Integrated proteogenomic characterization of glioblastoma evolution.

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.

Comparison of Postoperative Complications between Simultaneous and Staged Surgery in Cranioplasty and Ventriculoperitoneal Shunt Placement after Decompressive Craniectomy.

OBJECTIVE: Cranioplasty (CP) and ventriculoperitoneal shunt (VPS) are required procedures following decompressive craniectomy (DC) for craniofacial protection and to prevent hydrocephalus. This study assessed the safety and efficacy of simultaneous operation with CP and VPS after DC, and determined the preoperative risk factors for postoperative complications. METHODS: Between January 2009 and December 2019, 81 patients underwent CP and VPS in simultaneous or staged operations following DC. Cumulative medical records and radiologic data were analyzed using univariate analysis to identify factors predisposing patients to complications after CP and VPS. RESULTS: CP and VPS were performed as simultaneous or staged operations in 18 (22.2%) and 63 (77.8%) patients, respectively. The overall postoperative complication rate was 16.0% (13/81). Patients who underwent simultaneous CP and VPS were significantly more likely to experience complications when compared with patients who underwent staged operations (33.3% vs. 9.6%, p<0.01). Univariate analysis revealed that simultaneous CP and VPS surgery was the only significant predictor of postoperative complications (p=0.031). CONCLUSION: This study provided detailed data on surgical timing and complications for CP and VPS after DC. We showed that simultaneous procedures were a significant risk factor for postoperative complications.

Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP downregulates stemness phenotype and mesenchymal trans-differentiation after irradiation in glioblastoma multiforme.

Radiation therapy is among the most essential treatment methods for glioblastoma multiforme (GBM). Radio-resistance and cancer stem cell properties can cause therapeutic resistance, cancer heterogeneity, and poor prognoses in association with GBM. Furthermore, the GBM subtype transition from proneural to the most malignant mesenchymal subtype after radiation therapy also accounts for high resistance to conventional treatments. Here, we demonstrate that the inhibition of macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) by 4-iodo-6-phenylpyrimidine (4-IPP), a dual inhibitor targeting MIF and DDT, downregulates stemness phenotype, intracellular signaling cascades, mesenchymal trans-differentiation, and induces apoptosis in proneural glioma stem cells (GSCs). In an analysis of The Cancer Genome Atlas, high MIF and DDT expression were associated with poor prognosis. GSC growth was effectively inhibited by 4-IPP in a time- and dose-dependent manner, and 4-IPP combined with radiation therapy led to significantly reduced proliferation compared with radiation therapy alone. The expression of stemness factors, such as Olig2 and SOX2, and the expression of pAKT, indicating PI3K signaling pathway activation, were decreased in association with both 4-IPP monotherapy and combination treatment. The expression of mesenchymal markers, TGM2 and NF-κB, and expression of pERK (indicating MAPK signaling pathway activation) increased in association with radiation therapy alone but not with 4-IPP monotherapy and combination therapy. In addition, the combination of 4-IPP and radiation therapy significantly induced apoptosis compared to the monotherapy of 4-IPP or radiation. In vivo results demonstrated a significant tumor-suppressing effect of 4-IPP when combined with radiation therapy. Collectively, our results showed that the targeted inhibition of MIF and DDT has the potential to strengthen current clinical strategies by enhancing the anticancer effects of radiation therapy.

Clinical Pathway for Emergency Brain Surgery during COVID-19 Pandemic and Its Impact on Clinical Outcomes.

BACKGROUND: One of the challenges neurosurgeons are facing in the global public health crisis caused by the coronavirus disease 2019 (COVID-19) pandemic is to balance COVID-19 screening with timely surgery. We described a clinical pathway for patients who needed emergency brain surgery and determined whether differences in the surgery preparation process caused by COVID-19 screening affected clinical outcomes. METHODS: During the COVID-19 period, patients in need of emergency brain surgery in our institution were managed using a novel standardized pathway designed for COVID-19 screening. We conducted a retrospective review of patients who were hospitalized through the emergency room and underwent emergency brain surgery. A total of 32 patients who underwent emergency brain surgery from February 1 to June 30, 2020 were included in the COVID-19 group, and 65 patients who underwent surgery from February 1 to June 30, 2019 were included in the pre-COVID-19 group. The baseline characteristics, disease severity indicators, time intervals of emergency processes, and clinical outcomes of the two groups were compared. Subgroup analysis was performed between the immediate surgery group and the semi-elective surgery group during the COVID-19 period. RESULTS: There were no significant differences in baseline characteristics and severity indicators between the pre-COVID-19 group and COVID-19 group. The time interval to skin incision was significantly increased in the COVID-19 group (P = 0.027). However, there were no significant differences in the clinical outcomes between the two groups. In subgroup comparison, the time interval to skin incision was shorter in the immediate surgery group during the COVID-19 period compared with the pre-COVID-19 group (P = 0.040). The screening process did not significantly increase the time interval to classification and admission for immediate surgery. The time interval to surgery initiation was longer in the COVID-19 period due to the increased time interval in the semi-elective surgery group (P < 0.001). CONCLUSION: We proposed a clinical pathway for the preoperative screening of COVID-19 in patients requiring emergency brain surgery. No significant differences were observed in the clinical outcomes before and after the COVID-19 pandemic. The protocol we described showed acceptable results during this pandemic.

Growth profile assessment of young adults with tethered cord syndrome: a retrospective cohort analysis of Korean conscription data.

PURPOSE: Tethered cord syndrome (TCS) is characterized by progressive spinal cord degeneration secondary to congenital spinal dysraphism. The associated accompanying physical inactivity and musculoskeletal deformities have raised interest in the growth profile of adult TCS patients. However, few previous studies have investigated the growth profile of adult TCS patients. METHODS: We retrospectively reviewed the demographic data and medical records of 20-year-old Korean conscription examinees who were registered between April 2004 and September 2019. In total, 151 examinees with a diagnosis of TCS were enrolled. The height, weight, and body mass index (BMI) of 300 randomly selected examinees were compared to the TCS group. Obesity was defined by the World Health Organization and Asian-Pacific criteria for BMI and compared between the groups. Growth profile differences according to tethering location and musculoskeletal deformities were analyzed in both groups. RESULTS: The mean height, weight, and BMI values of the TCS group were lower than those of the control group. The TCS group had a lower proportion of obese and overweight individuals, and a higher proportion of underweight individuals, according to both BMI criteria. The tethering level was not associated with the degree of obesity in the tethered group. The mean height, weight, and BMI were lower in the tethered group regardless of the existence of musculoskeletal deformity. CONCLUSION: Enrollees with a history of TCS were smaller than controls of the same age. Monitoring of health behaviors, including nutrition, diet, and exercise, is warranted for TCS patients.

Comparison of Postoperative Surgical-Site Infection and Symptomatic Intracranial Hemorrhage between Staged and Simultaneous Cranioplasty with Ventriculoperitoneal Shunt Placement: A Meta-Analysis.

OBJECTIVE: Consensus about the sequence of cranioplasty and ventriculoperitoneal shunt placement to reduce postoperative complications has not been established. This meta-analysis investigated and collated further evidence to determine whether staged cranioplasty with ventriculoperitoneal shunt placement would significantly reduce the risk of postoperative surgical-site infection (SSI) and symptomatic intracranial hemorrhage. METHODS: Two independent reviewers identified articles and extracted the data of patients who underwent cranioplasty and ventriculoperitoneal shunt placement from PubMed, Embase, and Cochrane Central Register of Controlled Trials. A random effects model was used to compare the complication rates using odd ratios (ORs) and 95% confidence intervals (CIs). A meta-regression analysis for traumatic brain injury (TBI) was additionally performed. RESULTS: Data from 7 studies with 391 patients were consecutively included. The meta-analysis revealed that staged surgery was significantly associated with lower rates of SSI after decompressive craniectomy (staged group vs. simultaneous group: 6.2% vs. 23.7%, OR: 2.72, 95% CI: 1.46-5.06, I2=2.4%, p=0.407). Pooled analysis did not indicate a statistically significant difference between the 2 groups for symptomatic intracranial hemorrhage (staged group vs. simultaneous group: 10.4% vs. 23.0%, OR: 1.66, 95% CI: 0.74-3.73, I2=0.0%, p=0.407). The meta-regression analysis did not indicate any modifying effect of TBI on postoperative SSI development (p=0.987). CONCLUSION: This meta-analysis indicated that staged surgery is significantly associated with a lower rate of postoperative SSI as compared with simultaneous surgery, but there is no difference in symptomatic intracranial hemorrhage. Additionally, there is no modifying effect of TBI on SSI.

Relationship between Increased Intracranial Pressure and Mastoid Effusion.

OBJECTIVE: This study aimed to assess the relationship between increased intracranial pressure (ICP) and mastoid effusions (ME). METHODS: Between January 2015 and October 2018, patients who underwent intracranial surgery and had ICP monitoring catheters placed were enrolled. ICP was recorded hourly for at least 3 days. ME was determined by the emergence of opacification in mastoid air cells on follow-up brain imaging. C-reactive protein (CRP) levels, presence of endotracheal tube (ETT) and nasogastric tube (NGT), duration of intensive care unit (ICU) stay, duration of mechanical ventilator application, diagnosis, surgical modalities, and presence of sinusitis were recorded. Each factor's effect on the occurrence of ME was analyzed by binary logistic regression analyses. To analyze the independent effects of ICP as a predictor of ME a multivariable logistic regression analysis was performed. RESULTS: Total of 61 (53%) out of 115 patients had ME. Among the patients who had unilateral brain lesions, 94% of subject (43/50) revealed the ipsilateral development of ME. ME developed at a mean of 11.1±6.2 days. The variables including mean ICP, peak ICP, age, trauma, CRP, ICU stays, application of mechanical ventilators and presence of ETT and NGT showed statistically significant difference between ME groups and non-ME groups in univariate analysis. Sex and the occurrence of sinusitis did not differ between two groups. Adding the ICP variables significantly improved the prediction of ME in multivariable logistic regression analysis. CONCLUSION: While multiple factors affect ME, this study demonstrates that ICP and ME are probably related. Further studies are needed to determine the mechanistic relationship between ICP and middle ear pressure.

Arachnoid Plasty to Prevent and Reduce Chronic Subdural Hematoma after Clipping Surgery for Unruptured Intracranial Aneurysm : A Meta-Analysis.

OBJECTIVE: Recent studies have reported that arachnoid plasty (ARP) using gelatin sponges with fibrin glue reduced the occurrence of chronic subdural hematoma (CSDH) following clipping surgery for unruptured intracranial aneurysm (UIA). This metaanalysis was conducted to collate further evidence for the efficacy of ARP in preventing postoperative CSDH. METHODS: Data of patients who underwent clipping surgery were extracted from PubMed, EMBASE, and Cochrane Central Register of Controlled Trials by two independent reviewers. A random effects model was used to investigate the efficacy of ARP by using odd ratios (ORs) and 95% confidence intervals (CIs). A meta-regression analysis for male sex was additionally preformed. RESULTS: Data from six studies with 1715 patients were consecutively included. Meta-analysis revealed that ARP was significantly associated with lower rates of CSDH development after surgical clipping for UIA (ARP group vs. control group : 3.2% vs. 7.2%; OR, 0.40; 95% CI, 0.18-0.93; I2 =44.3%; p=0.110). Meta-regression analysis did not highlight any modifying effect of the male sex on postoperative CSDH development (p=0.951). CONCLUSION: This meta-analysis indicated that ARP reduced the incidence rates of CSDH following clipping surgery for UIA. If feasible, ARP would be implemented as an additional surgical technique to prevent postoperative CSDH development during surgical clipping of UIA.

Critical Depressed Brain Volume Influences the Recurrence of Chronic Subdural Hematoma after Surgical Evacuation.

Recurrence of chronic subdural hematoma (CSDH) frequently occurs after surgical evacuation. However, the value of follow-up postoperative imaging and measuring volumetric factors to predict recurrence are still controversial. Herein, we aimed to assess the optimal timing for follow-up referential imaging and the critical depressed brain volume for CSDH recurrence. A total of 291 patients with CSDH who underwent burr hole craniotomy between January 2012 and December 2018 were consecutively enrolled in this study. Patients' medical records and radiologic data were evaluated to predict the recurrence and analyzed using receiver operating characteristics (ROC) and binary logistic regression. Of the 291 patients, 29 (10.0%) showed recurrence after surgical evacuation. Based on ROC analysis, comparisons of depressed brain volume pre-operation, 24 h post-operation, and 7 days post-operation showed that the depressed brain volume at 7 days after surgery featured the largest area under the curve (AUC: 0.768, 95% CI, 0.709-0.811). The cut-off value of the depressed brain volume on postoperative day 7 was 51.6 cm3; this value predicted the recurrence of CSDH with a sensitivity and specificity of 79.3% and 67.9%, respectively. In the multivariate analysis, the depressed brain volume (>50 cm3) at 7 days was the sole significant risk factor related to the recurrence of CSDH in this series (OR: 6.765, 95% CI, 2.551-17.942, p < 0.001). The depressed brain volume > 50 cm3 visualized on CT scans at postoperative 7 day is the critical volume affecting recurrence of CSDHs. This result could be helpful carrying in patients with CSDH to determine the proper postoperative treatment strategy.

Psychopathological Influence of Middle Fossa Arachnoid Cysts in Young Men: Analysis of Korean Conscription Data.

BACKGROUND: A few reported studies have documented psychotic syndromes secondary to a middle fossa arachnoid cyst (AC). However, the association between middle fossa ACs and psychopathological symptoms remains to be determined. The present study investigated the psychopathological effects of middle fossa ACs in young men. METHODS: We reviewed military personal inventory test profiles and baseline demographic data of 19-year-old conscription examinees from February 2013 to December 2016. In total, 132 examinees with middle fossa ACs and 350 examinees with normal findings were enrolled in the present study. Two separate comparisons were performed. First, we compared the middle fossa AC group with the control group. Second, the middle fossa AC group was divided into 2 groups according to cyst size and compared with the control group. RESULTS: Faking bad response behavior, infrequency, inconsistency, depression, schizophrenia, paranoia, and personality disorder cluster A scales were significantly associated with the presence of a middle fossa AC. Abnormal responses to the military personal inventory were significantly and positively correlated with cyst size. The prediction rate to show abnormal psychological results with the presence of an AC was estimated to be 60.7%-68.8%. CONCLUSIONS: The presence of ACs and cyst size were associated with psychopathology in this select group of young men. The size-dependent psychopathological effects of ACs appear to result from a local mass effect on the brain.

Effect of a bisphosphonate and selective estrogen receptor modulator on bone remodeling in streptozotocin-induced diabetes and ovariectomized rat model.

BACKGROUND CONTEXT: Diabetes and menopause can cause severe osteoporosis. In general, menopause and diabetes can lead to an imbalance in bone turnover, which results in secondary osteoporosis. However, the efficacy of antiresorptive drugs against this form of osteoporosis has not been extensively evaluated. OBJECTIVE: The aim of this study was to determine the changes in vertebral bone remodeling when postmenopausal osteoporosis is accompanied by diabetes and to compare the efficacy of bisphosphonates and selective estrogen-receptor modulators (SERMs) against these outcomes. STUDY DESIGN: Streptozotocin-induced diabetic, ovariectomized Sprague-Dawley rats were used as the disease model. Alendronate and raloxifene were used as the bisphosphonate and SERM, respectively. METHODS: We divided 62 female rats into five groups: (1) control (n=14), (2) DM (diabetes) (n=12), (3) DM+OVX (diabetes+ovariectomy) (n=12), (4) DM+OVX+A (diabetes+ovariectomy+alendronate) (n=12), and (5) DM+OVX+R (diabetes+ovariectomy+raloxifene) (n=12). Serum biochemical markers of bone turnover, including osteocalcin and the C-telopeptide of type I collagen (CTX-1), were analyzed. We measured histomorphometric parameters of the fourth lumbar vertebrae using microcomputed tomography. Mechanical strength was evaluated by a compression test. RESULTS: In the DM and DM+OVX group, only the levels of osteocalcin significantly decreased compared with those of the control group at 8 weeks after OVX. At 12 weeks, the serum CTX-1 levels in the DM+OVX+A and DM+OVX+R groups were significantly lower than those of the DM+OVX group, but there were no changes in the levels of osteocalcin. Bone mineral density and mechanical strength were higher in the DM+OVX+A and DM+OVX+R groups than in the DM and DM+OVX groups (p<.05). CONCLUSIONS: Even if postmenopausal osteoporosis is accompanied by diabetes in this animal model, both alendronate and raloxifene seem to show antiresorptive effects, decreased bone turnover rates, and improved bone mechanical strength. Therefore, alendronate and raloxifene are effective in the treatment of osteoporosis even for bone loss caused by DM and postmenopausal osteoporosis.

A Case of Coincidental Intrasellar Chordoma and Pituitary Adenoma.

Although chordomas are midline tumors, primarily intrasellar chordomas are extremely rare. In this report, the authors describe the case of a 68-year-old female with partial abducens nerve palsy in the right eye due to the intrasellar cystic tumor. After endonasal trans-sphenoidal surgery, intraoperative and histopathological findings confirmed the co-occurrence of an entirely intrasellar chordoma and pituitary adenoma. To our knowledge, the present case is the third reported case of an intrasellar chordoma with a pituitary adenoma.

Use of Three-Dimensional Curved-Multiplanar Reconstruction Images for Sylvian Dissection in Microsurgery of Middle Cerebral Artery Aneurysms.

PURPOSE: The purpose of this study was to introduce a method of using three-dimensional (3D) curved-multiplanar reconstruction (MPR) images for sylvian dissection during microsurgical treatment of middle cerebral artery (MCA) aneurysms. MATERIALS AND METHODS: Forty-nine patients who had undergone surgery for MCA aneurysms were enrolled. We obtained the 3D curved-MPR images along the sphenoid ridge using OsiriX MD™ imaging software, compared sylvian dissection time according to several 3D MPR image factors, and investigated the correlations between these images and intraoperative findings. RESULTS: Utilizing preoperative information of the sylvian fissure (SF) and peri-aneurysmal space on 3D curved-MPR images, we could predict the feasibility of sylvian dissection for a safe surgery. 3D curved-MPR images showed several features: first, perpendicular images to the sylvian surface in the same orientation as the surgeon's view; second, simultaneous visualization of the brain cortex, vessels, and cisternal space; and third, more accurate measurement of various parameters, such as depth of the MCA from the sylvian surface and the location and width of the SFs. CONCLUSION: In addition to conventional image studies, 3D curved-MPR images seem to provide useful information for Sylvian dissection in the microsurgical treatment of MCA aneurysms.

Role of a Burr Hole and Calvarial Bone Marrow-Derived Stem Cells in the Ischemic Rat Brain: A Possible Mechanism for the Efficacy of Multiple Burr Hole Surgery in Moyamoya Disease.

OBJECTIVE: This study investigates the role of a burr hole and calvarial bone marrow-derived stem cells (BMSCs) in a transient ischemic brain injury model in the rat and postulates a possible mechanism for the efficacy of multiple cranial burr hole (MCBH) surgery in moyamoya disease (MMD). METHODS: Twenty Sprague-Dawley rats (250 g, male) were divided into four groups : normal control group (n=5), burr hole group (n=5), ischemia group (n=5), and ischemia+burr hole group (n=5). Focal ischemia was induced by the transient middle cerebral artery occlusion (MCAO). At one week after the ischemic injury, a 2 mm-sized cranial burr hole with small cortical incision was made on the ipsilateral (left) parietal area. Bromodeoxyuridine (BrdU, 50 mg/kg) was injected intraperitoneally, 2 times a day for 6 days after the burr hole trephination. At one week after the burr hole trephination, brains were harvested. Immunohistochemical stainings for BrdU, CD34, VEGF, and Doublecortin and Nestin were done. RESULTS: In the ischemia+burr hole group, BrdU (+), CD34 (+), and Doublecortin (+) cells were found in the cortical incision site below the burr hole. A number of cells with Nestin (+) or VEGF (+) were found in the cerebral parenchyma around the cortical incision site. In the other groups, BrdU (+), CD34 (+), Doublecortin (+), and Nestin (+) cells were not detected in the corresponding area. These findings suggest that BrdU (+) and CD34 (+) cells are bone marrow-derived stem cells, which may be derived from the calvarial bone marrow through the burr hole. The existence of CD34 (+) and VEGF (+) cells indicates increased angiogenesis, while the existence of Doublecortin (+), Nestin (+) cells indicates increased neurogenesis. CONCLUSION: Based on these findings, the BMSCs through burr holes seem to play an important role for the therapeutic effect of the MCBH surgery in MMD.

Leptomeningeal carcinomatosis of gastric cancer misdiagnosed as vestibular schwannoma.

Gastric cancer is one of the most common causes of cancer-related death in Asian countries, including Korea. We experienced a case of leptomeningeal carcinomatosis (LC) from gastric cancer that was originally misdiagnosed as vestibular schwannoma based on the similar radiological characteristics. To our knowledge, LC from gastric cancer is very rare. In conclusion, our experience with this case suggests that clinicians should consider the possibility of delayed leptomeningeal metastasis when treating patients with gastric cancer.

Locations and clinical significance of non-hemorrhagic brain lesions in diffuse axonal injuries.

OBJECTIVE: Detection of focal non-hemorrhagic lesion (NHL) has become more efficient in diffuse axonal injury (DAI) patients using an MRI. The aims of this study are to find out the radiological distribution, progress of NHL and its clinical significance. METHODS: Between September 2005 and October 2011, 32 individuals with NHLs on brain MRI were enrolled. NHLs were classified by brain location into 4 major districts and 13 detailed locations including cortical and subcortical, corpus callosum, deep nuclei and adjacent area, and brainstem. The severity of NHL was scored from grades 1 to 4, according to the number of districts involved. Fourteen patients with NHL were available for MRI follow-up and an investigation of the changes was conducted. RESULTS: Thirty-two patients had 59 NHLs. The most common district of NHL was cortical and subcortical area; 15 patients had 20 NHSs. However the most common specific location was the splenium of the corpus callosum; 14 patients had 14 lesions. The more lesions patients had, the lower the GCS, however, this was not a statistically meaningful difference. On follow-up MRI in 14 patients, out of 24 lesions, 13 NHLs resolved, 5 showed cystic change, and 6 showed atrophic changes. CONCLUSION: NHLs were located most commonly in the splenium and occur frequently in the thalamus and the mesial temporal lobe. Because most NHS occur concomitantly with hemorrhagic lesions, it was difficult to determine their effects on prognosis. Since most NHLs resolve completely, they are probably less significant to prognosis than hemorrhagic lesions.

Generation of cancerous neural stem cells forming glial tumor by oncogenic stimulation.

Neural stem cells in the brain have been shown to be 'cells of origin' of certain brain cancers, most notably astrocytomas and medulloblastoma. In particular, in a mouse model, the targeting of genetic modifications for astrocytoma-relevant tumor suppressors to neural stem cells causes malignant astrocytoma to arise, thereby suggesting that astrocytoma is derived from neural stem cells. However, it remains to be determined whether this important finding is reproducible in humans. Herein, we generated cancerous neural stem cells by introducing a set of oncogenes to human fetal neural stem cells (hfNSCs). Serial genetic modification with v-myc for immortalization and consequent H-Ras for oncogenic stimulation with viral gene delivery proved sufficient to induce the transformation of hfNSCs. The resultant F3.Ras cells evidenced a variety of the hallmarks of brain cancer stem cells and most importantly were tumorigenic, forming brain cancers consisting of both a large number of differentiated and a very few undifferentiated populations of cells in an in vivo mouse model. On the contrary, oligodendrocytes derived from the v-myc expressing parent neural stem cells were not transformed by H-Ras, which suggests that neural stem cells may be more susceptible to cancerous transformation by a combination of oncogenes. We also determined that v-myc expressing fetal neural stem cells were defective in p53 response upon the introduction of H-Ras; this finding suggests that an insufficient p53-dependent tumor suppressive mechanism would be associated with high oncogenic susceptibility to H-Ras introduction.

Radiological apoplexy and its correlation with acute clinical presentation, angiogenesis and tumor microvascular density in pituitary adenomas.

OBJECTIVE: Pituitary apoplexy is life-threatening clinical syndrome caused by the rapid enlargement of a pituitary tumor due to hemorrhage and/or infarction. The pathogenesis of pituitary apoplexy is not completely understood. We analyzed the magnetic resonance imaging (MRI) of pituitary tumors and subsequently correlated the radiological findings with the clinical presentation. Additionally, immunohistochemistry was also performed to determine whether certain biomarkers are related to radiological apoplexy. METHODS: Thirty-four cases of pituitary adenoma were enrolled for retrospective analysis. In this study, the radiological apoplexy was defined as cases where hemorrhage, infarction or cysts were identified on MRI. Acute clinical presentation was defined as the presence of any of the following symptoms: severe sudden onset headache, decreased visual acuity and/or visual field deficit, and acute mental status changes. Angiogenesis was quantified by immunohistochemical expression of fetal liver kinase 1 (Flk-1), neuropilin (NRP) and vascular endothelial growth factor (VEGF) expression, while microvascular density (MVD) was assessed using Endoglin and CD31. RESULTS: Clinically, fourteen patients presented with acute symptoms and 20 for mild or none clinical symptoms. Radiologically, fifteen patients met the criteria for radiological apoplexy. Of the fifteen patients with radiologic apoplexy, 9 patients presented acute symptoms whereas of the 19 patient without radiologic apoplexy, 5 patients presented acute symptoms. Of the five biomarkers tracked, only VEGF was found to be positively correlated with both radiological and nonradiological apoplexy. CONCLUSION: While pituitary apoplexy is currently defined in cases where clinical symptoms can be histologically confirmed, we contend that cases of radiologically identified pituitary hemorrhages that present with mild or no symptoms should be designated subacute or subclinical apoplexy. VEGF is believed to have a positive correlation with pituitary hemorrhage. Considering the high rate of symptomatic or asymptomatic pituitary tumor hemorrhage, additional studies are needed to detect predictors of the pituitary hemorrhage.

Supratentorial clear cell ependymoma mimicking oligodendroglioma : case report and review of the literature.

Clear cell ependymomas (CCEs) are rare variants of ependymomas. Tumors show anaplastic histological features and behave as an aggressive manner. CCEs have a predilection for extraneural metastases and early recurrence, and they demonstrate characteristic radiographic features. These tumors should be radiologically and pathologically differentiated from oligodendrogliomas. On microscopic examination, CCEs are composed of sheets of cells and resemble oligodendroglioma. However, upon closer examination, the nature of CCEs can be detected earlier, resulting in prompt treatment of the tumor. Although we report only one case, we emphasize the importance of early diagnosis and treatment. Future description of more cases of these rare cancers is necessary to aid in their diagnosis and treatment.