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Background : The respiratory adjusted shock index (RASI) is a risk score whose usefulness in patients with sepsis and trauma has previously been reported. However, its relevance in elderly emergency patients with medical diseases is yet to be clarified. This study assessed the usefulness of the RASI, which can be evaluated without requiring special equipment, to provide objective and rapid emergency responses. Methods : In this retrospective study, we recruited patients with medical diseases, aged 65 years or older, who were transported to the emergency room from Tokushima Prefectural Kaifu Hospital and underwent arterial blood gas testing from 1 January 2022 to 31 December 2023. We investigated the association of the RASI with other indices, including the lactate level, National Early Warning Score 2 (NEWS2), Shock Index (SI), Sequential Organ Failure Assessment (SOFA) score, quick SOFA (qSOFA) score, and systemic inflammatory response syndrome (SIRS). Results: In this study, we included 260 patients (mean age, 86 years), of whom 234 were admitted to the hospital; 27 and 49 patients died within 7 and 30 days of admission, respectively. The RASI was positively correlated with the lactate level, NEWS2, SI, and increase in the SOFA score ( p < 0.001). The RASI was higher in patients with a SIRS or qSOFA score ≥ 2 than in those without ( p < 0.001). It predicted death within 7 and 30 days of admission with an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.73-0.87), sensitivity of 96.3%, and specificity of 53.6% when the cutoff value was set to 1.58 and with an AUC of 0.73 (95% CI: 0.66-0.81), sensitivity of 69.4%, and specificity of 70.6% when the cutoff value was set to 1.83, respectively. Conclusions : The RASI is a simple indicator that can be used for predicting in-hospital outcomes in elderly emergency patients with medical diseases. Larger prospective studies based on this study are needed.

Background: Although the palliative prognostic index (PPI), objective prognostic score (OPS), and neutrophil-lymphocyte ratio/albumin ratio (NLR/Alb) are well-known prognostic indicators for cancer patients, they do not provide clarity when it comes to predicting prognosis in patients without cancer who receive home-visit palliative care., Objective: The aim of this study was to determine whether PPI, OPS, and NLR/Alb can predict prognosis for patients without cancer who received home-visit palliative care., Design: This is a retrospective study., Setting/subjects: We recruited 58 patients without cancer who received home-visit palliative care from Tokushima Prefectural Kaifu Hospital, Japan, and died at home or at the hospital within seven days of admission between January 2009 and March 2023., Measurements: The PPI, OPS, and NLR/Alb of the study patients were evaluated at regular intervals, and statistical analysis was performed on the relationship between these indices and the time to death., Results: Simple regression analysis showed that PPI, OPS, and NLR/Alb were negatively correlated with the period until death ( p  < 0.001). The survival curves of the groups classified according to PPI, OPS, and NLR/Alb were significantly stratified. The predictive capacities of PPI, OPS, and NLR/Alb for death within 21 days were as follows: PPI (area under the curve [AUC]: 0.71; sensitivity: 59%; specificity: 68%), OPS (AUC: 0.73; sensitivity: 88%; specificity: 47%), and NLR/Alb (AUC: 0.72; sensitivity: 72%; specificity: 73%)., Conclusions: PPI, OPS, and NLR/Alb were useful in predicting the survival period and short-term prognosis within 21 days for patients without cancer who received home-visit palliative care., Competing Interests: No competing financial interests exist., (© Taiki Hori et al., 2024; Published by Mary Ann Liebert, Inc.)

Purpose: We evaluated the utility of arterial spin labeling (ASL) imaging of tumor blood flow (TBF) for grading non-enhancing astrocytic tumors., Materials and Methods: Thirteen non-enhancing astrocytomas were divided into high-grade (n = 7) and low-grade (n = 6) groups. Both ASL and conventional sequences were acquired using the same magnetic resonance machine. Intratumoral absolute maximum TBF (TBF max ), absolute mean TBF (TBF mean ), and corresponding values normalized to cerebral blood flow (TBF max and TBF mean ratios) were measured. The Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were used to assess the accuracy of TBF variables for tumor grading., Results: Compared with low-grade astrocytoma, high-grade astrocytoma exhibited significantly greater absolute TBF max (90.93 ± 24.96 vs 46.94 ± 20.97 ml/100 g/min, P < 0.001), TBF mean (58.75 ± 19.89 vs 31.16 ± 17.63 ml/100 g/min, P < 0.001), TBF max ratio (3.34 ± 1.22 vs 1.35 ± 0.5, P < 0.001), and TBF mean ratio (2.15 ± 0.94 vs 0.88 ± 0.41, P < 0.001). The TBF max ratio yielded the highest diagnostic accuracy (sensitivity 100%, specificity 86.3%), while absolute TBF mean yielded the lowest accuracy (sensitivity 85.7%, specificity 70.1%) by ROC analysis., Conclusion: Parameters from ASL perfusion imaging, particularly TBF max ratio, may be useful for distinguishing high-grade from low-grade astrocytoma in cases with equivocal conventional MRI findings.

Background: The hypoxic microenvironment plays a crucial role in the malignant progression of tumor cells. Moreover, AKT, a serine/threonine kinase, is activated by various extracellular growth factors and is important for cell growth, survival, and motility of leukocytes, fibroblasts, endothelial cells, and tumor cells. Therefore, we aimed to design an anti-metastatic hypoxic cytotoxin which has inhibitory effects on AKT., Results: TX-2137 was designed and synthesized based on the structural similarity of a preexisting AKT1/2 kinase inhibitor and a hypoxic cytotoxin tirapazamine. TX-2137 effectively reduced the expression of phosphorylated AKT and matrix metalloproteinase 9 (MMP9) and showed strong inhibition of the proliferation of B16-F10, HT-1080, and MKN-45 cells. In addition, TX-2137 exhibited hypoxia-selective cytotoxicity towards A549 cells and inhibited liver metastasis of B16-F10 cells in a xenograft chick embryo model in the same way as doxorubicin., Conclusion: TX-2137 may be a potent lead compound in the development of a novel anti-metastatic AKT kinase inhibitor., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We administered a questionnaire to 5 th grade medical students to examine the effect of community-based clinical practice on their attitudes to remote area medicine and their course after the graduation. Data from 192 students were obtained. The intensity of students' attitudes was estimated by using visual analogue scale. The intensities of the interest and a sense of fulfillment in remote area medicine were significantly increased after the practice. A significantly lower level of the intensity to become a generalist than that to become a specialist was seen in the students with low intensity in a sense of fulfillment. The percentages of the students who answered that they can work for 5 years or more in remote area were significantly lower in students with low intensity of a sense of fulfillment than in those with high intensity. A significantly higher percentage in students who worked at a familiar prefecture to them after the graduation was seen in female than in male. This study shows that the community-based practice is meaningful in increasing motivation which desire to work in remote area medicine, and that the motivation may affect their course after the graduation. J. Med. Invest. 64: 210-216, August, 2017.

Purpose: To determine whether differences in tumor volume between arterial spin labeling (ASL) and contrast-enhanced T1-weighted MR images (CE+T1WI) can help differentiate glioblastoma (GBM) from brain metastasis., Materials and Methods: Patients with a diagnosis of GBM (n=25) or brain metastasis (n=13) were examined by both conventional and ASL MR imaging. Volumes of interest with high signal intensity on ASL and CE+T1WI were defined using three dimensional analysis software. Tumor volume difference (ASL-CE) and tumor volume ratio (ASL/CE) were obtained. Absolute maximal tumor blood flow (TBF) and TBF ratio (normalized to white matter) were also measured. The Mann-Whitney U test and receiver operating characteristic curve analysis were performed to compare measurements between the tumor groups., Results: Both tumor volume difference and tumor volume ratio were significantly higher in GBM than in metastasis. Both TBF and TBF ratio were higher for GBM than for metastasis, but the differences were not significant., Conclusion: The difference in tumor volume as measured by ASL high signal intensity and CE+T1WI might be useful for differentiating GBM from metastasis, whereas ASL-derived TBF is insufficient. J. Med. Invest. 64: 58-63, February, 2017.

There are a few stroke specialists in medically under-served areas in Japan. Consequently, in remote area patients may not receive thrombolysis with intravenous recombinant tissue plasminogen activator (iv rt-PA), the standard treatment for acute ischemic stroke. Using a mobile telestroke support system (TSS) that accesses the internet via a smart phone, we implemented iv rt-PA infusion therapy under a drip-and-ship protocol to treat the stroke patients in medically under-served areas. The physicians at the Tokushima Prefectural Kaifu Hospital (TPKH), located in rural Japan, can relay CT or MRI scans and other patient data via their smart phone to off-site stroke specialists. In the course of 34 months, we used the TSS in 321 emergencies. A total of 9 of 188 (4.8%) with acute ischemic stroke, received iv rt-PA infusion therapy using a mobile TSS; in 5 among these (55.6%), we obtained partial or complete recanalization of occluded arteries. None suffered post-treatment hemorrhage and their average NIH stroke score fell from 14.6 at the time of admission to 6.8 at 24 h post-infusion. The drip-and-ship protocol contributed to the safe and effective treatment of the stroke patients living in medically under-served rural areas., Competing Interests: The authors have no personal financial or institutional interest in any of the drugs, materials, or devices cited in this study.

Purpose: T1-Cube (GE HealthCare) is a relatively new 3-dimensional (3D) fast spin-echo (FSE)-based magnetic resonance (MR) imaging sequence that uses a variable flip angle to acquire gap-free volume scans. We compared the gadolinium enhancement characteristics of a heterogeneous population of brain tumors imaged by T1-Cube and then 3D fast spoiled gradient recall acquisition in steady state (3D FSPGR) 3-tesla MR imaging to identify the superior modality for specific diagnostic purposes., Methods: We examined 61 lesions from 32 patients using the 2 sequences after administration of gadopentetic acid (Gd-DTPA; 0.1 mmol/kg). Two neuroradiologists independently measured each lesion twice using a region-of-interest (ROI) method. We measured the contrast-to-noise ratio (CNR), the difference in signal intensity (SI) between the tumor and normal white matter relative to the standard deviation (SD) of the SI within the lesion, for both post-contrast 3D FSPGR and post-contrast T1-Cube images of the same tumor and compared modality-specific CNRs for all tumors and in subgroups defined by tumor size, enhancement ratio, and histopathology., Results: The mean CNR was significantly higher on T1-Cube images than 3D FSPGR images for the total tumor population (1.85 ± 0.97 versus 1.12 ± 1.05, P < 0.01) and the histologic types, i.e., metastasis (P < 0.01) and lymphoma (P < 0.05). The difference in CNR was even larger for smaller tumors in the metastatic group (4.95 to 23.5 mm(2)) (P < 0.01). In contrast, mean CNRs did not differ between modalities for high grade glioma and meningioma., Conclusions: Gadolinium enhancement of brain tumors was generally higher when imaged by T1-Cube than 3D FSPGR, and T1-Cube with Gd enhancement may be superior to 3D FSPGR for detecting smaller metastatic tumors.

This study sought to determine the diagnostic utility of perfusion parameters derived from dynamic contrast-enhanced (DCE) perfusion MRI with a short acquisition time (approximately 3.5 min) in patients with glioma, brain metastasis, and primary CNS lymphoma (PCNSL). Twenty-six patients with 29 lesions (4 low-grade glioma, 13 high-grade glioma, 7 metastasis, and 5 PCNSL) underwent DCE-MRI in a 3 T scanner. A ROI was placed on the hotspot of each tumor in maps for volume transfer contrast K (trans) , extravascular extracellular volume V e , and fractional plasma volume V p . We analyzed differences in parameters between tumors using the Mann-Whitney U test. We calculated sensitivity and specificity using receiver operating characteristics analysis. Mean K (trans) values of LGG, HGG, metastasis and PCNSL were 0.034, 0.31, 0.38, 0.44, respectively. Mean Ve values of each tumors was 0.036, 0.57, 0.47, 0.96, and mean Vp value of each tumors was 0.070, 0.086, 0.26, 0.17, respectively. Compared with other tumor types, low-grade glioma showed lower K (trans) (P < 0.01, sensitivity = 88%, specificity = 100%) and lower V e (P < 0.01, sensitivity = 96%, specificity = 100%). PCNSL showed higher V e (P < 0.01, sensitivity = 100%, specificity = 88%), but the other perfusion parameters overlapped with those of different histology. Kinetic parameters derived from DCE-MRI with short acquisition time provide useful information for the differential diagnosis of brain tumors.

Purpose: In the imaging of intra-axial brain tumors, we sometimes found areas of high signal intensity around the enhanced tumor lesions on arterial spin labeling (ASL) magnetic resonance (MR) imaging. We undertook this study to investigate the relationship between high signal intensity on ASL imaging outside the area of contrast enhancement (CE) and histological diagnosis of intra-axial brain tumors., Methods: We examined images from 28 consecutive patients with intra-axial brain tumors who underwent ASL and CE MR imaging-three with low grade glioma (LGG), 13 with high grade glioma (HGG), six with metastasis, and six with primary central nervous system lymphoma (PCNSL)-and divided imaging findings into an "ASL dominant" group when hyperintensity on ASL was found outside the CE area and a "CE dominant" group when hyperintensity on ASL was not found outside the area of enhancement. We then analyzed the relationship between imaging findings and the histological diagnosis of the tumors., Results: Four cases were excluded because of poor quality of ASL images, 7 cases were classified as ASL dominant, and 17 cases were classified as CE dominant. The histological diagnoses of ASL dominant cases were LGG in 3 cases, HGG in 3 cases, and PCNSL in one case. Those of CE dominant cases were HGG in 10 cases, metastasis in 5 cases, and PCNSL in 2 cases. All cases with brain metastasis were classified as CE dominant., Conclusion: The high signal intensity outside the area of contrast enhancement is probably caused by increased perfusion or vascular proliferation, which indicates the presence of glioma or PCNSL and not metastasis. This finding indicates a new utility for ASL images in the diagnosis of brain tumors as a supplement to the conventional measurement of perfusion obtained from ASL images.

Introduction: This report describes a patient with Von Hippel-Lindau (VHL) syndrome and uncontrolled hypertension due to pheochromocytoma who underwent craniotomy for the excision of a cerebellar hemangioblastoma combined with a laparoscopic adrenalectomy., Case Report: A 31-year-old man presented with severe headache. MRI showed areas of abnormal enhancement in the left cerebellum that were determined to be hemangioblastoma with mass effect and obstructive hydrocephalus. His blood pressure rose abruptly and could not be controlled. CT of the abdomen revealed bilateral suprarenal tumors, and the patient was diagnosed as having VHL syndrome.On the third day, he presented with increasing headache, a decreased level of consciousness, and hemiparesis. We were not able to perform an craniotomy because abdominal compression in the prone or sitting position resulted in severe hypertension. We performed ventricular drainage to control his ICP. On the fifth day, we first performed a bilateral laparoscopic adrenalectomy to control ICP and then moved the patient to the prone position before performing a craniotomy to remove the left cerebellar hemangioblastoma. DISCU: ssion & conclusion In patients with pheochromocytoma, the effects of catecholamine oversecretion can cause significant perioperative morbidity and mortality, but these can be prevented by appropriate preoperative medical management. When carrying out an excision of cerebellar hemangioblastomas in patients with intracranial hypertension complicated by abnormal hypertension due to pheochromocytoma whose blood pressure is not sufficiently controlled, tumor resection of the pheochromocytoma prior to cerebellar hemangioblastoma excision in the same surgery may prevent increased ICP and reduce perioperative risk., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.

Background and Purpose: The role of the phosphorylated signal transducer and activator of transcription-3 (p-STAT3) after cerebral ischemia by the peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone (PGZ) remains controversial. Whether the increase in p-STAT3 by estrogen is mediated by the estrogen receptor α is also obscure. We examined the role of p-STAT3, PPARγ, and estrogen receptor α against ischemic brain damage after PGZ treatment., Methods: Female Wistar rats subjected or not subjected to bilateral oophorectomy were injected with 1.0 or 2.5 mg/kg PGZ 2 days, 1 day, and 1 hour before 90-minute middle cerebral artery occlusion-reperfusion and compared with vehicle-control rats., Results: The cortical infarct size was larger in ovariectomized than in nonovarietomized rats; it was reduced by PGZ treatment. Inversely with the reduction of the infarct size, PPARγ, and p-STAT3 but not estrogen receptor α in the peri-infarct area were increased in PGZ-treated compared with vehicle-control rats. The increase in PPARγ and p-STAT3 was associated with the transactivation of antiapoptotic and survival genes and the reduction of caspase-3 in this area. Inhibitors of PPARγ or STAT3 abolished the PGZ-induced neuroprotection and the increase in p-STAT3. More importantly, p-STAT3 increased by PGZ was bound to PPARγ and the complex translocated to the nucleus to dock to the response element through p-STAT3., Conclusions: Our findings suggest that the activation in the peri-infarct region of p-STAT3 and PPARγ by PGZ is essential for neuroprotection after ischemia and that PGZ may be of benefit even in postmenopausal stroke patients.

Background and Purpose: The pathogenesis of cerebral aneurysms is linked to inflammation, degradation of the extracellular matrix, and vascular wall apoptosis. Statins exert pleiotropic effects on the vasculature, independent of their cholesterol-lowering properties. To explore the detailed pathogenesis of cerebral aneurysms, we examined their progression in a rat model and studied whether statins prevent their initiation and growth., Methods: Cerebral aneurysms were induced in female rats subjected to hypertension, increased hemodynamic stress, and estrogen deficiency. The development of aneurysm was assessed morphologically on corrosion casts. The effects of pravastatin (5, 25, or 50 mg/kg per day) and of simvastatin (5 mg/kg per day) on their aneurysms were studied. Human brain endothelial cells were also used to determine the effects of pravastatin., Results: Pravastatin (5 mg/kg per day) reduced endothelial damage and inhibited aneurysm formation; there was an association with increased endothelial nitric oxide synthase (eNOS) levels and a decrease in human brain endothelial cell adhesion molecules. Unexpectedly, 25 mg/kg per day and 50 mg/kg per day pravastatin and 5 mg/kg per day simvastatin promoted aneurysmal growth, and high-dose pravastatin induced aneurysmal rupture. The deleterious effects exerted by these statins were associated with an increase in apoptotic caspase-3 levels and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, suggesting that statins exert bidirectional effects., Conclusions: Our results provide the first evidence that cerebral aneurysm growth is partly associated with apoptosis and issue a warning that statins exert bidirectional effects on cerebral aneurysms. Additional intensive research is necessary to understand better their mechanisms and to identify patients in whom the administration of statins may elicit deleterious effects.

Like the angiotensin II type 1 receptor blocker, endogenous estrogen (17β-estradiol) is neuroprotective against cerebral ischemia; its effects are thought to be mediated by estrogen receptors (ERs). To verify the role of ERs and the brain renin-angiotensin system in estrogen-deficient rats with ischemia induced by middle cerebral artery occlusion, we compared rats subjected to oophorectomy (OVX(+)) with sham-oophorectomized rats (OVX(-)) and OVX(+) rats treated with 0.3 or 3.0 mg/kg of olmesartan for 2 weeks before middle cerebral artery occlusion. Independent of the blood pressure, the cortical infarct volume was larger in OVX(+) than in OVX(-) rats. It was smaller in olmesartan-pretreated OVX(+) rats. The expression of ERα in the peri-infarct region was correlated with the reduction of cortical infarct but not that of ERβ or G protein-coupled estrogen receptor. Olmesartan prevented ERα downregulation in the cortical peri-infarct area, without affecting ERβ or G protein-coupled estrogen receptor. Olmesartan also increased mRNA expression of angiotensin-converting enzyme 2, Bcl-2, and Bcl-xL and reduced angiotensin II and cleaved caspase 3. These effects were augmented by olmesartan and abolished by the ER inhibitor. In OVX(+) rats treated with the ERα agonist alone, the infarct size was decreased, and the neuroprotective genes were upregulated. These findings suggest that the transactivation of neuroprotective genes and the reduction in brain angiotensin II are ERα dependent and that this may augment neuroprotection together with an angiotensin II type 1 receptor blockade by olmesartan. We present the new insight that the activation of ERα independent of estrogen contributes at least partly to limiting cerebral ischemic damage.

Akt, one of the major downstream effectors of phosphatidylinositol 3-kinase, is hyper-expressed and activated in a variety of cancers including glioblastoma. However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well understood. Therefore, we examined the protein and mRNA expression patterns of Akt isoforms in tissues from human astrocytomas, glioblastomas, and non-neoplastic regions. We also explored the biological role of each Akt isoform in malignant glioma cells using RNA interference-mediated knock-down and the over-expression of plasmid DNA of each isoform. The expression of Akt1 protein and mRNA was similar in glioma and normal control tissues. Although the protein and mRNA level of Akt2 increased with the pathological grade of malignancy, the expression of Akt3 mRNA and protein decreased as the malignancy grade increased. In U87MG, T98G, and TGB cells, the down-regulation of Akt2 or Akt3 by RNA interference reduced the expression of the phosphorylated form of Bad, resulting in the induction of caspase-dependent apoptosis. Akt1 knock-down did not affect cell growth or survival. We first demonstrate that the over-expression of Akt2 or Akt3 down-regulated the expression of the other protein and that endogenous Akt3 protein showed high kinase activity in U87MG cells. Our data suggest that Akt2 and Akt3 play an important role in the viability of human malignant glioma cells. Targeting Akt2 and Akt3 may hold promise for the treatment of patients with gliomas.

A 15-month-old girl presented with a spinal pilomyxoid astrocytoma manifesting as a 3-month history of dysphagia. Magnetic resonance imaging showed an intramedullary mass of the cervical spinal cord at C1-C6 with syringobulbia. She underwent partial removal of the tumor and received postoperative chemotherapy with cisplatin and etoposide. The tumor completely responded to the treatment and has not relapsed for 64 months. Pilomyxoid astrocytoma frequently occurs in the opticohypothalamic regions but is rare in the spine. The present case suggests that surgery followed by chemotherapy with cisplatin and etoposide may be an effective therapeutic option for pilomyxoid astrocytoma of the cervical spinal cord.

Promyelocytic leukemia (PML) protein plays an essential role in the induction of apoptosis; its expression is reduced in various cancers. As the functional roles of PML in glioblastoma multiforme (GBM) have not been clarified, we assessed the expression of PML protein in GBM tissues and explored the mechanisms of PML-regulated cell death in GBM cells. We examined the PML mRNA level and the expression of PML protein in surgical GBM specimens. PML-regulated apoptotic mechanisms in GBM cells transfected with plasmids expressing the PML gene were examined. The protein expression of PML was significantly lower in GBM than in non-neoplastic tissues; approximately 10% of GBM tissues were PML-null. The PML mRNA levels were similar in both tissue types. The overexpression of PML activated caspase-8 and induced apoptosis in GBM cells. In these cells, PML decreased the expression of transactivated forms of NFkappaB/p65, and c-FLIP gene expression was suppressed. Therefore, PML-induced apoptosis resulted from the suppression of the transcriptional activity of NFkappaB/p65. PML overexpression decreased phosphorylated IkappaBalpha and nuclear NFkappaB/p65 and increased the expression of the suppressor of cytokine signaling (SOCS-1). A proteasome inhibitor blocked the reduction of activated p65 by PML. The reduction of PML is associated with the pathogenesis of GBM. PML induces caspase-8-dependent apoptosis via the repression of NFkappaB activation by which PML facilitates the proteasomal degradation of activated p65 and the sequestration of p65 with IkappaBalpha in the cytoplasm. This novel mechanism of PML-regulated apoptosis may represent a therapeutic target for GBM.

The progression of glioma to more malignant phenotypes results from the stepwise accumulation of genetic alterations and the consequent disruption of the apoptotic pathway and augmentation of survival signaling. REIC/Dkk-3, a member of the human Dickkopf (Dkk) family, plays a role as a suppressor of the growth of several human cancers; however, to date it has not been identified in brain tumors. We compared the gene and protein expression of REIC/Dkk-3 in human malignant glioma and normal brain tissues using quantitative real-time PCR, Western blotting, and immunohistochemistry. We also performed small interfering REIC/Dkk-3 (siREIC/Dkk-3) knockdown and REIC/Dkk-3 overexpression experiments to examine the role of REIC/Dkk-3 in human malignant glioma cells in vitro. In brain tissue from patients with malignant glioma, the gene and protein expression of REIC/Dkk-3 was lower than in normal brain tissue and was related to the malignancy grade. In the primary glioblastoma cell line, REIC/Dkk-3 transfection led to apoptosis owing to the activation of phosphorylated JUN, caspase-9, and caspase-3 and the reduction of beta-catenin; in REIC/Dkk-3 knockdown experiments, cell growth was augmented. Our results suggest that REIC/Dkk-3 regulates the growth and survival of these cells in a caspase-dependent and -independent way via modification of the Wnt signaling pathway. Our work is the first documentation that the gene and protein expression of REIC/Dkk-3 is down-regulated in human malignant glioma. Our demonstration of the mechanisms underlying REIC/Dkk-3-induced cell death indicates that REIC/Dkk-3 plays a pivotal role in the biology of human malignant glioma and suggests that REIC/Dkk-3 is a promising candidate for molecular target therapy.

A 64-year-old woman presented with a rare anaplastic ganglioglioma in the right cerebellopontine angle manifesting as dizziness persisting for 2 weeks. Preoperative magnetic resonance (MR) imaging revealed a partially enhanced cystic lesion of the right cerebellopontine angle. The tumor was subtotally removed through a right lateral suboccipital craniectomy. The tumor was thought to originate from the brain stem with exophytic growth into the right cerebellopontine angle. Histological examination showed neoplastic ganglional and glial cells with anaplastic features such as mitosis, pleomorphism, and endothelial proliferation. The MIB-1 labeling index of the glial components was 40% to 60%. The diagnosis was anaplastic ganglioglioma (World Health Organization grade IV). She received postoperative radiotherapy but died of respiratory failure with tumor recurrence 11 months after the operation. Gangliogliomas usually have a good prognosis. Histological features of anaplasia and a high MIB-1 labeling index may be predictive of a poor clinical outcome.

A 16-year-old woman presented with a non-germinomatous germ cell tumor in the neurohypophysis manifesting as progressive visual disturbance, amenorrhea, hydrodipsia, and polyuria. Her serum alpha-fetoprotein and human chorionic gonadotropin levels were elevated. She experienced sudden, rapid visual deterioration and underwent emergency partial tumor removal to decompress the optic nerves. Her vision subsequently improved. Histological examination of the surgical specimens confirmed immature teratoma. She received chemotherapy (ifosphamide 900 mg/m2, cisplatin 20 mg/m2, etoposide 60 mg/m2) for 5 consecutive days. Although the tumor marker levels decreased remarkably, her vision again declined rapidly due to enlargement of the tumor after the first course of chemotherapy. A second radical operation resulted in vision improvement. The tumor specimen showed only mature teratoma elements. This phenomenon, called the growing teratoma syndrome, is very rare in intracranial non-germinomatous germ cell tumors.

The differential diagnosis between brain abscesses and necrotic tumors such as glioblastomas is sometimes difficult to establish by conventional computed tomography and magnetic resonance imaging. Combined proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted magnetic resonance imaging (DWI) were used to establish the preoperative diagnosis of brain abscess and glioblastoma. DWI visualized the brain abscess as a homogeneous hyperintense lesion and 1H-MRS revealed the presence of acetate, lactate, and amino acids and the absence of the normal brain components. DWI sometimes shows glioblastoma as a hyperintense lesion, but 1H-MRS reveals markedly increased lactate and decreased N-acetyl-aspartate. Combined DWI and 1H-MRS findings can distinguish brain abscess and glioblastoma.

A 57-year-old man developed visual loss following craniofacial surgery for an inflammatory ethmoidal sinus mass. Surgery was preceded by endovascular occlusion of the ophthalmic artery distal to central retinal artery (CRA). Routine angiography obtained immediately after endovascular ophthalmic artery occlusion showed patency of the CRA. He complained of visual loss one day after craniofacial surgery (2 days after embolization). Repeat emergency angiography confirmed the patent CRA. Ophthalmic examination and fluorescein angiography showed that the visual loss was due to anterior ischemic optic neuropathy (AION). Preservation of the CRA is critical during ophthalmic artery embolization to avoid visual complications. Neurosurgeons should be aware of the possibility of AION as a complication of ophthalmic artery embolization.

The authors report a case of endolymphatic sac tumor (ELST) associated with Von Hippel-Lindau disease (VHL). A 20-year-old female VHL patient received a resection of a cerebellar hemangioblastoma 3 years ago and she had a co-existing of left petrous tumor. The petrous tumor showed a remarkable progression in 3 years and was resected subtotally. Histologically, the resected petrous tumor showed a papillary structure containing cuboidal or columnar cells with fibrous stroma and numerous microvessels and destructed temporal bone, all of which are consistent with ELST. We studied the expression of various kinds of cytokeratins (CKs) immunohistochemically and found distinct expression of CKs (CAM 5.2, 34betaE-12, CK7, CK8 and CK19), but not for CK10/13 or CK20. Vascular endothelial growth factor and neuron specific enolase showed strong immunoreactivity in the tumor cells. CD34 also had weak expression. Ki-67 antigen (MIB-1) immunoreactivity was found in focal areas, and the labeling index in the highest-density area was 48.9%. These findings suggest that vascular endothelial growth factor overexpression is an important factor for angiogenesis in ELST, much like other VHL-associated tumors, and that ELST may have a more highly aggressive component than the low-grade malignancy noted in previous reports.