Prognostic importance of temozolomide-induced neutropenia in glioblastoma, IDH-wildtype patients.

Standard treatment for patients with primary glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Recent reports have demonstrated that TMZ-induced myelosuppression correlates with survival in patients with GBM. However, those results were evaluated before the 2016 revision of the World Health Organization classification. This study examined whether myelosuppression during concomitant TMZ phase correlates with prognosis in GBM, IDH-wildtype patients. We examined circulating blood cell counts in 50 patients with GBM, IDH-wildtype who received the standard treatment protocol between August 2005 and November 2015. We assessed relationships between rates of decrease in blood cells (white blood cells (WBC), neutrophils, lymphocytes, red blood cells, and platelets) during the concomitant TMZ phase and overall survival (OS) using univariate and multivariate analyses including other clinicopathological factors (age, sex, Karnofsky Performance Status (KPS), extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) status). Log-rank testing revealed that age, KPS, extent of resection, MGMT status, and decrease rates of WBC, neutrophils, and platelets correlated significantly with OS. On multivariate analysis, age, MGMT status, and decrease rate of neutrophils correlated significantly with OS. Patients with a ≥ 40% decrease in neutrophils showed significantly longer OS than those with < 40% (hazard ratio = 2.815; 95% confidence interval = 1.177-7.038; P = 0.0196). A decrease of ≥ 40% in neutrophils represents a predictor of good prognosis for GBM, IDH-wildtype. Blood cell counts during the concomitant TMZ phase can help predict OS in patients with GBM, IDH-wildtype receiving the standard treatment protocol.

Multicentric Glioma Develops via a Mutant IDH1-Independent Pathway: Immunohistochemical Study of Multicentric Glioma.

Multicentric gliomas are very rare. Due to differences in their tumor types they remain enigmatic. We focused on the pathogenesis of multicentric gliomas and compared their immunoprofile with that of solitary gliomas. This retrospective study included 6 males and 8 females with multicentric glioma (8 glioblastomas, 2 anaplastic astrocytomas, 4 diffuse astrocytomas). Their age ranged from 27 to 75 years and all were treated between 2004 and June 2015. The expression of mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, phosphatase and tensin homolog (PTEN), and epidermal growth factor receptor (EGFR) was examined immunohistochemically; for 1p19q analysis we used fluorescence in situ hybridization (FISH). In all patients, immunohistochemical staining was negative for mutant IDH1 and cytoplasmic PTEN; only 1 patient (7.1%) manifested nuclear PTEN positivity. FISH for 1p19q codeletion was negative in all 9 examined samples; 5 of 14 specimens (35.7%) were p53-positive, 9 (64.3%) were EGFR-positive, and 4 (28.6%) were ATRX-negative. The MIB-1 labeling index was 0.9-15.6% for grades II and III, and ranged between 17.3 and 52.4% for glioblastoma. Our results suggest that the pathogenesis of multicentric gliomas is different from the mutant IDH1-R132H pathogenesis of lower-grade glioma and secondary glioblastomas. More studies are needed to confirm the molecular mechanisms underlying the pathogenesis of multicentric glioma.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) mimicking Whipple's disease: a case report and literature review.

INTRODUCTION: Diffuse leptomeningeal glioneuronal tumor is a new entity under the neuronal and mixed neuronal-glial tumors in the WHO 2016 updated classification and commonly found in children and adolescents. The initial diagnosis is challenging because of its non-specific radiologic feature and negative CSF cytology analysis. A 17 years male was presented with intractable headache subsequently followed by back pain and joint pain. MRI showed enhancement of arachnoid membrane at basal cistern, bilateral sylvian fissure and cerebral cistern with slight enlargement of ventricles. There were no evidences of infection in CSF and blood samples. Based on the duodenal biopsy and prodromal symptom of joint pain, the patient was suspected of having Whipple's disease. Eleven months after the onset, a small mass lesion was observed at the anterior horn of right lateral ventricle. The histology was remarkable for anaplastic oligodendroglioma. Immunostainings revealed positivity for GFAP, Olig2, synaptophysin and negativity for IDH1 mutation, H3K27M. MIB1 labeling index was 40% and 1p19q FISH analysis showed only 1p deletion. Therefore, a final diagnosis of DLGNT was made. CONCLUSION: DLGNT should be included as a differential diagnosis of patients with leptomeningeal-enhanced and high CSF protein level with normal white blood cell count.

Development of cystic malacia after high-dose cranial irradiation of pediatric CNS tumors in long-term follow-up.

PURPOSE: The purpose of this study is to investigate the incidence of cystic malacia in long-term survivors of pediatric brain tumors treated with high-dose cranial irradiation. MATERIALS AND METHODS: Between 1997 and 2015, we treated 41 pediatric patients (26 males, 15 females; age ranging from 3.3 to 15.7 years, median 9-year-old) of pediatric brain tumors [17 medulloblastomas, 7 primitive neuroectodermal tumors (PNET), 3 pineoblastomas, 6 non-germinomatous germ cell tumors (NGGCT), 8 gliomas (including 4 ependymomas, 1 anaplastic astrocytoma, 1 oligodendroglioma, 1 pilocytic astrocytoma, 1 astroblastoma)] with high-dose craniospinal irradiation. Follow-up ranged from 14.0 to 189.2 months (median 86.0 months, mean 81.5 months), the irradiation dose to the whole neural axis ranged from 18 to 41.4 Gy, and the total local dose from 43.2 to 60.4 Gy. All patients underwent follow-up magnetic resonance imaging (MRI) studies at least once a year. Diagnosis of cystic malacia was based solely on MRI findings. Of the 41 patients, 31 were censored during their follow-up due to recurrence of the primary disease (n = 5), detection of secondary leukemia after development of cystic malacia (n = 1), or the absence of cystic malacia on the last follow-up MRI study (n = 25). We also evaluated the development of post-irradiation cavernous angioma and white matter changes. RESULTS: Following irradiation treatment, 11 patients developed 19 cystic malacia during a median course of 30.8 months (range 14.9 to 59.3 months). The site of predilection for cystic malacia was white matter around trigone of lateral ventricles with an incidence of 47.4% (9 of 19 lesions, 7 in 11 patients). Patients with supratentorial tumors developed cystic malacia statistically earlier than the patients with infratentorial tumors (P = 0.0178, log-rank test). Among the same patient group, incidence of post-irradiation cavernous angioma increased progressively, while the incidence of post-irradiation cystic malacia did not increase after 5 years. White matter degeneration developed earlier than cystic malacia or cavernous angioma, and these three clinical entities developed mutually exclusive of each other. CONCLUSION: We attribute the higher incidence of post-irradiation cystic malacia, in our long-term follow-up study, to the cranial irradiation for pediatric brain tumors, particularly supratentorial brain tumors, and recommend a regular, long-term follow-up of brain tumor patients treated with cranial irradiation.

Cavernous angioma after chemotherapy for desmoplastic/nodular medulloblastoma associated with anhidrotic ectodermal dysplasia.

PURPOSE: While cavernous angioma (CVA) after cranial irradiation has been documented, its development after high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) has not. We present a patient with desmoplastic/nodular medulloblastoma (DNMB) associated with anhidrotic ectodermal dysplasia (AED) who developed CVA 2 years after high-dose chemotherapy and PBSCT. METHODS: A 1-year-old boy with ingravescent vomiting was admitted to our institute. He presented with a large head, a depressed nasal bridge, low-set ears, thick lips with peg-shaped teeth, hypohidrosis, sparse hair, thin atrophic skin, scaly dermatitis with frontal bossing, and a bulging anterior fontanel. Neuroradiological examination revealed multiple cerebellar masses with heterogeneous enhancement and speckled calcifications and severe obstructive hydrocephalus. The histological diagnosis of surgical specimens was DNMB, and he underwent postoperative multiple-drug chemotherapy with autologous PBSCT. The outcome was favorable and he did not undergo radiotherapy. RESULTS: After 2 years, intracranial hemorrhage was detected at his regular radiological check-up and he again underwent surgery. The histological diagnosis was CVA. CONCLUSIONS: To our knowledge, this is the first report of AED-associated DNMB and CVA.

Benign fibrous histiocytoma arising at the temporal bone of an infant--case report and review of the literature.

PURPOSE: We report a very rare case of a fast-growing benign fibrous histiocytoma at the temporal bone. METHODS: A 1-year-old girl was referred for investigation of a right temporal mass that increased during 2-week observation. Imaging studies showed a lytic, loculated skull tumor at the left temporal bone. On magnetic resonance imaging scans, the tumor was isointense on T1- and relatively high-intense on T2-weighted images. The tumor was mostly homogeneously enhanced by gadolinium. On diffusion-weighted images, it was iso- to relatively low-intense; perfusion-weighted images revealed low perfusion. RESULTS: Complete macroscopic resection of the tumor was performed. Immunohistochemical analysis showed that the tumor was positive for CD68 and α-smooth muscle actin and negative for CD1a and CD34; the MIB-1 labeling index was 4 %. A diagnosis of primary benign fibrous histiocytoma of the skull was made. At 6-month follow-up, there were no clinical or radiological signs of tumor recurrence and/or metastasis. CONCLUSIONS: We review the clinical, radiological, and immunohistochemical characteristics of benign fibrous histiocytoma at the skull.

p16 Gene Transfer Induces Centrosome Amplification and Abnormal Nucleation Associated with Survivin Downregulation in Glioma Cells.

OBJECTIVE: In human glioma cells, p16 gene transfer induced G1/S arrest, increased radiosensitivity and abnormal nucleation (especially bi- and multinucleation). Survivin suppression caused G2/M arrest, radiosensitization and an increase in aneuploidy accompanied by centrosome amplification. Abnormal nucleation and aneuploidy represent chromosome instability (CIN), and it is well known that centrosome amplification leads to CIN. However, little has been reported that suggests that transferring p16 causes centrosome overduplication during the G1/S phase. METHODS: The p16 gene was transferred into p16-null human glioma cell lines (U251MG and D54MG) using adenovirus with or without irradiation. Centrosome amplification was evaluated by immunofluorescence. We also investigated the DNA replication licensing factor CDT1, its inhibitor geminin and survivin expression as regulators of chromosomal segregation. RESULTS: p16 gene transfer with radiation initiated the greatest degree of centrosome overduplication. CDT1 showed low levels, geminin was unchanged and survivin decreased in Ax-hp16-infected cells with radiation. Those changes of factors affecting DNA licensing or chromosomal segregation might contribute to CIN. CONCLUSION: p16 transfer caused centrosome amplification even in G1/S phase-arrested cells. This suggests that p16 is involved in abnormal nucleation and radiosensitization in human glioma cells. © 2015 S. Karger AG, Basel.

The postirradiation incidence of cavernous angioma is higher in patients with childhood pineoblastoma or primitive neuroectodermal tumors than medulloblastoma.

PURPOSE: The purpose of this study is to investigate the incidence of cavernous angioma (CVA) in long-term survivors of childhood embryonal tumors treated by cranial irradiation. MATERIALS AND METHODS: Between 1990 and 2012, we treated 25 patients (13 males, 12 females) with embryonal tumors (17 medulloblastomas, 5 primitive neuroectodermal tumors (PNET), 3 pineoblastomas) with craniospinal irradiation. Follow-up ranged from 15.5 to 289.9 months, the irradiation dose to the whole neural axis from 18 to 36 Gy, and the total local dose from 49.6 to 60 Gy. All patients underwent follow-up magnetic resonance imaging (MRI) studies at least once a year, and the diagnosis of posttreatment CVA was based solely on MRI findings. RESULTS: At the time of this writing, 18 were alive and free of the recurrence of the original disease or the development of secondary neoplasms other than CVA; another 2 were alive with medulloblastoma or diffuse astrocytoma. Posttreatment, 14 patients developed CVAs in the course of a median of 56.7 months; 13 of these presented with multiple CVAs. Patients who underwent radiation therapy (RT) at an age younger than 6 years developed multiple CVAs significantly earlier than those treated at a later age (p = 0.0110). Patients with PNET or pineoblastoma developed Zabramski type 1 and 2 CVA significantly earlier than did medulloblastoma patients (p = 0.0042). CONCLUSION: We attribute the high rate of post-RT CVA in our long-term follow-up study of pediatric patients to the delivery of cranial irradiation for embryonal tumors, especially PNET and pineoblastoma, and recommend the regular, long-term follow-up of patients whose embryonal tumors were treated by cranial irradiation.

[Anti-emetic effect of granisetron in patients undergoing cranial and craniospinal radiotherapy].

PURPOSE: Approximately 30-59% of patients undergoing cranial or craniospinal radiotherapy experience nausea and/or vomiting. Here, we evaluated the effectiveness of granisetron for controlling emesis in patients treated with cranial or craniospinal radiotherapy. PATIENTS AND METHODS: Between December 2011 and January 2013, 34 patients(19 males, 15 females;age range, 3-80 years)received cranial or craniospinal radiotherapy at our department. All but one male patient, who developed meningitis during the irradiation period were enrolled in this retrospective study. Patients who experienced irradiation-induced vomiting(grade 1)or nausea(grade 2)were treated with granisetron as a rescue anti-emetic. Episodes were graded as(1)no vomiting, no nausea, no anti-emetic;(2)no vomiting, nausea, no anti-emetic;(3)no vomiting, nausea with anti-emetic;and(4)vomiting. RESULTS: Of the 9 patients who underwent whole-brain or whole neural-axis irradiation, 5(55.6%)experienced grade 2 nausea or vomiting. Two of 6 patients(33.3%)treated with whole ventricle irradiation experienced grade 2 nausea or vomiting. Three of 18 patients(16.7%)who underwent local-field irradiation experienced grade 2 nausea or vomiting. Patients who underwent wide-field irradiation experienced nausea, vomiting, and anorexia(p<0.05). Complete response(no vomiting, no additional rescue anti-emetic, and no nausea)was observed in 5 of 9 patients treated with granisetron. Four of 9 patients(44.4%)treated with granisetron experienced constipation(grade 1 or 2);its administration had no major adverse effects in our study population. CONCLUSION: Rescue therapy with granisetron is safe and effective to treat nausea and vomiting in patients subjected to cranial or craniospinal irradiation.

[A case of occipital diploic dermoid tumor with perforation of the dura].

Along with epidermoid cysts, dermoid cysts are uncommon, benign and slow-growing lesions. We described a case of diploic dermoid cyst of the occipital bone with an intracranial extension in the right posterior fossa diagnosed and subjected to pathological examination. A 63-year-old man presented with dizziness at the time of posture conversion. Magnetic resonance imaging(MRI)showed a heterogenous hypo-intensity area on T1-weighted image, hyper-intensity on T2-weighted image and remarkably-strong intensity on diffusion-weighted image. Gadolinium enhancement was partially seen in the tumor capsule. Bone density computed tomography (CT) and 3-dimensional CT using helical CT scan revealed the osteolytic range with destruction of the inner and outer table. From these findings, this tumor was diagnosed as diploic epidermoid cyst before surgery. The tumor was totally removed and underwent cranioplasty with a titanium plate. However, pathological examination confirmed dermoid cyst with existence of sebaceous gland in some cyst-walls. It was difficult to diagnose this case as dermoid tumor from radiological features before surgery.

[Transorbital penetrating intracranial injury by a chopstick: a case report and review of the literature].

This 4-year-old girl fell while holding plastic chopsticks and a chopstick penetrated her left eye. The chopstick was removed immediately by herself. Conventional CT and MR images showed a penetration track from the orbital roof to the basal ganglia. On susceptibility-and diffusion-weighted images the track and surrounding cytotoxic edema were visualized more clearly. Although antibiotics were started at the time of admission to prevent intracranial infection, she developed meningitis. Subsequent treatment with carbapenem antibiotic-and vancomycin therapy was curative and she was discharged home 4 weeks after the injury. In our review of the literature on intracranial penetrating injuries via the orbita we compared the injury patterns inflicted by and the clinical observations reported on damage induced by wooden-, plastic-, and metal chopsticks. We also evaluated diagnostic CT and MR images in patients with intracranial penetrating injuries caused by chopsticks and documented the advantage of susceptibility-and diffusion-weighted imaging over conventional CT-and MR imaging.

Advantages of high b-value diffusion-weighted imaging for preoperative differential diagnosis between embryonal and ependymal tumors at 3 T MRI.

PURPOSE: It is often difficult to distinguish between embryonal and ependymal tumors using conventional MR imaging. The apparent diffusion coefficient (ADC) calculated from diffusion-weighted images (DWI) has been widely used for diagnosis, but its usefulness for differential diagnosis between embryonal and ependymal tumors has not been determined yet. Both DWI properties and ADC values of these two types of tumor at regular and high b-values on a 3 T MR scanner were retrospectively reviewed. MATERIALS AND METHODS: DWI at 3 T was acquired for 16 patients with embryonal tumors (including medulloblastoma, CNS embryonal tumors (NOS), and atypical teratoid/rhabdoid tumor), and 7 patients with ependymal tumors (including ependymoma and anaplastic ependymoma). ADC was measured by manually placing multiple regions of interest (ROIs) on ADC maps corresponding to enhancing lesions on contrast-enhanced T1-weighted images, both on standard (b-1000) and high (b-4000) b-value DWI. The minimum ADC (ADC-MIN) was calculated from several ROIs placed on each tumor. The relationship between tumor cell density and ADC-MIN was also investigated. RESULTS: Both at b-1000 and b-4000, ADC-MIN was significantly lower in embryonal tumors than in ependymal tumors. Embryonal tumors could be completely discriminated from ependymal tumors using both b-values, but ADC-MIN at b-4000 (t-value = -8.312, p < 0.001) was better than ADC-MIN at b-1000. There was a stronger negative correlation between cell density and ADC-MIN at b-4000 (r2 = 0.50, p < 0.001) than with ADC-MIN at b-1000 (r2 = 0.41, p < 0.001). CONCLUSION: Evaluating ADC-MIN at b-4000 would be a useful tool for distinguishing embryonal from ependymal tumors.

Nonenhancing peritumoral hyperintense lesion on diffusion-weighted imaging in glioblastoma: a novel diagnostic and specific prognostic indicator.

OBJECTIVE Glioblastoma differentials include intracranial tumors, like malignant lymphomas and metastatic brain tumors with indiscernible radiological characteristics. The purpose of this study was to identify a distinct radiological feature for the preoperative differentiation of glioblastoma from its differentials, which include malignant lymphomas and metastatic brain tumors. METHODS Preoperative MR images, including diffusion-weighted imaging (DWI) studies (b = 1000 and 4000 sec/mm2), obtained in patients with newly diagnosed malignant tumor, were analyzed retrospectively after receiving approval from the institutional review board. Sixty-four patients with histologically confirmed glioblastoma, 32 patients with malignant lymphoma, and 46 patients with brain metastases were included. The presence of a nonenhancing peritumoral DWI high lesion (NePDHL, i.e., hyperintense lesion in a nonenhancing peritumoral area on DWI) was confirmed in both DWI sequences. Gray matter lesions were excluded. Lesions were termed "definite" if present within 3 cm of the hyperintense tumor border with a signal intensity ratio ≥ 30% when compared with the contralateral normal white matter in both sequences. Discriminant analysis between the histological diagnosis and the presence of Definite-NePDHL was performed, as well as Kaplan-Meier survival analysis incorporating the existence of Definite-NePDHL. RESULTS In 25% of glioblastoma patients, Definite-NePDHL was present, while it was conspicuously absent in patients with malignant lymphoma and metastatic brain tumors. The specificity and positive predictive value were 100%. In the glioblastoma subset, a higher preoperative Karnofsky Performance Scale score (p = 0.0028), high recursive partitioning analysis class (p = 0.0006), and total surgical removal (p = 0.0012) were associated with better median overall survival. Patients with Definite-NePDHL had significantly early local (p = 0.0467) and distant/dissemination recurrence (p < 0.0001) and poor prognosis (p = 0.0007). CONCLUSIONS The presence of Definite-NePDHL is very specific for glioblastoma and indicates poor prognosis. Definite-NePDHL is a significant indicator of early local and distant/dissemination recurrence in patients with glioblastoma. Studying peritumoral DWI and high-b-value DWI is useful for tumor differentiation.

Prognostic implications of the subcellular localization of survivin in glioblastomas treated with radiotherapy plus concomitant and adjuvant temozolomide.

OBJECTIVE Currently, the standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Various prognostic biomarkers for GBM have been described, including survivin expression. The aim of this study was to determine whether the subcellular localization of survivin correlates with GBM prognosis in patients who received the standard treatment protocol. METHODS The authors retrospectively examined the subcellular localization of survivin (nuclear, cytoplasmic, or both) using immunohistochemistry in 50 patients with GBM who had received the standard treatment. The relationship between survivin localization and overall survival (OS) was assessed with uni- and multivariate analyses including other clinicopathological factors (age, sex, Karnofsky Performance Scale [KPS] score, extent of resection, the use of second-line bevacizumab, O6-methylguanine-DNA methyltransferase [MGMT] status, and MIB-1 labeling index). RESULTS Log-rank tests revealed that patient age, KPS score, extent of resection, MGMT status, and survivin localization (p < 0.0001) significantly correlated with OS. Multivariate analysis indicated that patient age, MGMT status, and survivin localization significantly correlated with OS. Patients with nuclear localization of survivin had a significantly shorter OS than those in whom survivin expression was exclusively cytoplasmic (median OS 19.5 vs 31.7 months, respectively, HR 5.690, 95% CI 2.068-17.612, p = 0.0006). There was no significant difference in OS between patents whose survivin expression was exclusively nuclear or nuclear/cytoplasmic. CONCLUSIONS Nuclear expression of survivin is a factor for a poor prognosis in GBM patients. Subcellular localization of survivin can help to predict OS in GBM patients treated with the standard protocol.

Permeability Surface Area Product Using Perfusion Computed Tomography Is a Valuable Prognostic Factor in Glioblastomas Treated with Radiotherapy Plus Concomitant and Adjuvant Temozolomide.

OBJECTIVE: The current standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). We hypothesized that the permeability surface area product (PS) from a perfusion computed tomography (PCT) study is associated with sensitivity to TMZ. The aim of this study was to determine whether PS values were correlated with prognosis of GBM patients who received the standard treatment protocol. METHODS: This study included 36 patients with GBM that were newly diagnosed between October 2005 and September 2014 and who underwent preoperative PCT study and the standard treatment protocol. We measured the maximum value of relative cerebral blood volume (rCBVmax) and the maximum PS value (PSmax). We statistically examined the relationship between PSmax and prognosis using survival analysis, including other clinicopathologic factors (age, Karnofsky performance status [KPS], extent of resection, O6-methylguanine-DNA methyltransferase [MGMT] status, second-line use of bevacizumab, and rCBVmax). RESULTS: Log-rank tests revealed that age, KPS, MGMT status, and PSmax were significantly correlated with overall survival. Multivariate analysis using the Cox regression model showed that PSmax was the most significant prognostic factor. Receiver operating characteristic curve analysis showed that PSmax had the highest accuracy in differentiating longtime survivors (LTSs) (surviving more than 2 years) from non-LTSs. At a cutoff point of 8.26 mL/100 g/min, sensitivity and specificity were 90% and 70%, respectively. CONCLUSIONS: PSmax from PCT study can help predict survival time in patients with GBM receiving the standard treatment protocol. Survival may be related to sensitivity to TMZ.

Role for loss of nuclear PTEN in a harbinger of brain metastases.

BACKGROUND: Earlier studies proposed phosphatase and tensin homolog (PTEN) acts as a 3'-specific phosphatidylinositol phosphatase and inhibits the PI3K pathway. Recent reports show that PTEN mRNA expression is significantly downregulated in brain metastases compared to primary breast cancer. We focused on the differential expression of nuclear and cytoplasmic PTEN between primary tumors and brain metastases. MATERIALS AND METHODS: We retrospectively studied 30 patients with histologically confirmed primary tumors and brain metastases. PTEN and PDK1 expression levels were examined by immunohistochemical staining and categorized as negative, positive, or strong positive expression. The difference in PTEN expression levels were compared, and the values with P<0.05 were considered statistically significant. RESULTS: Expression of cytoplasmic PTEN was 100% at primary site, and 70% at brain metastases. Expression of nuclear PTEN was 87% at primary site, and 20% at brain metastases. Study results demonstrated that PTEN expression levels in brain metastases are lower compared with that of primary tumors. Especially, nuclear PTEN expression was significantly downregulated in various brain metastases. Higher PDK1 expression at brain metastases also confirmed the down regulation of PTEN function. CONCLUSIONS: Our findings indicate that decreased PTEN function by loss of nuclear PTEN expression may be associated with brain metastases.

High Expression of Glypican-1 Predicts Dissemination and Poor Prognosis in Glioblastomas.

OBJECTIVE: Glioblastoma (GBM) relapses locally or in a disseminated pattern and is highly resistant to chemoradiotherapy. Although dissemination is associated with poor prognosis for patients with GBM, the clinicopathologic factors that promote dissemination have not been elucidated. Glypican-1 (GPC-1) is a heparin sulfate proteoglycan that is attached to the extracytoplasmic surface of the cell membrane and regulates cell motility. The aim of this study was to determine whether GPC-1 expression correlated with GBM dissemination and patient prognosis. METHODS: GPC-1 expression was examined by immunohistochemistry in 53 patients with GBM who received radiotherapy and temozolomide treatment. We assessed the relationship between dissemination and clinicopathologic factors, including GPC-1 expression. We also evaluated the relationship between GPC-1 expression and overall survival (OS) by uni- and multivariate analyses of a range of clinicopathologic factors, including age, Karnofsky Performance Status, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) status. RESULTS: Logistic regression analysis revealed that GPC-1 expression correlated with dissemination (P = 0.0116). Log-rank tests revealed that age, Karnofsky Performance Status, extent of resection, MGMT status, dissemination (P = 0.0008) and GPC-1 expression (P = 0.0011) were significantly correlated with OS. Multivariate analysis indicated that age, MGMT status, and GPC-1 expression were significantly correlated with OS. GPC-1 expression had the highest hazard ratio (2.392) among all regressors. CONCLUSIONS: GPC-1 expression significantly correlated with OS in patients with GBM who received radiotherapy and temozolomide treatment. GPC-1 expression can help predict the occurrence of dissemination and shorter OS in patients with GBM.

Advantage of High b Value Diffusion-Weighted Imaging for Differentiation of Hemangioblastoma from Brain Metastases in Posterior Fossa.

OBJECTIVE: It is sometimes difficult to make a differential diagnosis between brain metastases and hemangioblastomas in the posterior fossa. We assessed whether high b value diffusion-weighted image (DWI) at b = 4000 could differentiate these tumors. METHODS: We acquired DWI at 3-T magnetic resonance imaging with b = 1000 and b = 4000 seconds/mm2 in histologically confirmed 12 patients of hemangioblastoma without von Hippel-Lindau disease and 16 patients with brain metastases originating at the posterior fossa. Apparent diffusion coefficient (ADC) values were measured by manually placing regions of interest on ADC maps at the site of enhanced tumor confirmed on contrast-enhanced T1- weighed image. ADC was expressed as the minimum (ADCMIN), mean (ADCMEAN), and maximum (ADCMAX) values. RESULTS: All the ADC values of hemangioblastomas were statistically higher than those of metastatic tumor in both b = 1000 and b = 4000 (P < 0.0001 in ADCMIN, ADCMEAN, and ADCMAX; Mann-Whitney U test). With the cutoff value at 0.6 × 10-3 mm2/second, the positive predictive value of ADCMIN at b = 4000 was higher than that of ADCMIN at b = 1000 (100% vs. 89.3%, logistic analysis) to differentiate hemangioblastomas from brain metastases. Moreover, we studied the pathologic subtype of hemangioblastoma and confirmed that ADCs (b = 4000MIN) of cellular subtype were statistically lower than those of reticular subtype (P = 0.03; Mann-Whitney U test). CONCLUSIONS: High b value DWI reflects diffusion more accurately than does regular b value. Our results showed that ADC calculation by high b value (b = 4000) DWI at 3-T magnetic resonance imaging is clinically useful for differentiating hemangioblastomas from brain metastases.

Post-traumatic Unilateral Avulsion of the Abducens Nerve with Damage to Cranial Nerves VII and VIII: Case Report.

Traumatic injuries of the abducens nerve as a consequence of facial and/or head trauma occur with or without associated cervical or skull base fracture. This is the first report on unilateral avulsion of the abducens nerve in a 29-year-old man with severe right facial trauma. In addition, he exhibited mild left facial palsy, and moderate left hearing disturbance. Magnetic resonance imaging (MRI) using fast imaging employing steady-state acquisition (FIESTA) revealed avulsion of left sixth cranial nerve. We recommend thin-slice MR examination in patients with abducens palsy after severe facial and/or head trauma.