Occipital transtentorial approach and combined treatments for pineal parenchymal tumors.

The deep-seated location of pineal parenchymal tumors (PPTs) and their associations with critical structures make their surgical resection technically challenging; further, the rarity of PPTs and repeated changes in their histopathological diagnostic criteria makes the study of their biological behavior and clinical outcomes difficult. Here, we describe the surgical techniques and results of an occipital transtentorial approach for PPTs together with the results in the clinicopathological study of PPTs. Since 1982, we have treated 93 patients with pineal region tumors, including 17 PPTs, with the occipital transtentorial approach using the lateral semiprone position. The infrasplenial approach is helpful in separating the internal cerebral veins from the tumor, particularly when the tumor is tightly adherent to the veins. Permanent homonymous hemianopsia occurred in 1 of the 17 patients with PPTs. Permanent ocular movement disorders were not encountered. Extensive removal of the tumor significantly prolongs survival at least in patients with pineocytomas and PPT of intermediate differentiation (PPTIMD). Despite extensive resection and adjuvant radiochemotherapy, the prognosis of the patients with pineoblastomas is extremely poor. Although the proliferative potentials of pineocytomas and PPTIMD were significantly lower than those of pineoblastomas, there was no such difference between pineocytomas and PPTIMD.

Tentorial cavernous angioma with profuse bleeding. Case report.

This 15-year-old boy with a tentorial cavernous angioma reported occasional headache and scintillation in his left visual field. Magnetic resonance imaging revealed a well-demarcated, homogeneously enhanced tumor originating from the right cerebellar tentorium and extending into both the supratentorial and infratentorial spaces. Although a meningioma was suspected, vertebral artery angiography revealed a thickened meningeal branch originating from the right posterior inferior cerebellar artery and flecked tumor stain with pooling of contrast medium until the late venous phase. A cavernous angioma of the tentorium was suspected based on this finding, and as expected from the radiological findings, profuse bleeding was encountered during tumor removal. The histological diagnosis was a cavernous angioma. A cavernous angioma of the tentorium is extremely rare but should be differentiated from a meningioma preoperatively given that a cavernous angioma of dural origin tends to bleed massively during removal.

Efficacy of doxorubicin thermosensitive liposomes (40 degrees C) and local hyperthermia on rat rhabdomyosarcoma.

The efficacy of novel thermosensitive liposomes (40 degrees C) containing doxorubicin (Dox-Lip) together with local hyperthermia (HT) was studied on solid growing rat rhabdomyosarcomas. Tumor response and systemic toxicity were evaluated by comparing to free doxorubicin (Free Dox) with or without hyperthermia. Tumors were heated with infrared-A-radiation and drugs were infused intravenously after preheating the tumors followed by a further 60 min of heating at 42.5 degrees C. Recorded temperatures at various locations in the tumors indicated that all intratumoral temperatures, especially at the back rim, were definitely >40 degrees C. After single doses, tumor growth was further inhibited by Dox-Lip+HT compared to Free Dox+HT or Free Dox alone. Repeated treatments with Dox-Lip+HT (2x2.5 mg/kg+HT/2 weeks) resulted in a statistically significant tumor growth delay and was associated with a much lower systemic toxicity. Uptake studies of drugs in blood, tumor and normal tissues showed that Dox-liposomes (40 degrees C) are long circulating liposomes in the blood. However, the enhanced tumor response did not correlate with an increased uptake of Dox-Lip+HT in the tumor. The findings suggest that repeated applications of thermosensitive liposomal doxorubicin (40 degrees C) and local hyperthermia can control primary rat rhabdomyosarcomas while reducing the systemic toxicity of free doxorubicin.

Results of treatment of 112 cases of primary CNS lymphoma.

BACKGROUND: Chemotherapy with or without radiotherapy is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, either as a single agent or in combination with other drugs. Due to the lack of well-conducted randomized trials, the optimal treatment remains controversial. Available retrospective studies are difficult to discuss, however, some common themes can be found. METHODS: One hundred and twelve patients with PCNSL were treated with four different regimens over a period of 24 years. Treatment regimens were: whole-brain irradiation (WBI) alone, MVP (MTX, vincristine, and predonisolone), ProMACE-MOPP hybrid (cyclophosphamide, pirarubicin, etoposide, vincristine, procarbazine, prednisone, and MTX) and R-MTX (rituximab, MTX, pirarubicin, procarbazine, and prednisone) combined-modality therapy. RESULTS: The median failure-free survival was 16 months, and the median overall survival (OS) was 24 months. The 2- and 5-year actuarial probability of survival was 52.4 +/- 4.8% [95% confidence intervals (CI)] and 30.2 +/- 4.8% (95% CI), respectively. The ProMACE-MOPP protocol, Karnofsky performance status (KPS), MTX dose and WBI were associated with good OS by univariate models. By multivariate analysis, MTX dose, WBI dose, and its square dose were significantly associated with good OS. 20-30 Gy WB, and 500 mg/m(2) of MTX dose appeared important determinants of OS. CONCLUSIONS: A modest dose of MTX (500 mg/m(2)) followed by reduced-dose WBI for patients who respond appears a feasible treatment approach that minimizes serious toxicity.

Etiopathological factors related to hydrocephalus associated with vestibular schwannoma.

OBJECTIVE: We retrospectively analyzed various clinical factors to determine whether or not these factors are etiopathologically related to the development of hydrocephalus in patients with vestibular schwannomas. METHODS: There were 68 patients (29 men, 39 women) in this study who underwent resection of a vestibular schwannoma. The age at the time of surgery ranged from 19 to 76 years (mean age, 51.4 yr). The maximum diameter of the tumor in the cerebellopontine cistern ranged from 0 (localized within the internal auditory canal) to 56 mm (mean, 32.0 +/- 12.9 mm). Cerebrospinal fluid (CSF) protein concentration in the cerebellomedullary cistern was measured intraoperatively in all patients. RESULTS: Sixteen (23.5%) of the 68 patients exhibited radiographic evidence of hydrocephalus. Univariate analysis of various factors revealed that both tumor size and CSF protein concentration were positively related to development of hydrocephalus (P < 0.05 and P < 0.01, respectively). However, in multiple logistic regression analysis, only the CSF protein concentration was predictive for development of hydrocephalus (P = 0.022). There was a trend toward increased CSF protein concentration in patients with a large tumor (> or = 40 mm) compared with those with a small tumor (< 40 mm) (P = 0.06). CONCLUSION: A high CSF protein concentration in fluid from the cerebellomedullary cistern is one of the most important factors contributing to hydrocephalus associated with vestibular schwannoma. It is important to judge whether or not any further treatment is required for hydrocephalus, in addition to tumor resection, especially in patients with communicating hydrocephalus.

Salvage therapy and late neurotoxicity in patients with recurrent primary CNS lymphoma treated with a modified ProMACE-MOPP hybrid regimen.

We report the efficacy of salvage therapy with a modified ProMACE-MOPP combined with radiation in patients with primary central nervous system lymphoma (PCNSL). Thirty-two immunocompetent patients were treated with a regimen of pirarubicin, cyclophosphamide, etoposide, vincristin, and methotrexate (MTX: 500 mg/m(2)) administered in 21-day cycles. Patients received 20 Gy of whole-brain radiotherapy after three cycles of chemotherapy. A single cycle of chemotherapy was repeated every four months for two years. Nine patients with CNS relapse were retreated with additional cycles of the ProMACE-MOPP hybrid regimen with a 90% objective response rate. Median complete response (CR) duration was 13.2 months and median survival time (MST) for the nine patients treated after initial relapse was 30 months. One of 17 patients (5.8%) who had less than 20 Gy of whole brain irradiation developed dementia. In contrast, six of seven (85.7%) patients who had more than 30 Gy of whole brain radiotherapy became demented. Maintaining a moderate dose of MTX, while adding chemotherapeutic agents and 20 Gy of whole brain radiation therapy, improved disease control and overall survival and lowered the incidence of delayed neurologic toxicity in patients with PCNSL. Additional treatment with a ProMACE-MOPP hybrid regimen is still effective for relapsed disease.

Frontal anaplastic oligodendroglioma showing multi-organ metastases after a long clinical course. Case report.

A 17-year-old woman presented with an anaplastic oligodendroglioma manifesting as generalized seizure. Neuroimaging studies revealed a right frontal tumor. Histological examinations of biopsy specimens revealed that the tumor was oligodendroglial in nature. Total resection was repeated four times, and malignant change was evident within the tissues. The final diagnosis was anaplastic oligodendroglioma. Despite irradiation, combination chemotherapy, and interstitial hyperthermia, the tumor grew rapidly but was confined to the cavity created by previous removal operations. She suffered bone pain in the last 3 months of her life, when neuroimaging examinations disclosed multiple bone lesions. She died at the age of 29 years. At autopsy, generalized metastases from the tumor were identified at various sites, including the dura mater covering the frontal lobes and thoracic cord, cavernous sinus, tuberculum sellae, spleen, liver, pancreas, lungs, paratracheal lymph nodes, vertebral bodies, ribs, sternum, pelvis, dorsal root ganglia, and iliopsoas muscle. This rare case of cerebral anaplastic oligodendroglioma developed in adolescence, and rapid hematogenous spread of the glioma cells into the systemic organs occurred after a relatively long clinical course.

Current status of neuroendoscopic surgery in Japan and discussion on the training system.

OBJECTIVES: The objectives of this study was to investigate the current status of neuroendoscopic surgery in Japan and to discuss the issue disclosed by the survey. METHODS: We delivered questionnaires about neuroendoscopic surgeries to 1,237 of Japan Neurosurgical Society certified training institutions. RESULTS: Of these institutions, 592 (47.9%) returned completed questionnaires, and 316 (53.4%) among them experienced neuroendoscopic surgeries in the past. Two hundred seventy-six institutions had at least one procedure in the year 2003, but 208 (75.5%) had only one to ten procedures per year. Total number of procedures was 2,796, and trans-sphenoidal surgery was performed most frequently (705). Aneurysmal neck clipping (637) was second, and the third place was third ventriculostomy (ETV, 357). ETV was performed at 126 institutions, and 112 (88.9%) of them had only five cases or under per year. DISCUSSION: Neuroendoscopic surgeries are performed at many institutions, but little experience per institution was reported. We refer to the on-going project of the Japanese Society for Neuroendoscopy on establishing training system of neuroendoscopic surgeries.

Modified buddy wire technique for coil embolization of posterior circulation aneurysms.

INTRODUCTION: In coil embolization of a posterior circulation aneurysm, tortuosity or a small vessel caliber frequently prevents placement of a guiding catheter in the vertebral artery. Even in such difficult situations, however, coil embolization is the only treatment option when the patient's clinical condition is very poor, or the aneurysm is inaccessible by microsurgery. METHODS: Three patients with a posterior circulation aneurysm were treated by coil embolization with the use of a modified buddy wire technique to stabilize a guiding catheter that could not be placed into the vertebral artery. RESULTS: The guiding catheter was stabilized in the subclavian artery and the microcatheter was firmly supported. As a result, coil embolization was performed safely in all patients. There were no procedural complications. CONCLUSION: The modified buddy wire technique could provide patients with a chance to undergo endovascular surgery despite having a tortuous or narrow vertebral artery.

Expression level of ECT2 proto-oncogene correlates with prognosis in glioma patients.

The ECT2 (epithelial cell transforming sequence 2) proto-oncogene encodes a guanine nucleotide exchange factor for Rho GTPases, and regulates cytokinesis. ECT2 plays a critical role in Rho activation during cytokinesis, and thus may play a role in the pathogenesis of glioma. In this study, we investigated relationships between ECT2 expression, tumor histology, and prognosis in glioma patients. ECT2 mRNA expression was examined using quantitative real-time PCR, while its protein expression was examined by immunohistochemistry of 54 glioma tissue samples. Expressions of ECT2 mRNA and protein were markedly increased in high-grade gliomas compared to low-grade gliomas. Patients in whom expression of ECT2 mRNA and protein in tumor tissues was the lowest survived longer than patients who had higher expression. In vitro, ECT2 siRNA inhibited glioma cell proliferation and invasion. These data suggest that increased expression of ECT2 contribute to promotion of tumor invasiveness and progression, implying that evaluation of ECT2 expression is a prognostic marker for glioma patients.

[Abnormal muscle response monitoring during microvascular decompression for hemifacial spasm and long term results].

OBJECTIVE: There is some debate over the reliability of intraoperative abnormal muscle response (AMR) monitoring as an indicator of postoperative long-term outcome in patients with hemifacial spasm (HFS). We investigated whether AMR findings obtained during microvascular decompression reflect postoperative long-term outcome. MATERIAS AND METHODS: Subjects were 51 HFS patients who underwent AMR monitoring during surgery. AMR recordings were obtained from the mentalis muscle by electrical stimulation of the temporal branch of the facial nerve and from the orbicularis oculi muscles by stimulation of the marginal mandibular branch. Postoperative follow-up was more than 5 years (range 61-118 months, mean 87 months). RESULTS: In 37 patients, AMR disappeared after vascular decompression. Among those patients, only one presented with spasm at the final follow-up examination. In 6 of 7 patients with AMR that disappeared early before the completion of decompression, hemifacial spasm resolved completely. Five of six patients in whom AMR still remained but with decreased amplitude at the end of surgery experienced complete resolution. CONCLUSIONS: Our findings suggest that intraoperative cessation including prior to decompression or decreased amplitude of AMR at the end of surgery indicates a high likelihood of postoperative long-term relief of HFS. We believe that intraoperative AMR monitoring is useful in MVD surgery for HFS.

Increased expression of pituitary tumor-transforming gene (PTTG)-1 is correlated with poor prognosis in glioma patients.

Pituitary tumor-transforming gene (PTTG), which is homologous to a mammalian securin, plays a pivotal role in cell transformation and is overexpressed in numerous cancer cell lines and tissues. PTTG functions in the control of mitosis, cell transformation, DNA repair and gene regulation. In the present study, we investigated whether the expression of PTTG1 is correlated with tumorigenicity and prognosis in glioma patients. Expression of PTTG1 was confirmed in three glioma cell lines at the mRNA and protein levels using RT-PCR analysis and Western blotting, respectively. Furthermore, PTTG1 protein was detected in 44 glioma tissue samples using immunohistochemical techniques, markedly increased in high-grade gliomas compared to low-grade gliomas and associated with an unfavorable patient outcome. Moreover, siRNA against the PTTG1 gene inhibited cell proliferation and invasion in glioma cell lines. These data suggest that increased expression of PTTG1 contributes to the tumorigenicity of glioma cells and may be useful as a prognostic marker for glioma patients.

Increased expression of CCAAT/enhancer binding protein beta correlates with prognosis in glioma patients.

C/EBP beta (CCAAT/enhancer binding protein beta) is a transcriptional factor that belongs to the basic region-leucine zipper class DNA-binding proteins and plays a role in cell differentiation and inflammatory reactions. Although high tissue levels of inflammatory cytokines, such as interleukin (IL)-6, IL-8 and transforming growth factor-beta, have been observed in glioma patients, the mechanisms underlying this phenomenon remain to be elucidated. C/EBP beta induces a variety of cytokines and thus may play a role in the pathogenesis of glioma. In this study, we investigated the relationship between C/EBP beta expression, tumor histology, and prognosis in glioma. The expression of C/EBP beta mRNA was examined with quantitative real-time PCR and protein expression was examined with immunohistochemical techniques in 47 glioma tissue samples. Expression of C/EBP beta mRNA and protein was markedly increased in high grade glioma compared with low grade glioma. Patients whose expression of C/EBP beta mRNA and protein in tumor tissue was lower survived longer than those whose expressions were higher. In vitro, C/EBP beta siRNA inhibited glioma cell proliferation and invasion. Moreover, IL-8 production by glioma cells was inhibited by C/EBP beta siRNA transfection. These data suggest that increased expression of C/EBP beta may contribute to the promotion of tumor invasiveness and progression. The data imply that the comparison of C/EBP beta expression could be a prognostic marker for patients with glioma.

Transcranial imaging of audiogenic epileptic foci in the cortex of DBA/2J mice.

Exposure to intense sound stimuli induces audiogenic seizures in DBA/2J mice. We investigated cortical activities during sound stimulation using flavoprotein fluorescence imaging. Most DBA/2J mice had seizures during intense sound stimulation, with more than half surviving after seizures. Surviving mice were anesthetized with urethane (1.6 g/kg, intraperitoneal), and the skull was exposed and then covered with clear resin. More than 3 days after surgery, the mice were lightly anesthetized with urethane (0.8 g/kg) and cortical activities during intense sound stimulation were visualized. Focal responses appeared near the somatosensory cortex together with spike activities localized in the response area. These findings indicate that epileptic foci of audiogenic seizure are formed in the cortex of DBA/2J mice.

Interstitial hyperthermia with intra-arterial injection of adriamycin for malignant glioma.

A new method for treating malignant glioma by concurrent intra-arterial injection of adriamycin during thermotherapy was performed in seven patients with malignant glioma, four males and three females, with five cases of glioblastoma and two of anaplastic oligodendroglioma. Adriamycin was intra-arterially injected at a dose of 20 mg via the common carotid artery during thermotherapy. The heating procedure was repeated three times combined with chemotherapy in one therapy course, and a total of nine therapy courses were performed in the seven patients. All patients tolerated the protocol well. Based on post-therapy computed tomography, five of the therapy courses achieved partial response, one course resulted in disease progression, and the remaining three courses showed no change. The median time to progression was 3.4 months and the overall median length of survival following stereotactic biopsy was 13.2 months. Facial flushing was observed during eight therapy courses, and extensive alopecia in six therapy courses. Intracystic concentrations of adriamycin were determined in three patients, and marked increases were observed. Intra-arterial injection chemotherapy during hyperthermia is a promising therapeutic method for treatment of malignant glioma with few adverse effects.

Ictal SPECT analyzed by three-dimensional stereotactic surface projection in frontal lobe epilepsy patients.

We analyzed preoperative ictal SPECT results from 18 frontal lobe epilepsy patients who underwent epilepsy surgery (mean age 22.9 years). Seizure onset at implanted subdural electrodes was defined as the epileptic focus in 16 of 18 patients. In two additional patients, the resected area on postoperative magnetic resonance images was defined as the epileptic focus. The radioisotope 99mTc-ECD was injected in all patients within 5 s after seizure onset. SPECT images were analyzed by three-dimensional stereotactic surface projection (3-D SSP). Areas of hyperperfusion identified by ictal SPECT were concordant with the site of epileptic focus in 11 patients (61.1%, concordant group) and were non-concordant in 7 patients (38.9%, non-concordant group). The non-concordant group had a higher number of patients with a history of acquired brain damages, such as encephalitis or brain surgery (p < 0.05). Only 3 of 11 patients in the concordant group showed areas of localized hyperperfusion within epileptic foci, whereas 8 patients showed areas of hyperperfusion extending to other regions. Ictal SPECT analyzed by 3-D SSP is useful as a mode of presurgical evaluation in frontal lobe epilepsy patients without a history of encephalitis or surgical treatment. We caution that rapid seizure spread may result occasionally in areas of hyperperfusion extending to adjacent or remote regions.

Ictal SPECT in supplementary motor area seizures.

OBJECTIVES: We used ictal single photon emission computed tomography (SPECT) to clarify the propagation pathways of epileptic discharges in patients with supplementary motor area (SMA) seizure. METHODS: In four patients (four males, age range, 18-27 years) with SMA seizures, SPECT studies by radioisotope 99mTc-ECD were performed as a preoperative evaluation. Two of the patients remained seizure-free after complete resection of the focal cortical dysplasia on magnetic resonance (MR) images including epileptic foci. In the other two patients, MR images were normal, but subdural electrode monitoring allowed for verifying the ictal onset in the left SMA. After partial resection of the SMA including epileptic foci, these patients experienced a significant (>90%) reduction of seizure frequency. Regional cerebral blood flow (rCBF) measurements obtained under ictal and interictal conditions were compared on a voxel-by-voxel basis by means of the SPM99 paired t-test option (uncorrected p<0.001). RESULTS: Significant increases in rCBF under ictal conditions were identified in the bilateral anterior cingulate cortex (ACC), the globus pallidus ipsilateral to epileptic foci and the contralateral cerebellar hemisphere. The right ACC included a cluster with a submaximum in the right primary sensorimotor area. DISCUSSION: In patients with SMA seizures, the hyperperfusion areas of ictal SPECT did not localize within the SMA but spread to the adjacent cortex such as the ACC and sensorimotor cortex ipsilateral to epileptic foci. Additionally, the epileptic discharges propagated to the remote areas such as the globus pallidus and cerebellum. We caution that ictal SPECT localization in patients with SMA seizures is not always concordant to epileptic focus but reveals already spread seizure activities.