Ependymoma-like tumor with mesenchymal differentiation harboring C11orf95-NCOA1/2 or -RELA fusion: A hitherto unclassified tumor related to ependymoma.

Recurrent fusion genes involving C11orf95, C11orf95-RELA, have been identified only in supratentorial ependymomas among primary CNS tumors. Here, we report hitherto histopathologically unclassifiable high-grade tumors, under the tentative label of "ependymoma-like tumors with mesenchymal differentiation (ELTMDs)," harboring C11orf95-NCOA1/2 or -RELA fusion. We examined the clinicopathological and molecular features in five cases of ELTMDs. Except for one adult case (50 years old), all cases were in children ranging from 1 to 2.5 years old. All patients presented with a mass lesion in the cerebral hemisphere. Histologically, all cases demonstrated a similar histology with a mixture of components. The major components were embryonal-appearing components forming well-delineated tumor cell nests composed of small uniform cells with high proliferative activity, and spindle-cell mesenchymal components with a low- to high-grade sarcoma-like appearance. The embryonal-appearing components exhibited minimal ependymal differentiation including a characteristic EMA positivity and tubular structures, but histologically did not fit with ependymoma because they lacked perivascular pseudorosettes, a histological hallmark of ependymoma, formed well-delineated nests, and had diffuse and strong staining for CAM5.2. Molecular analysis identified C11orf95-NCOA1, -NCOA2, and -RELA in two, one, and two cases, respectively. t-distributed stochastic neighbor embedding analysis of DNA methylation data from two cases with C11orf95-NCOA1 or -NCOA2 and a reference set of 380 CNS tumors revealed that these two cases were clustered together and were distinct from all subgroups of ependymomas. In conclusion, although ELTMDs exhibited morphological and genetic associations with supratentorial ependymoma with C11orf95-RELA, they cannot be regarded as ependymoma. Further analyses of more cases are needed to clarify their differences and similarities.

Subthalamic nucleus deep brain stimulation restores normal rapid eye movement sleep in Parkinson's disease.

BACKGROUND: In Parkinson's disease, sleep disturbance is a common occurrence. METHODS: We evaluated sleep in 10 patients with Parkinson's disease (age, 57.5 ± 9.8 years; disease duration, 12.3 ± 2.7 years) before and after subthalamic nucleus deep brain stimulation using the Parkinson's disease sleep scale and polysomnography. RESULTS: Their total sleep scale scores and daytime sleepiness subscale scores significantly improved after subthalamic nucleus-deep brain stimulation. The novel findings from this study significantly increased normal rapid eye movement sleep, and decreased abnormal rapid eye movement sleep without atonia after deep brain stimulation in patients with Parkinson's disease. The improved total sleep scale score correlated with decreased wakefulness after sleep onset. Moreover, improved daytime sleepiness correlated with increased normal rapid eye movement sleep time. Sleep improvement did not significantly correlate with resolution of motor complication or reduced dopaminergic dosages. CONCLUSIONS: Subthalamic nucleus-deep brain stimulation may have beneficial effects on sleep disturbance in advanced Parkinson's disease by restoring sleep architecture and normal rapid eye movement sleep.

Hypofractionated stereotactic radiotherapy for acoustic neuromas: safety and effectiveness over 8 years of experience.

BACKGROUND: Little information is available about long-term outcomes of hypofractionated stereotactic radiotherapy (hypo-FSRT) for acoustic neuromas. In this study, the safety and effectiveness of hypo-FSRT for unilateral acoustic neuroma were reviewed over 8 years of experience at our institution. METHODS: Between May 1998 and October 2006, 27 patients were consecutively treated by linear accelerator-based hypo-FSRT. Two patients were excluded from this study because they were lost to follow-up within 12 months. The median follow-up period for the rest was 59 (range 24-133) months. Two types of treatment schedules were adopted. Thirteen patients received 30-39 Gy, given in 10-13 fractions (regimen A), whereas after July 2003, 12 patients received 20-24 Gy, given in 5-6 fractions at the tumor periphery (regimen B). These treatments were scheduled to be delivered in three fractions per week (Monday, Wednesday, Friday). The median planning target volume was 2.0, with 1.7 ml (range 0.7-10.6) in regimen A and 5.2 ml (range 0.9-9.3) in regimen B. In the pretreatment audiogram, seven patients (two in regimen A and five in regimen B) had serviceable hearing (Gardner-Robertson Class I-II). RESULTS: Local control rates were 100% with regimen A and 92% with regimen B. Serviceable hearing was preserved in four of five patients in regimen B but no patients in regimen A at the last follow-up. No permanent facial or trigeminal nerve morbidity was observed following treatment, and no salvage surgery was needed. CONCLUSIONS: Hypo-FSRT for acoustic neuromas achieved a high local control rate with minimal facial and trigeminal nerve morbidity.

Conversion of a molecular classifier obtained by gene expression profiling into a classifier based on real-time PCR: a prognosis predictor for gliomas.

BACKGROUND: The advent of gene expression profiling was expected to dramatically improve cancer diagnosis. However, despite intensive efforts and several successful examples, the development of profile-based diagnostic systems remains a difficult task. In the present work, we established a method to convert molecular classifiers based on adaptor-tagged competitive PCR (ATAC-PCR) (with a data format that is similar to that of microarrays) into classifiers based on real-time PCR. METHODS: Previously, we constructed a prognosis predictor for glioma using gene expression data obtained by ATAC-PCR, a high-throughput reverse-transcription PCR technique. The analysis of gene expression data obtained by ATAC-PCR is similar to the analysis of data from two-colour microarrays. The prognosis predictor was a linear classifier based on the first principal component (PC1) score, a weighted summation of the expression values of 58 genes. In the present study, we employed the delta-delta Ct method for measurement by real-time PCR. The predictor was converted to a Ct value-based predictor using linear regression. RESULTS: We selected UBL5 as the reference gene from the group of genes with expression patterns that were most similar to the median expression level from the previous profiling study. The number of diagnostic genes was reduced to 27 without affecting the performance of the prognosis predictor. PC1 scores calculated from the data obtained by real-time PCR showed a high linear correlation (r=0.94) with those obtained by ATAC-PCR. The correlation for individual gene expression patterns (r=0.43 to 0.91) was smaller than for PC1 scores, suggesting that errors of measurement were likely cancelled out during the weighted summation of the expression values. The classification of a test set (n=36) by the new predictor was more accurate than histopathological diagnosis (log rank p-values, 0.023 and 0.137, respectively) for predicting prognosis. CONCLUSION: We successfully converted a molecular classifier obtained by ATAC-PCR into a Ct value-based predictor. Our conversion procedure should also be applicable to linear classifiers obtained from microarray data. Because errors in measurement are likely to be cancelled out during the calculation, the conversion of individual gene expression is not an appropriate procedure. The predictor for gliomas is still in the preliminary stages of development and needs analytical clinical validation and clinical utility studies.

Suppressed levels of growth hormone and insulin-like growth factor-1 during successful pregnancy in persistent acromegaly.

Pregnancy is a rather rare event in acromegaly because fertility is often reduced during active disease. Previous reports of pregnancy in acromegalic patients showed that the pituitary growth hormone (GH) level was unaffected and the insulin-like growth factor (IGF)-1 level was elevated during the second and third trimesters. We describe here a case of persistent acromegaly that showed suppressed levels of GH and IGF-1 during pregnancy. The suppression of GH secretion and IGF-1 may be due to increased estrogen or other factors circulating in mid- to late pregnancy.

Phase II study of ifosfamide, carboplatin, and etoposide in patients with a first recurrence of glioblastoma multiforme.

OBJECT: The prognosis of recurrent glioblastoma multiforme (GBM) remains unsatisfactory. The authors conducted a Phase II study of ifosfamide, carboplatin, and etoposide (ICE) for a first recurrence of GBM to determine whether it prolonged a patient's good-quality life. METHODS: This trial was an open-label, single-center Phase II study. Forty-two patients with a first GBM relapse after surgery followed by standard radiotherapy (60 Gy) and first-line temozolomide- or nimustine-based chemotherapy were eligible to participate. The primary end point was progression-free survival at 6 months after the ICE treatment (PFS-6), and secondary end points were response rate, toxicity, and overall survival. Chemotherapy consisted of ifosfamide (1000 mg/m(2) on Days 1, 2, and 3), carboplatin (110 mg/m(2) on Day 1), etoposide (100 mg/m(2) on Days 1, 2, and 3), every 6 weeks. RESULTS: Progression-free survival at 6 months after ICE treatment was 35% (95% CI 22-50%). The median duration of PFS was 17 weeks (95% CI 10-24 weeks). The response rate was 25% (95% CI 9-34%). Adverse events were generally mild and consisted mainly of alopecia. CONCLUSIONS: This regimen was well tolerated and has some activity and could be one of the options for patients with recurrent GBM.

[An advantage of T2*-weighted MRI for early detection of straight sinus thrombosis: a case report].

A 44-year-old man presented with a 12-day history of severe non-throbbing headache. He showed no physical abnormality but obesity. On day 12, ring-shaped low intensity lesions inside straight sinus were revealed on T2*-weighted MRI image (T2*WI). On the following day (day 13), he was found unresponsive at home, and ambulated with disturbed consciousness. FLAIR and diffusion-weighted MRI image disclosed high intensity signals in bilateral thalamus which were postulated as vasogenic edema. MR venography and conventional cerebral angiography showed an absence of flow in inferior sagittal sinus, vein of Galen, and straight sinus. These findings confirmed the diagnosis of cerebral venous thrombosis (CVT). Anticoagulant treatment was introduced and his consciousness level was gradually improved. On day 43, he was discharged with no neurological sequelae. A delay of correct diagnosis and treatment with CVT can lead to devastating disability or even to death. An early diagnosis of CVT is often dismissed owing to the nonspecific symptoms such as headache and nausea. Recent reports described high sensitivity of T2*WI for detecting CVT. Alterations in blood flow and oxyhemoglobin reduced products, deoxyhemoglobin, in thrombosed veins often produce the magnetic susceptibility on T2*WI. A detection of ring-shaped low intensity lesions within venous sinus on T2*WI were quite rare, and the signal changes of these sinus lesions were successfully visualized by chronological T2*WI. Taken together, our case implies that T2*WI is the powerful tool for the early detection of CVT, even before the critical symptoms might happen.

Intracerebral schwannoma in a child with infiltration along perivascular spaces resembling meningioangiomatosis.

Schwannoma arising within brain parenchyma is a rare lesion, usually found in children. Reported herein is a case of intracerebral schwannoma in a 5-year-old boy, with a review of the English-language literature on the subject, in which 47 cases were found. Few detailed histological reviews of intracerebral schwannoma exist. The tumor had a distinctive plexiform growth pattern, and small aggregates of Schwann cells spread extensively into the surrounding brain tissue along perivascular spaces adjacent to the tumor nodule. Histological differential diagnoses included perivascular schwannosis and meningioangiomatosis. A few intratumoral axons, seen on immunostaining for neurofilament protein, were trapped at the periphery of the main lesion, but there was no evidence of intralesional axons in the multiple nodules of Schwann cell proliferations that extended into the perivascular spaces, suggesting that the lesions are neoplastic. Because Schwann cells are not a natural component of the central nervous system, the origin of intracerebral schwannomas remains unknown. The histology suggests that Schwann cells of the perivascular nerve plexus are a likely site of origin.

Endogenous tenascin-C enhances glioblastoma invasion with reactive change of surrounding brain tissue.

Tenascin-C is an extracellular matrix glycoprotein implicated in embryogenesis, wound healing and tumor progression. We previously revealed that tenascin-C expression is correlated with the prognosis of patients with glioblastoma. However, the exact role of endogenous tenascin-C in regulation of glioblastoma proliferation and invasion remains to be established. We show here that endogenous tenascin-C facilitates glioblastoma invasion, followed by reactive change of the surrounding brain tissue. Although shRNA-mediated knockdown of endogenous tenascin-C does not affect proliferation of glioblastoma cells, it abolishes cell migration on a two-dimensional substrate and tumor invasion with brain tissue changes in a xenograft model. The tyrosine phosphorylation of focal adhesion kinase, a cytoplasmic tyrosine kinase that associates with integrins, was decreased in tenascin-C-knockdown cells. In the analysis of clinical samples, tenascin-C expression correlates with the volume of peritumoral reactive change detected by magnetic resonance imaging. Interestingly, glioblastoma cells with high tenascin-C expression infiltrate brain tissue in an autocrine manner. Our results suggest that endogenous tenascin-C contributes the invasive nature of glioblastoma and the compositional change of brain tissue, which renders tenascin-C as a prime candidate for anti-invasion therapy for glioblastoma.

Effect of early optic canal unroofing on the outcome of visual functions in surgery for meningiomas of the tuberculum sellae and planum sphenoidale.

OBJECTIVE: The aim of this study was to evaluate the effect of early optic canal unroofing on visual function in patients with meningiomas of the tuberculum sellae and planum sphenoidale. METHODS: We retrospectively reviewed the clinical records of 20 consecutive patients with tuberculum sellae meningiomas and two patients with planum sphenoidale meningiomas who were admitted to our institution from 1999 to 2007. Factors that may influence postoperative visual functions were analyzed, including patient's age and sex, duration of preoperative visual symptoms, preoperative visual acuity, tumor size, tumor consistency, tumor extension into the optic canal, tumor adhesion to the optic nerve, timing of optic canal unroofing, and tumor resection rate. RESULTS: The mean patient age was 52.9 +/- 13.7 years (range, 27-73 yr); 18 patients were women and four were men. The mean maximum tumor size was 2.3 +/- 0.7 cm (range, 1.5-3.5 cm). Visual symptoms were present preoperatively in 19 patients, and three patients were asymptomatic. The mean duration of visual symptoms was 12.0 +/- 16.4 months (range, 0-72 mo). Tumor resection was evaluated according to Simpson's grade, and Grade II was achieved in 14, Grade III in two, and Grade IV in six (two patients were recurrent cases). Tumors were extended into the optic canal in 15 patients, and severe adhesion to the optic nerve was observed in nine patients. Tumor consistency was soft in eight patients, intermediate in eight patients, and hard in six patients. The optic canal was unroofed early before dissection or manipulation of tumor in nine patients (early group) and after dissection of tumor in seven patients (late group), and optic canal unroofing was not performed in six patients (none group; no canal extension in two and intentional incomplete resection in four patients). Visual symptoms were improved in 10 patients, unchanged in seven patients, and worsened in five patients (transient in two and permanent in three). Logistic regression analysis revealed that early optic canal unroofing was an independent factor for postoperative improvement of visual symptoms. CONCLUSION: Early optic canal unroofing may increase the possibility of improved preoperative visual symptoms in surgical resection of tuberculum sellae meningiomas and planum sphenoidale meningiomas.

Long term outcomes in patients with intracranial germinomas: a single institution experience of irradiation with or without chemotherapy.

Complete remission can be achieved soon after irradiation in patients with intracranial germinoma. This study aimed to analyze the follow-up outcome of intracranial germinoma patients. About 39 intracranial germinoma patients (29 males and 10 females; average age, 15 years; range, 7-27 years) treated at Kyoto University Hospital from 1978 to 2004 were included in the study group. Six patients had multifocal disease at initial diagnosis, and 10 had human chorionic gonadotropin (HCG)-producing tumors. Thirteen patients were treated with craniospinal axis irradiation, 6 with whole-brain irradiation, 17 with whole-ventricle irradiation, and 3 with local field irradiation. Since 1997, 15 patients were treated with reduced-dose whole-ventricle irradiation (median, 23.4 Gy; range, 20.4-27 Gy) followed by a local boost (median, 40.8 Gy; range, 36-54 Gy) combined with chemotherapy. The median follow-up was 94 months (18 months to 25 years). The 5- and 10-year overall survival (OS) rates of the entire group were 97 and 90%, respectively. The 5- and 10-year progression-free survival (PFS) rates of the entire group were 91 and 87%, respectively. The 8-year OS and PFS in 15 patients treated by whole-ventricle irradiation combined with chemotherapy were 100% and 92%, respectively. Four patients had recurrences within a median period of 59.5 months (51-85 months). All relapses occurred outside the radiation fields. Tumor site, tumor size, HCG production, multifocal disease and radiation dose to the primary site or whole ventricle did not significantly affect PFS. All initial recurrences of intracranial germinoma occurred at the distant site out of the radiation field. Our data suggested that reduced doses to the whole ventricle, combined with chemotherapy, should be sufficiently effective in patients with intracranial germinoma.

Gene expression-based molecular diagnostic system for malignant gliomas is superior to histological diagnosis.

PURPOSE: Current morphology-based glioma classification methods do not adequately reflect the complex biology of gliomas, thus limiting their prognostic ability. In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which typically follow distinct clinical courses. Our goal was to construct a clinically useful molecular diagnostic system based on gene expression profiling. EXPERIMENTAL DESIGN: The expression of 3,456 genes in 32 patients, 12 and 20 of whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma, respectively, was measured by PCR array. Next to unsupervised methods, we did supervised analysis using a weighted voting algorithm to construct a diagnostic system discriminating anaplastic oligodendroglioma from glioblastoma. The diagnostic accuracy of this system was evaluated by leave-one-out cross-validation. The clinical utility was tested on a microarray-based data set of 50 malignant gliomas from a previous study. RESULTS: Unsupervised analysis showed divergent global gene expression patterns between the two tumor classes. A supervised binary classification model showed 100% (95% confidence interval, 89.4-100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic genes. Applied to a gene expression data set from a previous study, our model correlated better with outcome than histologic diagnosis, and also displayed 96.6% (28 of 29) consistency with the molecular classification scheme used for these histologically controversial gliomas in the original article. Furthermore, we observed that histologically diagnosed glioblastoma samples that shared anaplastic oligodendroglioma molecular characteristics tended to be associated with longer survival. CONCLUSIONS: Our molecular diagnostic system showed reproducible clinical utility and prognostic ability superior to traditional histopathologic diagnosis for malignant glioma.

Clinical impact of integrated functional neuronavigation and subcortical electrical stimulation to preserve motor function during resection of brain tumors.

OBJECT: The authors evaluated the clinical impact of combining functional neuronavigation with subcortical electrical stimulation to preserve motor function following the removal of brain tumors. METHODS: Forty patients underwent surgery for treatment of brain tumors located near pyramidal tracts that had been identified by fiber tracking. The distances between the electrically stimulated white matter and the pyramidal tracts were measured intraoperatively with tractography-integrated functional neuronavigation, and correlated with subcortical motor evoked potentials (MEPs) and clinical symptoms during and after resection of the tumors. Motor function was preserved after appropriate tumor resection in all cases. In 18 of 20 patients, MEPs were elicited from the subcortex within 1 cm of the pyramidal tracts as measured using intraoperative neuronavigation. During resection, improvement of motor weakness was observed in two patients, whereas transient mild motor weakness occurred in two other patients. In 20 patients, the distances between the stimulated subcortex and the estimated pyramidal tracts were more than I cm, and MEPs were detected in only three of these patients following stimulation. CONCLUSIONS: Intraoperative functional neuronavigation and subcortical electrical stimulation are complementary techniques that may facilitate the preservation of pyramidal tracts around 1 cm of resected tumors.

Clinical significance of preoperative fibre-tracking to preserve the affected pyramidal tracts during resection of brain tumours in patients with preoperative motor weakness.

OBJECTIVE: To clarify the clinical usefulness of preoperative fibre-tracking in affected pyramidal tracts for intraoperative monitoring during the removal of brain tumours from patients with motor weakness. METHODS: We operated on 10 patients with mild to moderate motor weakness caused by brain tumours located near the pyramidal tracts under local anaesthesia. Before surgery, we performed fibre-tracking imaging of the pyramidal tracts and then transferred this information to the neuronavigation system. During removal of the tumour, motor function was evaluated with motor evoked potentials elicited by cortical/subcortical electrical stimulation and with voluntary movement. RESULTS: In eight patients, the locations of the pyramidal tracts were estimated preoperatively by fibre-tracking; motor evoked potentials were elicited on the motor cortex and subcortex close to the predicted pyramidal tracts. In the remaining two patients, in which fibre-tracking of the pyramidal tracts revealed their disruption surrounding the tumour, cortical/subcortical electrical stimulation did not elicit responses clinically sufficient to monitor motor function. In all cases, voluntary movement with mild to moderate motor weakness was extensively evaluated during surgery and was successfully preserved postoperatively with appropriate tumour resection. CONCLUSIONS: Preoperative fibre-tracking could predict the clinical usefulness of intraoperative electrical stimulation of the motor cortex and subcortical fibres (ie, pyramidal tracts) to preserve affected motor function during removal of brain tumours. In patients for whom fibre-tracking failed preoperatively, awake surgery is more appropriate to evaluate and preserve moderately impaired muscle strength.

Hypophysitis caused by Rathke's cleft cyst. Case report.

A 62-year-old woman presented with general malaise persisting for 2 months and narrowing of her visual field. T1-weighted magnetic resonance (MR) imaging showed swelling of the pituitary gland and stalk, and a homogeneous isointense intra- and suprasellar mass enhanced by gadolinium. During outpatient follow up, her condition deteriorated rapidly and she developed diabetes insipidus and panhypopituitarism. T1-weighted MR imaging demonstrated shrinkage of the lesion and disappearance of the central hypointense area indicating the cyst cavity, especially in the pituitary stalk. She underwent surgical exploration via the transsphenoidal approach under a provisional diagnosis of lymphocytic hypophysitis. Histological examination revealed ciliated columnar cells and squamous metaplasia on the inner surface of the cyst wall, with many foamy cells, infiltration by many lymphoid cells and some eosinophils, and fibrosis in the adenohypophysitis and inflammatory hypophysitis in the anterior and posterior pituitary gland. The present neuroimaging findings of cyst shrinkage associated with rapid clinical deterioration strongly support the suggestion that rupture of Rathke's cleft cyst causes inflammatory hypophysitis.

Stereotactic radiosurgery for atypical and anaplastic meningiomas.

Atypical and anaplastic meningiomas frequently recur in the relatively short-term after surgery. We have followed such postoperative cases by short-interval repeated MRI and have performed stereotactic radiosurgery (SRS) for progressive tumors as a salvage therapy. The objective of this report was assessment of the degree of tumor control, the risk of complications, and the presence of variables that predict outcome in patients treated with SRS for high-grade meningiomas. We reviewed 12 high-grade meningioma patients with 30 lesions treated by Linac-based SRS at Kyoto University Hospital between 1997 and 2002. They included 10 atypical meningiomas and 2 anaplastic ones according to the WHO classification. A mean tumor volume was 4.40cc and a mean marginal dose of SRS was 18.0 Gy (12-20 Gy). After a mean follow-up period of 43.4 months (6-84 months), 13 lesions had progression tumor within the SRS field and 6 lesions had out of the SRS field. Nine of 14 lesions, which were treated by SRS with a marginal dose of less than 20 Gy, had local recurrence in the SRS field. In contrast, four of 16 lesions, which were treated with marginal dose of 20 Gy, had local recurrence in the SRS field. The marginal dose <20 Gy was a statistically significant factor for a short-term progression in high-grade meningiomas (P = 0.0139). Five-year progression-free survival ratio in lesions treated with SRS below 20 Gy and 20 Gy were 29.4% and 63.1%, respectively. In conclusion, based on our findings, we suggest that recurrent high-grade meningiomas be treated by SRS with a marginal dose exceeding 20 Gy.

Evaluation of pituitary macroadenomas with multidetector-row CT (MDCT): comparison with MR imaging.

INTRODUCTION: It is important to have information on cavernous sinus extension and bony destruction in pituitary macroadenomas before surgery, but magnetic resonance (MR) imaging cannot always depict them. In the present study we sought to determine whether multidetector-row computed tomography (MDCT) could provide preoperative information in addition to that provided by MR imaging in pituitary macroadenoma. METHODS: The subjects comprised 33 consecutive patients (15 women, 18 men; mean age 50 years) with surgically proven macroadenoma. For MDCT, using the soft-tissue window and bone window, three orthogonal multiplanar reconstruction images were generated from venous-phase contrast-enhanced 0.5-mm isotropic voxel data. MDCT and MR images were evaluated with regard to: (1) clarity of tumor margins; (2) identification of the normal pituitary gland; (3) identification of erosion or destruction of the sellar floor; and (4) visualization of the adjacent optic pathways. RESULTS: MDCT more clearly demonstrated the lateral tumor margin than MR imaging (P = 0.002). No significant differences in visualization of the normal pituitary gland were noted between MDCT and dynamic MR imaging (P = 0.7). MDCT more clearly demonstrated sellar floor erosion or destruction at the sphenoid sinus than MR imaging (P < 0.001). MR imaging was superior to MDCT for visualizing the adjacent optic pathways (P < 0.001). CONCLUSION: MDCT is superior to MR imaging for assessing lateral tumor margin and the sellar floor at the sphenoid sinus. MDCT offers useful preoperative information in addition to that obtained from MR imaging.

Neuropoietin induces neuroepithelial cells to differentiate into astrocytes via activation of STAT3.

Neuropoietin (NP) is a recently identified member of the interleukin (IL)-6 family of cytokines, which share glycoprotein 130 (gp130) as a signal-transducing receptor component, and is highly expressed in embryonic brain. In this study, we show that NP has the potential to induce neuroepithelial cells to differentiate into astrocytes. NP stimulation leads to promoter activation of the gene for an astrocyte marker, glial fibrillary acidic protein (GFAP), which is clearly inhibited by either expression of a dominant-negative form of a transcription factor, signal transducer and activator of transcription 3 (STAT3) or by a nucleotide-substitution in the STAT3-binding element within the gene promoter. We further show that NP induces binding of endogenous STAT3 to its cognate sequence within the gfap gene promoter in neuroepithelial cells. Moreover, like the other IL-6 cytokine family members, NP promotes astrocyte differentiation in a synergistic manner with bone-morphogenetic protein (BMP)-2. Taken together, our data indicate that NP can be considered as a new astrocyte-inducing cytokine in the developing brain.

Evaluation of primary brain tumors with FLT-PET: usefulness and limitations.

PURPOSE OF THE REPORT: The purpose of this report was to investigate the potential of positron emission tomography using F-18 fluorodeoxythymidine (FLT-PET) in evaluating primary brain tumors. MATERIALS AND METHODS: FLT-PET was performed in 25 patients with primary brain tumors. FLT uptake in the lesion was semiquantitatively evaluated by measuring the maximal standardized uptake value (SUVmax) and the tumor-to-normal tissue ratio (TNR). SUVmax and TNR were compared with the histologic grade and the expression of the proliferation marker (Ki-67). RESULTS: FLT uptake in normal brain parenchyma was very low, resulting in the visualization of brain tumors with high contrast. Both SUVmax and TNR significantly correlated with the malignant grade of brain gliomas, in which high SUVmax/TNR was obtained for high-grade gliomas. Patients with primary lymphoma also showed SUVmax/TNR equivalent to glioblastoma. There was a positive correlation between SUVmax/TNR and the Ki-67 index. In contrast, spuriously high SUVmax and TNR were obtained in 3 of 6 patients with suspected recurrent tumors (2 patients with recurrent grade 2 glioma and one patient with postoperative granuloma), all of which showed lesion enhancement on MRI after Gd administration. CONCLUSIONS: FLT-PET can be used to evaluate the malignant grade and proliferation activity of primary brain tumors, especially malignant brain tumors. However, the presence of benign lesions showing blood-brain barrier disruption cannot be distinguished from malignant tumors and needs to be carefully evaluated.

Increased expression of aquaporin 1 in human hemangioblastomas and its correlation with cyst formation.

Aquaporins (AQPs) is a water channel family which facilitates the passage of water across cell membranes. Recently, expression of aquapporin 1 (AQP1) was found to be involved in not only water transport but also tumorigenesis. In present study, we analyzed the expression of AQP1 in 26 consecutive cases of human hemangioblastomas. Significant upregulation of AQP1 expression was found in hemangioblastomas compared with control brain (P=0.002). In hemangioblastomas, expression of AQP1 was predominantly localized on membranes of stromal cells. The expression level of AQP1 in cystic group of hemangioblastomas is much higher than that of solid group (P=0.021). Most hemangioblastomas showed a negative expression of AQP1 on endothelial cells. These results imply that increased expression of AQP1 in stromal cells may play a role in cyst formation and tumorigenesis of heman-gioblastomas.