Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s10143-024-03019-2

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Other Link： https://link.springer.com/article/10.1007/s10143-024-03019-2/fulltext.html

Language：Japanese  

Recent advances in endovascular treatment have improved the safety and efficacy of this procedure, and the number of cases in which preoperative embolization is performed is likely to increase. Preoperative tumor embolization is still a controversial treatment, and as long as it carries a risk of complications, its primary benefit of reducing blood loss during surgery may not be sufficient to justify treatment. We recently reported that preoperative embolization does not significantly increase complications, but may prolong recurrence-free survival. However, currently, tumor embolization is only a preoperative adjunctive therapy, and there is no evidence that it is a stand-alone option for meningioma treatment. Nevertheless, the possibility that tumor embolization alone can promote tumor shrinkage and reduce peripheral oedema has been reported, although the number of cases is small. Further research is needed, but in the future, tumor embolization may become an in-office treatment under certain conditions, such as in cases of poor general condition, multiple meningiomas, recurrent and refractory cases, difficult surgery and cases where re-irradiation is difficult after post-radiation therapy.

DOI： 10.11477/mf.1436204983

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco's mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca2+. METHODS: A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2',7'-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells. RESULTS: CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE. CONCLUSION: Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca2+ signaling and CaMKK2 pathways.

DOI： 10.1186/s12576-024-00928-1

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti‐cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti‐cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF‐induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming.

DOI： 10.1111/cas.16243

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.inat.2024.101974

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Language：Japanese   Publishing type：Research paper (scientific journal)  

This article describes the concept and technical aspects of the occipital transtentorial approach(OTA)for tumor extraction in the pineal region, based on the author's experience and literature review. Awareness of the successful completion of each surgical step is essential. Preoperative preparation and imaging evaluations, with particular attention to the veins and venous sinuses, are especially important. It is also helpful to perform a complete dura incision and inversion up to the edge of confluence, superior sagittal sinus, and transverse sinus. Subsequently, it is necessary to understand the usefulness of adequate dissection in the vicinity of the corpus callosum and internal occipital vein(IOV)so that the occipital lobe can be moved without difficulty. Furthermore, development of the IOV with adequate tentoriotomy facilitates contralateral work. Finally, complete understanding of each step during the bilateral, ambient cistern and cerebellomesencephalic fissure dissection process, where the cerebellar vermis can be moved without difficulty, is necessary for a safe OTA to pineal region tumor extraction.

DOI： 10.11477/mf.1436204958

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Takotsubo cardiomyopathy (TC) is a well-known complication of subarachnoid haemorrhage (SAH), often accompanied by neurogenic myocardial dysfunction. Although TC has been reported to be associated with higher morbidity and mortality among patients with aneurysmal SAH (aSAH), some patients have been reported to recover, the profiles and follow-up outcomes of these survivors remain unclear. MATERIALS AND METHODS: To characterize the profiles of patients with aSAH complicated by TC who experienced favourable outcomes using long-term follow-up data, a consecutive series of patients with aSAH were enrolled and TC diagnosis was based on the revised version of the Mayo Clinic criteria. Clinical outcomes were assessed at 6 months according to modified Rankin Scale scores. RESULTS: Among 165 consecutive patients with aSAH, 15 cases were complicated by TC, corresponding to an occurrence rate of 9.0%. Five patients with aSAH complicated by TC (33.3%) experienced a favourable outcome, and the mean value of systolic blood pressure on arrival was significantly lower than in those who experienced an unfavourable outcome (p = 0.032). CONCLUSION: According to analysis, it is possible cardiac dysfunction with decreased cerebral perfusion pressure and catecholamine toxicity transiently worsens conscious disturbance in aSAH complicated by TC. Therefore, it is important to carefully screen patients with aSAH to identify those complicated by TC, and for close collaboration of the multidisciplinary team to design appropriate treatment strategies.

DOI： 10.1080/02688697.2024.2334432

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Language：Japanese   Publisher：(一社)日本小児神経外科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Introduction Preoperative embolization can potentially facilitate surgical resection of challenging tumors in the intracranial and facial regions; however, its clinical efficacy remains controversial, mainly due to potential morbidity risks. We explored negative factors of the combined treatment of preoperative embolization and tumor resection that affect neurological prognosis. Method This retrospective study used clinical data from 132 consecutive tumors that underwent combined treatment at multiple facilities between January 2016 and May 2021. Basic patient information, tumor characteristics, and treatment details were assessed to identify predictors of deterioration as measured using the modified Rankin scale (mRS) score at three months post-treatment. Results Among the 126 eligible combined treatments, a deterioration in the postoperative mRS score was observed in 19/126 (15.1%). Complications related to embolization and tumor resection occurred in 8/126 (6.3%) and 19/125 (15.2%) of procedures, respectively. Multivariate analyses indicated significant associations between migration of embolic material (adjusted odds ratio 13.80; 95% confidence interval 1.25-152.52; p=0.03), elevated intraoperative blood loss (p=0.04), and deterioration of postoperative mRS score. Embolic material migration was identified as the primary prognostic factor for the deterioration of score. An analysis of 192 procedures, excluding those that exclusively used coils, identified embolization targeting the accessory meningeal artery (p=0.046) and the third segment of the internal maxillary artery (p=0.03) as a risk factor for embolic material migration. Conclusions Embolic material migration is the predominant factor associated with declining neurological outcome that persists into the chronic phase after combined treatment. Given that preoperative embolization is a supplementary treatment option, a thorough understanding of vascular anatomy and striving safe procedure are critical.

DOI： 10.7759/cureus.57315

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Introduction This study aimed to determine the optimal timing for surgical intervention and the prognostic factors of cerebrospinal fluid (CSF) leakage. Methods We identified 25 patients with probable CSF leaks from 472 consecutive patients with head trauma. In addition to baseline characteristics and findings on admission, injury severity score (ISS), abbreviated injury score (AIS), and other factors related to CSF leakage were considered. We analyzed the prognostic factors after setting the primary endpoint as the modified Rankin Scale (mRS) at the time of discharge to determine the appropriate timing for surgical intervention. Results Univariate analysis revealed significantly poorer prognoses for elderly patients (p<0.001) and cases with low Glasgow Coma Scale (GCS) levels (p=0.039) and high D-dimer levels (p=0.028), which was consistent with findings from the analyses of all patients with head trauma. We found that multiple traumas (AIS≥3 at two or more sites, p=0.047) and high lactate levels (p=0.043) were poor prognostic factors specific to CSF leakage cases, while a longer time to CSF leakage cessation was also associated with a poorer prognosis (median, six days versus 13 days, p=0.014). An evaluation of the time to closure found that spontaneous cessation occurred within 14 days in most cases. Conclusions Conservative medical treatment is the first choice for most cases of traumatic CSF leakage. Surgical intervention should be considered if leakage does not cease after 14 days post injury. Furthermore, severe multiple injuries and high lactate levels were poor prognostic factors specific to patients with CSF leakage.

DOI： 10.7759/cureus.52874

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: The superiority and usefulness of liquid material over particles for embolization have been a topic of debate due to differences in materials and techniques. This study aimed to identify the complications and outcomes associated with both embolization materials. METHODS: This retrospective multicenter cohort study included 93 patients from an endovascular treatment registry, treated from January 1, 2018 to May 31, 2022. It included patients who underwent preoperative embolization for meningioma, solitary fibrous tumor/hemangiopericytoma, and hemangioblastoma. Data for patient characteristics, procedural factors, complications, and outcomes were collected from medical records. RESULTS: A tortuous access route was the only factor independently associated with complications (p = 0.020). Although liquid material was more frequently used for embolization in relatively high-risk conditions, complication rates did not differ significantly between the groups (p = 0.999). In the liquid material group, the tip of the microcatheter could be guided closer to the tumor (p <0.001) using a distal access catheter and flow-guide microcatheters. The subgroup middle meningeal artery embolization had less operative bleeding in the liquid material group (p <0.001), whereas the particles group exhibited less intraoperative blood loss than the liquid material group (p = 0.006). CONCLUSION: The vascular tortuosity of the access route was only associated with complications in preoperative tumor embolization. Liquid material and particles showed no difference in complication rates. The use of particles in embolization may reduce intraoperative bleeding, but not in all cases can it be used safely. Therefore, a thorough understanding of the characteristics of both approaches and their relative advantages in clinical practice is essential to opt for the appropriate material according to the case.

DOI： 10.5797/jnet.oa.2023-0083

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Carotid artery stenting embolic protection devices offer various options, among which distal filter protection is the simplest and easiest to handle. However, compared to balloon protection systems, distal filter protection has more embolic complications. Therefore, we explored the risk factors of distal filter protection, intending to achieve a safer carotid artery stenting. This retrospective study was conducted to identify prognostic factors following carotid artery stenting with only distal filter protection from July 2010 to June 2021. METHODS: Information on patient background, procedures and devices, and complications was collected using medical records. The data pertaining to 187 patients were analyzed after excluding the data of patients in whom other protection devices (8 cases) were used. We used FilterWire EZ as the first choice for embolic protection device and SpiderFX when the patients had difficult-to-cross lesions. RESULTS: The patients' mean age was 71.9 ± 6.9 years, and 72 (38.5%) were symptomatic. Symptomatic (odds ratio: 2.02, p = 0.035) and difficult-to-cross lesions (odds ratio: 3.63, p = 0.0013) were factors independently associated with symptomatic complications. CONCLUSION: This retrospective single-center study established independent prognostic factors for carotid artery stenting with distal filter protection. For patients with symptomatic lesions and severe stenosis or bends that are difficult to pass through, it is necessary to be careful when performing carotid artery stenting with distal filter protection.

DOI： 10.5797/jnet.oa.2023-0096

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BACKGROUND: Vertebral artery (VA) stenosis can be caused by several factors, including arteriosclerosis, arterial dissection, and mechanical compression. Symptomatic vertebrobasilar insufficiency caused by VA stenosis due to mechanical compression associated with head rotation is well-known as Bow Hunter's syndrome. However, an accurate diagnosis of asymptomatic osteophyte compression-induced nonrotational VA stenosis is difficult. We report a case of left posterior inferior cerebellar artery aneurysm with severe left VA stenosis, treated with stent-assisted coil embolization following appropriate diagnosis. CASE DESCRIPTION: A 72-year-old female patient was found to have severe asymptomatic VA stenosis at the V2 segment (C4-5 level of the cervical spine) on cerebral angiography. Osteophyte compression-induced VA stenosis was suspected, which was confirmed by cone-beam computed tomography. The VA stenosis improved by flexing the neck and fixing the head position, following which the endovascular treatment was successfully completed. CONCLUSION: The site of the VA stenosis is critical in determining the etiology. Atherosclerotic VA stenosis often occurs at the origin of the artery or V4 segment, whereas bony compression-induced stenosis is more likely to occur at the V2 segment. Diagnosis and appropriate management of VA stenosis is based on determining the site.

DOI： 10.25259/SNI_772_2024

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Intraosseous clival arteriovenous fistulas (AVFs), in which the shunt drains extracranially from the posterior and anterior condylar veins rather than from the cavernous sinus (CS), are rare. Targeting embolization of an intraosseous clival AVF is challenging because of its complex venous and skull base anatomy; therefore, a therapeutic strategy based on detailed preoperative radiological findings is required to achieve a favorable outcome. Here, the authors report the successful targeted embolization of an intraosseous clival AVF using an ingenious access route. OBSERVATIONS: A 74-year-old woman presented with left-sided visual impairment, oculomotor nerve palsy, and right facial pain. A fusion image of three-dimensional rotational angiography and cone-beam computed tomography revealed a left CS dural AVF and a right intraosseous clival AVF. The shunt flow of the clival AVF drained extracranially from the posterior and anterior condylar veins via the intraosseous venous route. Transvenous embolization was performed by devising suboccipital, posterior condylar, and intraosseous access routes. The symptoms resolved after the bilateral AVFs were treated. LESSONS: Accurate diagnosis and proper transvenous access based on detailed intraosseous and craniocervical venous information obtained from advanced imaging modalities are key to resolving intraosseous clival AVF.

DOI： 10.3171/CASE23492

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: For patients who undergo endovascular treatment for acute ischemic stroke, the total time for treatment may increase during off-duty hours leading to worse outcomes. The present study compared endovascular treatment outcomes for on-duty and off-duty hours and examined factors that could be responsible for the prolonged treatment of patients in a multicenter registry. METHODS: The study group comprised 1571 patients listed in the multicenter stroke registry (K-NET) who had undergone endovascular treatment between January 2018 and June 2020. The modified Rankin Scale (mRS), evaluated at 90 days after stroke onset, was utilized as the primary outcome. Patients were divided into on-duty and off-duty patients based on admission time. Multivariate logistic regression analysis was used to identify the independent factors that increased the time from admission to puncture during the off-duty period. RESULTS: The mean mRS score at 90 days after stroke onset was 2.9, similar in both on-duty and off-duty patients, with no significant difference (p = 0.77); however, significant differences were observed in time from door-to-puncture (74.7 vs. 88.8, p < 0.01). Additionally, the mRS score at 90 days worsened significantly for door-to-puncture time >60 min in the off-duty period. Multivariate logistic regression analysis revealed that a low National Institute of Health Stroke Scale (NIHSS) score, high pre-mRS score, posterior circulation, and diabetes were independent indicators of door-to-puncture time >60 min during the off-duty period. CONCLUSION: Door-to-puncture time >60 min during off-duty hours was associated with poor outcomes related to low NIHSS, high pre-mRS, posterior circulation, and diabetes.

DOI： 10.1177/15910199231205050

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Biologically compatible vascular grafts are urgently required. The scaffoldless multi-layered vascular wall is considered to offer theoretical advantages, such as facilitating cells to form cell-cell and cell-matrix junctions and natural extracellular matrix networks. Simple methods are desired for fabricating physiological scaffoldless tissue-engineered vascular grafts. Here, we showed that periodic hydrostatic pressurization under hypoxia (HP/HYP) facilitated the fabrication of multi-layered tunica media entirely from human vascular smooth muscle cells. Compared with normoxic atmospheric pressure, HP/HYP increased expression of N-myc downstream-regulated 1 (NDRG1) and the collagen-cross-linking enzyme lysyl oxidase in human umbilical artery smooth muscle cells. HP/HYP increased N-cadherin-mediated cell-cell adhesion via NDRG1, cell-matrix interaction (i.e., clustering of integrin α5β1 and fibronectin), and collagen fibrils. We then fabricated vascular grafts using HP/HYP during repeated cell seeding and obtained 10-layered smooth muscle grafts with tensile rupture strength of 0.218-0.396 MPa within 5 weeks. Implanted grafts into the rat aorta were endothelialized after 1 week and patent after 5 months, at which time most implanted cells had been replaced by recipient-derived cells. These results suggest that HP/HYP enables fabrication of scaffoldless human vascular mimetics that have a spatial arrangement of cells and matrices, providing potential clinical applications for cardiovascular diseases. STATEMENT OF SIGNIFICANCE: Tissue-engineered vascular grafts (TEVGs) are theoretically more biocompatible than prosthetic materials in terms of mechanical properties and recipient cell-mediated tissue reconstruction. Although some promising results have been shown, TEVG fabrication processes are complex, and the ideal method is still desired. We focused on the environment in which the vessels develop in utero and found that mechanical loading combined with hypoxia facilitated formation of cell-cell and cell-matrix junctions and natural extracellular matrix networks in vitro, which resulted in the fabrication of multi-layered tunica media entirely from human umbilical artery smooth muscle cells. These scaffoldless TEVGs, produced using a simple process, were implantable and have potential clinical applications for cardiovascular diseases.

DOI： 10.1016/j.actbio.2023.09.041

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: Carotid artery stenting is sometimes adapted for some at-risk cases; however, appropriate treatment timing with stroke onset is controversial. This study aims to identify factors that have an impact on complications and outcomes, especially in patients at high risk. MATERIALS AND METHODS: We examined the characteristics of 152 consecutive patients treated by carotid artery stenting between January 2018 and March 2022 and retrospectively analyzed the risk factors for complications and poor outcomes (modified-Rankin-Scale deterioration), such as patient background, carotid artery stenting risks (access route tortuosity, severe calcification, vulnerable plaque, estimated glomerular filtration rate <30 mL/min/1.73 m2, etc.), characteristics of the stenosis, details of treatment, and treatment timing. RESULTS: The average North American Symptomatic Carotid Endarterectomy Trial criteria score was 68.3% and the lesion length was 20.5±9.7mm. Among patients, 107 (70.4%) had a carotid artery stenting risk. In high-risk carotid artery stenting cases, symptomatic complications occurred in 32 (30.0%), and the 90-day modified Rankin scale score deteriorated in 15 cases (14.0%). Multivariate analysis showed that cases with triple antithrombotic therapy (p=0.003), stenting within 7 days (p=0.0032), and after 28+ days (p=0.0035) of stroke onset were independently associated factors for complications. CONCLUSIONS: This study showed that among risk factors, triple antithrombotic therapy in particular was a risk factor for perioperative complications. Carotid artery stenting for patients with stroke after 28 days of onset affects the prognosis. Therefore, although further study is warranted, waiting more than one month for treatment in patients requiring carotid artery stenting is a potential risk.

DOI： 10.1016/j.jstrokecerebrovasdis.2023.107329

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Authorship：Lead author,　Corresponding author   Language：English  

BACKGROUND: Meningiomas are often embolized preoperatively to reduce intraoperative blood loss and facilitate tumor resection. However, the procedure is controversial and its effects have not yet been reported. We evaluated preoperative embolization for meningiomas and its effect on postoperative outcome and recurrence. METHODS: We retrospectively reviewed the medical records of 186 patients with WHO grade I meningiomas who underwent surgical treatment at our hospital between January 2010 and December 2020. We used propensity score matching to generate embolization and no-embolization groups (42 patients each) to examine embolization effects. RESULTS: Preoperative embolization was performed in 71 patients (38.2%). In the propensity-matched analysis, the embolization group showed favorable recurrence-free survival (RFS) (mean 49.4 vs 24.1 months; Wilcoxon p=0.049). The embolization group had significantly less intraoperative blood loss (178±203 mL vs 221±165 mL; p=0.009) and shorter operation time (5.6±2.0 hours vs 6.8±2.8 hours; p=0.036). There were no significant differences in Simpson grade IV resection (33.3% vs 28.6%; p=0.637) or overall perioperative complications (21.4% vs 11.9%; p=0.241). Tumor embolization prolonged RFS in a subanalysis of cases who experienced recurrence (n=39) among the overall cases before variable control (mean RFS 33.2 vs 16.0 months; log-rank p=0.003). CONCLUSIONS: After controlling for variables, preoperative embolization for meningioma did not improve the Simpson grade or patient outcomes. However, it might have effects outside of surgical outcomes by prolonging RFS without increasing complications.

DOI： 10.1136/neurintsurg-2022-019080

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BACKGROUND: This study assessed the efficacy and safety of thrombectomy for acute ischaemic stroke in a population with pre-stroke modified Rankin scale (mRS) scores of 2-3 using real-world data. METHODS: Our sample set included 2313 consecutive patients enrolled in the Kanagawa Registry of Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry between January 2018 and June 2020 in 40 stroke centres in Kanagawa Prefecture, Japan. Patients treated with intravenous tissue plasminogen activator (t-PA), thrombectomy, or both were included. Patients with pre-stroke mRS scores of 4-5 and those treated only with intra-arterial thrombolysis were excluded. The primary outcome of this study was an mRS score of 0-3 at 90 days after onset to assess the efficacy of thrombectomy for pre-stroke disabled individuals. We performed multivariate logistic regression analyses to investigate independent factors for a 90-day mRS score of 0-3. We also performed nearest-neighbour within-calliper matching between thrombectomy and t-PA only. RESULTS: After excluding patients meeting the exclusion criteria, we analysed data of 2136 consecutive patients, of which 315 (14.7%) had pre-stroke disabilities (mRS score 2-3). A 90-day mRS score of 0-3 was achieved by 33.3% of patients with pre-stroke mRS scores of 2-3. According to multivariate analysis, the National Institutes of Health Stroke Scale (NIHSS) score was an independent factor. Furthermore, after propensity-score matching, thrombectomy showed considerable superiority for achieving a 90-day mRS score of 0-3. CONCLUSION: Intravenous t-PA and especially thrombectomy were safe and effective for the population with pre-stroke disabilities, particularly for patients with low NIHSS scores.

DOI： 10.1177/15910199231185637

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Hemichorea-hemiballism (HCHB) due to transient ischemic attacks (TIAs) is rare. An 83-year-old woman had repeated episodes of right-sided HCHB for 3 months. Magnetic resonance (MR) angiography demonstrated occlusion of the left carotid and middle cerebral arteries and severe stenosis of the innominate artery, and 24-h ambulatory blood pressure monitoring showed a blood pressure decrease of >20 mmHg after each meal. We speculated that HCHB developed as TIAs due to hemodynamic failure in the left cerebral hemisphere, caused by a combination of severe stenosis of the innominate artery concomitant with occlusion of the left carotid and middle cerebral arteries as well as postprandial hypotension.

DOI： 10.2169/internalmedicine.0633-22

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Common carotid artery (CCA) occlusion (CCAO) is a rare cause of ischemic stroke and bypass surgery is the common treatment approach. However, safer alternatives should be developed to treat CCAO. A 68-year-old male was diagnosed with left-sided CCAO with decreased left visual acuity due to neck radiation therapy for laryngeal cancer. Recanalization therapy using a pull-through technique was initiated because cerebral blood flow progressively decreased during the follow-up period. First, after a short sheath was inserted into the CCA, the occluded CCA was retrogradely penetrated through the sheath. Second, a micro-guidewire was guided to the aorta from the femoral sheath where it was caught using a snare wire guided from the cervical sheath. Subsequently, the micro-guidewire was gently pulled out from the cervical sheath, penetrated the occluded lesion, and was secured to the femoral and cervical sheaths. Finally, the occluded lesion was dilated using a balloon, and the stent was placed. Five days postprocedure, the patient was discharged uneventfully and exhibited improved left visual acuity. In terms of reliable penetration of obstructive lesions and reduction of embolic and hemorrhagic complications, combined endovascular antegrade and direct retrograde carotid artery stenting is a versatile and minimally invasive treatment option for CCAO.

DOI： 10.2176/jns-nmc.2022-0397

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BACKGROUND: Subarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital. CASE PRESENTATION: The patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient's symptoms improved, and she became lucid. In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient's condition. CONCLUSION: If a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient's condition is critical, and early diagnosis will lead to a favorable outcome for the patient.

DOI： 10.1186/s12245-023-00490-4

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)  

Background: Risk-benefit analysis results for the treatment of unruptured aneurysms smaller than 5 mm are controversial. This study aimed to identify the outcomes and complication associated with treating such unruptured aneurysms. Methods: This was a retrospective study of 165 consecutive patients who underwent endovascular procedures for unruptured cerebral aneurysms of a maximum diameter 5 mm between January 2018 and March 2021. Patient background, aneurysm characteristics, adjuvant technique, volume embolization rate (VER), symptomatic complications, and modified Rankin Scale (mRS) scores were examined. Results: Sixty patients with sufficient data were included in the study. The mean age was 62.1 ± 14.6 years, and the median follow-up period was 12 months. The mean maximum diameter was 4.16 ± 0.63 mm, the neck diameter was 2.73 ± 0.82 mm, and 90% of patients had anterior circulation. Complete occlusion was achieved in 34 cases (57.6%). Although there were no intraoperative ruptures, complications were observed in four patients (6.7%), and one patient (1.7%) had worsened mRS score. Only one patient (1.7%) required retreatment. The first coil VER was independently associated with complete occlusion after endovascular treatment. Univariate analysis of complications showed an association between hypertension, hyperlipidaemia, and the estimated glomerular filtration rate. Conclusions: No patient experienced mRS score deterioration, and only one patient developed permanent disability due to ischemic complications; hence, we could safely treat small unruptured aneurysms. Complications are not related to procedural factors such as coiling adjuvant technique. However, lifestyle-related diseases are related to complications, and we suggest that physicians should remain vigilant of the indication for coiling when treating patients with underlying diseases.

DOI： 10.1016/j.inat.2022.101678

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OBJECTIVES: A foreign body granuloma after an endovascular intervention is a rare complication. Some cases of foreign body granulomas, especially after coil embolization, have been reported. However, only four cases of foreign body granulomas after mechanical thrombectomy (MT) have previously been reported. The current study reports two cases of post-MT foreign body granulomas, including a biopsy-proven case. MATERIAL AND METHODS: Case 1: A 73-year-old woman presented with complete occlusion of the right middle cerebral artery. Cerebral angiography and MT were successfully performed with improvement in clinical symptoms. Left hemiparesis and a disturbance in attention appeared after discharge and progressed slowly. She was re-admitted to our hospital 120 days after cerebral infarction owing to foreign body granulomas diagnosed on biopsy. Case 2: A 78-year-old man presented with occlusion of the left cervical internal carotid artery and the left middle cerebral artery. Cerebral angiography, percutaneous transluminal angioplasty, and MT were successfully performed. On the 34th day, he experienced progressive consciousness disorder because of foreign body granulomas. Both cases were successfully treated with steroid therapy. RESULTS: MRI after steroid treatment showed the disappearance of most nodular lesions and improvement of the encephalopathy. CONCLUSIONS: The cause of the granuloma may be an allergic reaction to the hydrophilic polymers that peel from endovascular devices. Steroid therapy is an effective treatment; therefore, neurologists should consider this complication when neurological symptoms or signs on image appears or worsens. A reliable diagnosis is important for prompt treatment.

DOI： 10.1016/j.jstrokecerebrovasdis.2023.106990

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PURPOSE: There have been several reports of central nervous system impairments associated with severe coronavirus disease 2019 (COVID-19) infection on head magnetic resonance imaging and angiography (MRI/A). However, head MRI/A is rarely performed in mild cases, and there have been few reports on intracranial changes after COVID-19 infection in these cases. Here, we report a comparative examination of the findings seen in common head MRI/A sequences in mild cases of COVID-19. METHODS: Of the 15,376 patients who underwent head MRI/A examination called "Brain Dock" between June 2020 and June 2021, 746 patients who received a COVID-19 antibody test were evaluated. Positive and negative patients were comparatively examined for head MRI/A findings such as cerebral white matter lesions, ischemic changes, cerebral microbleeds, cerebral aneurysms, arterial stenosis, sinusitis, and other abnormal findings. RESULTS: Overall, 31 (4.2%) patients were COVID-19 positive, and all of them had mild infections not requiring hospitalization. There was no significant difference in patient characteristics and head MRI/A findings between positive and negative patients. All positive patients showed no particular abnormalities in the nasal findings such as olfactory bulb atrophy or thickening of the olfactory mucosa. CONCLUSION: Intracranial lesions in mild patients do not show a clear difference from those in negative patients. This indicates that findings seen in common MRI/A sequences of severe patients are not likely in mild patients, supporting that there is relatively no damage to the central nervous system in mild patients.

DOI： 10.7759/cureus.34229

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Language：English  

OBJECTIVE: To report a case of symptomatic large cerebral aneurysm of the internal carotid artery (ICA), associated with a primitive trigeminal artery variant (PTAv), which was treated with a balloon occlusion test (BOT) to evaluate ischemic tolerance. CASE PRESENTATION: A 79-year-old woman was diagnosed with a symptomatic large cerebral aneurysm of the ICA bifurcating the PTAv due to diplopia. After confirming the ischemic tolerance of the perfusion area and PTAv by BOT, we performed ICA parent artery occlusion with selective embolization of the PTAv. Postoperative MRI showed no ischemic lesion and the diplopia was resolved. CONCLUSION: ICA parent artery occlusion with PTAv selective embolization after evaluation by BOT is useful in the treatment of large aneurysms.

DOI： 10.5797/jnet.cr.2022-0029

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society for Neuroendovascular Therapy  

OBJECTIVE: To identify factors associated with the outcome and prognosis of coil embolization for poor-grade aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We retrospectively reviewed 118 patients with World Federation of Neurosurgical Societies (WFNS) grade IV or V subarachnoid hemorrhage at our institute between January 2010 and December 2020. Outcomes were assessed using modified Rankin Scale (mRS) scores at discharge and at six months after aSAH onset. In addition, patient background, aneurysm characteristics, and treatment outcome were compared between patients showing favorable (mRS scores: 0-2) and unfavorable (mRS scores: 3-6) outcomes at six months. Factors for change of mRS during follow-up were explored, and cut off values were calculated for age using the receiver operating characteristic analysis. RESULTS: Endovascular treatment was performed in 51 of the 118 enrolled patients. Data were analyzed for 43 of these patients who underwent coil embolization of ruptured aneurysms and had complete datasets. The mean age was 61.7 years and 24 (55.8%) patients had WFNS grade V aSAH. Coil embolization-related complications were observed in three patients. There were no treatment-related deaths; however, eight patients (18.6%) died at three months. Multivariate analysis showed that the maximum diameter of the aneurysm (p=0.041) and the postoperative dual antiplatelet therapy (DAPT) (p=0.040) were associated with unfavorable and favorable outcomes, respectively. Older age (p=0.033) was independently associated with mRS score deterioration following discharge. Age 72 years and older was the cut off value for mRS deterioration. CONCLUSION: Aneurysm size and postoperative DAPT might be associated with outcomes at 6 months. Moreover, we identified older age as an independent factor that influences mRS deterioration following discharge; thus, especially in cases of elderly patients over 72 years of age, it is highly likely that long-term care to prevent disuse and regular follow-up on imaging will be necessary.

DOI： 10.5797/jnet.oa.2022-0043

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1227/neuopn.0000000000000019

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Observation is the first management option in asymptomatic meningiomas, but when an enlargement or mass effect is observed, surgery is indicated. This study is aimed at exploring risk factors for complications and recurrence after surgery for asymptomatic meningioma. We also examined the impact of preoperative tumor embolization, which is considered controversial. METHODS: We retrospectively reviewed 109 patients with primary asymptomatic meningiomas surgically treated at our institute between April 2007 and March 2021. Patients who only had headaches as a nonspecific complaint were included in the asymptomatic group. Complications, time to recurrence, and Glasgow Outcome Scale (GOS) score were the endpoints of the study. Risk factors for complications and recurrence were explored. Moreover, the effect of the resection on nonspecific headaches was also explored. RESULTS: The permanent postoperative complication rate related to the surgical procedure was 1.8%. Of the total, 107 patients (98.2%) with asymptomatic meningiomas who were surgically treated achieved a GOS score of 5 1 year after the operation. Preoperative headache was present in 31 patients and improved postoperatively in 21 patients. Multivariate analysis using the Cox proportional hazard model showed that preoperative tumor embolization with > 80% resolution of tumor staining (p < 0.001) was negatively related to recurrence, whereas age (p = 0.046) and Simpson grade IV resection (p = 0.041) were positively related to recurrence. CONCLUSION: Although surgery for asymptomatic meningiomas can, in many cases, be safe, it is not free of complications Thus, surgical intervention for asymptomatic meningiomas should be considered cautiously. However, more than half the patients with headaches showed improvement. Simpson grade IV resection cases should be assessed for recurrence, and preoperative tumor embolization might be effective in controlling recurrence.

DOI： 10.1007/s00701-022-05420-6

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.inat.2022.101583

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Authorship：Lead author   Publishing type：Research paper (scientific journal)  

DOI： 10.1159/000525229

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Parent artery occlusion (PAO) is an effective treatment for hemorrhagic diseases associated with the internal carotid artery. There are several reports of long-term cerebral infarction or the formation of de novo cerebral aneurysms following PAO. MATERIALS AND METHODS: We retrospectively reviewed these complications in 38 patients who underwent PAO for therapeutic treatment. We investigated perioperative cerebral infarctions, long-term cerebral infarctions, and de novo aneurysms. RESULTS: The mean age of the patients was 64.0 years, and 25 patients (65.8%) were female. The causative diseases were unruptured (n = 19; 50.0%) and ruptured (n = 8; 21.1%) aneurysms. PAO was performed after ischemic tolerance was assessed with balloon test occlusion (BTO), and BTO was performed in 34 patients, of whom 25 (73.5%) had ischemic tolerance. Twenty-six patients (68.4%) were treated with PAO alone, eight (23.5%) with low-flow bypass, and six (17.6%) with high-flow bypass. Perioperative complications occurred in five patients (13.2%): two of the 26 patients (7.7%) who underwent scheduled treatment and three of the 12 patients (25.0%) who underwent emergency treatment. One patient (2.6%) had long-term de novo aneurysm, and none developed cerebral infarction. CONCLUSIONS: These results showed that the assessment of ischemic tolerance by performing BTO and appropriate revascularization in scheduled treatments are important to reduce perioperative and long-term cerebral infarctions. PAO must be performed with greater caution in emergency treatment.

DOI： 10.1177/15910199221095786

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Language：English  

OBJECTIVE: We report a case of embolic occlusion of the common carotid artery (CCA) in which a giant thrombus was retrieved using the parallel stent retriever technique. CASE PRESENTATION: An 84-year-old woman without anticoagulant therapy despite a history of cardioembolic stroke presented to our hospital because of left hemiparesis after developing sudden vision loss in her right eye. Emergency angiography revealed a giant thrombus in the right CCA. After arresting flow in the CCA using a balloon-guided catheter (BGC), we deployed two stent retrievers in parallel from the internal carotid artery to the CCA, and slowly retrieved them simultaneously under manual aspiration through the BGC. As a result, complete recanalization was achieved. CONCLUSION: Thrombi causing acute embolic occlusion of the CCA are often too large to be completely retrieved using conventional thrombectomy techniques. The parallel stent retriever technique may be effective in such cases.

DOI： 10.5797/jnet.cr.2020-0164

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：FRONTIERS MEDIA SA  

This study investigated the effect of Mahjong, which is a table game played by three or four players and involves intellectual activity, on the intelligence quotient (IQ) of children. The participants were children between the age of 6 and 15 years, and their IQ was assessed immediately after enrolling in children's Mahjong classes and 1 year after the enrollment using the Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV). Twenty children were included in the analysis. Their mean age at the time of the initial evaluation was 9 years and 6 months. In addition, we conducted a 1-year post-examination. The change in the IQ of this group was compared to that of a historical control group with a similar age range and test-retest interval. The mean overall full-scale IQ of the 20 children during the initial and post-1-year examinations was 106.05 and 113.75, respectively, and showed a statistically significant increase (p < 0.01). Based on the subscale index, the verbal comprehension index (VCI) and processing speed index (PSI) scores both showed a statistically significant increase from 100.6 to 106.75 and from 108.05 to 119.05 (p < 0.01), respectively. The PSI of the children included in the analysis showed a statistically significant increase compared to the historical control group. This study suggests that children who participate in Mahjong classes during their childhood have increased PSI scores of WISC-IV.

DOI： 10.3389/fpsyg.2022.934453

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Through the progression of devices, the adaptation of carotid artery stenting (CAS) has been expanded according to the non-inferiority of CAS for carotid endarterectomy reported by several randomized control trials. To maintain favorable outcomes, identifying prognostic factors is essential for optimizing treatment indications and periprocedural management. This study focused on the prognostic factors of CAS using real-world data. METHODS: This retrospective multicenter cohort study aimed to identify the prognostic factors after CAS using real-world data from the stroke registry of Yokohama (STrOke Registry of Yokohama; STORY) from January 1, 2018 to May 31, 2021. Patient characteristics, procedural factors, complications, and prognoses were collected using medical records. RESULTS: Data from 107 patients were enrolled in this study after excluding those with insufficient data (2 cases). The mean participant age was 74.9±8.2 years, and 66 patients (61.7%) were symptomatic. Symptomatic lesions were a significant prognostic factor in the overall analysis (p=0.003). A multivariate analysis showed that the estimated glomerular filtration rate (eGFR) (odds ratio: 1.11, p=0.003) and staged CAS (odds ratio: 38.9, p=0.04) were independent prognostic factors. The odds ratio and relative risk of mRS deterioration when eGFR was under 49 mL/min/1.73 m2 compared with when eGFR was above 49 mL/min/1.73 m2 were 5.2 and 3.74, respectively. CONCLUSIONS: In this real-world multicenter study, we established independent prognostic factors for CAS using high totality data. For patients with symptomatic lesions and low eGFR (≤49 mL/min/1.73 m2), indication for treatment should be considered strictly.

DOI： 10.1016/j.jstrokecerebrovasdis.2021.106269

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INTRODUCTION: Recently, the efficacy of middle meningeal artery (MMA) embolization for chronic subdural hematoma (cSDH) in the elderly has been reported. However, no previous reports of MMA embolization for cSDH in children with ventricular assist devices (VAD) have been published. Here, we report a case of MMA embolization for cSDH in a child with VAD. CASE: A 15-month-old female was diagnosed with dilated cardiomyopathy at 7 months old. Soon, a VAD was inserted, and anticoagulant and antiplatelet therapy was started. Bilateral cSDH was observed at 15 months, and, 2 months later, an acute exacerbation of the right cSDH necessitated intracerebral hemorrhage removal. Afterwards, increased intracranial pressure occurred due to a contralateral subdural hematoma but, 4 months after intracerebral hemorrhage removal, CT showed new hemorrhaging in the left cSDH. MMA embolization was then conducted to prevent rebleeding in the hematoma. Selective angiography of the left MMA demonstrated stains of hematoma capsules from the frontal and parietal branches, which were embolized using liquid embolic material. During the procedure, the material migrated into the intracranial vessels via an undetected transdural anastomosis. Postoperatively, no new neurological abnormalities, including hemiparesis, were observed. Two months later, CT showed a decrease in hematoma size. CONCLUSION: MMA embolization for cSDH in pediatric patients with VAD may be effective, if vigilance is maintained against transdural anastomoses.

DOI： 10.1007/s00381-021-05418-y

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BACKGROUND: The occipital transtentorial approach (OTA) is a very useful but challenging approach to expose the pineal region because the deep-seated arachnoid membranes usually fold and extend over the great vein of Galen (GVG), leading to dense and poor visibility. In addition, the practical aspects of arachnoid anatomy are not well understood. We aimed to develop a safe surgical procedure for the OTA according to the practical aspects of arachnoid anatomy. METHODS: The procedure is shown through an illustrative video of surgery and cadaver. Five cadavers were analyzed for their arachnoid structures and the surgical procedures via the OTA, in strict compliance with legal and ethical requirements. RESULTS: All cadavers showed a 2-layered arachnoid structure-one belonging to the occipital lobe, and the other to the cerebellum. According to our cadaveric analysis, the arachnoid attachment of the tentorial apex can be peeled bluntly, with an average distance of 10.2 mm. For our clinical presentation, a pineal tumor with hydrocephalus was detected in a 14-year-old boy. While using the OTA and expanding the deep surgical field, we detached the membrane from the tentorial apex and bluntly peeled it to reveal the deep veins. Finally, gross total removal of the tumor was achieved. CONCLUSIONS: A 2-layered arachnoid structure interposes the GVG from above and below the tentorium. The arachnoid membrane below the tentorium can be peeled off bluntly from the GVG to the attachment bundle limited by the penetrating veins. This detachment technique is useful for safe enlargement of the surgical field for the OTA.

DOI： 10.1016/j.wneu.2021.04.041

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Language：English   Publishing type：Research paper (scientific journal)  

ABSTRACT: The Coronavirus disease 2019 pandemic continues to spread worldwide. Because of the absence of reliable rapid diagnostic systems, patients with symptoms of Coronavirus disease 2019 are treated as suspected of the disease. Use of computed tomography findings in Coronavirus disease 2019 are expected to be a reasonable method for triaging patients, and computed tomography-first triage strategies have been proposed. However, clinical evaluation of a computed tomography-first triage protocol is lacking.The aim of this study is to investigate the real-world efficacy and limitations of a computed tomography-first triage strategy in patients with suspected Coronavirus disease 2019.This was a single-center cohort study evaluating outpatients with fever who received medical examination at Yokohama City University Hospital, prospectively registered between 9 February and 5 May 2020. We treated according to the computed tomography-first triage protocol. The primary outcome was efficacy of the computed tomography-first triage protocol for patients with fever in an outpatient clinic. Efficacy of the computed tomography-first triage protocol for outpatients with fever was evaluated using sensitivity, specificity, positive predictive value, and negative predictive value. We conducted additional analyses of the isolation time of feverish outpatients and final diagnoses.In total, 108 consecutive outpatients with fever were examined at our hospital. Using the computed tomography-first triage protocol, 48 (44.9%) patients were classified as suspected Coronavirus disease 2019. Nine patients (18.8%) in this group were positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction; no patients in the group considered less likely to have Coronavirus disease 2019 tested positive for the virus. The protocol significantly shortened the duration of isolation for the not-suspected versus the suspected group (70.5 vs 1037.0 minutes, P < .001).Our computed tomography-first triage protocol was acceptable for screening patients with suspected Coronavirus disease 2019. This protocol will be helpful for appropriate triage, especially in areas where polymerase chain reaction is inadequate.

DOI： 10.1097/MD.0000000000026161

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Language：English   Publishing type：Research paper (scientific journal)  

Thiel's embalming method provides natural coloration, flexibility, and tissue plasticity, and is used widely to prepare specimens for cadaver surgical training. However, this method causes brain softening, thereby restricting the cadaver surgical training of intra-cranial procedures. In this study, three cadavers were embalmed using formalin fixation, Thiel's embalming method, and Thiel's embalming method with additional intra-cerebral ventricular formalin injection, respectively. We also established rat models of the three embalming methods to develop and determine the best method for retaining adequate brain elasticity. The intra-ventricular formalin injection in the cadaver was performed through the Kocher's point, as in the classical external ventricular drain procedure. Both, the cadaver brains and rat models yielded consistent shear wave measurements and brain surface stiffness data. Notably, the Thiel's embalming method with additional intra-cerebral ventricular formalin injection yielded suitable elasticity for brain cadaver surgical training in terms of brain mobilization and surgical field deployment, and also discharged formaldehyde in undetectable quantities. To our knowledge, this is the first report in which a fixed quality, namely, brain elasticity for the performance of head and brain cadaver surgical training, has been evaluated in a cadaver subjected to the Thiel's embalming method with immersion fixation in the cerebrospinal fluid space. We conclude that the Thiel's embalming method with additional intra-cerebral ventricular formalin injection can maintain the brain elasticity, and may therefore improve the quality of head and brain cadaver surgical training safely and easily.

DOI： 10.1007/s12565-020-00545-z

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：The Japanese Society for Pediatric Neurosurgery  

In cases of recurrent ependymoma with dissemination, the efficacy of adjuvant therapies is still being investigated.

In this study, we present a case of a 6-year-old Japanese girl with ependymoma in the posterior fossa. The 45-mm tumor is located mainly at the fourth ventricle and extended to the right foramen of Luschka, the jugular foramen, and the space between the basilar artery and clivus, which induced obstructive hydrocephalus. Because the patient underwent a three-stage surgery for 3 months, a gross total resection was almost achieved. During the third operation, the pathological diagnosis was anaplastic ependymoma. Therefore, she underwent fractionated radiation therapy of 54 Gy for the posterior fossa after 4 months since the initial surgery. No disseminated regions were observed at that time. A magnetic resonance imaging is performed every 3 months to show the progress of the recurrent tumor in a span of 21 months and the dissemination in the cerebrospinal cavity at 35 months since the first operation. Overall, she underwent 14 intracranial tumor removal procedures and 11 stereotactic radiosurgeries for all the 34 targets.

The recurrent but irradiated tumors had been under controlled for about 1 year. She maintained a good quality of life, with a Karnofsky Performance Status (KPS) score of 90, and had no major neurological deficits. In the course of another year, the tumor recurred, and she died six and half years later from the onset. Moreover, the combination of surgery and radiosurgery can achieve local control of anaplastic ependymoma even in a disseminated case for about 1 year keeping a good KPS score. Palliative therapy as multiple surgery or radiation therapy for recurrent tumor might also increase the patient's burden. Furthermore, stereotactic radiotherapy will be the preferred treatment option to decrease the frequency of surgery, maintaining a good quality of life.

DOI： 10.34544/jspn.45.4_358

CiNii Research

J-GLOBAL

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Language：English   Publishing type：Research paper (scientific journal)  

We previously reported the efficacy of anti-cancer therapy with hyperthermia using an alternating magnetic field (AMF) and a magnetic compound. In the course of the study, unexpectedly, we found that an AMF enhances the cytotoxicity of Compound C, an activated protein kinase (AMPK) inhibitor, although this compound is not magnetic. Therefore, we examined the cellular mechanism of AMF-induced cytotoxicity of Compound C in cultured human glioblastoma (GB) cells. An AMF (280 kHz, 250 Arms) for 30 minutes significantly enhanced the cytotoxicity of Compound C and promoted apoptosis towards several human GB cell lines in vitro. The AMF also increased Compound C-induced cell-cycle arrest of GB cells at the G2 phase and, thus, inhibited cell proliferation. The AMF increased Compound C-induced reactive oxygen species production. Furthermore, the AMF decreased ERK phosphorylation in the presence of Compound C and suppressed the protective autophagy induced by this compound. The application of an AMF in cancer chemotherapy may be a simple and promising method, which might reduce the doses of drugs used in future cancer treatment and, therefore, the associated side effects.

DOI： 10.1111/cas.13781

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Language：English   Publishing type：Research paper (scientific journal)  

Iron-salen, i.e., μ-oxo-N,N'-bis(salicylidene)ethylenediamine iron (Fe(Salen)) was a recently identified as a new anti-cancer compound with intrinsic magnetic properties. Chelation therapy has been widely used in management of metallic poisoning, because an administration of agents that bind metals can prevent potential lethal effects of particular metal. In this study, we confirmed the therapeutic effect of deferoxamine mesylate (DFO) chelation against Fe(Salen) as part of the chelator antidote efficacy. DFO administration resulted in reduced cytotoxicity and ROS generation by Fe(Salen) in cancer cells. DFO (25 mg/kg) reduced the onset of Fe(Salen) (25 mg/kg)-induced acute liver and renal dysfunction. DFO (300 mg/kg) improves survival rate after systematic injection of a fatal dose of Fe(Salen) (200 mg/kg) in mice. DFO enables the use of higher Fe(Salen) doses to treat progressive states of cancer, and it also appears to decrease the acute side effects of Fe(Salen). This makes DFO a potential antidote candidate for Fe(Salen)-based cancer treatments, and this novel strategy could be widely used in minimally-invasive clinical settings.

DOI： 10.1016/j.jphs.2017.07.002

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Melanoma has an extremely poor prognosis due to its rapidly progressive and highly metastatic nature. Several therapeutic drugs have recently become available, but are effective only against melanoma with specific BRAF gene mutation. Thus, there is a need to identify other target molecules. We show here that Transient receptor potential, canonical 3 (TRPC3) is widely expressed in human melanoma. We found that pharmacological inhibition of TRPC3 with a pyrazole compound, Pyr3, decreased melanoma cell proliferation and migration. Similar inhibition was observed when the TRPC3 gene was silenced with short-hairpin RNA (shRNA). Pyr3 induced dephosphorylation of signal transducer and activator of transcription (STAT) 5 and Akt. Administration of Pyr3 (0.05 mg/kg) to mice implanted with human melanoma cells (C8161) significantly inhibited tumor growth. Our findings indicate that TRPC3 plays an important role in melanoma growth, and may be a novel target for treating melanoma in patients.

DOI： 10.1007/s12576-016-0480-1

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Language：English   Publishing type：Research paper (scientific journal)  

Shortage of autologous blood vessel sources and disadvantages of synthetic grafts have increased interest in the development of tissue-engineered vascular grafts. However, tunica media, which comprises layered elastic laminae, largely determines arterial elasticity, and is difficult to synthesize. Here, we describe a method for fabrication of arterial grafts with elastic layer structure from cultured human vascular SMCs by periodic exposure to extremely high hydrostatic pressure (HP) during repeated cell seeding. Repeated slow cycles (0.002 Hz) between 110 and 180 kPa increased stress-fiber polymerization and fibronectin fibrillogenesis on SMCs, which is required for elastic fiber formation. To fabricate arterial grafts, seeding of rat vascular SMCs and exposure to the periodic HP were repeated alternatively ten times. The obtained medial grafts were highly elastic and tensile rupture strength was 1451 ± 159 mmHg, in which elastic fibers were abundantly formed. The patch medial grafts were sutured at the rat aorta and found to be completely patent and endothelialized after 2.5 months, although tubular medial constructs implanted in rats as interpositional aortic grafts withstood arterial blood pressure only in early acute phase. This novel organized self-assembly method would enable mass production of scaffold-free arterial grafts in vitro and have potential therapeutic applications for cardiovascular diseases.

DOI： 10.1038/s41598-017-00237-1

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Language：English   Publishing type：Research paper (scientific journal)  

We previously reported that μ-oxo N,N'-bis(salicylidene)ethylenediamine iron [Fe(Salen)], a magnetic organic compound, has direct anti-tumor activity, and generates heat in an alternating magnetic field (AMF). We showed that Fe(Salen) nanoparticles are useful for combined hyperthermia-chemotherapy of tongue cancer. Here, we have examined the effect of Fe(Salen) on human glioblastoma (GB). Fe(Salen) showed in vitro anti-tumor activity towards several human GB cell lines. It inhibited cell proliferation, and its apoptosis-inducing activity was greater than that of clinically used drugs. Fe(Salen) also showed in vivo anti-tumor activity in the mouse brain. We evaluated the drug distribution and systemic side effects of intracerebrally injected Fe(Salen) nanoparticles in rats. Further, to examine whether hyperthermia, which was induced by exposing Fe(Salen) nanoparticles to AMF, enhanced the intrinsic anti-tumor effect of Fe(Salen), we used a mouse model grafted with U251 cells on the left leg. Fe(Salen), BCNU, or normal saline was injected into the tumor in the presence or absence of AMF exposure. The combination of Fe(Salen) injection and AMF exposure showed a greater anti-tumor effect than did either Fe(Salen) or BCNU alone. Our results indicate that hyperthermia and chemotherapy with single-drug nanoparticles could be done for GB treatment.

DOI： 10.1038/srep42783

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Language：English   Publisher：JAPANESE PHARMACOLOGICAL SOC  

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Language：English   Publisher：JAPANESE PHARMACOLOGICAL SOC  

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Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞Point・髄膜腫に対する腫瘍塞栓術は主に術中出血量の低減目的で行われるが,長期的にみると再発を抑制する効果も有している可能性がある.

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＜文献概要＞I はじめに OTA(occipital transtentorial approach)は松果体部近傍への代表的な手術アプローチであり,ほかにinfratentorial supracerebellar approach,transcallosal interforniceal approach,parietal transcortical trans/sub-choroidal approachなどが用いられる.OTAはテント切痕上下および小脳テント直下の手術に対応でき,中脳視蓋,松果体,内大脳静脈(internal cerebral vein:ICV)下面,中間帆槽,モンロー孔直下の第三脳室側壁・後半部までの広い範囲を視野に収め,これらに発生する種々の病変に対処できる汎用性の高い術式である.OTAを用いた自験例83症例(89手技)では,germ cell tumorが36例で最も頻度が多く(43.4%),続いて松果体実質腫瘍15例(18.1%),毛様細胞性星細胞腫11例(13.3%),その他のグリオーマ8例(9.6%)の順であった(Table 1).OTAでは,頭尾側方向のcorridorを用いる.Parietooccipital interhemispheric routeを用いることで,中脳水道周囲から第四脳室上部,視蓋およびcerebellomesencephalic fissureの病変に対処する.逆にoccipital interhemispheric/occipitobasal/transtentorial routeでは,視床枕やモンロー孔より後方の第三脳室,脳梁膨大部から上方へ進展する病変,さらに中脳被蓋から視蓋に進展した病変に対処できる.テント下に向けた視軸では,"transtentorial"の名称が示すとおり,テント切開部を経由して視野を確保するというのが教科書的なコンセプトである.しかし,実際の手術では,十分なテント切開によって可動化した大脳鎌を対側後頭葉に向かって圧排偏位させることで,両側のテント縁や迂回槽での視軸を確保し,静脈や腫瘍の剥離操作を行いやすくすることがテント切開のもう1つの意義となっている.

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