 11-year-old boy with nasal obstruction and headache. The clinical diagnoses were ossifying fibroma and aneurysmal bone cyst, respectively. Lesions in both patients extended to the nasal cavity, the sphenoid and posterior ethmoid sinuses, and the skull base, where the planum sphenoidale, the sella turcica, the upper two-thirds of the clivus, and the medial portion of the middle cranial base were involved. The lesions were totally removed using an anterior craniofacial approach. Characteristics of these lesions and the surgical approach are discussed.

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Yoshihisa Kida, Tatsuya Kobayashi, Jun Yoshida, Kyouzou Kato and Naoki Kageyama

✓ Therapeutic results in 17 cases of alpha-fetoprotein (AFP)-secreting tumors of the central nervous system are reported. Twelve of the patients were male and five female. The patients' ages ranged from 5 years to 25 years (mean 13.6 years). The tumors originated in the pineal region in 10 cases, in the suprasellar region in four cases, and in both regions in one case; of the other two tumors, one originated in the basal ganglia and one in the sacrococcygeal region. Extraneural metastases or subarachnoid dissemination occurred in seven cases. Increased AFP titer in the serum or cerebrospinal fluid was verified in 13 cases. The patients were divided into two groups: those treated before (Group A) and those treated after (Group B) the introduction in 1980 of cisplatin as a chemotherapeutic agent. All seven Group A patients died, even after extensive therapy consisting of surgery, radiotherapy, and chemotherapy (ACNU or adriamycin) in some of the cases. The mean survival time following diagnosis for Group A was 23.7 months. Six of the 10 Group B patients died an average of 25.8 months after diagnosis; however, the other four were still alive and well an average of 25.3 months after diagnosis. The tumors responded well to chemotherapy consisting of cisplatin either alone or combined with bleomycin and vinblastine. The initial response rate to treatment in Group B was 100% and five cases had a complete remission, verified by computerized tomography or the serum AFP level. Once the tumor recurred, the response to cisplatin was markedly decreased. It is suggested that an effective therapy must still be sought for recurrent tumors.