An exploratory prospective phase II study of preoperative neoadjuvant bevacizumab and temozolomide for newly diagnosed glioblastoma.

PURPOSE: This multi-institutional phase I/II study was conducted to confirm the safety and explore the clinical utility of preoperative Bevacizumab (Bev) for newly diagnosed glioblastoma (GB). METHODS: Patients were enrolled based on magnetic resonance imaging (MRI) findings typically suggestive of GB. Preoperative Bev and temozolomide (TMZ) were administered at doses of 10 mg/kg on day 0 and 150 mg/m2 on days 1-5, respectively. Surgical resection was performed between days 21 and 30, inclusive. The safety and efficacy were evaluated in a total of 15 cases by progression-free survival (PFS), changes in tumor volume, Karnofsky Performance Scale (KPS) and Mini-Mental State Examination (MMSE) scores after preoperative therapy. RESULTS: Tumor resection was performed on a mean of day 23.7. Pathological diagnosis was GB, isocitrate dehydrogenase (IDH)-wildtype in 14 cases and GB, IDH-mutant in 1 case. Severe adverse events possibly related to preoperative Bev and TMZ were observed in 2 of the 15 patients, as wound infection and postoperative hematoma and thrombocytopenia. KPS and MMSE scores were significantly improved with preoperative therapy. Tumor volume was decreased in all but one case on T1-weighted imaging with contrast-enhancement (T1CE) and in all cases on fluid-attenuated inversion recovery, with mean volume decrease rates of 36.2% and 54.0%, respectively. Median PFS and overall survival were 9.5 months and 16.5 months, respectively. CONCLUSION: Preoperative Bev and TMZ is safe as long as the instructions are followed. The strategy might be useful for GB in some patients, not only reducing tumor burden, but also improving patient KPS preoperatively. TRIAL REGISTRATION NUMBER: UMIN000025579, jRCT1031180233 https://jrct.niph.go.jp/latest-detail/jRCT1031180233 . Registration Date: Jan. 16, 2017.

Prognostic survival biomarkers of tumor-fused dendritic cell vaccine therapy in patients with newly diagnosed glioblastoma.

Dendritic cell (DC)-based immunotherapy has been applied to glioblastoma (GBM); however, biomarkers informing response remain poorly understood. We conducted a phase I/IIa clinical trial investigating tumor-fused DC (TFDC) immunotherapy following temozolomide-based chemoradiotherapy in patients with newly diagnosed GBM and determined prognostic factors in patients receiving TFDC immunotherapy. Twenty-eight adult patients with GBM isocitrate dehydrogenase (IDH) wild-type (IDH-WT) were enrolled; 127 TFDC vaccine injections (4.5 ± 2.6 times/patient) were administered. Patients with GBM IDH-WT had a respectable 5-year survival rate (24%), verifying the clinical activity of TFDC immunotherapy, particularly against O6-methylguanine-DNA methyltransferase (MGMT) unmethylated GBM (5-year survival rate: 33%). To identify novel factors influencing overall survival (OS) in GBM IDH-WT treated with TFDC immunotherapy, clinical parameters were assessed and comprehensive molecular profiling involving transcriptome and exome analyses was performed. MGMT promoter methylation status, extent of tumor resection, and vaccine parameters (administration frequency, DC and tumor cell numbers, and fusion ratio) were not associated with survival following TFDC immunotherapy. Old age and pre- and post-operative Karnofsky performance status were significantly correlated with OS. Low HLA-A expression and lack of CCDC88A, KRT4, TACC2, and TONSL mutations in tumor cells were correlated with better prognosis. We validated the activity of TFDC immunotherapy against GBM IDH-WT, including chemoresistant, MGMT promoter unmethylated cases. The identification of molecular biomarkers predictive of TFDC immunotherapy efficacy in GBM IDH-WT will facilitate the design of and patient stratification in a phase-3 trial to maximize treatment benefits.

Thromboelastography 6s for assessment of platelet function during coil embolization of unruptured intracranial aneurysms.

OBJECTIVES: Methods for assessing platelet function in patients with neurovascular disease remain controversial and poorly studied. This study aimed to assess associations between thromboelastography 6s (TEG6s) measurements and postoperative ischemic complications in patients with unruptured intracranial aneurysms (UIAs) treated by coil embolization. METHODS: Eighty-four patients with UIAs taking a combined aspirin and clopidogrel protocol were retrospectively reviewed from January 2021 to May 2022. Blood samples were obtained for TEG6s to assess platelet function on the day of coil embolization. To identify acute ischemic complications, diffusion-weighted imaging (DWI) was performed within 24 h after coil embolization. Multivariate logistic regression analysis was conducted to identify potential risk factors for postoperative positive DWI (DWI (+)) lesions. RESULTS: Forty-three of the 84 patients (51%) with DWI (+) lesions were identified. Compared with patients without DWI (+) lesions, Adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MAADP) was significantly higher (53.6 mm [Interquartile range (IQR): 48.3-58.3 mm] vs 46.7 mm [IQR: 36.8-52.2 mm]; p=0.001) and ADP inhibition rate (ADP%) was significantly lower (19% [IQR: 11-31%] vs 31% [IQR: 21-44%]; p=0.001) in DWI (+) patients. Multivariate analysis identified MAADP, ADP%, and procedure time as significant independent predictors of subsequent DWI (+) lesions (odds ratios: 1.07, 0.96, and 1.02, respectively). Based on receiver operating characteristic curve analysis, MAADP >50.9 mm and ADP% <28.8% were associated with postoperative DWI (+) lesions in patients undergoing coil embolization for UIAs. CONCLUSIONS: MAADP and ADP% as assessed by TEG6s can offer reliable parameters to predict postoperative ischemic complications after coil embolization of UIAs. Lower MAADP values and higher ADP% may decrease the risk of postoperative ischemic complications.

[Technical "Tips" for Epidural Tenting Using DuraGen® for Surgical Management of Large Dural Defects:A Technical Note].

DuraGen®, an absorbable, engineered collagen-based artificial graft was introduced in Japan in September 2019 for cranial, transsphenoidal, and spinal surgeries. In addition to its efficacy and safety profile, owing to sutureless dural repair, DuraGen® is widely accepted by neurosurgeons. Direct tenting with DuraGen® is occasionally required in patients with large dural defects, particularly in cases of tumors adherent to the dura. To overcome this limitation, we introduced a surgical technique for epidural tenting using DuraGen®. A 78-year-old man with a history of alexia underwent craniotomy for resection of a left temporal lobe metastatic tumor. We completely removed the recurrent tumor, which was strongly adherent to the dura in the middle cranial fossa. A layer of DuraGen® was used as a subdural underlay beneath the autologous dura to close the wide dural defect. To avoid postoperative epidural fluid collection, we retracted the DuraGen® from the epidural aspect and interposed several pieces of muscle, which were sutured on the subdural aspect to ensure that the muscle pieces securely plugged the dural defect. We placed an additional overlay of DuraGen® along the autologous dura. The patient's postoperative course was uneventful without cerebrospinal fluid leakage, tension pneumocephalus, or wound infection. Reoperations for tumor resection, particularly surgical procedures for refractory meningiomas and malignant tumors cause increasing fragility and wide defects of the dura. DuraGen® placement enables sutureless closure and is less time-consuming. Our technique of epidural direct tenting with DuraGen® using muscle pieces sutured on the subdural aspect could be useful in patients with significantly large dural defects and can prevent postoperative epidural fluid collection to ensure complete dural sealing.

Persistent restoration to the immunosupportive tumor microenvironment in glioblastoma by bevacizumab.

Although vascular endothelial growth factor (VEGF) promotes the immunosuppressive microenvironment, the efficacy of bevacizumab (Bev) on tumor immunity has not been fully investigated. The present study used 47 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naïve Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory Bev group). The paired samples of the initial and post-Bev recurrent tumors from 9 patients were included. The expression of programmed cell death-1 (PD-1)/PD ligand-1 (PD-L1), CD3, CD8, Foxp3, and CD163 was analyzed by immunohistochemistry. The PD-L1+ tumor cells significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (P < .01 for each). The PD-1+ cells significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (P < .01 for each). The amount of CD3+ and CD8+ T cell infiltration increased in the refractory Bev group compared with the naïve Bev group (CD3, P < .01; CD8, P = .06). Both Foxp3+ regulatory T cells and CD163+ tumor-associated macrophages significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (Foxp3, P < .01 for each; CD163, P < .01 for each). These findings were largely confirmed by comparing paired initial and post-Bev recurrent tumors. Bevacizumab restores the immunosupportive tumor microenvironment in glioblastomas, and this effect persists during long-term Bev therapy.

[Outcome of Coil Embolization for Subarachnoid Hemorrhage Accompanied with Intracerebral Hematoma].

OBJECT: Aneurysmal subarachnoid hemorrhage(SAH)associated with intracerebral hematoma(ICH)typically has a poor outcome. SAH with ICH tends to have a worse prognosis than SAH alone. The aim of the present study was to evaluate whether coil embolization during endovascular surgery with ventricle drainage and without ICH evacuation is an appropriate treatment. METHODS: A retrospective review was conducted between March 2012 and May 2015. Thirteen patients with SAH with ICH who underwent coil embolization were retrospectively analyzed. Modified Rankin Scale(mRS)scores were compared for postoperative clinical outcomes of different hematoma locations. RESULTS: All ruptured aneurysms in the present series of patients were treated using endovascular surgery. Six patients underwent additional ventricle drainage. Only one patient underwent craniotomy for evacuation of the hematoma following coil embolization. Despite ten out of thirteen patients(76.9%)having a preoperative SAH clinical grade, as evaluated using the World Federation of Neurosurgical Societies grading system of IV or V, six(46.2%)patients had a favorable outcome(mRS=0-2). CONCLUSIONS: Coil embolization for ruptured aneurysms, especially those located in the frontal lobe, with ICH and without cerebral herniation may be a feasible alternative and less invasive treatment.

Phase I/II trial of combination of temozolomide chemotherapy and immunotherapy with fusions of dendritic and glioma cells in patients with glioblastoma.

BACKGROUND: This trial was designed to evaluate the safety and clinical responses to a combination of temozolomide (TMZ) chemotherapy and immunotherapy with fusions of DCs and glioma cells in patients with glioblastoma (GBM). METHOD: GBM patients were assigned to two groups: a group of recurrent GBMs after failing TMZ-chemotherapy against the initially diagnosed glioma (Group-R) or a group of newly diagnosed GBMs (Group-N). Autologous cultured glioma cells obtained from surgical specimens were fused with autologous DCs using polyethylene glycol. The fusion cells (FC) were inoculated intradermally in the cervical region. Toxicity, progression-free survival (PFS), and overall survival (OS) of this trial were evaluated. Expressions of WT-1, gp-100, and MAGE-A3, recognized as chemoresistance-associated peptides (CAP), were confirmed by immunohistochemistry of paraffin-embedded tumor samples. Patient's PBMCs of pre- and post-vaccination were evaluated by tetramer and ELISPOT assays. RESULTS: FC-immunotherapy was well tolerated in all patients. Medians of PFS and OS of Group-R (n = 10) were 10.3 and 18.0 months, and those of Group-N (n = 22) were 18.3 and 30.5 months, respectively. Up-regulation and/or cytoplasmic accumulation of CAPs was observed in the recurrent tumors of Group-R patients compared with their initially excised tumors. Specific immune responses against CAPs were observed in the tetramer and ELISPOT assays. CONCLUSIONS: The combination of TMZ-treatment leading to up-regulation and/or cytoplasmic accumulation of CAPs, with FC-immunotherapy as a means of producing specific immunity against CAPs, may safely induce anti-tumor effects in patients with GBM.

[Transient charles bonnet syndrome after excision of a right occipital meningioma: a case report].

Charles Bonnet syndrome is a condition characterized by visual hallucinations. These simple or complex visual hallucinations are more common in elderly individuals with impaired peripheral vision. The current report describes a case of transient Charles Bonnet syndrome appearing after the removal of a meningioma. The patient was a 61-year-old man who already had impaired visual acuity due to diabetic retinopathy. Brain MRI revealed a cystic tumor severely compressing the right occipital lobe. Starting on day 2 postoperatively, the patient was troubled by recurring visual hallucinations involving people, flowers, pictures, and familiar settings(the train and a coffee shop). These continued for 3.5 months. This period roughly coincided with the time for the occipital lobe to recover from the compression caused by the tumor, a fact that was confirmed by several MRI scans. ¹²³I-IMP SPECT performed 1 month after the surgical operation showed an area of hypoperfusion in the right parieto-occipital lobe. Based on the patient's clinical course and MRI findings, the mechanism of onset of visual hallucinations in this patient was put forward. The release of pressure in the brain by tumor removal and subsequent recovery changed the blood flow to the brain. This triggered visual hallucinations in the patient, who was already predisposed to developing Charles Bonnet syndrome because of diabetic retinopathy. This case is interesting since it indicates that central neurological factors, as well as visual deficits, may induce the appearance of visual hallucinations in Charles Bonnet syndrome.

"TIPS" and Technical Nuances for Digital Illustration in Neurointerventional Surgery.

Medical illustrations represent a precious resource for learning surgical anatomy and surgical techniques, allowing pre- and postoperative reviews. As traditional hand-drawn illustrations are difficult to use and expressing the area of neurointerventional surgery is time-consuming, we proposed methods for neurointerventional surgeons to create digital illustrations (DIs) for neurointerventional surgery using the iPad-exclusive Procreate application (Savage Interactive, Hobart, Australia). Dedicated "digital pens" were created and used for each endovascular device, creating straightforward representations of neurointerventional procedures and changes over time. DIs in neurointervention easily depict changes to highlighted surgical scenes for various devices with complex configurations and structures. DIs are also versatile, allowing easy intra- and inter-institutional sharing and discussion of technical tips on the manipulation of medical devices (coils, catheters, stents, etc.) among neurointerventional surgeons worldwide. DIs can be applied as educational tools not only in neurointerventional surgery, but also in craniotomy surgery and for surgical records from other specialties.

The white-collar sign after Neuroform Atlas stent-assisted coil embolization of unruptured intracranial aneurysms.

PURPOSE: Although stent-assisted technique is expected to help provide a scaffold for neointima formation at the orifice of the aneurysm, not all aneurysms treated with stent-assisted technique develop complete neointima formation. The white-collar sign (WCS) indicates neointimal tissue formation at the aneurysm neck that prevents aneurysm recanalization. The aim of this study was to explore factors related to WCS appearance after stent-assisted coil embolization of unruptured intracranial aneurysms (UIAs). METHODS: A total of 59 UIAs treated with a Neuroform Atlas stent were retrospectively analyzed. The WCS was identified on digital subtraction angiography (DSA) 1 year after coil embolization. The cohort was divided into WCS-positive and WCS-negative groups, and possible predictors of the WCS were explored using logistic regression analysis. RESULTS: The WCS appeared in 20 aneurysms (33.9%). In the WCS-positive group, neck size was significantly smaller (4.2 (interquartile range (IQR): 3.8-4.6) versus 5.4 (IQR: 4.2-6.8) mm, p = .006), the VER was significantly higher (31.8% (IQR: 28.6%-38.4%) versus 27.6% (IQR: 23.6%-33.8%), p = .02), and the rate of RROC class 1 immediately after treatment was significantly higher (70% vs 20.5%, p < .001) than in the WCS-negative group. On multivariate analysis, neck size (odds ratio (OR): 0.542, 95% confidence interval (CI): 0.308-0.954; p = .03) and RROC class 1 immediately after treatment (OR: 6.99, 95% CI: 1.769-27.55; p = .006) were independent predictors of WCS appearance. CONCLUSIONS: Smaller neck size and complete occlusion immediately after treatment were significant factors related to WCS appearance in stent-assisted coil embolization for UIAs using the Neuroform Atlas stent.

Intermediate catheter use is associated with complete occlusion and dense packing in coil embolization of unruptured cerebral aneurysms: a propensity score matched study.

BACKGROUND: An intermediate catheter (IMC) can improve the maneuverability and stability of the microcatheter. OBJECTIVE: To investigate the efficacy and safety of using an IMC in triaxial systems for coil embolization of unruptured cerebral aneurysms (UCAs). METHODS: A total of 2430 consecutive saccular UCAs (2259 patients) that underwent initial coil embolization at three institutions between November 2003 and May 2023 were retrospectively reviewed. Patients were classified into two groups: with IMC (IMC(+)) and without IMC (IMC(-)). To investigate whether IMC use increased the rate of complete occlusion and the packing density, a propensity score-matched analysis was used to control for clinical, anatomical, and procedural features. RESULTS: Ultimately, 595 (24.5%) coil embolization used an IMC. Propensity score matching was successful for 424 paired IMC(+) and IMC(-) aneurysms. Compared with the IMC(-) group, the IMC(+) group had significantly higher rate of Raymond-Roy Occlusion Classification class 1 immediately after treatment (30.0% vs 20.8%, P=0.003) and at 6 months (28.8% vs 20.0%, P=0.004) and a higher volume embolization ratio (27.2% (SD 6.5%) vs 25.9% (SD 6.2%), P=0.003). Re-treatment rates were not significantly different between the two groups (0.7% vs 0.2%, P=0.624). No significant differences in the incidences of ischemic and hemorrhagic complications and IMC-related parent artery dissection were found between the two groups. CONCLUSION: Use of IMCs in triaxial systems can provide effective and safe support in coil embolization of UCAs because complete occlusion and dense coil packing can be achieved without increased complications.

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment.

Glioblastoma multiforme (GBM) acquires resistance to bevacizumab (Bev) treatment. Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28 specimens from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the naïve Bev group (p = 0.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the naïve Bev group (p = 0.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (p = 0.036). PLGF was more abundant in T2 diffuse/circumscribe patterns (p = 0.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens.

Local thrombolytics via balloon-assisted intra-arterial infusion as rescue therapy for thromboembolism during endovascular coil embolisation.

Thromboembolism is the most frequent complication of coil embolisation for intracranial aneurysm. Complications of thromboembolism can lead to stroke and have a serious impact on sequelae and mortality, necessitating appropriate rescue therapy. Here, we succeeded in recanalisation of an occluded stent by balloon-assisted local infusion of a thrombolytic agent following stent-assisted coil embolisation of an unruptured posterior communicating artery aneurysm. This method involves inflating a microballoon just distal to the occluded vessel and then administering a thrombolytic agent through a microcatheter. This technique may increase the rate of vessel reopening by maximising the local drug concentration. This method can be applied to any type of thrombolytic agent and helps reduce the dose of systemic drugs, which might decrease the incidence of haemorrhagic complications. Balloon-assisted intra-arterial thrombolytic infusion for an occluded vessel during endovascular coil embolisation could offer an alternative rescue therapy when conventional thrombolytic agent administration fails to improve thromboembolism.

Compartment syndrome associated with vascular avulsion caused by transradial access in neurointervention for unruptured intracranial aneurysm: illustrative case.

BACKGROUND: Transradial access (TRA) has a lower risk of access-site complications than transfemoral access but can cause major puncture-site complications, including acute compartment syndrome (ACS). OBSERVATIONS: The authors report a case of ACS associated with radial artery avulsion after coil embolization via TRA for an unruptured intracranial aneurysm. An 83-year-old woman underwent embolization via TRA for an unruptured basilar tip aneurysm. Following embolization, strong resistance was felt during removal of the guiding sheath due to vasospasm of the radial artery. One hour after neurointervention via TRA, the patient complained of severe pain in the right forearm, with motor and sensory disturbance of the first 3 fingers. The patient was diagnosed with ACS causing diffuse swelling and tenderness over the entire right forearm due to elevated intracompartmental pressure. The patient was successfully treated by decompressive fasciotomy of the forearm and carpal tunnel release for neurolysis of the median nerve. LESSONS: TRA operators should be aware that radial artery spasm and the brachioradial artery pose a risk of vascular avulsion and resultant ACS and warrant precautionary measures. Prompt diagnosis and treatment are essential because ACS can be treated without the sequelae of motor or sensory disturbance if properly addressed.

Therapeutic efficacy and complications of radial versus femoral access in endovascular treatment of unruptured intracranial aneurysms.

PURPOSE: The transradial approach (TRA) in neuroendovascular treatment is known to have a lower risk of complications than the transfemoral approach (TFA). However, little research has focused on assessments of efficacy and risk of complications in the treatment of intracranial aneurysms. This study aimed to compare the efficacy and complications of TRA and TFA in coil embolization of unruptured intracranial aneurysms (UIAs) at our institution. METHODS: Consecutive patients who underwent endovascular surgery via TRA or TFA at a single institution from 1 April 2019, to 28 February 2022, were retrospectively analyzed. Patients were classified into TRA and TFA groups and assessed using propensity-adjusted analysis for outcomes including fluoroscopy time, volume embolization ratio (VER), and complications. RESULTS: A total of 163 consecutive UIAs were treated with coil embolization during the 35-months study period. The incidence of minor access site complications (ASCs) was significantly higher with TFA (20%, 25/126) than with TRA (2.7%, 1/37; p = 0.01). Propensity-adjusted analysis (matched for age, sex, aneurysm volume, embolization technique, and sheath size) revealed that TRA was associated with a lower risk of minor ASCs (odds ratio, 0.085; 95% confidence interval 0.0094-0.78; p = 0.029). However, TRA did not differ significantly from TFA with respect to fluoroscopy time, VER, major ASCs, and non-ASCs. CONCLUSIONS: Coil embolization for UIAs via TRA can reduce risk of minor ASCs without increasing the risk of non-ASCs compared with conventional TFA, and can achieve comparable results in term of efficacy and fluoroscopy time.

Efficacy and safety of fetal posterior cerebral artery stented coil embolization for fetal posterior cerebral aneurysms.

PURPOSE: Aneurysms at the origin of the fetal posterior cerebral artery (fPCA) often show fPCA bifurcation from the aneurysm dome, impeding complete embolization and dense coil packing. The recanalization rate for fPCA aneurysms is therefore high. This study aimed to evaluate the efficacy and safety of stenting into fPCA for aneurysms with fPCA incorporated into the aneurysm to determine whether stenting can provide effective embolization results and prevent recanalization. METHODS: A total of 19 consecutive coil embolization procedures between February 2012 and June 2022 for unruptured fPCA aneurysms with fPCA branching from the dome of the aneurysm were divided into two groups: non-stenting (NS) group (n = 11) and stenting into fPCA (PS) group (n = 8). Data were obtained retrospectively and compared regarding embolization results, complications, and recanalization. RESULTS: Compared with the NS group, the PS group achieved significantly higher complete occlusion rate and packing density (p < 0.001, p = 0.01, respectively). No symptomatic complications were observed in the PS group. Both immediately after stenting and at the 1-year follow-up, no stent kinking, stenosis, occlusion, or malposition were observed in any patients in the PS group. During 1-year follow-up, the cumulative minor and major recanalization-free rate after coil embolization for fPCA aneurysms were significantly higher in the PS group compared with the NS group (p = 0.022, 0.0024, respectively). CONCLUSION: Stenting into fPCA for aneurysms with fPCA incorporated into the aneurysm achieved high-density complete embolization without increasing complications, and prevented recanalization. The fPCA stent-assisted coil embolization can offer an alternative treatment for fPCA aneurysms.

Risk factors for radial artery occlusion after neurointervention for unruptured intracranial aneurysm via transradial access.

PURPOSE: Neurointervention via transradial access (TRA) is less invasive than via transfemoral access. However, radial artery occlusion (RAO) may occur with TRA. The purpose of this study was to explore risk factors for RAO after coil embolization of unruptured intracranial aneurysms (UIAs) via TRA. METHODS: Forty-two consecutive patients who underwent coil embolization for UIAs via TRA between March 2021 and March 2022 and were available for angiographic evaluation 1 year after treatment were retrospectively reviewed. Multivariate logistic regression analysis was conducted to identify potential risk factors for RAO. RESULTS: Seventeen (40%) of the 42 patients showed RAO. Compared with the non-RAO group, radial artery size was significantly smaller (2.2 mm [interquartile range (IQR): 2.1, 2.4 mm] vs 2.6 mm [IQR: 2.5, 2.7 mm]; p = 0.001) and the incidence of radial artery spasm (RAS) was significantly higher in the RAO group. Multivariate analysis identified radial artery size (odds ratio [OR] 4.9 × 10-3, 95% confidence interval [CI] 6.4 × 10-5-0.38) and incidence of RAS (OR 14.8, 95%CI 2.1-105) as significant independent predictors of subsequent RAO. Based on receiver operating characteristic (ROC) curve analysis, the optimal cutoff for radial artery size was 2.5 mm (sensitivity, 82.4%; specificity, 76.0%; area under the ROC curve, 0.80 [95%CI 0.66-0.95]). CONCLUSION: Radial artery size and RAS represent reliable parameters for predicting RAO 1 year after coil embolization for UIA via TRA. Prophylaxis against RAS and limiting neurointervention via TRA to patients with radial artery larger than 2.5 mm in diameter may reduce the risk of postoperative RAO.

Predicting difficult transradial approach guiding into left internal carotid artery on unruptured intracranial aneurysms.

Background: The transradial approach (TRA) is less invasive than the transfemoral approach (TFA), but the higher conversion rate represents a drawback. Among target vessels, the left internal carotid artery (ICA) is particularly difficult to deliver the guiding catheter to through TRA. The purpose of this study was thus to explore anatomical and clinical features objectively predictive of the difficulty of delivering a guiding catheter into the left ICA via TRA. Methods: Among 78 consecutive patients who underwent coil embolization for unruptured intracranial aneurysms through TRA in a single institution between March 1, 2021, and August 31, 2022, all 29 patients (37%) who underwent delivery of the guiding catheter into the left ICA were retrospectively analyzed. Clinical and anatomical features were analyzed to assess correlations with difficulty in guiding the catheter into the left ICA. Results: Of the 29 aneurysms requiring guidance of a catheter into the left ICA, 9 aneurysms (31%) required conversion from TRA to TFA. More acute innominate-left common carotid artery (CCA) angle (P < 0.001) and older age (P = 0.015) were associated with a higher conversion rate to TFA. Receiver operating characteristic analysis revealed that optimal cutoff values for the innominate-left CCA angle and age to distinguish between nonconversion and conversion to TFA were 16° (area under the curve [AUC], 0.93; 95% confidence interval [CI], 0.83-1.00) and 74 years (AUC, 0.79; 95% CI, 0.61-0.96), respectively. Conclusion: A more acute innominate-left CCA angle and older age appear associated with difficulty delivering the guiding catheter into the left ICA for neurointervention through TRA.

18F-Fluoromisonidazole-Positron Emission Tomography and Immunohistochemistry Verified Tumor Oxygenation, Stemness, and Immunosupportive Microenvironment After Preoperative Neoadjuvant Bevacizumab for Newly Diagnosed Glioblastoma.

BACKGROUND: Cancer stemness and immunosuppressive tumor microenvironment (TME) in accordance with tumor oxygenation are variable during bevacizumab (Bev) therapy for glioblastoma (GBM). Positron emission tomography (PET) using 18F-fluoromisonidazole (FMISO) reflects hypoxic TME. The aim of this study was to compare FMISO-PET and immunohistochemical findings of tumor oxygenation in the TME of GBM during Bev treatment. METHODS: Seven patients with newly diagnosed IDH-wildtype GBM underwent FMISO-PET during follow-up. Three patients received preoperative neoadjuvant Bev (neo-Bev) and subsequently underwent surgical resection. Reoperation was performed at the recurrence. FMISO-PET was performed before and after neo-Bev. Four patients who underwent tumor resection without neo-Bev were included as the control group. Expressions of hypoxic markers (carbonic anhydrase; CA9), stem cell markers (nestin, FOXM1), and immunoregulatory molecules (CD163, FOXP3, PD-L1) in tumor tissues were analyzed by immunohistochemistry (IHC). RESULTS: All 3 patients treated with neo-Bev showed decrease in FMISO accumulation in accordance with expressions of CA9 and FOXM1 compared with the control group. Two of these 3 patients at the recurrence showed increase in FMISO accumulation. IHC showed increased CA9-and FOXM1-positive cells in recurrent tumors. Expression of PD-L1 tended to be lower after neo-Bev compared with the control group. CONCLUSIONS: FMISO-PET effectively visualized TME oxygenation after neo-Bev. Increased FMISO accumulation at the time of recurrence, even under Bev treatment, suggests that FMISO-PET might be useful for monitoring the duration of Bev efficacy by reflecting tumor oxygenation.

Long-term survival following gross total resection of pediatric supratentorial ependymomas without adjuvant therapy.

Pediatric supratentorial ependymoma is very rare. In pediatric patients with supratentorial ependymoma, surgery alone may be an acceptable treatment when postoperative imaging confirms a gross total resection. Surgical resection is the standard and the most important treatment for ependymoma. The role of radiation therapy and/or chemotherapy following a gross total resection of supratentorial ependymoma has been uncertain. We report 2 cases of pediatric supratentorial ependymomas treated by gross total resection without postoperative adjuvant therapy. The first patient was a 7-year-old girl who presented with motor weakness and a hemiconvulsion of the right leg. Magnetic resonance imaging (MRI) revealed a large heterogeneously enhanced tumor in the left frontal lobe. The second patient was an 8-year-old girl who presented with headache. MRI revealed a huge heterogeneously enhanced tumor in the left frontal lobe. Gross total resection was achieved in both patients. Postoperative radiotherapy and chemotherapy were avoided following gross total resection. Histologically, the lesions demonstrated grade II ependymoma and anaplastic ependymoma, respectively. After follow-up of 120 months, neither patient had recurrence or dissemination. These results suggest that patients with pediatric supratentorial ependymoma treated by gross total resection alone have a favorable outcome, and postoperative radiotherapy and chemotherapy may be avoided.