Makoto Hishii

Human Glioma-derived Interleukin-10 Inhibits Antitumor Immune Responses In Vitro

Intracranial malignant gliomas are sequestered from the immune system yet are associated with broad suppression of host immunocompetence. Immune system dysfunction in patients with gliomas seems to be related to inhibitory mediators produced by glioma cells. We investigated the physiological roles of glioma-derived interleukin (IL)-10 in Class II expression of monocytes, cytokine secretion from lymphocytes, and T cell proliferation in vitro. We could detect the messenger ribonucleic acid transcript of IL-10 in four gliomas by the reverse-transcribed polymerase chain reaction. Glioma-derived IL-10 greatly down-regulated human lymphocyte antigens-DR expression on monocytes. The inhibitory effect of IL-10 on interferon-gamma and tumor necrosis factor-alpha was neutralized by the anti-IL-10 monoclonal antibody; however, the inhibitory effect on IL-2 was not neutralized. Next, supernatants of glioma cells remarkably suppressed T cell proliferation in a dose-dependent fashion; however, this inhibitory effect was not restored by adding anti-IL-10 monoclonal antibodies. The supernatant also inhibited the allocytolytic activity of lymphocytes that were not neutralized by anti-IL-10 monoclonal antibody. IL-10 plays an important role in cytokine synthesis; nevertheless, impaired T cell responsiveness cannot be solely explained by glioma-derived IL-10.

Selective expression of interleukin-10 gene within glioblastoma multiforme

Little information exists regarding which glioma cells are able to escape immune system detection and progress within the host. In order to elucidate some of the mediators which facilitate the growth and spread of glioma cells, the expression of cytokines, TNF-alpha, IL-6, gamma-IFN, IL-10, and GM-CSF, within 12 human glioma specimens was investigated by the polymerase chain reaction. The twelve patients with malignant glioma were categorized into a localized (n = 4) and an invasive glioma (n = 8) groups, mostly glioblastoma multiforme, based upon the CT and MRI scans. We examined the correlation between specific cytokine gene expression and the clinical category of each patient. The results showed that while IL-10 mRNA transcripts were expressed in most of the tumors from the invasive glioma group (7/8), they were not expressed in tumors from the localized group. On the other hand, gamma-IFN gene expression was more frequent in tumors from the localized group (3/4 vs 1/8 from the invasive group). The mRNA transcripts of IL-6 and GM-CSF were more frequently expressed in tumors from the localized group. No consistent pattern was seen in TNF-alpha gene expression between the two groups. Among the five cytokines studied, IL-10 mRNA was selectively expressed within invasive gliomas compared to less malignant, localized glioma group. Our results demonstrate specific cytokine mRNA profiles in glioma patients, which might have prognostic significance for immunotherapy.

Transcranial transsphenoidal approach for tuberculum sellae meningiomas.

Summary Objective. A series of 21 patients with tuberculum sellae meningioma who received surgical treatment is reported. Patients and Methods. All 9 females and 12 males (mean age 49 years) presented visual disturbances of varying degrees in either one or both eyes. Eighteen of the tumours were less than 3 cm in size, and 3 were larger. Tumour resection of uniform surgical technique was performed in all cases. Following a bicoronal scalp incision, bifrontal craniotomy combined with removal of the orbital rim bilaterally was performed. The frontal dura was opened bilaterally, and the most anterior portion of the superior sagittal sinus was transected. Bifrontal retraction and arachnoid dissection along the proximal olfactory tracts brought the tumour into view. Additional dissection of the interhemispheric fissure extended the operative field to the anterior communicating artery. The anterior skull base was drilled out to resect the basal part of the tumour. In all cases, the optic canal and sphenoid sinus, and additionally in some cases the ethmoid sinus were opened. The tumour uniformly extended inferomedially to the optic nerve, and direct visualization of this portion of the tumour was possible with our approach. The opened paranasal sinuses were reconstructed with adipose tissue harvested from the patients abdomen and the pericranial flap. Results. In all patients, total or almost total resection of the tumour was accomplished. Postoperatively, visual function was improved in 11 patients, was unchanged in 8, and worsened in 2. There were no operative deaths. Cerebrospinal fluid leakage was occurred in two patients but could be conservatively managed. In a mean 3-year follow-up, tumour recurrence was observed in only one patient who presented a malignant histology. Conclusions. We are confident that our surgical approach has great clinical value in surgical resection of tuberculum sellae meningioma. The good accessibility to a tumour extending inferomedially to the optic nerve should, in particular, be stressed.

Surgical Experience of 120 Patients with Lumbosacral Lipomas

Summary.The surgical experience of 120 patients with lumbosacral lipomas is described. 47 of 120 patients were preoperatively found to be neurologically intact, the remaining 73 patients presented with various neurological signs including reflex changes, sensory disturbances, muscle weakness and sphincter problems. Neuro-imagings allowed a classification of lumbosacral lipomas into five types: (1) dorsal type; (2) caudal type; (3) combined type; (4) filar type; and (5) lipomyelomeningocele. Although all 120 patients underwent untethering of the spinal cord, the nerve roots passing through the lipoma itself and the neural tissues protruding externally to the spinal canal, respectively, tended to prevent satisfactory surgical removal of the lipoma in combined type lipomas and lipomyelomeningoceles. During 8.96 years of a mean postoperative follow-up period, there was no significant deterioration in most of the patients and some patients even improved in function. However, two patients with combined type lipomas developed neurological deterioration just after surgery, and five (two dorsal, two caudal and one combined type lipomas) did in the fashion of a late-onset. There are two different patient groups of lumbosacral lipomas; one group (caudal and filar type lipomas, and most of dorsal type lipomas) in whom the surgical anatomy is simple and satisfactory untethering surgery could be done without risk, and another (combined type lipomas and lipomyelomeningocele) in whom surgery would be accompanied with some risk and sometimes complete untethering could not be achieved because of the complicated anatomy of the lesion. Surgical difficulty of the latter group can be correlated with the increased frequency of neurological deterioration occurring just after the operation, but not of delayed one. Concerning prophylactic surgery for asymptomatic patients, the former group of patients are obviously good candidates, but the latter group is not.

Sensitization of human glioblastomas to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by NF-κB inhibitors

Glioblastoma is the most malignant form of primary brain tumor in adults, with no effective therapy and a low survival rate. TRAIL is a member of the TNF family, which selectively induces apoptosis in certain neoplastic cells, but not normal cells. In this study, we investigated the sensitivity of 7 human glioblastoma cell lines to TRAIL and the expression in them of TRAIL receptors. TRAIL exhibited significant cytotoxicity in 5 of 7 glioma cell lines. These glioblastoma cell lines expressed TRAIL‐R2, but not TRAIL‐R1, R3, or R4. However, no correlation was observed between the TRAIL sensitivity and the TRAIL‐R2 expression level, suggesting that there is an additional determinant of TRAIL sensitivity. Treatments with NF‐κB inhibitors, such as LLnL, MG132, and SN50, significantly increased the sensitivity of glioma cells to TRAIL. These results suggested that activation of NF‐κB is a protective mechanism against TRAIL‐induced cell death in some glioma cells, and thus NF‐κB inhibitors may be useful to improve the clinical treatment of glioblastoma with TRAIL.

Successful transarterial glue embolisation by wedged technique for a tentorial dural arteriovenous fistula presenting with a conjunctival injection

Abstract Many tentorial dural arteriovenous fistulae (TDAVF) present with intracranial haemorrhage. We report a patient who presented with conjunctival injection. Transarterial embolisation of the TDAVF was undertaken with a wedged injection of a low concentration of N-butyl cyanoacrylate, arresting the flow next to the proximal segment of the venous outlet. After three sessions, a complete cure was achieved. We present a useful method which has not been reported previously.

Endodermal cyst of the quadrigeminal cistern: case report

BACKGROUND Endodermal cysts usually develop in the subdural space in the anterior spinal cord and rarely occur inside the cranium. Most intracranial endodermal cysts develop in the posterior fossa. We report the first case of an endodermal cyst in the quadrigeminal cistern. CASE DESCRIPTION The patient was a 71-year-old man who suffered from gait disturbance for 6 months. Although head computed tomography (CT) scanning 4 years previously did not show any cystic lesion, CT and magnetic resonance imaging (MRI) on admission showed a cystic lesion extending from the quadrigeminal cistern to the right ambient cistern. The cyst was subtotally removed via a suboccipital transtentorial approach. The cyst wall consisted of a layer of columnar epithelium and connective tissue. Based on the results of immunostaining, it was diagnosed as an endodermal cyst. CONCLUSIONS It is possible that the increase of secretion from the cells lining the cyst may have caused a difference in osmotic pressure between the cerebrospinal fluid and the cyst contents, leading to rapid enlargement of the cyst. An endodermal cyst should be removed as completely as possible because its cells have the ability to grow and produce secretions.

Early experience with poly L-lactic acid bioabsorbable fixation system for paediatric craniosynostosis surgery. Report of 3 cases.

Summary¶ Objective. The authors describe early experience in the use of bioabsorbable fixation devices for cranial reconstruction of paediatric craniosynostosis patients. Methods. Three patients, individually respectively presenting sagittal synostosis, metopic synostosis, and clover leaf skull deformity, underwent cranial reconstruction using poly L-lactic acid (PLLA) plates and screws. The patients ranged in age from 2 to 10 months at the time of surgery. The postoperative clinical follow-up ranged from 16 to 18 months. All patients showed satisfactory wound healing without signs of infection or local inflammation. The plates provided satisfactory fixation and were not palpable through the skin after 16 to 18 postoperative months. Conclusion. Our experience demonstrated the efficacy of PLLA bioabsorbable plates and screws for cranial reconstruction in cases of infant craniosynostosis. Prospective studies and longer follow-up of a larger number of patients is desirable for confirmation of these findings.

A case of neonatal cerebellar abscess

Case reportA 1-month-old boy presented with repeated vomiting without signs of infection and was eventually found to have staphylococcal cerebellar abscess. The initial diagnosis was hypertrophic pyloric stenosis.ResultHe was successfully treated by drainage surgery combined with intravenous antibiotic therapy.ConclusionsNeonatal brain abscess, particularly cerebellar abscess, is seldom encountered, but may cause disability in later years even after successful treatment. Early diagnosis and appropriate treatment are mandatory for these patients.

Surgical management of comatose patients with cerebellar infarction

A series of 20 patients with cerebellar infarction were classified into four groups based on the clinical and CT findings. Two comatose patients who developed acute hydrocephalus (Group 2) are presented and were successfully treated with external ventricular drainage (EVD) alone. Continuous post-operative monitoring of intracranial pressure (ICP) demonstrated that EVD had sufficiently controlled ICP and therefore suboccipital decompression of the cerebellum was not indicated even though the patients were not immediately responsive to EVD. Both patients made a gradual recovery: a 57-year-old woman, independently ambulatory, was discharged to her home and a 76-year-old woman, ambulatory with assistance, was discharged to a rehabilitation hospital. The results of our two cases suggest that EVD should be the first treatment in cases of cerebellar infarction with cerebellar swelling or oedema accompanied by hydrocephalus. Posterior fossa decompression and removal of infarcted cerebellar tissue should be indicated only in cases where ICP can not be controlled by EVD, even if there is no immediate recovery of the patients impaired consciousness. Reviewing the literature pertinent to our two cases, the use of ventricular drainage alone in the management of cerebellar infarction with ischaemic cerebellar swelling is discussed.