5-Aminolevulinic acid increases boronophenylalanine uptake into glioma stem cells and may sensitize malignant glioma to boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is a high-LET particle radiotherapy clinically tested for treating malignant gliomas. Boronophenylalanine (BPA), a boron-containing phenylalanine derivative, is selectively transported into tumor cells by amino acid transporters, making it an ideal agent for BNCT. In this study, we investigated whether the amino acid 5-aminolevulinic acid (ALA) could sensitize glioma stem cells (GSCs) to BNCT by enhancing the uptake of BPA. Using human and mouse GSC lines, pre-incubation with ALA increased the intracellular accumulation of BPA dose-dependent. We also conducted in vivo experiments by intracerebrally implanting HGG13 cells in mice and administering ALA orally 24 h before BPA administration (ALA + BPA-BNCT). The ALA preloading group increased the tumor boron concentration and improved the tumor/blood boron concentration ratio, resulting in improved survival compared to the BPA-BNCT group. Furthermore, we found that the expression of amino acid transporters was upregulated following ALA treatment both in vitro and in vivo, particularly for ATB0,+. This suggests that ALA may sensitize GSCs to BNCT by upregulating the expression of amino acid transporters, thereby enhancing the uptake of BPA and improving the effectiveness of BNCT. These findings have important implications for strategies to improve the sensitivity of malignant gliomas to BPA-BNCT.

Influence of surgical position and registration methods on clinical accuracy of navigation systems in brain tumor surgery.

The aim of this study was to evaluate the influence of skin distortion due to surgical positioning on the clinical accuracy of the navigation system. The distance errors were measured in four fiducial markers (anterior, posterior, right, and left of the head) after the registration of the navigation system. The distance errors were compared between the surface-merge registration (SMR) method using preoperative imaging and the automatic intraoperative registration (AIR) method using intraoperative imaging. The comparison of the distance errors were performed in various surgical positions. The AIR method had the significant accuracy in the lateral markers than the SMR method (lateral position, 3.8 mm vs. 8.95 mm; p < 0.0001; prone position, 4.5 mm vs. 13.9 mm; p = 0.0001; 5.2 mm vs. 11.5 mm; p = 0.0070). The smallest distance errors were obtained close to the surgical field in the AIR method (3.25-3.85 mm) and in the forehead in the SMR method (3.3-8.1 mm). The AIR method was accurate and recommended for all the surgical positions if intraoperative imaging was available. The SMR method was only recommended for the supine position, because skin distortion was frequently observed in the lateral region.

Ablation efficacy of 5-aminolevulinic acid-mediated photodynamic therapy on human glioma stem cells.

BACKGROUND: Cancer cells with stem cell-like features are generally more resistant to chemotherapy and radiotherapy than differentiated tumor cells. Thus, these cells tend to increase the propensity for tumor recurrence and metastasis. This study investigated the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in destructing glioma stem cells (GSCs), including the mesenchymal subtype (MES-GSCs) demonstrated to have the lowest radio- and chemosensitivity. METHODS: Five high-grade glioma (HGG) GSC lines and derived differentiated glioma cell (DGC) lines were examined for protoporphyrin-IX (PpIX) expression using fluorescence-activated cell sorting (FACS) and then assessed for ALA-PDT sensitivity using cell viability assays. MES-GSCs surviving ALA-PDT were then isolated and evaluated for stem cell and mesenchymal marker expression levels (CD44, ALDH1A3, KLF4, nestin) by qRT-PCR. The ability of these surviving cells to form tumors was then examined using colony forming and by xenograft tumor assays in athymic mice. Finally, the relationship between PpIX expression level (high versus low) and ALA-PDT sensitivity was examined by FACS and colony forming assays. RESULTS: ALA-PDT was effective against all GSC lines including MES-GSCs. MES-GSC lines exhibited higher PpIX expression than derived DGCs. Surviving MES-GSCs demonstrated lower stem cell marker expression and tumor forming potential than naive MES-GSCs. Higher PpIX production capacity by MES-GSCs was associated with greater colony forming ability, and ALA-PDT was more effective against MES-GSCs with greater PpIX accumulation. CONCLUSION: ALA-PDT may be clinically effective against HGG by targeting GSCs, including MES-GSCs.

The Characteristic of Light Sources and Fluorescence in the 3-Dimensional Digital Exoscope "ORBEYE" for 5-Aminolevulinic Acid-Induced Fluorescence-Guided Surgery Compared with a Conventional Microscope.

BACKGROUND: The ORBEYE (ORB), an innovative 3-dimensional digital exoscope, is an equipped system for fluorescence-guided surgery with 5-aminolevulinic acid. Therefore, this study aimed to verify the characteristics of fluorescence-guided surgery with 5-aminolevulinic acid and excitation light source with ORB. METHODS: The same operative field of glioblastoma was recorded under blue light (BL) excitation using a conventional microscope (MS) and ORB. For in vitro studies, the energy of 405-nm wavelength light in white light and BL modes of each scope was examined in various focal lengths. To examine the degree of photobleaching with BL for each scope, protoporphyrin IX-soaked filter papers were continuously exposed with BL of an MS and ORB, and the video-recorded red fluorescence intensity was analyzed. RESULTS: The color tone of tumor-induced red fluorescence was remarkably different under each scope. Furthermore, nonfluorescent normal structures without red fluorescence were well recognized under ORB. The energy of 405-nm wavelength light in BL was significantly higher in ORB than that in an MS, especially in the short focal length. With continuous BL excitation to filter papers, the relative red fluorescence intensity of filter papers was significantly decreased over time in ORB than in an MS. In low protoporphyrin IX concentration, the difference was more significant. CONCLUSIONS: With ORB, the good visibility due to BL energy as compared with an MS might improve the surgical manipulation even in BL mode. However, the weak fluorescent tissue and short focal length should be carefully considered because photobleaching might be critical for FGS.

Characteristic and Management of Symptomatic Septum Pellucidum Cyst in Extreme Elderly Patient: Case Report and Literature Review.

Septum pellucidum cyst is rare and is defined as a fluid-filled space between the lateral ventricles; it has a width of 10 mm or more. In this case report, a surgical patient of symptomatic septum pellucidum cyst (SPC) in extreme age is described. To the best our knowledge, this is the first report of an extremely aged patient with symptomatic SPC that was successfully treated using a flexible neuroendoscope. An 85-year-old male complained of gradually worsening gait disturbance, dementia, and urinary incontinence without headache and was admitted to our hospital. MRI revealed a huge cyst between the lateral ventricles as well as ventricle dilatation with periventricular hyperintensity in T2-weighted image. The patient was diagnosed with symptomatic hydrocephalus with SPC and underwent neuroendoscopic fenestration of the cyst with the use of a flexible endoscope without cerebrospinal fluid shunt placement. Immediately after the surgery, the patient's gait disturbance and dementia were dramatically improved. In extremely aged patients, SPC tended to develop with idiopathic normal pressure hydrocephalus-like symptoms, including gait disturbance without increasing intracranial pressure, sensorimotor disturbances, and psychological disorders. Neuroendoscopic cyst fenestration with the use of a flexible scope for SPC is a less-invasive procedure and should be considered even for extreme elderly symptomatic patients.

Frameless Stereotactic Biopsy with Intraoperative Computed Tomography "Assessment of Efficacy and Real Target Registration Error".

Frameless stereotactic brain biopsy (FSB) with navigation system has been widely used. We reported preliminary experience of FSB with intraoperative computed tomography (iCT) and examined the usefulness of this novel adjuvant technique and real target registration error (rTRE) of FSB. The FSB with 5-aminolevulinic acid (5-ALA) and iCT was performed on 10 patients. The gadolinium-enhanced lesions on magnetic resonance image were defined as the biopsy target. In the procedure, iCTs were scanned twice, for autoregistration of the navigation system and for confirmation of the position of the actual inserted biopsy needle. The red fluorescence of the samples was observed under excitation with violet-blue light through a low-cut filter of neurosurgical microscope. The distance between the planned target and the tip of the biopsy needle in the image of iCT was calculated in a workstation for the assessment of rTRE. The median volume of the target was 12.13 mL (0.06-39.15 mL). We performed the surgical procedure in a prone position in four patients. None to faint 5-ALA-induced fluorescence was observed in six samples. There existed no sampling errors. The mean target distance between the planned and real targets of the mean rTRE of FSB was 2.7 ± 0.56 mm. The real TRE of FSB was first reported and was larger than the reported rTRE exactly calculated from the fiducial registration error. iCT guarantees accurate tumor sampling with autoregistration regardless of the surgical position and prevents inaccurate biopsy to occur even with ALA fluorescence assistance.

Chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression.

Radiation therapy is one of standard treatment for malignant glioma after surgery. The microenvironment after irradiation is considered not to be suitable for the survival of tumor cells (tumor bed effect). This study investigated whether the effect of changes in the microenvironment of parenchymal brain tissue caused by radiotherapy affect the recurrence and progression of glioma. 65-Gy irradiation had been applied to the right hemisphere of Fisher rats. After 3 months from irradiation, we extracted RNA and protein from the irradiated rat brain. To study effects of proteins extracted from the brains, we performed WST-8 assay and tube formation assay in vitro. Cytokine production were investigated for qPCR. Additionally, we transplanted glioma cell into the irradiated and sham animals and the median survival time of F98 transplanted rats was also examined in vivo. Immunohistochemical analyses and invasiveness of implanted tumor were evaluated. X-ray irradiation promoted the secretion of cytokines such as CXCL12, VEGF-A, TGF-ß1 and TNFα from the irradiated brain. Proteins extracted from the irradiated brain promoted the proliferation and angiogenic activity of F98 glioma cells. Glioma cells implanted in the irradiated brains showed significantly high proliferation, angiogenesis and invasive ability, and the post-irradiation F98 tumor-implanted rats showed a shorter median survival time compared to the Sham-irradiation group. The current study suggests that the microenvironment around the brain tissue in the chronic phase after exposure to X-ray radiation becomes suitable for glioma cell growth and invasion.

[Intraoperative Fluorescence Imaging of Brain Tumors].

Malignant gliomas are highly invasive tumors. Accurate identification of tumor tissue is essential for enabling tumor resection as much as possible without damaging important neurological functions. One of the methods is intraoperative fluorescence imaging. This method visualizes in real time the boundary between the tumor and normal brain, which cannot be identified using conventional surgical microscope under white light. Although many fluorescent dyes have been reported for intraoperative fluorescence imaging of brain tumors, only 5-aminolevulinic acid(5-ALA)is approved by Ministry of Health, Labour and Welfare in Japan. After the oral administration of 5-ALA, fluorescence is emitted by protoporphyrin Ⅸ, a metabolite of 5-ALA in tumor cells(red fluorescence with a peak at 635 nm, induced by an excitation light of 405 nm). The intensity of fluorescence is correlated with tumor cell density, proliferation rate, and vascular density. In a multicenter randomized controlled study in Germany, compared with white light imaging, fluorescence imaging with 5-ALA increased the tumor resection rate and significantly prolonged progression-free survival at 6 months. However, no difference was observed in overall survival. Regarding other fluorescent substances, fluorescein sodium is a dye that leaks from tumor vessels without the blood-brain barrier, like contrast media used for computed tomography and magnetic resonance imaging(green fluorescence with a peak at 520 nm, induced by an excitation light of 493 nm). This dye spreads in the interstitial tissue of the tumor to visualize the tumor area. Indocyanine green emits a near-infrared light of 820-920 nm, induced by an excitation light of 760- 810 nm. This dye was expected to be useful for visualizing deep tumors as it emits light with high tissue permeability; however, it does not leak out of blood vessels because of its large molecular weight. Subsequently, this dye is used for intraoperative angiography of highly vascularized tumors. Talaporfin sodium was originally developed for photodynamic therapy in Japan and is readily taken up by tumor cells. This substance is also used for intraoperative fluorescence imaging because it emits the fluorescence of 672 nm, induced by an excitation light of 664 nm. Here, we review various fluorescent dyes used for intraoperative imaging of brain tumors.

A Case of Puncture-Site Giant Pseudoaneurysm Following Recanalization Therapy for Acute Ischemic Stroke: Marked Growth and Rupture of a Femoral Artery Pseudoaneurysm.

Objective: We report a case of the marked growth and rupture of a giant femoral artery pseudoaneurysm at the puncture site that developed after recanalization therapy for acute basilar artery occlusion. Case Presentation: A 79-year-old woman developed acute ischemic stroke due to atherosclerotic basilar artery occlusion. Endovascular intervention was performed and recanalization of the affected vessel was achieved. However, she developed brainstem infarction and consciousness disturbance persisted. The femoral access site was treated using a vascular closure device at the end of the procedure. A right femoral artery pseudoaneurysm of approximately 5 cm in size was found 2 weeks after onset during the examination for deep venous thrombosis with right lower extremity edema. Manual compression did not achieve thrombotic occlusion of the aneurysm due to obesity and leg edema. Considering the severe neurological status of the patient, the pseudoaneurysm was followed up without surgical treatment. Dual antiplatelet therapy and direct oral anticoagulant agents were administered. Four weeks after onset, the pseudoaneurysm presented rapid growth, and on the 35th day after onset, it exceeded 15 cm in size and ruptured, causing hemorrhagic shock with massive femoral hematoma. Pseudoaneurysm resection and hematoma removal were performed surgically, and the patient recovered. However, improvement of neurological manifestations was poor and the modified Rankin Scale at 90 days after onset was 5. Conclusion: A case of giant femoral artery pseudoaneurysm following recanalization therapy for acute ischemic stroke was reported. Pseudoaneurysms at the puncture site can rupture after significant growth. Curative treatment is required without delay.

PD-L1 and PD-L2 expression in the tumor microenvironment including peritumoral tissue in primary central nervous system lymphoma.

BACKGROUND: The prevalence of programmed death-ligand 1 (PD-L1) and PD-L2 expression on tumor cells and tumor-infiltrating immune cells in primary central nervous system lymphoma (PCNSL) remains unclear. In the present study, we analyzed needle biopsy and craniotomy specimens of patients with PCNSL to compare the PD-L1 and PD-L2 levels in the tumor and surrounding (peritumoral) tissue. We also assessed the correlation between biological factors and the prognostic significance of PD-L1 and PD-L2 expression. METHODS: We retrospectively analyzed the cases of 70 patients histologically diagnosed with PCNSL (diffuse large B-cell lymphoma). Immunohistochemistry for CD20, CD68, PD-L1, and PD-L2 was performed. In cases with specimens taken by craniotomy, the percentages of PD-L1- and PD-L2-positive macrophages were evaluated in both tumor and peritumoral tissue. The Kaplan-Meier method with log-rank test and Cox proportional hazard model were used for survival analysis. RESULTS: The tumor cells expressed little or no PD-L1 and PD-L2, but macrophages expressed PD-L1 and PD-L2 in most of the patients. The median percentage of PD-L2-positive cells was significantly higher among peritumoral macrophages (32.5%; 95% CI: 0-94.6) than intratumoral macrophages (27.5%; 95% CI: 0-81.1, p = 0.0014). There was a significant correlation between the percentages of PD-L2-positive intratumoral macrophages and PD-L2-positive peritumoral macrophages (p = 0.0429), with very low coefficient correlation (ρ = 0.098535). PD-L1 expression on macrophages was significantly associated with biological factors (intratumoral macrophages: better KPS, p = 0.0008; better MSKCC score, p = 0.0103; peritumoral macrophages: low proportion of LDH elevation, p = 0.0064) and longer OS (for intratumoral macrophages: high PD-L1 = 60 months, 95% CI = 30-132.6; low PD-L1 = 24 months, 95% CI = 11-48; p = 0.032; for peritumoral macrophages: high PD-L1 = 60 months, 95% CI = 30.7-NR; low PD-L1 = 14 months, 95% CI = 3-26). PD-L1 expression on peritumoral macrophages was strongly predictive of a favorable outcome (HR = 0.30, 95% CI = 0.12-0.77, p = 0.0129). CONCLUSIONS: Macrophages in intratumoral and peritumoral tissue expressed PD-L1 and PD-L2 at a higher rate than tumor cells. PD-L1 expression, especially on peritumoral macrophages, seems to be an important prognostic factor in PCNSL. Future comprehensive analysis of checkpoint molecules in the tumor microenvironment, including the peritumoral tissue, is warranted.

Other Hospital-onset Acute Ischemic Stroke Due to Large Vessel Occlusion Treated by Mechanical Thrombectomy after Inter-hospital Transfer.

The purpose of this study was to investigate the in-hospital acute ischemic stroke due to large vessel occlusion (LVO) that developed in another thrombectomy-incapable hospital, treated by mechanical thrombectomy after inter-hospital transfer. In eight other hospital-onset LVO patients, clinical characteristics, treatment results, and the timeline of thrombectomy were retrospectively investigated and compared to the results of 17 patients developed LVO at our own hospital and 18 developed in the community. In the analysis of timeline, the mean recognition-to-arrival time in other hospital-onset patients was 169 ± 78 min, significantly longer than for the community-onset patients (79 ± 78 min). Arrival-to-puncture time was 42 ± 19 min, significantly shorter than for the own hospital-onset patients (166 ± 80 min) and the community-onset patients (155 ± 76 min). Recognition-to-puncture times for the other hospital-onset patients, the own hospital-onset patients, and the community-onset patients were 212 ± 74, 166 ± 80, and 216 ± 83 min, respectively, and recognition-to-recanalization times were 285 ± 73, 200 ± 81, and 275 ± 125 min. Both these times were shorter for the own hospital-onset patients. The rates of modified Rankin Scale (mRS) of 0-2 in the three groups were 12%, 30%, and 23%, respectively. The rate of mRS 0-2 was lowest in the other hospital-onset patients. In conclusion, the other hospital-onset patients required additional time for their initial management and inter-hospital transfer although arrival-to-puncture time was shorter. Favorable outcomes were observed less frequently in them. Improving inter-hospital cooperation systems and to educate the medical staff in a thrombectomy-incapable hospital concerning stroke management is important measures for other hospital-onset stroke with LVO.

Long-Term Prognosis of Cognitive Function in Patients With Idiopathic Normal Pressure Hydrocephalus After Shunt Surgery.

The long-term prognosis of cognitive function in patients with idiopathic normal pressure hydrocephalus (iNPH) remains unclear. This study aimed to determine the long-term prognosis of cognitive function in patients with iNPH, as well as the factors related to it. It included 48 patients with iNPH who were treated with cerebrospinal fluid shunting between January 2015 and December 2017 at Osaka Medical College Hospital, with follow-up evaluation of their cognitive function for >2 years. Cognitive function was measured using the Mini-Mental State Examination (MMSE) preoperatively and at 3 months, 1 and 2 years post-operatively. The mean MMSE score (22.4 ± 5.4 preoperatively) improved at 3 months [23.8 ± 5.0 (p = 0.0002)] and 1 year [23.7 ± 4.8 (p = 0.004)] post-operatively. At 2 years post-operatively, they were able to maintain their preoperative level (22.6 ± 5.3). The patients were classified in to the cognitive decline group [11 (23%) patients; a decrease in the MMSE score by ≥ 2 points 2 years after surgery] and the maintenance/improvement group [37 (77%) patients]. Univariate and receiver operating characteristic analyses were performed for the two groups to identify factors associated with cognitive prognosis. In both groups, the patients who were younger (p = 0.009) or had milder symptoms (p = 0.035) had a better long-term prognosis of cognitive function. The cutoffs for age and disease severity (idiopathic normal-pressure hydrocephalus grading scale; INPHGS) were 78 years (area under the curve = 0.77) and 5 points (area under the curve = 0.71), respectively. In conclusion, most patients (77%) were able to improve and maintain cognitive function for at least 2 years after surgery. The fact that disease severity and age are associated with cognitive prognosis suggests that early iNPH intervention is desirable to improve cognitive prognosis.

A Patient with a Large Aneurysm Complicated by Stenosis of the Internal Carotid Artery Distal to the Aneurysm in Whom Treatment Using a Pipeline Flex Was Performed.

Objective: We report a case of in-stent stenosis as a complication at 6 months after the deployment of Pipeline Flex. This case necessitated retreatment for parent artery occlusion. Case Presentation: A 55-year-old woman with right-side visual disorder was referred to our hospital for the deployment of Pipeline Flex. Cerebral digital subtraction angiography (DSA) demonstrated a large right-side paraclinoid aneurysm in combination with severe internal carotid artery (ICA) stenosis just beyond the aneurysm. We deployed Pipeline Flex under general anesthesia. After deployment, we performed angioplasty through the Pipeline. Six months after deployment, this patient exhibited exacerbation of visual disorder. Follow-up DSA revealed in-stent stenosis at 6 months after the deployment of Pipeline Flex. Therefore, we performed parent artery occlusion. Right-side visual disorder was improved in this patient. Conclusion: If Pipeline is deployed for patients with ICA stenosis just beyond an aneurysm, we need to be aware of in-stent stenosis after deployment.

Refractory Chronic Subdural Hematoma Associated with Dural Metastasis of Lung Adenocarcinoma Treated with Endovascular Embolization for the Middle Meningeal Artery: A Case Report and Review of the Literature.

BACKGROUND: Endovascular embolization of the middle meningeal artery (MMA) is effective for recurrent chronic subdural hematoma (CSDH). CSDH associated with dural metastasis is generally refractory to burr hole surgery and has poor prognosis even if any interventions are applied. To the best of our knowledge, this study is the first to report a case of refractory CSDH associated with dural metastasis that was successfully treated with embolization of the MMA. CASE DESCRIPTION: A 66-year-old man with a 1-year history of lung adenocarcinoma had also undergone whole-brain irradiation for multiple brain metastases 5 months before presentation, surgical removal of relapse of brain metastases 3 months prior, and stereotactic radiotherapy for the relapses 1 month prior. He was admitted to our institution with speech disturbance, severe headache, and right-sided motor weakness. Head computed tomography on admission revealed left-sided CSDH, and emergency burr hole irrigation surgery was performed. However, CSDH recurred twice in a short period after hospitalization. Histological examination revealed adenocarcinoma cells in the dura mater and in hematoma samples during the first surgery; therefore, the patient was diagnosed with refractory CSDH associated with dural metastasis of lung adenocarcinoma. We performed endovascular embolization of the MMA, followed by systemic chemotherapy at 1 month after embolization, and no recurrence of the CSDH was observed. CONCLUSIONS: Embolization of the MMA has few surgical risks and could be a treatment option for refractory CSDH associated with dural metastasis because it might prolong the therapeutic time window until radical therapies are administered.

[Tentorial Dural Arteriovenous Fistula with Bithalamic Lesions and Bilateral Basal Ganglia Hemorrhage:A Case Report].

OBJECTIVE: We report an unusual case of tentorial dural arteriovenous fistula(DAVF)with bithalamic lesions and bilateral intracranial hemorrhage. CASE PRESENTATION: A 73-year-old man presented with lethargy and progressive cognitive decline. Imaging demonstrated bithalamic edematous lesions and bilateral basal ganglia hemorrhage in the right putamen and left internal capsule. Angiography revealed tentorial DAVF fed by both the internal and external carotid arteries. A shunted pouch was present in the superior petrosal sinus, and retrograde reflux drainage was see in the deep venous system, including the basal vein, vein of Galen, and internal cerebral veins with congestion. Initially, transarterial embolization was palliatively performed, and subsequently, a microsurgery achieved obliteration of the tentorial DAVF. Postoperatively, the bilateral thalamic changes disappeared, although sequela of the intracranial hemorrhage persisted. CONCLUSION: Deep venous congestion due to tentorial DAVF induced unusual bithalamic lesions and bilateral basal ganglia hemorrhage. Tentorial DAVF was treated with combined endovascular and surgical operations. Tentorial AVF is an aggressive vascular disease, and prompt diagnosis and treatment are necessary.

[The Efficacy of the Emergent Shunt-Clamp System for Secondary Hydrocephalus Associated with Fourth Ventricle Outlet Obstruction Syndrome:A Report of Two Cases].

Endoscopic third ventriculostomy(ETV)is the first-line treatment for fourth ventricle outlet obstruction(FVOO)-associated hydrocephalus. However, because FVOO is difficult to diagnose in the acute stage, ventriculoperitoneal shunt(VPS)is also used. Herein, we report two cases of shunted FVOO resulting in overdrainage or slit ventricle syndrome(SVS)that were treated successfully with the shunt-clamp system. In addition, we discuss the efficacy of the shunt-clamp system for FVOO-associated hydrocephalus. CASE 1:A 79-year-old man complained of severe postural headaches. One year earlier, he underwent VPS for secondary hydrocephalus associated with hemorrhagic cerebellar infarction. CT revealed that the ventricle had become slit-like. Although the shunt valve adjusted the maximum pressure, his complaint and the ventricle shape did not improve. After the on-off valve was inserted in the shunt system and clamped, his symptoms were resolved and the ventricle size was normalized. CASE 2:A 21-year-old man who complained of drowsiness, diplopia, and severe intermittent retroocular pain was admitted to our hospital. One year earlier, he underwent VPS with the shunt-clamp system for a secondary hydrocephalus after surgery for medulloblastoma. CT on admission revealed ventricle dilatation;however, the shape of the ventricle became slit-like 3 days after admission. We made a diagnosis of SVS and planned ETV. Owing to the difficulty in approaching the lateral ventricle, the shunt system was clamped 8 hours before the operation. After confirming ventricle dilatation, ETV was successfully performed. After the operation, the symptoms were resolved, and magnetic resonance imaging confirmed that the ventricle size was normalized.

Radiological diagnosis of brain radiation necrosis after cranial irradiation for brain tumor: a systematic review.

INTRODUCTION: This systematic review aims to elucidate the diagnostic accuracy of radiological examinations to distinguish between brain radiation necrosis (BRN) and tumor progression (TP). METHODS: We divided diagnostic approaches into two categories as follows-conventional radiological imaging [computed tomography (CT) and magnetic resonance imaging (MRI): review question (RQ) 1] and nuclear medicine studies [single photon emission CT (SPECT) and positron emission tomography (PET): RQ2]-and queried. Our librarians conducted a comprehensive systematic search on PubMed, the Cochrane Library, and the Japan Medical Abstracts Society up to March 2015. We estimated summary statistics using the bivariate random effects model and performed subanalysis by dividing into tumor types-gliomas and metastatic brain tumors. RESULTS: Of 188 and 239 records extracted from the database, we included 20 and 26 studies in the analysis for RQ1 and RQ2, respectively. In RQ1, we used gadolinium (Gd)-enhanced MRI, diffusion-weighted image, MR spectroscopy, and perfusion CT/MRI to diagnose BRN in RQ1. In RQ2, 201Tl-, 99mTc-MIBI-, and 99mTc-GHA-SPECT, and 18F-FDG-, 11C-MET-, 18F-FET-, and 18F-BPA-PET were used. In meta-analysis, Gd-enhanced MRI exhibited the lowest sensitivity [63%; 95% confidence interval (CI): 28-89%] and diagnostic odds ratio (DOR), and combined multiple imaging studies displayed the highest sensitivity (96%; 95% CI: 83-99%) and DOR among all imaging studies. In subanalysis for gliomas, Gd-enhanced MRI and 18F-FDG-PET revealed low DOR. Conversely, we observed no difference in DOR among radiological imaging in metastatic brain tumors. However, diagnostic parameters and study subjects often differed among the same imaging studies. All studies enrolled a small number of patients, and only 10 were prospective studies without randomization. CONCLUSIONS: Differentiating BRN from TP using Gd-enhanced MRI and 18F-FDG-PET is challenging for patients with glioma. Conversely, BRN could be diagnosed by any radiological imaging in metastatic brain tumors. This review suggests that combined multiparametric imaging, including lesional metabolism and blood flow, could enhance diagnostic accuracy, compared with a single imaging study. Nevertheless, a substantial risk of bias and indirectness of reviewed studies hindered drawing firm conclusion about the best imaging technique for diagnosing BRN.

Fluoroscopic-Guided Paramedian Approach for Lumbar Catheter Placement in Cerebrospinal Fluid Shunting: Assessment of Safety and Accuracy.

BACKGROUND: Spinal catheter insertion in lumboperitoneal (LP) shunt surgery for idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with technical difficulties especially in patients with obesity and elderly patients with vertebral deformities. OBJECTIVE: To elucidate the accuracy and safety of image-guided spinal catheter placement using a paramedian approach (PMA). METHODS: We retrospectively analyzed 39 consecutive iNPH patients treated by LP shunting with spinal catheter insertion via the PMA. The success rate of catheter placement and the number of changes in puncture location were evaluated. Accuracy of catheter insertion was assessed by measuring both vertical and horizontal deviations in the point of catheter dural penetration from the center of the interlaminar space. RESULTS: The success rate of catheter placement was 100% (39/39). The difficulty rate for catheter insertion, measured by the number of changes in puncture location, was 2.6% (1/39). No bloody punctures or surgical infections were observed. Accuracy of catheter insertion, measured as the degree of deviation, was 0.5 ± 1.9 mm horizontally and 0.0 ± 2.4 mm vertically. The rates of minor complications, including caudal catheter insertion, transient low-pressure headache, and root pain, were 5.1% (2/39), 10.4% (4/39), and 0% (0/43), respectively. Subdural hematoma requiring surgical intervention occurred in 1 case (2.6%). During the mean follow-up period of 36 mo, spinal catheter rupture at the level of the spinous processes was not observed. CONCLUSION: Fluoroscopic-guided spinal catheter placement via the PMA was safe, accurate, and reliable, even for use in geriatric and obese patients.

Folate receptor-targeted novel boron compound for boron neutron capture therapy on F98 glioma-bearing rats.

Folic acid (FA) has high affinity for the folate receptor (FR), which is limited expressed in normal human tissues, but over-expressed in several tumor cells, including glioblastoma cells. In the present work, a novel pteroyl-closo-dodecaborate conjugate (PBC) was developed, in which the pteroyl group interacts with FR, and the efficacy of boron neutron capture therapy (BNCT) using PBC was investigated. Thus, in vitro and in vivo studies were performed using F98 rat glioma cells and F98 glioma-bearing rats. For the in vivo study, boronophenylalanine (BPA) was intravenously administered, while PBC was administered by convection-enhanced delivery (CED)-a method for direct local drug infusion into the brain of rats. Furthermore, a combination of PBC administered by CED and BPA administered by intravenous (i.v.) injection was also investigated. In the biodistribution experiment, PBC administration at 6 h after CED termination showed the highest cellular boron concentrations (64.6 ± 29.6 µg B/g). Median survival time (MST) of untreated controls was 23.0 days (range 21-24 days). MST of rats administered PBC (CED) followed by neutron irradiation was 31 days (range 26-36 days), which was similar to that of rats administered i.v. BPA (30 days; range 25-37 days). Moreover, the combination group [PBC (CED) and i.v. BPA] showed the longest MST (38 days; range 28-40 days). It is concluded that a significant MST increase was noted in the survival time of the combination group of PBC (CED) and i.v. BPA compared to that in the single-boron agent groups. These findings suggest that the combination use of PBC (CED) has additional effects.

Boron Neutron Capture Therapy Combined with Early Successive Bevacizumab Treatments for Recurrent Malignant Gliomas - A Pilot Study.

Recurrent malignant gliomas (RMGs) are difficult to control, and no standard protocol has been established for their treatment. At our institute, we have often treated RMGs by tumor-selective particle radiation called boron neutron capture therapy (BNCT). However, despite the cell-selectivity of BNCT, brain radiation necrosis (BRN) may develop and cause severe neurological complications and sometimes death. This is partly due to the full-dose X-ray treatments usually given earlier in the treatment course. To overcome BRN following BNCT, recent studies have used bevacizumab (BV). We herein used extended BV treatment beginning just after BNCT to confer protection against or ameliorate BRN, and evaluated; the feasibility, efficacy, and BRN control of this combination treatment. Seven patients with RMGs (grade 3 and 4 cases) were treated with BNCT between June 2013 and May 2014, followed by successive BV treatments. They were followed-up to December 2017. Median overall survival (OS) and progression-free survival (PFS) after combination treatment were 15.1 and 5.4 months, respectively. In one case, uncontrollable brain edema occurred and ultimately led to death after BV was interrupted due to meningitis. In two other cases, symptomatic aggravation of BRN occurred after interruption of BV treatment. No BRN was observed during the observation period in the other cases. Common terminology criteria for adverse events grade 2 and 3 proteinuria occurred in two cases and necessitated the interruption of BV treatments. Boron neutron capture therapy followed by BV treatments well-prevented or well-controlled BRN with prolonged OS and acceptable incidence of adverse events in our patients with RMG.