Search

Jin Iwazawa1, Shoichi Ohue2, Naoko Hashimoto1, Takashi Mitani11Department of Radiology, Nissay Hospital, Nishiku, Osaka, 2Department of Radiology, Komatsu Hospital, Neyagawa, JapanPurpose: We aimed to compare the local control rates between miriplatin and epirubicin in lipiodol-based transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Patients and methods: Patients who underwent targeted TACE using miriplatin (47 patients, 66 lesions) or epirubicin (64 patients, 79 lesions) as the sole therapy were enrolled. The local control rates were compared using the Kaplan–Meier estimator with the log-rank test. The patient and tumor parameters were subjected to univariate and multivariate analyses using the Cox proportional hazards model.Results: The overall local recurrence rates were 39.3% and 31.6% for the miriplatin and epirubicin groups, respectively. The local control rate was significantly higher in the epirubicin group than in the miriplatin group (P < 0.001). The local control rates at 6 months and 1 year were 70.7% and 44.8% for the miriplatin group and 83.4% and 69.2% for the epirubicin group, respectively. Multivariate analysis showed that the serum a-fetoprotein level ≥20 ng/mL (hazard ratio 2.96; P < 0.001), miriplatin usage (hazard ratio 2.53; P = 0.002), and Child-Pugh class B (hazard ratio 1.89; P = 0.042) affected local progression.Conclusion: Lipiodol-based targeted TACE using miriplatin had inferior local control rates as compared to epirubicin in patients with HCC.Keywords: chemoembolization, miriplatin, epirubicin, liver, neoplasms

Twelve cases of hepatocellular carcinoma treated by arterial embolization were followed with ultrasonography. Shrinkage of the tumor after the therapy was confirmed in all cases. Echo level reduction in the tumor occurred in 10 cases. High-level reverberation echoes with acoustic shadows emerged in seven cases; however, these echoes were not detected in any cases 3 weeks after the procedure. Echoes were considered either as the consequence of gas produced in the tumor or air trapped in the embolic substance. Ultrasonography, therefore, is an effective technique for the posttherapeutic evaluation of arterial embolization therapy for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Although magnetic resonance angiography (MRA) is accepted for showing chronic intracranial stenotic or occlusive lesions, the method has not been practically examined in patients with acute cerebral ischaemia. We carried out three-dimensional time-of-flight MRA in six patients with acute ischaemia treated by local thrombolysis, and compared the findings with those of digital subtraction angiography (DSA). In all patients, MRA before thrombolysis clearly demonstrated the occluded arteries, which corresponded precisely to those shown by DSA. In four patients with complete recanalisation of the occluded vessels after thrombolysis, the recanalisation could be demonstrated by postoperative MRA. In one patient with reocclusion of the recanalised artery, repeat MRA also demonstrated the reocclusion, confirmed by DSA. These results suggest that MRA may be helpful for noninvasive investigation before and after thrombolysis. [ABSTRACT FROM AUTHOR]

During retrograde transvenous sclerotherapy for gastric varices, sufficient opacification of the target varices on venography is essential for successful treatment. However, venography sometimes cannot identify target varices due to overlapping adjacent collateral vessels or leakage of contrast medium to other outflow veins. We report how C-arm CT images acquired using a flat-panel detector angiography system helped to identify target varices and predict the distribution of a sclerosant, which resulted in safer sclerotherapy and increased operator confidence.

This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term "midline" areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4-78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9-11.9, 95% CI) and 16.6 ± 1.4 (13.9-19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma., (© 2024. The Author(s).)

The effectiveness of carmustine (BCNU) wafers on local recurrence of glioblastoma (GBM) remains contentious. We investigated the accumulating high-dose effects of BCNU released from the wafers on the survival of GBM patients by measuring BCNU concentration in the resection cavity of GBM over time. BCNU wafers (Gliadel ® ) were implanted with an Ommaya device in 15 patients, including 12 patients with GBM. BCNU concentrations in the tumor resection cavity were measured for 30 days postoperatively. The area under the curve (AUC) all was calculated from BCNU concentration curves, and the relationships between AUC all and survival, tumor phenotypes on MRI, and recurrence patterns were analyzed. The BCNU concentration was maximal 1 h postoperatively, rapidly decreased within 24 h, and remained relatively high for 7 days. GBM patients were classified into two groups: early recurrence (ER) and late or no recurrence (LN), using median progression-free survival as the cut-off. AUC all tended to be lower in the ER group than in the LN group, but the difference was not significant. MRI revealed that all patients in the ER group had highly invasive GBMs, whereas all patients in the LN group had less-invasive GBMs. A total of 9 patients experienced recurrence, with 6 local, 2 diffuse, and 1 disseminated patterns. No differences in AUC all were seen between local and non-local recurrence groups. Total BCNU concentrations did not correlate with tumor progression or survival. However, a high concentration of BCNU may have potential to provide some survival benefit for less-invasive type GBM.

The poor prognosis of glioblastoma multiforme (GBM) is primarily due to highly invasive glioma stem-like cells (GSCs) in tumors. Upon GBM recurrence, GSCs with highly invasive and highly migratory activities must assume a less-motile state and proliferate to regenerate tumor mass. Elucidating the molecular mechanism underlying this transition from a highly invasive phenotype to a less-invasive, proliferative tumor could facilitate the identification of effective molecular targets for treating GBM. Here, we demonstrate that severe hypoxia (1% O 2 ) upregulates CD44 expression via activation of hypoxia-inducible factor (HIF-1α), inducing GSCs to assume a highly invasive tumor. In contrast, moderate hypoxia (5% O 2 ) upregulates osteopontin expression via activation of HIF-2α. The upregulated osteopontin inhibits CD44-promoted GSC migration and invasion and stimulates GSC proliferation, inducing GSCs to assume a less-invasive, highly proliferative tumor. These data indicate that the GSC phenotype is determined by interaction between CD44 and osteopontin. The expression of both CD44 and osteopontin is regulated by differential hypoxia levels. We found that CD44 knockdown significantly inhibited GSC migration and invasion both in vitro and in vivo. Mouse brain tumors generated from CD44-knockdown GSCs exhibited diminished invasiveness, and the mice survived significantly longer than control mice. In contrast, siRNA-mediated silencing of the osteopontin gene decreased GSC proliferation. These results suggest that interaction between CD44 and osteopontin plays a key role in tumor progression in GBM; inhibition of both CD44 and osteopontin may represent an effective therapeutic approach for suppressing tumor progression, thus resulting in a better prognosis for patients with GBM., (Copyright © 2021. Published by Elsevier Inc.)

Intracranial anaplastic hemangiopericytoma (AHPC) is a rare and malignant subset of solitary fibrous tumor/hemangiopericytoma (SFT/HPC) as per the WHO 2016 Classification of Tumors of the Central Nervous System. AHPC portends a poor prognosis and is associated with higher rates of recurrence/metastasis in comparison with SFT/HPC. Accordingly, it is critical to continue to define the clinical course of patients with AHPC and in so doing further refine clinicopathologic/immunohistochemical (IHC) criteria needed for definitive diagnosis. Herein, we describe clinical/histological characteristics of six patients with AHPC. In addition, we reviewed and analyzed the expression of various IHC markers reported within the literature (i.e., a total of 354 intracranial SFT/HPCs and 460 meningiomas). Histologically, tumors from our six patients were characterized by a staghorn-like vascular pattern, mitotic cells, and strong nuclear atypia. Immunohistochemically, all tumors displayed positive nuclear staining for STAT6; other markers, including CD34 and Bcl-2, were expressed only in three patients. Analysis of IHC expression patterns for SFT/HPC and meningioma within the literature revealed that nuclear expression of STAT6 had the highest specificity (100%) for SFT/HPC, followed by ALDH1 (97.2%) and CD34 (93.6%). Of note, SSTR2A (95.2%) and EMA (85%) displayed a high specificity for meningioma. Anaplastic SFT/HPC is a tumor with poor prognosis that is associated with higher rates of recurrence and metastasis in comparison with SFT/HPC. Given that anaplastic SFT/HPC requires more aggressive treatment than meningioma despite of a similar presentation on imaging, it is crucial to be able to distinguish between these tumors.

Antiangiogenic therapy with bevacizumab (Bev), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is a common treatment for recurrent glioblastoma (GBM), but its survival benefit is limited. Resistance to Bev is thought to be a major cause of ineffectiveness on Bev therapy. To optimize Bev therapy, identification of a predictive biomarker for responsiveness to Bev is required. Based on our previous study, we focused on the expression and functions of CD44 and VEGF in the Bev therapy. Here, we analyze a relationship between CD44 expression and responsiveness to Bev and elucidate the role of CD44 in anti-VEGF therapy. CD44 and VEGF expression in the tumor core and periphery of 22 GBMs was examined, and the relationship between expression of these molecules and progression-free time on Bev therapy was analyzed. The degree of CD44 expression in the tumor periphery was evaluated by the ratio of the mRNA expression in the tumor periphery to that in the tumor core (P/C ratio). VEGF expression was evaluated by the amount of the mRNA expression in the tumor periphery. To elucidate the roles of CD44 in the Bev therapy, in vitro and in vivo studies were performed using glioma stem-like cells (GSCs) and a GSC-transplanted mouse xenograft model, respectively. GBMs expressing high P/C ratio of CD44 were much more refractory to Bev than those expressing low P/C ratio of CD44, and the survival time of the former was much shorter than that of the latter. In vitro inhibition of VEGF with siRNA or Bev-activated CD44 expression and increased invasion of GSCs. Bev showed no antitumor effects in mice transplanted with CD44-overexpressing GSCs. The P/C ratio of CD44 expression may become a useful biomarker predicting responsiveness to Bev in GBM. CD44 reduces the antitumor effect of Bev, resulting in much more highly invasive tumors., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Glioblastoma multiforme (GBM) is largely due to glioma stem cells (GSCs) that escape from total resection of gadolinium (Gd)-enhanced tumor on MRI. The aim of this study is to identify the imaging requirements for maximum resection of GBM with infiltrating GSCs. We investigated the relationship of tumor imaging volume between MRI and 11 C-methionine (Met)-PET and also the relationship between Met uptake index and tumor activity. In ten patients, tumor-to-contralateral normal brain tissue ratio (TNR) was calculated to evaluate metabolic activity of Met uptake areas which were divided into five subareas by the degrees of TNR. In each GBM, tumor tissue was obtained from subareas showing the positive Met uptake. Immunohistochemistry was performed to examine the tumor proliferative activity and existence of GSCs. In all patients, the volume of Met uptake area at TNR ≦ 1.4 was larger than that of the Gd-enhanced area. The Met uptake area at TNR 1.4 beyond the Gd-enhanced tumor was much wider in high invasiveness-type GBMs than in those of low invasiveness type, and survival was much shorter in the former than the latter types. Immunohistochemistry revealed the existence of GSCs in the area showing Met uptake at TNR 1.4 and no Gd enhancement. Areas at TNR > 1.4 included active tumor cells with relatively high Ki-67 labeling index. In addition, it was demonstrated that GSCs could exist beyond the border of Gd-enhanced tumor. Therefore, to obtain maximum resection of GBMs, including infiltrating GSCs, aggressive surgical excision that includes the Met-positive area at TNR 1.4 should be considered.

Dermoid cysts are rare benign intracranial neoplasms derived from embryonal remnant tissues. Here, we describe a case of dermoid cyst located in the right frontal lobe, which showed repeated changes on CT. An 11-year-old girl was referred to our hospital to treat a brain neoplasm. Brain CT and MRI revealed a cystic tumor in the right frontal lobe. Incidentally, brain CT had been performed 6, 2, and 1 year before the presentation, which demonstrated repeated changes in the tumor over the clinical course. Gross total resection of the tumor was achieved through right frontal craniotomy. Histological findings revealed keratin flakes, mature bones, cholesterol crystals, and granulation with macrophages. The cyst wall was composed of squamous epithelium with adnexal structures, such as hair follicles and sebaceous glands. Therefore, we diagnosed the tumor as a dermoid cyst. The postoperative course was uneventful, and she was discharged on postoperative day 10 without neurological deficits. Dermoid cysts are difficult to be diagnosed on routine neuroimaging. An accurate diagnosis requires details of the clinical course and analysis of both imaging and pathological studies.

Primary central nervous system lymphoma (PCNSL) has been immunohistochemically classified into two subtypes, germinal center (GC) B-cell and non-GC B-cell, but the prognostic impact of these subtypes remains debated. We investigated clinical features and prognostic significance of immunohistochemical subtypes that were identified by expression patterns of three B-cell differentiation markers in PCNSL. We also analyzed a factor related to responsiveness to high-dose methotrexate (HD-MTX) chemotherapy. Tumors from 32 PCNSL patients were immunohistochemically evaluated for expression of cluster of differentiation (CD) 10, B-cell lymphoma-6 (BCL-6), and multiple myeloma oncogene-1 (MUM-1) and classified into subtypes according to the expression patterns of these markers. Clinical features and prognostic outcome of these subtypes were investigated. Twenty-three patients were treated with HD-MTX-based chemotherapy followed by whole-brain radiation therapy (WBRT), and nine were treated with WBRT alone. Three immunohistochemical subtypes were identified, including A-type expressing CD10, BCL-6, and MUM-1 (12 patients), B-type expressing BCL-6 and MUM-1 (12 patients) and C-type expressing MUM-1 only (8 patients). Response rate in the HD-MTX therapy group was 57.1% (4/7) in A-type, 87.5% (7/8) in B-type, and 75% (6/8) in C-type. C-type with the lowest metabolic activity showed significantly longer overall survival than A-type with the higher uptake of methionine (71.6 versus 39.6 months) (P<0.05). Immunohistochemical identification of PCNSL based on the B-cell differentiation stage revealed three types of tumors, showing different metabolic activity and survival time. Refined immunohistochemical classification of PCNSL subtypes may become a useful tool for predicting more accurate prognosis and accessing sensitivity to HD-MTX therapy., Competing Interests: None., (IJCEP Copyright © 2019.)

OBJECTIVEHigh invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA-mediated SDT (5-ALA-SDT).METHODSIn vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry and TUNEL staining. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined by analysis of the effect of pretreatment with the radical scavenger edaravone. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated.RESULTSThe 5-ALA-SDT inhibited cell growth and changed cell morphology, inducing cell shrinkage, vacuolization, and swelling. Flow cytometric analysis and TUNEL staining indicated that 5-ALA-SDT induced apoptotic cell death in all gliomas. The 5-ALA-SDT generated significantly higher ROS than in the control group, and inhibition of ROS generation by edaravone completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. The proliferative activity of the entire tumor was markedly decreased. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact.CONCLUSIONSThe 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field, whereas the surrounding brain tissue remained normal, resulting in longer survival of the HIFU-treated mice compared with that of untreated mice. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and a subpopulation of glioma stem-like cells (GSCs) is likely responsible for the invariable recurrence following maximum resection and chemoradiotherapy. As most GSCs that are located in the perivascular and perinecrotic niches should be removed during tumor resection, it is very important to know where surviving GSCs are localized. Here, we investigated the existence and functions of GSCs in the tumor periphery, which is considered to constitute the invasion niche for GSCs in GBM, by analyzing expression of stem cell markers and stem cell-related molecules and measuring particular activities of cultured GSCs. In addition, the relationship between GSCs expressing particular stem cell markers and pathological features on MRI and prognosis in GBM patients was analyzed. We showed that GSCs that express high levels of CD44 are present in the tumor periphery. We also found that vascular endothelial growth factor (VEGF) is characteristically expressed at a high level in the tumor periphery. Cultured GSCs obtained from the tumor periphery were highly invasive and have enhanced migration phenotype, both of which were markedly inhibited by CD44 knockdown. Higher expression of CD44 in the tumor periphery than in the core was correlated with a highly invasive feature on MRI and was associated with early tumor progression and worse survival, whereas lower expression of CD44 in the tumor periphery corresponded to low invasion and was associated with longer survival. The low invasion type on MRI tended to show high levels of VEGF expression in the tumor periphery, thus presenting the tumor with high proliferative activity. These results imply the significance of GSCs with high levels of CD44 expression in the tumor periphery compared to the core, not only in tumor invasion but also rapid tumor progression and short survival in patients with GBM.

Purpose Whereas whole-brain radiotherapy (WBRT) has been the standard treatment of brain metastases (BMs), stereotactic radiosurgery (SRS) is increasingly preferred to avoid cognitive dysfunction; however, it has not been clearly determined whether treatment with SRS is as effective as that with WBRT or WBRT plus SRS. We thus assessed the noninferiority of salvage SRS to WBRT in patients with BMs. Patients and Methods Patients age 20 to 79 years old with performance status scores of 0 to 2-and 3 if caused only by neurologic deficits-and with four or fewer surgically resected BMs with only one lesion > 3 cm in diameter were eligible. Patients were randomly assigned to WBRT or salvage SRS arms within 21 days of surgery. The primary end point was overall survival. A one-sided α of .05 was used. Results Between January 2006 and May 2014, 137 and 134 patients were enrolled in the WBRT and salvage SRS arms, respectively. Median overall survival was 15.6 months in both arms (hazard ratio, 1.05; 90% CI, 0.83 to 1.33; one-sided P for noninferiority = .027). Median intracranial progression-free survival of patients in the WBRT arm (10.4 months) was longer than that of patients in the salvage SRS arm (4.0 months). The proportions of patients whose Mini-Mental Status Examination and performance status scores that did not worsen at 12 months were similar in both arms; however, 16.4% of patients in the WBRT arm experienced grade 2 to 4 cognitive dysfunction after 91 days postenrollment, whereas only 7.7% of those in the SRS arm did ( P = .048). Conclusion Salvage SRS is noninferior to WBRT and can be established as a standard therapy for patients with four or fewer BMs.

Postoperative neurological deficits frequently occur in adult moyamoya disease. In this case report, we describe the time course and disease state of a patient with adult moyamoya disease, who experienced a postoperative neurological deficit due to transient hypoperfusion in the pretreated contralateral hemisphere. A 68-year-old female presented with a sudden onset of left hemianopia due to ischemic moyamoya disease. She had severely low cerebral blood flow(CBF)in the right hemisphere and deterioration of cerebrovascular reactivity in the left hemisphere. First, right combined bypass surgery was performed; subsequently, left combined bypass surgery was performed. Two days after left hemisphere surgery, left hemiparesis gradually appeared. Hypoperfusion of the right hemisphere and hyperperfusion of the left hemisphere were revealed by SPECT and CT perfusion imaging. Blood pressure was controlled to normal levels, and an antiepileptic drug, antiplatelet drug, and edaravone were administered. The patient gradually recovered 2 weeks later, and was able to resume her normal daily life. During the clinical course, laterality of CBF was improved following improvement of clinical symptoms. Abnormal postoperative disproportion of the CBF may occur after revascularization surgery for adult moyamoya disease. Prompt assessment of CBF and proper treatment are needed.

Intracranial pure germinomas in children generally respond well to standard chemo-radiotherapy. However, some patients are refractory to standard therapy and require additional treatment. To investigate the characteristics of this subgroup, we retrospectively analyzed the clinical features and treatment outcomes of a cohort of 21 patients with intracranial pure germinomas who were diagnosed between April 2002 and December 2016 at Ehime University Hospital in Japan. Pure germinoma diagnosis was verified by histological examination of the tumor after surgery, and all patients received standard chemo-radiotherapy. A suite of clinical features, including neuroimaging, human chorionic gonadotropin-β subunit (HCG-β), and α-fetoprotein (AFP) in the cerebrospinal fluid (CSF), as well as immunohistochemical expression of HCG-β, AFP, and Ki-67 in the tumor tissue were analyzed. Nineteen of the 21 patients had a complete response to standard chemo-radiotherapy without early recurrence of the tumors. Of these 19 patients, 17 did not have elevated CSF HCG-β levels or express HCG-β in the tumor tissue. However, the two patients who were refractory to standard therapy had elevated CSF HCG-β levels and expressed HCG-β in the tumor cells. These data suggest that patients with pure germinoma presenting with both an elevation of HCG-β in the CSF and HCG-β expression in the tumor tissue may be refractory to frontline treatment. These markers may predict aggressive germinoma and may ultimately facilitate the development of more effective treatment options.

The aim of the study is to identify characteristic features of pineal germinoma that enhance preoperative accuracy in differentiating germinoma from other pineal region tumors. Twenty-one consecutive patients with pineal region tumors were enrolled. In all patients, tumor resection was performed to verify the histology. Clinical records including upward gaze palsy of Parinaud's syndrome and neuroimaging were analyzed. In addition, we evaluated the relationship between magnetic resonance imaging (MRI) findings and tumor progression patterns in pineal germinoma. Among 21 patients, 15 patients were diagnosed with germ cell tumor, 4 with pineal parenchymal cell tumor, and 2 with meningioma. Upward gaze palsy was seen in 11 patients; nine had pure germinomas and two had mixed germ cell tumors. These tumors occupied the pineal region with extension to the area of the mesodiencephalic junction (MDJ) and the bi-epithalamic area between the bilateral pulvinar and the third ventricle. Tumor involvement of the former area could cause upward gaze palsy by insulting the rostral interstitial nucleus of the medial longitudinal fasciculus located in the MDJ area. Tumor invasion into the latter area is commonly seen as a cardioid-shaped tumor as the tumor image on the axial MRI view. Upward gaze palsy and a cardioid-shaped tumor image on the axial MRI views were demonstrated to be specific features of pineal pure germinoma. It is suggested that combination of both features may become useful tools to preoperatively differentiate germinoma from other pineal tumors, resulting in achievement of the optimum treatment of pineal region tumors.

We report the case of a patient who has progressed well over 5 years following single-stage aneurysm clipping and superficial temporal artery-middle cerebral artery(STA-MCA)double anastomoses in the acute phase, for a ruptured distal anterior choroidal artery(AChA)aneurysm accompanied by a twig-like MCA. The patient was a 49-year-old female who developed a sudden severe headache and disturbance of consciousness due to subarachnoid hemorrhage and intraventricular hemorrhage(IVH). Cerebral angiography showed a right twig-like MCA associated with an abnormal vascular network and a ruptured aneurysm in the distal AChA. A day after emergency ventricular drainage for acute hydrocephalus, right frontotemporal craniotomy enabled distal AChA aneurysm clipping, together with removal of the IVH via transchoroidal fissure approach, in addition to STA-MCA double anastomoses to prevent recurrence of hemorrhage. The IVH resolved after surgery and no new infarct area was observed. Cerebral angiography revealed the disappearance of the aneurysm, good patency of the double bypass, and reduction of the abnormal vascular network. The patient gradually recovered without any neurological deficits, except for mild memory disturbance. Five years after the surgery, the patient has experienced no recurrence. The single-stage operation of aneurysm clipping and STA-MCA double anastomoses was made possible by devising an approach for a ruptured cerebral aneurysm, even in the acute stage. The successful improvement of cerebral circulation and prevention of cerebral hemorrhage from an early stage could serve as a reference for the treatment of similar hemorrhagic cases.

Background: We investigated the efficacy of early superficial temporal artery-middle cerebral artery (STA-MCA) double anastomoses for patients with progressing stroke due to atherosclerotic occlusion., Materials and Methods: Nine consecutive patients who underwent early STA-MCA double anastomoses were enrolled. All patients presented with progressing stroke despite maximal medical treatment. Cerebral blood flow in 7 patients was analyzed by single-photon emission tomography. Clinical outcomes were investigated postoperatively, and we evaluated the utility of early STA-MCA double anastomoses., Results: Nine patients in the present study included those with middle cerebral artery occlusion (n = 6) and internal carotid artery occlusion (n = 3). The mean age was 58.4 years. Subjects comprised 1 female (11.1%) and 8 males (88.9%). The cause was low perfusion ischemia due to atherosclerotic occlusion with a small infarct. The mean regional cerebral blood flow (rCBF) ratio in the middle cerebral artery territory compared to the normal side was 69.6 ± 5.3%. The duration from onset to surgery was 1-8 days (median, 3.11 days). All patients underwent early STA-MCA double anastomoses, and no reperfusion-induced hemorrhage occurred. All of them slowly achieved obvious remission compared to symptoms on admission and achieved a good functional outcome., Conclusions: Early STA-MCA double anastomoses were safe and effective, and early revascularization resulted in rapid neurological improvement. We recommend this procedure for patients with progressive ischemia due to main trunk artery occlusion, when the rCBF flow ratio with the normal side was 70 ± 10%, even at the subacute stage., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Purpose: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma. The purpose of this study was to determine whether VPA use during radiotherapy for high-grade glioma is associated with decreased side effects of radiotherapy and an improvement in overall survival (OS) and progression-free survival (PFS)., Methods: Medical records of 112 patients with high-grade glioma were retrospectively reviewed. We grouped patients by VPA use or non-use during radiotherapy, and evaluated hair loss, OS, and PFS., Results: The radiation dose and fractionation at the onset of hair loss were 4 Gy and two fractions higher, respectively, in the VPA group compared with the VPA non-use group (P < 0.01). Median OS was 42.2 and 20.3 months in the VPA use and non-use groups, respectively (P < 0.01; hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.18-0.74). Median PFS was 22.7 and 11.0 months in the VPA use and non-use groups, respectively (P = 0.099; HR, 0.62; 95% CI, 0.36-1.09)., Conclusions: VPA use during radiotherapy for glioma is associated with delayed hair loss and improvement in survival. Hair loss prevention benefits patients suffering from the deleterious effects of radiation.

We investigated whether thrombin-cleaved osteopontin N-terminal is useful as a blood biomarker of acute atherothrombotic ischemic stroke. Acute ischemic stroke patients were prospectively evaluated with brain magnetic resonance imaging and cardiac evaluations for etiological diagnosis according to the Trial of Org 10172 in Acute Stroke Treatment classification. They were divided into the atherothrombotic and non-atherothrombotic groups. Thrombin-cleaved osteopontin N-terminal, osteopontin, matrix metalloproteinase-9, S100B, C-reactive protein and D-dimer levels were measured from blood samples collected at admission. After excluding patients who met the exclusion criteria or had stroke of other/undetermined etiology, 60 of the 100 patients initially enrolled were included in the final analysis. The ischemic stroke subtypes were atherothrombotic (n=28, 46.7%), cardioembolic (n=19, 31.7%) and lacunar (n=13, 21.7%). Thrombin-cleaved osteopontin N-terminal and matrix metalloproteinase-9 levels were significantly higher in the atherothrombotic than in the non-atherothrombotic group (median (interquartile range): 5.83  (0.0-8.6 ) vs. 0.0  (0.0-3.3) pmol l -1 , P=0.03 and 544   (322-749 ) vs. 343   (254-485) ng ml -1 , P=0.01, respectively). After adjustment for the prevalence of hypertension, diabetes and dyslipidemia, thrombin-cleaved osteopontin N-terminal levels of >5.47 pmol l -1 (odds ratio, 16.81; 95% confidence interval, 3.53-80.10) and matrix metalloproteinase-9 levels of >605.5 ng ml -1 (6.59; 1.77-24.60) were identified as independent predictors of atherothrombosis. Within 3 h from stroke onset, only thrombin-cleaved osteopontin N-terminal independently predicted atherothrombosis and thus may add valuable, time-sensitive diagnostic information in the early evaluation of ischemic stroke, especially the atherothrombotic subtype.

Introduction: Crowned dens syndrome is a rare disease entity which radiologically shows calcification of the cruciform ligament around the odontoid process. We report a patient with crowned dens syndrome who improved dramatically in 5days following treatment with oral nonsteroidal anti-inflammatory medication., Presentation of Case: A 61-year-old man was admitted to our hospital with a severe occipital headache and sudden onset of neck stiffness. Neurological examination on admission revealed a high fever and cervical rigidity. Laboratory examination revealed a markedly elevated white blood cell count and C-reactive protein level, but cerebrospinal fluid studies revealed only a slight abnormality. A cervical computed tomography scan and its three-dimensional reconstruction detected a remarkable crown-like calcification surrounding the odontoid process. Cervical magnetic resonance imaging did not demonstrate strong direct compression of the cervical cord; however, the soft tissue surrounding the odontoid process was hyperintense on T2-weighted imaging with fat suppression. Based on the radiological findings, the patient was diagnosed with crowned dens syndrome and was immediately treated with non-steroidal anti-inflammatory drugs. The patient's condition drastically improved within 5days., Discussion: It was very interesting that the soft tissue surrounding the odontoid process was hyperintense on magnetic resonance T2-weighted imaging with fat suppression, and the signal change disappeared 2 weeks after the administration of oral non-steroidal anti-inflammatory drugs. We think that magnetic resonance imaging is useful for proving inflammation in patients with crowned dens syndrome., Conclusion: This is the first report making reference to the magnetic resonance imaging findings of crowned dens syndrome., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: The long-term outcome of patients with adult moyamoya disease following revascularization surgery remains unclear. Here, we investigated these outcomes more than five years after revascularization surgery., Patients and Methods: This study included 48 cerebral hemispheres from 26 patients who underwent revascularization surgery for adult moyamoya disease. The mean follow-up duration was 14.3(5.5-25.6)years. The risk factors of late-onset hemorrhage after revascularization surgery were compared between the bleeding and non-bleeding groups. We also estimated cumulative bleeding-free survival rates using Kaplan-Meier curves., Results: Four patients experienced late-onset bleeding during the follow-up period. Bleeding occurred after an average of 11(8.5-16.4)years following revascularization surgery. The annual hemorrhagic rate was 1.14%. In the bleeding group, higher Suzuki stage(p=0.02), posterior cerebral artery(PCA)involvement(p<0.01), cerebral aneurysm(p=0.04), microbleeds(p=0.03), and post-operative periventricular anastomosis, especially in the thalamus and the choroidal artery(p<0.01 and p=0.01 respectively), were significantly different from those in the non-bleeding group. Kaplan-Meier analysis showed that the probability of late-onset bleeding was higher with postoperative periventricular anastomosis(p<0.01 for thalamic type, p=0.01 for choroidal type), higher Suzuki stage(p<0.01), PCA involvement(p<0.01), and cerebral aneurysm(p=0.02)., Conclusions: In spite of good perfusion and reduction in moyamoya vessels after revascularization surgery, the risk of bleeding persisted. Periventricular anastomosis, especially in the thalamus and choroidal artery, after surgery, higher Suzuki stage, presence of obstructive lesions in the PCA, and cerebral aneurysm may be associated with late-onset bleeding after surgery. More studies are needed to identify the risk factors for late-onset bleeding after revascularization surgery for moyamoya disease.

Background and Propose: Glioblastoma (GBM) is the most common type of malignant primary central nervous system tumor in adults; however, the prevalence of GBM arising in the cerebellum is extremely low. This study aimed to demonstrate the radiological features of cerebellar GBMs, including computed tomography (CT), magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and (18)F-fluorodeoxyglucose (FDG)- and (11)C methionine (MET)-positron emission tomography (PET) findings., Materials and Methods: We retrospectively reviewed seven patients with cerebellar GBM (six men and one woman: mean age: 56 years, range: 18-73 years). We reviewed medical records and radiological data, including preoperative CT, MRI and PET. All patients underwent CT and MRI. DWI data were acquired in four patients. Three patients underwent FDG- and MET-PET examinations. All patients underwent total or subtotal tumor resection and received pathological diagnoses., Results: Four patients had imaging findings consistent with GBM and received preoperative cerebellar GBM diagnoses. Two patients exhibited homogeneous patchy and nodular enhancement without necrosis on MRI, which resembled malignant lymphoma and metastasis. One case exhibited Lhermitte-Duclos disease-like parallel linear striations (i.e.,"tiger-striped" appearance). Although the imaging findings of these three patients were inconsistent with GBM, pathological diagnosis confirmed cerebellar GMB., Conclusions: Some evaluated cases of cerebellar GBM did not exhibit the common CT, MRI, and PET findings of supratentrial GBM, leading to considerable difficulty with preoperative differential diagnosis., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Giant cell tumors (GCTs) are histologically benign bone neoplasms with a locally aggressive nature that primarily occur in the epiphyses of the long bones. A small proportion of these tumors, however, occur in the pelvis, spine, or skull bones. Among these, GCTs of the skull base cannot be completely resected and require adjuvant therapy. We report a juvenile case of clival GCT that was successfully treated by endoscopic endonasal transsphenoidal surgery and subsequent adjuvant therapy with denosumab, a monoclonal antibody to receptor activator of nuclear factor-κB ligand., Case Description: A 16-year-old boy was admitted to our hospital with progressively intolerable headache and right oculomotor nerve palsy. Computed tomography and magnetic resonance imaging showed a large tumor mass in the sphenoid sinus with extensive erosion of the clivus and compression of the right cavernous sinus. The tumor was resected by endonasal transsphenoidal surgery and histologically diagnosed as GCT. The giant cells showed positive immunostaining for CD68 and Mib-1 labeling index was less than 1.0%. Postoperative course was uneventful and the oculomotor disturbance was markedly improved. However, magnetic resonance imaging 2 weeks after surgery revealed marked enlargement of the tumor. Adjuvant therapy with denosumab was therefore initiated, resulting in marked reductions in tumor size., Conclusions: This is the first report to describe beneficial effects of denosumab in the treatment of GCT of the skull base., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Multicentric gliomas are well-separated tumors in different locations of the brain, without anatomical continuity between lesions. We report a rare case of multicentric gliomas that occurred in both supra- and infratentorial regions with different histopathology., Case Presentation: A 27-year-old man was admitted to our hospital with mild motor weakness of the right leg. Magnetic resonance imaging (MRI) showed a large tumor occupying the left insula, extending to the left basal ganglia, so tumor resection was performed. Histological diagnosis was diffuse astrocytoma. Tumor cells showed sporadic immunoreactivity for p53 and negative immunostaining for epidermal growth factor receptor (EGFR). Postoperative course was uneventful, and adjuvant therapy was not performed. At 7 months after surgery, MRI disclosed a left cerebellar tumor displaying an irregular ring formation on enhancement with gadolinium (Gd) and marked peritumoral edema. MRI studies including T2-weighted imaging demonstrated that this paravermian tumor had no contact with the initial left insular tumor. In addition, MRI studies of the whole neuraxis, cytological examination of the cerebrospinal fluid, and neurological findings demonstrated that no dissemination had occurred through the subarachnoid space or as intracerebral metastases. Therefore, the second surgery was performed. Histological diagnosis was glioblastoma. Immunohistochemistry revealed that most tumor cells were positively stained for both p53 and EGFR but negatively stained for isocitrate dehydrogenase 1 (IDH1)., Conclusions: We reported a case of multicentric gliomas occurring in both supra- and infratentorial regions with different histopathology. Immunohistochemical examinations suggest that different genetic pathways may participate in the occurrence of these tumors.

Blood vessels in brain tumors, particularly glioblastomas, have been shown to express CD90. CD90(+) cells in and around blood vessels in cancers including brain tumors have been identified as endothelial cells, cancer stem cells, fibroblasts or pericytes. In this study, we aimed to determine the nature or type(s) of cells that express CD90 in human brain tumors as well as an experimental rat glioma model by double immunofluorescence staining. The majority of CD90(+) cells in human glioblastoma tissue expressed CD31, CD34 and von Willebrand factor, suggesting that they were endothelial cells. Vasculatures in a metastatic brain tumor and meningioma also expressed CD90. CD90(+) cells often formed glomeruloid structures, typical of angiogenesis in malignant tumors, not only in glioblastoma but also in metastatic tumors. Some cells in the middle and outer layers of the vasculatures expressed CD90. Similar results were obtained in the rat glioma model. There were cells expressing both α-smooth muscle actin and CD90 in the middle layer of blood vessels, indicating that smooth muscle cells and/or pericytes may express CD90. CD90(+) vasculatures were surrounded by tumor-associated macrophages (TAMs). Thus, in addition to endothelial cells, some other types of cells, such as smooth muscle cells, pericytes and fibroblasts constituting the vasculature walls in brain tumors expressed CD90. Because CD90 has been shown to interact with integrins expressed by circulating monocytes, CD90 might be involved in angiogenesis through recruitment and functional regulation of TAMs in tumors. CD90(+) vasculatures may also interact with tumor cells through interactions with integrins. Because CD90 was not expressed by vasculatures in normal brain tissue, it might be a possible therapeutic target to suppress angiogenesis and tumor growth., (© 2015 Japanese Society of Neuropathology.)

Glioblastoma (GBM)-initiating cells (GIC) are a tumorigenic subpopulation that are resistant to radio- and chemotherapies and are the source of disease recurrence. Therefore, the identification and characterization of GIC-specific factors is critical toward the generation of effective GBM therapeutics. In this study, we investigated the role of epithelial V-like antigen 1 (Eva1, also known as myelin protein zero-like 2) in stemness and GBM tumorigenesis. Eva1 was prominently expressed in GICs in vitro and in stem cell marker (Sox2, CD15, CD49f)-expressing cells derived from human GBM tissues. Eva1 knockdown in GICs reduced their self-renewal and tumor-forming capabilities, whereas Eva1 overexpression enhanced these properties. Eva1 deficiency was also associated with decreased expression of stemness-related genes, indicating a requirement for Eva1 in maintaining GIC pluripotency. We further demonstrate that Eva1 induced GIC proliferation through the activation of the RelB-dependent noncanonical NF-κB pathway by recruiting TRAF2 to the cytoplasmic tail. Taken together, our findings highlight Eva1 as a novel regulator of GIC function and also provide new mechanistic insight into the role of noncanonical NF-κB activation in GIC, thus offering multiple potential therapeutic targets for preclinical investigation in GBM., (©2015 American Association for Cancer Research.)

Carmustine wafers are approved for localized treatment of malignant glioma. In this study, overall changes in computed tomography (CT) and magnetic resonance (MR) images of malignant glioma patients treated with carmustine wafer implantation were evaluated. The subjects were 25 patients undergoing craniotomy for malignant glioma resection and carmustine wafer implantation. Changes in the appearance of wafers, the resection cavity, and the adjacent parenchyma on CT and MR imaging were evaluated retrospectively. On CT, the wafers changed from an initially high-dense to an iso-dense appearance. All MR studies showed a low-intense wafer within 2 days. The wafers changed to a high- or iso-intense appearance on fluid attenuated inversion recovery and T1-weighted imaging, whereas they changed to an iso- to low-intense appearance on T2-weighted imaging. Gas in the cavity increased gradually after surgery, achieved a peak at 1 week postoperatively, and then disappeared in 1-3 months. Increased volume of the resection cavity was observed in 48% of patients. Regarding changes in the adjacent parenchyma, obvious contrast enhancement at the wall of the resection cavity was seen in 91% of cases at 1 month, but this disappeared gradually. Edema around the resection cavity was increased in 7 patients (28%), of whom only two experienced symptoms due to edema. We conclude that these radiological changes after carmustine wafer implantation should be carefully followed up, because these changes can easily be mistaken for infectious disease or recurrent tumors.

Background: We present two rare cases of pineal-region meningiomas. These tumors are the first reported cases of dura-unrelated meningiomas originating from the arachnoid membrane over the vein of Galen (AMG)., Case Description: In Case 1, a 37-year-old woman presented with a progressing headache. Magnetic resonance imaging (MRI) showed a large tumor in the pineal region, displacing the vein of Galen upward. Angiography disclosed occlusion of the vein of Galen, with deep venous flow draining through the veins on the right medial surface of the occipital lobe to the superior sagittal sinus. In Case 2, a 67-year-old man presented with dizziness. MRI demonstrated a large mass in the pineal region, displacing the vein of Galen inferiorly. Angiography disclosed occlusion of the vein of Galen, with deep venous flow draining through the collateral venous channel into the transverse sinus. Both tumors were totally excised (Simpson Grade III for Case 1, Grade I for Case 2) via a left occipital transtentorial approach. No dural attachment was recognized in either case, but the tumor in Case 1 was firmly adherent to the inferior portion of the AMG, while that in Case 2 was attached to the superior portion of the AMG, but remained dissectible., Conclusions: We reported two cases of pineal-region meningiomas originating from the arachnoid membrane over the vein of Galen, resulting in meningioma without dural attachment. These tumors can be totally resected by careful dissection of the tumor from the arachnoid membrane surrounding the vein of Galen.

Endoscopic endonasal transsphenoidal surgery (ETSS) has been widely applied to pituitary adenomas. However, anatomical orientation is difficult when structures of the sphenoidal sinus are complicated. This study investigated the usefulness of three-dimensional computed tomography (3D-CT) modeling in planning surgical procedures for ETSS and providing anatomical guidance during surgery. CT data from 99 consecutive patients with pituitary adenoma treated between January 2008 and March 2014 were used to reconstruct 3D-CT models. Based on these images, the architecture of sphenoidal sinus, particularly structures surrounding the sellar floor, was visualized for preoperative simulation of surgical procedures. These 3D-CT images were also compared to surgical views during ETSS to evaluate applicability of the images. These models clearly demonstrated the morphology of the nasal cavity and structures of the sphenoidal sinus, including bony prominences of the internal carotid arteries (ICAs) and optic canals by successively eliminating sphenoidal structures. The 3D-CT images permitted determination of the maximum marginal line of the opening of the sellar floor by presenting vital structures such as ICAs and optic canals. With this 3D-CT model, the surgeon could access the sella more easily, open the floor widely enough for each individual patient, and resect the tumor maximally without complications. Preoperative 3D-CT models distinctly visualized the optic canals, bilateral ICAs, and complicated structures of sphenoidal septa. The 3D-CT images were useful for preoperative planning and as a road map during endoscopic surgery for pituitary adenoma, facilitating maximum tumor resection without complications.

Background: Drug resistance is a major obstacle for the efficacy of chemotherapeutic treatment of tumors. Oct-3/4, a self-renewal regulator in stem cells, is expressed in various kinds of solid tumors including glioblastoma. Although Oct-3/4 expression has been implicated in the malignancy and prognosis of glioblastomas, little is known of its involvement in drug resistances of glioblastoma., Methods: The involvement of Oct-3/4 in drug resistance of glioblastoma cells was assessed by lactate dehydrogenase assay, efflux assay of an anticancer drug, poly ADP-ribose polymerase cleavage, and in vivo xenograft experiments. Involvement of a drug efflux pump ATP binding cassette transporter G2 in Oct-3/4-induced drug resistance was evaluated by quantitative PCR analysis and knockdown by shRNA., Results: Oct-3/4 decreased the susceptibility to chemotherapeutic drugs by enhancing excretion of drugs through a drug efflux pump gene, ATP binding cassette transporter G2. Moreover, the expression of Oct-3/4 was well correlated to ATP binding cassette transporter G2 expression in clinical GB tissues., Conclusion: Oct-3/4 elevated the ATP binding cassette transporter G2 expression, leading to acquisition of a drug-resistant phenotype by glioblastoma cells., General Significance: If the drug-resistance of glioblastoma cells could be suppressed, it should be a highly ameliorative treatment for glioblastoma patients. Therefore, signaling pathways from Oct-3/4 to ATP binding cassette transporter G2 should be intensively elucidated to develop new therapeutic interventions for better efficacy of anti-cancer drugs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Two types of macrophages in lesion core of rat stroke model were identified according to NG2 chondroitin sulfate proteoglycan (NG2) and CD200 expression. NG2(+) macrophages were CD200(-), and vice versa. NG2(-) macrophages expressed two splice variants of CD200 that are CD200L and CD200S. CD200(+) macrophages expressed CD8, CD68, CD163, CCL2, inducible nitric oxide synthase, interleukin-1β, Toll-like receptor 4 and transforming growth factor β, whilst NG2(+) cells expressed a costimulatory factor CD86. Both cell types expressed insulin-like growth factor 1 and CD200R. These results demonstrate that the two macrophage types cannot be classified as either M1 or M2., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The current optimal surgery for glioblastomas (GBMs) near the pyramidal tract (PT) is to remove as much tumor as possible and to preserve motor function. The purpose of this study is to investigate the usefulness of tractography-integrated navigation-guided fence-post catheter techniques and motor-evoked potentials (MEPs) for preserving postoperative motor function after GBM surgery. We retrospectively examined 49 patients who underwent resection for GBM near the PT. Diffusion tensor (DT) imaging-based tractography of the PT was performed preoperatively and integrated into the navigation system. When possible, silicon catheters were used as "fence-posts" and were inserted along the tumor boundaries, avoiding the PT, before tumor removal using the navigation system (fence-post catheter techniques). Cortical and subcortical MEPs were also monitored during resection of the tumor. Fence-post catheter techniques using a tractography-integrated navigation system were used in 45 of 49 patients. This technique enabled placement of the catheters, avoided the motor pathways, and allowed easier resection of the tumors. Tumors near the PT were resected using subcortical and cortical MEPs. The amplitudes of cortical MEPs after tumor removal were maintained at over 33 % of those obtained before resection. Thirty-six patients showed obvious responses of subcortical MEPs at ≤20 mA. The degree of resection was gross total in 21 patients, subtotal in 21, and partial in seven. One month after surgery, only one patient showed worsened motor function. Therefore, fence-post catheter techniques using a tractography-integrated navigation system and MEPs may contribute to preserving motor function after surgery for GBMs that are near the PT.

Patients with severe internal carotid artery (ICA) stenosis with multiple medical problems generally undergo carotid artery stenting (CAS). However, it is difficult to perform CAS in some patients because iodinated contrast medium is hard to use. We report a patient with asymptomatic ICA stenosis and chronic renal failure, in whom successful treatment was achieved using CAS with minimal use of iodinated contrast medium. A 68-year-old man with severely chronic renal failure was consulted for treatment of left ICA stenosis. Magnetic resonance angiography (MRA) and carotid echography revealed left ICA severe stenosis, and systemic non-contrast MRA showed left femoral artery constriction, but right femoral artery to be intact. CAS was therefore performed through the right femoral artery, using non-contrast three-dimensional computed tomography (3D-CT) with MRA fusion imaging, intravascular ultrasonography, and a small amount of iodinated low-osmolar contrast medium. Postoperative course was uneventful with no aggravation of renal dysfunction, and he was discharged 7 days postoperatively. These techniques are very useful for patients with chronic renal failure, and this present case represents the first report of CAS treated by using non-contrast 3D-CT with MRA fusion image technique., (© The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Glioma-initiating cells (GIC) have stem-like cell properties thought to be sufficient for recurrence, progression, and drug resistance in glioblastomas. In the present study, we defined miRNA (miR)-340 as a differentially expressed miRNA in human GICs that inhibit GIC-mediated tumorigenesis. Furthermore, we defined tissue plasminogen activator (PLAT) as a critical direct target of miR340 for inhibition. Among miRNAs screened, we found that miR340 expression was decreased in all human GICs and in human glioblastoma tissues, compared with human neural stem cells and normal brain tissues. miR340 overexpression in GICs suppressed their proliferative, invasive, and migratory properties in vitro, triggering cell senescence in vitro and inhibiting GIC-induced tumorigenesis in mouse brains. shRNA-mediated silencing of PLAT in GICs phenocopied the effects of miR340 overexpression in vitro and in vivo, suggesting a potential role for tissue factor in stem-like cell function. Taken together, our results identified miR340 as a tumor suppressor that functions in GIC to enforce PLAT blockade and ablate their stem-like functions., (©2015 American Association for Cancer Research.)

Purpose. We investigate the usefulness of multimodal assistant systems using a fusion model of preoperative three-dimensional (3D) computed tomography (CT) and magnetic resonance imaging (MRI) along with endoscopy with indocyanine green (ICG) fluorescence in establishing endoscopic endonasal transsphenoidal surgery (ETSS) as a more effective treatment procedure. Methods. Thirty-five consecutive patients undergoing ETSS in our hospital between April 2014 and March 2015 were enrolled in the study. In all patients, fusion models of 3D-CT and MRI were created by reconstructing preoperative images. In addition, in 10 patients, 12.5 mg of ICG was intravenously administered, allowing visualization of surrounding structures. We evaluated the accuracy and utility of these combined modalities in ETSS. Results. The fusion model of 3D-CT and MRI clearly demonstrated the complicated structures in the sphenoidal sinus and the position of the internal carotid arteries (ICAs), even with extensive tumor infiltration. ICG endoscopy enabled us to visualize the surrounding structures by the phasic appearance of fluorescent signals emitted at specific consecutive elapsed times. Conclusions. Preoperative 3D-CT and MRI fusion models with intraoperative ICG endoscopy allowed distinct visualization of vital structures in cases where tumors had extensively infiltrated the sphenoidal sinus. Additionally, the ICG endoscope was a useful real-time monitoring tool for ETSS.

Accumulating evidence shows that the expression level of Oct-3/4, a self-renewal regulator in stem cells, is positively correlated with the progression of various solid tumors. However, little is known regarding the influence of Oct-3/4 in the tumor angiogenesis of glioblastomas. In the present study, we subcutaneously transplanted Oct-3/4-overexpressing human glioblastoma U251 (U251/EGFP-Oct-3/4) cells into the right thighs of nude mice to evaluate the roles of Oct-3/4 in the tumor angiogenesis. Both tumor size and the number of large vessels growing in the tumor were markedly increased. In an in vitro model of angiogenesis, the conditioned media from U251/EGFP-Oct-3/4 cells significantly accelerated capillary-like tube formation compared with that of U251/EGFP cells. In comparison with U251/EGFP cells, U251/EGFP-Oct-3/4 cells had markedly elevated the expression of vascular endothelial growth factor mRNA under the control of hypoxia-inducible factor (HIF) 1α. In U251/EGFP-Oct-3/4 cells, enhanced protein expression and nuclear translocation of HIF1α were observed. Furthermore, we demonstrated that the involvement of AKT, an oncogenic signaling molecule, in the Oct-3/4 induced upregulation of HIF1α protein. Our findings suggest that Oct-3/4-expressing glioblastoma cells have the ability to adapt to low-oxygen environments within tumor masses by promoting tumor angiogenesis through AKT-HIF1 pathway.

Aim: We aimed to evaluate hepatic vascular changes following lipiodol-based transarterial chemoembolization of hepatocellular carcinoma using epirubicin (EPI), miriplatin (MPT) and miriplatin plus low-dose epirubicin (MPT+EPI)., Methods: A total of 185 arteries in 118 patients who underwent chemoembolization using EPI (67 arteries in 48 patients), MPT (64 arteries in 37 patients) and MPT+EPI (54 arteries in 33 patients) were retrospectively examined. The maximum dose limit of MPT was 140 mg and that of EPI was 50 and 20 mg for the EPI and MPT+EPI groups, respectively. Vascular changes and local recurrence were evaluated by subsequent angiography. Factors affecting arterial damage were analyzed using multivariate logistic regression analysis., Results: More severe arterial damage was observed in the EPI group (88.1%) than in the MPT+EPI (72.2%) and the MPT (18.7%) groups (P = 0.044 and P < 0.001, respectively). EPI usage (hazard ratio [HR] = 12.8, P < 0.001), selective chemoembolization (HR = 5.4, P < 0.001) and MPT usage (HR = 0.28, P = 0.020) were significant predictors for arterial damage induction. The local recurrence rate was lower for the lesions exhibiting arterial occlusion after chemoembolization (39.4%) than for the lesions exhibiting no vascular attenuation (73.9%) or wall irregularity (75.8%) (P = 0.001 and P = 0.005, respectively)., Conclusion: High-dose EPI, MPT, and low-dose EPI plus MPT usage in chemoembolization for hepatocellular carcinoma induced the greatest, the least, and intermediate vascular damages, respectively. Therapeutic occlusion of tumor feeder vessels is associated with lower local recurrence., (© 2013 The Japan Society of Hepatology.)

Here, we report a case of primary intracranial tumor in a chronic hemodialysis patient in which neurosurgery was successful. A 50-year-old man who had been on hemodialysis for 4 years was admitted to our hospital with general fatigue. Neurological examination on admission revealed mild restless. Computed tomography and magnetic resonance imaging performed on admission revealed a large (55 mm×40 mm) tumor mass in contact with the falx. The size of this tumor rapidly increased over the next month. 201Thallium-chloride single photon emission computed tomography revealed abnormal uptake in the same location as the lesion. This suggested a malignant brain tumor and surgical excision was scheduled. Two weeks prior to surgery, frequent hemodialysis was performed using nafamostat mesilate instead of heparin to prevent bleeding and to maintain electrolyte balance, and red cell concentrates and erythropoietin were administered for the improvement of anemia. A triple lumen catheter was inserted in the right internal jugular vein in preparation for emergency continuous hemodiafiltration to maintain homeostasis of circulatory dynamics. Surgery was completed without incident and the tumor was resected totally. During surgery, cerebral edema was well controlled by hyperventilation and a slightly upturned head position. Histopathological examination of the specimen confirmed atypical meningioma. Continuous hemodiafiltration was performed for 24 hours after surgery, and hemodialysis was initiated on the third day after surgery. The postoperative course was uneventful. Three weeks after surgery, the patient was discharged with no neurological deficit and resumed his daily life on maintenance hemodialysis.

Purpose: To evaluate the clinical utility and limitations of a computer software program for detecting tumor feeders of hepatocellular carcinoma (HCC) during transarterial chemoembolization (TACE)., Materials and Methods: Forty-six patients with 59 HCC nodules underwent nonselective digital subtraction angiography (DSA) and C-arm computed tomography (CT) in the same hepatic artery. C-arm CT data sets were analyzed using the software to identify potential tumor feeders during each TACE session. For DSA analysis, 3 radiologists were independently assigned to identify tumor feeders using the DSA images in a separate session. The sensitivity of the 2 techniques in detecting tumor feeders was compared, with TACE findings as the reference standard. Factors affecting the failure of the software to detect tumor feeders were assessed by univariate and multivariate analyses., Results: We detected 65 tumor feeders supplying 59 HCC nodules during TACE sessions. The sensitivity of the software to detect tumor feeders was significantly higher than that of the manual assessment using DSA (87.7% vs. 71.8%, P<0.001). Multivariate analysis showed that a tumor feeder diameter of <1.0mm (hazard ratio [HR], 56.3; P=0.003) and lipiodol accumulation adjacent to the tumor (HR, 11.4; P=0.044) were the significant predictors for failure to detect tumor feeders., Conclusion: The software analysis was superior to manual assessment with DSA in detecting tumor feeders during TACE for HCC. However, the capability of the software to detect tumor feeders was limited by vessel caliber and by prior lipiodol accumulation to the tumor., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)