Trends in Incidence of Intracranial and Spinal Arteriovenous Shunts: Hospital-Based Surveillance in Okayama, Japan.

BACKGROUND AND PURPOSE: To date, the incidence of intracranial and spinal arteriovenous shunts has not been thoroughly investigated. We aimed to clarify recent trends in the rates of intracranial and spinal arteriovenous shunts in Japan. METHODS: We conducted multicenter hospital-based surveillance at 8 core hospitals in Okayama Prefecture between April 1, 2009 and March 31, 2019. Patients who lived in Okayama and were diagnosed with cerebral arteriovenous malformations, dural arteriovenous fistulas (DAVFs), or spinal arteriovenous shunts (SAVSs) were enrolled. The incidence and temporal trends of each disease were calculated. RESULTS: Among a total of 393 cranial and spinal arteriovenous shunts, 201 (51.1%) cases of DAVF, 155 (39.4%) cases of cerebral arteriovenous malformation, and 34 (8.7%) cases of SAVS were identified. The crude incidence rates between 2009 and 2019 were 2.040 per 100 000 person-years for all arteriovenous shunts, 0.805 for cerebral arteriovenous malformation, 1.044 for DAVF, and 0.177 for SAVS. The incidence of all types tended to increase over the decade, with a notable increase in incidence starting in 2012. Even after adjusting for population aging, the incidence of nonaggressive DAVF increased 6.0-fold while that of SAVS increased 4.4-fold from 2010 to 2018. CONCLUSIONS: In contrast to previous studies, we found that the incidence of DAVF is higher than that of cerebral arteriovenous malformation. Even after adjusting for population aging, all of the disease types tended to increase in incidence over the last decade, with an especially prominent increase in SAVSs and nonaggressive DAVFs. Various factors including population aging may affect an increase in DAVF and SAVS.

Cellular therapy for myocardial ischemia using a temperature-responsive biodegradable injectable polymer system with adipose-derived stem cells.

Adipose-derived stem cell (AdSC) has been attracting attention as a convenient stem cell source. Not only AdSC can differentiate into various tissue cells, but it can also accelerate cell proliferation, anti-inflammation, and angiogenesis by secreting paracrine factors. Studies have demonstrated AdSC treatment of ischemic heart. However, an improvement in the remaining live AdSCs administered at the injected site while maintaining paracrine factor secretion is desired to achieve effective regenerative medicine. We previously reported the ABA-type tri-block copolymer of poly(ɛ-caprolactone-co-glycolic acid) and poly(ethylene glycol) (tri-PCG), exhibiting temperature-responsive sol-to-gel transition as biodegradable injectable polymer (IP) systems. Moreover, we recently reported that the biodegradable temperature-triggered chemically cross-linked gelation systems exhibited longer gel state durations using tri-PCG attaching acryloyl groups and a polythiol derivative. In this study, we explored this IP-mediated AdSC delivery system. We investigated the cell viability, mRNA expression, and cytokine secretion of AdSCs cultured in the physical or chemical IP hydrogels. Both of these IP hydrogels retained a certain number of viable cells, and RT-PCR and ELISA analyses revealed that mRNA expression and secretion of vascular endothelial growth factor of the AdSCs cultured in the chemical hydrogel were higher than the physical hydrogel. Moreover, AdSCs injected with the chemical hydrogel into ischemic heart model mice showed longer retention of the cells at the injected site and recovery from the ischemic condition. The results mean that the IP system is a promising candidate for a stem cell delivery system that exhibits the recovery of cardiac function for myocardial infarction treatment.

Increased plasma plasmin-α2-plasmin inhibitor complex levels correlate with postoperative rebleeding after endoscopic surgery for spontaneous intracerebral hemorrhage.

BACKGROUND: Postoperative rebleeding (PR) is one of the most severe complications of endoscopic surgery, often performed to remove spontaneous intracerebral hemorrhage (sICH). However, the risk factors for PR remain unclear. OBJECTIVE: This study retrospectively investigated whether increased preoperative plasma plasmin-α2-plasmin inhibitor complex (PIC) levels, indicating activation of fibrinolysis, are associated with PR. METHODS: A total of 101 patients underwent endoscopic surgery to evacuate sICH at our institution from January 2010 to June 2019, and 79 patients who underwent examinations of plasma PIC levels at admission with available radiographical data were included. Correlations between PR and increased plasma PIC levels were retrospectively evaluated. RESULTS: PR occurred in eight patients (10.1%), and high PIC levels (≥ 4 or 6 µg/ml) were significantly associated with PR. The sensitivities employing high PIC levels of ≥ 4 µg/ml and ≥ 6 µg/ml were both 0.63, and the specificities using the same PIC levels were 0.86 and 0.92, respectively. Multivariable analyses showed that high plasma PIC levels of ≥ 4 µg/ml (odds ratio (OR), 12.77; 95% confidence interval (CI), 1.65-98.77; p = 0.02) or ≥ 6 µg/ml (OR, 18.33; 95% CI, 2.32-144.82; p = 0.006) were independent predictors of PR. CONCLUSIONS: This study found that increased plasma PIC levels were associated with PR following the endoscopic evacuation of sICHs, indicating that increased plasma PIC levels could be potentially used to predict PR. Further studies are needed to establish new surgical strategies and adjuvant treatments to improve surgical outcomes in patients with sICH prone to PR.

Prestroke Conditions of Acute Ischemic Stroke Patients are Associated with Functional Outcome after Mechanical Thrombectomy.

BACKGROUND AND AIM: Mechanical thrombectomy was demonstrated to be useful for acute ischemic stroke. However, whether it is beneficial for patients with poor prestroke conditions, such as older adults and those with low activity of daily living, is unclear. METHODS: A total of 134 patients who underwent mechanical thrombectomy in our hospital between April 2015 and January 2019 were retrospectively evaluated. Good outcome was defined as modified Rankin scale score of 0-2 at 90 days after stroke onset. Several factors were analyzed to assess their effects on clinical outcomes. RESULTS: At 90 days after stroke onset, 37.3% (50 of 134) of patients had a good outcome. Prestroke modified Rankin scale score was independently associated with a good outcome (odds ratio .39, 95% confidence interval .22-.67, P < .001). In patients with prestroke modified Rankin scale score 0-1, 55.4% (46 of 83) had a good outcome, and no significant difference in prognosis was found between patients aged less than 80 years and those aged greater than or equal to 80 years (P = .64). More than half the patients with prestroke modified Rankin scale score greater than or equal to 2 were graded as modified Rankin scale score 5-6 at 90 days regardless of age, which was significantly higher than those with prestroke modified Rankin scale score 0-1 (P < .001). CONCLUSIONS: Patients with prestroke modified Rankin scale score 0-1 are expected to have a good prognosis after mechanical thrombectomy even if aged greater than or equal to 80 years. Patients with prestroke modified Rankin scale score greater than or equal to 2 might have an extremely poor prognosis, and we should be more careful in selecting candidates for mechanical thrombectomy.

Dose-finding study of the checkpoint kinase 1 inhibitor, prexasertib, in Japanese patients with advanced solid tumors.

Prexasertib is a novel inhibitor of checkpoint kinase 1. The primary objective of this study was to evaluate prexasertib tolerability in Japanese patients with advanced solid tumors. This nonrandomized single-arm open-label phase 1 study of prexasertib consisted of 2 dose levels, 80 mg/m2 and the global-recommended dose based on a US study of 105 mg/m2 , administered intravenously once every 14 days (n = 6 for each dose). Transition to the higher dose proceeded if the frequency of dose-limiting toxicity observed in cycle 1 was <33% at the lower dose. Safety measures, pharmacokinetics and antitumor activity were assessed. A total of 12 patients were treated. Two patients, one in each dose group, experienced dose-limiting toxicities of febrile neutropenia, one grade 4 and the other grade 3; both patients recovered and continued the study treatment. The grade 4 treatment-emergent adverse events related to study treatment were neutropenia (6 patients [50.0%]), leukopenia (4 patients [33.3%]), and 1 instance each (8.3%) of anemia, febrile neutropenia and thrombocytopenia. Neutropenia was generally transient and reversible; 11 patients (91.7%) required granulocyte colony-stimulating factor treatment during the study. There were no discontinuations due to adverse events or deaths. The prexasertib pharmacokinetics displayed dose-independent and time-independent behavior across both dose levels, similar to the profile observed in the US-based phase 1 study. Eight patients had a best overall response of stable disease. These data are consistent with the known safety profile for prexasertib and confirm its tolerability in Japanese patients with advanced solid tumors.

Plaque Characteristics of Patients with Symptomatic Mild Carotid Artery Stenosis.

BACKGROUND: Carotid revascularization may be considered for severe stenosis, but its use for symptomatic mild stenosis (<50%) with vulnerable plaque or ulcer remains uncertain. The characteristics of patients with symptomatic mild stenosis who underwent revascularization are reviewed. METHODS: The subjects of this study were 18 patients with symptomatic mild stenosis (<50%) on angiography from among 175 patients who underwent revascularization in our department. The plaques were evaluated by black-blood magnetic resonance imaging (BB-MRI) and ultrasonography (US) and classified into 2 types: type 1 (n = 15), a lesion with an ulcer or mobile plaque or thrombosis on angiography or US; and type 2 (n = 3), a lesion without any of the above. Fourteen patients underwent carotid endarterectomy (CEA), and 4 patients underwent carotid artery stenting. RESULTS: The stenosis on angiography was 27.2% ± 10.7 (5%-41%), and the area carotid artery stenosis rate on US was 69.8 ± 14.5% (44.5%-97%). The stenosis rate of these 2 methods was not at all correlated. In type 1 plaque that underwent CEA, 10 of 11 patients had vulnerable plaque by histopathology, and 1 patient had thrombus on the plaque by operative findings. In type 2 plaque that underwent CEA, all patients had vulnerable plaque by histopathology. During the follow-up period, none of the patients had restenosis or stroke. CONCLUSIONS: The findings of US and BB-MRI in patients with symptomatic mild stenosis (<50%) on angiography are important for determining treatment. If BB-MRI or US shows the findings of vulnerable plaque in mild stenosis, surgical treatment may be considered for these patients.

Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population.

BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer in Japan. Smoking and drinking alcohol are environmental risk factors for ESCC, whereas single nucleotide polymorphisms in ADH1B and ALDH2, which increase harmful intermediates produced by drinking alcohol, are genetic risk factors. We conducted a large-scale genomic analysis of ESCCs from patients in Japan to determine the mutational landscape of this cancer. METHODS: We performed whole-exome sequence analysis of tumor and nontumor esophageal tissues collected from 144 patients with ESCC who underwent surgery at 5 hospitals in Japan. We also performed single-nucleotide polymorphism array-based copy number profile and germline genotype analyses of polymorphisms in ADH1B and ALDH2. Polymorphisms in CYP2A6, which increase harmful effects of smoking, were analyzed. Functions of TET2 mutants were evaluated in KYSE410 and HEK293FT cells. RESULTS: A high proportion of mutations in the 144 tumor samples were C to T substitution in CpG dinucleotides (called the CpG signature) and C to G/T substitutions with a flanking 5' thymine (called the APOBEC signature). Based on mutational signatures, patients were assigned to 3 groups, which associated with environmental (drinking and smoking) and genetic (polymorphisms in ALDH2 and CYP2A6) factors. Many tumors contained mutations in genes that regulate the cell cycle (TP53, CCND1, CDKN2A, FBXW7); epigenetic processes (MLL2, EP300, CREBBP, TET2); and the NOTCH (NOTCH1, NOTCH3), WNT (FAT1, YAP1, AJUBA) and receptor-tyrosine kinase-phosphoinositide 3-kinase signaling pathways (PIK3CA, EGFR, ERBB2). Mutations in EP300 and TET2 correlated with shorter survival times, and mutations in ZNF750 associated with an increased number of mutations of the APOBEC signature. Expression of mutant forms of TET2 did not increase cellular levels of 5-hydroxymethylcytosine in HEK293FT cells, whereas knockdown of TET2 increased the invasive activity of KYSE410 ESCC cells. Computational analyses associated the mutations in NFE2L2 we identified with transcriptional activation of its target genes. CONCLUSIONS: We associated environmental and genetic factors with base substitution patterns of somatic mutations and provide a registry of genes and pathways that are disrupted in ESCCs. These findings might be used to design specific treatments for patients with esophageal squamous cancers.

[A Case of an Orbital Angioleiomyoma].

A 70-year-old woman presented with a 4-year history of painless conjunctival congestion and proptosis of the right eye. Computed tomography and magnetic resonance imaging revealed a 48-mm lesion in the right medial orbit. As the symptoms progressed, the tumor was resected by performing fronto-orbital craniotomy. Histopathological examination revealed a vascular tumor surrounded by smooth muscle fibers and immunohistochemistry demonstrated tumor positivity for smooth muscle actin and desmin. The tumor was diagnosed as an angioleiomyoma, and no recurrence has been observed as of 5 years postoperatively. Angioleiomyomas in the orbit are extremely rare;thus, we have reported this case with reference to the literature.

[A mixed germ cell tumor that underwent dramatic size changes].

This report describes a mixed germ cell tumor that underwent dramatic size changes. A 12-year-old boy presented to our hospital with a headache that had persisted for two months. Initial magnetic resonance imaging (MRI) revealed a pineal tumor and hydrocephalus. The patient required external ventricular drainage and underwent two endoscopic biopsies. His evaluation involved a total of nine computed tomography (CT) scans prior to the second biopsy;the tumor size had decreased before the second endoscopic biopsy. The tumor consisted of both a germinoma and a teratoma component. The patient was treated with three courses of carboplatin-etoposide (CBDCA-VP) chemotherapy and whole-ventricle radiotherapy (32.1 Gy). However, during the adjuvant therapy, the tumor size increased, necessitating total tumor resection. We speculate that the tumor's initial size reduction was caused by leakage of the cyst component and exposure to the brain CT irradiation. The tumor's subsequent increase in size was due to the recollection of the cystic components and intracranial growing teratoma syndrome (iGTS). Therefore, frequent brain CTs and angiography should be avoided before definitive pathological diagnosis is achieved. Further, the tumor size should be considered, with surgical resection being performed at the optimal time.

Preoperative elevated eosinophils in peripheral blood for prediction of postoperative recurrence of chronic subdural hematoma.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a common neurological disease with a significant postoperative recurrence rate. There are numerous reported studies of the development of CSDH. In recent years, fibrinolysis, angiogenesis, and inflammation have all been identified as relevant factors in the development of CSDH. While several authors have reported risk factors associated with CSDH recurrence, differential blood count of leukocytes has not yet been discussed. Therefore, in this study the authors aimed to retrospectively investigate the association between differential blood leukocyte count and the rate of CSDH recurrence. METHODS: The authors retrospectively reviewed 476 patients with 529 CSDHs who underwent surgery at a single institution between January 2011 and December 2021. After exclusion of patients who had not undergone a differential blood test of leukocytes preoperatively, CSDHs in 517 cerebral hemispheres of 466 patients were included in the study. Peripheral blood eosinophil counts ≥ 100/µL were considered eosinophil rich. RESULTS: CSDHs in 494 cerebral hemispheres of 445 patients were followed up postoperatively for at least 3 months or until resolution indicated by CSDH disappearance. Postoperative recurrence of CSDH was observed in 46 cerebral hemispheres (9.3%). Among the preoperative differential blood counts of all leukocytes, eosinophils alone were significantly associated with CSDH recurrence (median [IQR] 76/µL [30-155/µL] vs 119/µL [39-217/µL]; p = 0.03). Multivariable regression analysis showed thrombocytopenia (adjusted OR [aOR] 5.23, 95% CI 1.85-14.79; p = 0.002), use of anticoagulant drugs (aOR 2.51, 95% CI 1.17-5.38; p = 0.02), hematoma volume (10 mL per increase) (aOR 1.08, 95% CI 1.00-1.16; p = 0.04), and eosinophil-rich peripheral blood (aOR 2.22, 95% CI 1.17-4.23; p = 0.02) were all independent predictors for CSDH recurrence. CONCLUSIONS: This study showed that preoperative peripheral blood eosinophil count was an independent risk factor for CSDH recurrence. Therefore, patients with CSDH who have elevated eosinophils preoperatively in peripheral blood require careful follow-up.

Association between Carotid Bifurcation Angle and Vulnerable Plaque Volume Using Black Blood Magnetic Resonance Imaging.

The morphology of the internal carotid artery (ICA) bifurcation is increasingly being recognized as the cause of atherosclerosis and vulnerable plaque leading to cerebral infarction. In this study, we investigated the relationship between carotid bifurcation angle and carotid plaque volume evaluated using black blood magnetic resonance imaging (BB-MRI). Among the 90 patients who underwent revascularization for atherosclerotic symptomatic carotid stenosis between April 2016 and October 2022 using BB-MRI, carotid plaque was evaluated in 57 patients. Relative overall signal intensity (roSI) was defined as the signal intensity of the plaque on T1-weighted images relative to the signal intensity of the sternocleidomastoid muscle in the same slice as the common carotid bifurcation. Regions showing roSI ≥ 1.0 were defined as plaque, and the plaque volume and relative plaque volume were measured from roSI ≥1.0 to ≥2.0 in 0.1 increments. We calculated the angles between the common carotid artery (CCA) and the ICA and between the CCA and the external carotid artery (ECA) on magnetic resonance angiography. We classified two groups according to carotid bifurcation angles based on the ICA angle: Group A = <35° and Group B = ≥35°. Compared with Group A (n = 42), Group B (n = 15) showed a greater relative plaque volume between roSI ≥ 1.3 and roSI ≥ 1.5. A significant correlation was identified between relative plaque volume with roSI ≥ 1.4 and ICA angle (p = 0.049). Vulnerable plaque was significantly more frequent in the group with an ICA angle of ≥35. Moreover, the ICA angle was significantly greater in patients with a roSI of ≥1.4.

Incidence and clinical characteristics of spinal arteriovenous shunts: hospital-based surveillance in Okayama, Japan.

OBJECTIVE: There have been no accurate surveillance data regarding the incidence rate of spinal arteriovenous shunts (SAVSs). Here, the authors investigate the epidemiology and clinical characteristics of SAVSs. METHODS: The authors conducted multicenter hospital-based surveillance as an inventory survey at 8 core hospitals in Okayama Prefecture between April 1, 2009, and March 31, 2019. Consecutive patients who lived in Okayama and were diagnosed with SAVSs on angiographic studies were enrolled. The clinical characteristics and the incidence rates of each form of SAVS and the differences between SAVSs at different spinal levels were analyzed. RESULTS: The authors identified a total of 45 patients with SAVSs, including 2 cases of spinal arteriovenous malformation, 5 cases of perimedullary arteriovenous fistula (AVF), 31 cases of spinal dural AVF (SDAVF), and 7 cases of spinal epidural AVF (SEAVF). The crude incidence rate was 0.234 per 100,000 person-years for all SAVSs including those at the craniocervical junction (CCJ) level. The incidence rate of SDAVF and SEAVF combined increased with advancing age in men only. In a comparative analysis between upper and lower spinal SDAVF/SEAVF, hemorrhage occurred in 7/14 cases (50%) at the CCJ/cervical level and in 0/24 cases (0%) at the thoracolumbar level (p = 0.0003). Venous congestion appeared in 1/14 cases (7%) at the CCJ/cervical level and in 23/24 cases (96%) at the thoracolumbar level (p < 0.0001). CONCLUSIONS: The authors reported detailed incidence rates of SAVSs in Japan. There were some differences in clinical characteristics of SAVSs in the upper spinal levels and those in the lower spinal levels.

Single mutation makes Escherichia coli an insect mutualist.

Microorganisms often live in symbiosis with their hosts, and some are considered mutualists, where all species involved benefit from the interaction. How free-living microorganisms have evolved to become mutualists is unclear. Here we report an experimental system in which non-symbiotic Escherichia coli evolves into an insect mutualist. The stinkbug Plautia stali is typically associated with its essential gut symbiont, Pantoea sp., which colonizes a specialized symbiotic organ. When sterilized newborn nymphs were infected with E. coli rather than Pantoea sp., only a few insects survived, in which E. coli exhibited specific localization to the symbiotic organ and vertical transmission to the offspring. Through transgenerational maintenance with P. stali, several hypermutating E. coli lines independently evolved to support the host's high adult emergence and improved body colour; these were called 'mutualistic' E. coli. These mutants exhibited slower bacterial growth, smaller size, loss of flagellar motility and lack of an extracellular matrix. Transcriptomic and genomic analyses of 'mutualistic' E. coli lines revealed independent mutations that disrupted the carbon catabolite repression global transcriptional regulator system. Each mutation reproduced the mutualistic phenotypes when introduced into wild-type E. coli, confirming that single carbon catabolite repression mutations can make E. coli an insect mutualist. These findings provide an experimental system for future work on host-microbe symbioses and may explain why microbial mutualisms are omnipresent in nature.

An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke.

BACKGROUND: Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. METHODS: We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. RESULTS: Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p < 0.001) and higher extent of NETosis (p = 0.006). Restricted mean survival time analysis revealed that older thrombi were associated with longer puncture-to-reperfusion times (difference: 15.6 minutes longer for older thrombi, p = 0.002). This association remained significant even after adjustment for erythrocyte content and the extent of NETosis (adjusted difference: 10.8 minutes, 95% confidence interval [CI]: 0.6-21.1 minutes, p = 0.039). Compared with fresh thrombi, older thrombi required more device passes before reperfusion (p < 0.001) and were associated with poorer functional outcomes (adjusted common odds ratio: 0.49; 95% CI: 0.24-0.99). CONCLUSION: An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

Emergent stenting after intravenous thrombolysis for isolated basilar artery dissection in a patient with acute ischemic stroke: a case report.

BACKGROUND: Isolated basilar artery dissection (IBAD) is a rare but important cause of ischemic stroke. Anti-thrombotic therapy is often used to treat IBAD-related ischemic stroke, but selected cases might need more aggressive treatment. There is no previous report of emergent stenting for IBAD-related ischemic stroke after intravenous thrombolysis. CASE PRESENTATION: A 53-year-old Japanese woman was admitted to our hospital with disturbance of consciousness, right hemiplegia, severe dysarthria, and total gaze paralysis. Brain magnetic resonance imaging revealed no ischemic lesion, but magnetic resonance angiography showed stenosis in the basilar artery. After initiation of intravenous thrombolysis, her neurological symptoms dramatically improved. Five hours later, however, her symptoms deteriorated again. Cerebral angiography showed IBAD. Emergent stenting was successfully performed. At 90 days after stroke onset, she had no significant disability, with a modified Rankin scale score of 1. CONCLUSIONS: Emergent stenting can be an effective treatment for patients with IBAD-related ischemic stroke who are resistant to IV-rtPA.

Improvement of Hemifacial Spasm after Stent-assisted Coil Embolization for Ipsilateral Vertebral Artery Dissecting Aneurysm.

Microvascular decompression (MVD) is the gold standard in the treatment of hemifacial spasm (HFS), and endovascular surgery has been described as a treatment only for aneurysm-induced HFS in several previous cases. We describe symptomatic HFS caused by a normal vertebral artery (VA) trunk adjacent to the ipsilateral dissecting VA aneurysm completely cured after stent-assisted coil embolization. A 52-year-old man presented with a 2-month history of gradually worsening left HFS. Magnetic resonance imaging (MRI) and cerebral angiography revealed a dissecting VA aneurysm on the left side. Based on the findings from preoperative MRI, not the aneurysmal dome itself, but the VA trunk just distal to the aneurysmal dome was considered likely to be compressing the root exit zone (REZ) of the facial nerve. Stent-assisted coil embolization was conducted for the VA aneurysm, and the stent was deployed to cover the wide neck of the aneurysm and offending zone of the VA trunk simultaneously. HFS started to show improvement just after the procedure and complete disappearance within 1 year. HFS was completely resolved by stenting of the offending artery. Stents may show efficacy for "intra-arterial decompression" by reducing pulsatility against the REZ of the facial nerve due to the thickness and rigidity of the stent metal and delayed endothelialization.

Variations and management for patients with craniocervical junction arteriovenous fistulas: Comparison of dural, radicular, and epidural arteriovenous fistulas.

BACKGROUND: Craniocervical junction arteriovenous fistulas (CCJAVFs) are known to be rare, but variations and clinical behaviors remain controversial. METHODS: A total of 11 CCJAVF patients (M: F=9:2, age 54-77 years) were investigated. Based on the radiological and intraoperative findings, they were categorized into three types: dural AVF (DAVF), radicular AVF (RAVF), and epidural AVF (EDAVF). RESULTS: There were four symptomatic patients (subarachnoid hemorrhage in two, myelopathy in one, and tinnitus in one) and seven asymptomatic patients in whom coincidental CCJAVFs were discovered on imaging studies for other vascular diseases (arteriovenous malformation in one, intracranial DAVF in two, ruptured cerebral aneurysm in two, and carotid artery stenosis in two). Of these 11 patients, 2 (18.2%) had multiple CCJAVFs. Of 14 lesions, the diagnoses were DAVF in 5, RAVF in 3, and EDAVF in 6 (C1-C2 level ratio =5:0, 2:1, 3:3). Patients with DAVF/RAVF in four lesions with intradural venous reflux underwent surgery, although an RAVF remained in one lesion after embolization/radiation. Since all six EDAVFs, two DAVFs, and one RAVF had neither feeder aneurysms nor significant symptoms, no treatment was provided; of these nine lesions, one DAVF and one RAVF remained unchanged, whereas six EDAVFs showed spontaneous obliteration within a year. Unfortunately, however, one DAVF bled before elective surgery. CONCLUSION: CCJAVFs have many variations of shunting site, angioarchitecture, and multiplicity, and they were frequently associated with coincidental vascular lesions. For symptomatic DAVF/RAVF lesions with intradural drainage, surgery is preferred, whereas asymptomatic EDAVFs without dangerous drainage may obliterate during their natural course.

Effectiveness of Transvenous Aspiration Thrombectomy for Cerebral Venous Sinus Thrombosis: A Report of Three Cases.

Objective: We report three patients successfully treated by emergent transvenous thrombectomy for cerebral venous sinus thrombosis (CVST). Case Presentation: (Case 1) A 77-year-old man presented with vomiting, dizziness, and headache. CT revealed local subarachnoid hemorrhage (l-SAH), and angiography confirmed occlusion of the right transverse sigmoid sinus and superior sagittal sinus (SSS). Emergent transvenous aspiration thrombectomy using a Penumbra catheter (PC) resulted in effective reperfusion. (Case 2) A 60-year-old man developed disorientation, sensory aphasia, and right hemiparesis. MRI demonstrated extensive cerebral edema caused by venous congestion in both thalami, and angiography revealed poor opacification of the SSS, straight sinus, and bilateral transverse sinuses. Venous sinus flow was restored by catheter aspiration using a PC and topical infusion of urokinase (UK). (Case 3) A 19-year-old man developed a headache, numbness of the right upper limb, motor paralysis, and convulsions. CT revealed l-SAH and dense clot sign in the SSS. The SSS was poorly delineated on angiography. Thrombus aspiration using a PC and topical UK administration achieved partial recanalization. Conclusion: Transvenous aspiration thrombectomy using large lumen catheters for patients with CVST is effective and safe. In particular, this method may be a better option than anti-coagulation therapy alone for patients presenting with a severe neurological condition or intracranial hemorrhage.

Surgical Technique for Carotid Endarterectomy: Current Methods and Problems.

Over the last 60 years, many reports have investigated carotid endarterectomy (CEA) and techniques have thus changed and improved. In this paper, we review the recent literature regarding operational maneuvers for CEA and discuss future problems for CEA. Longitudinal skin incision is common, but the transverse incision has been reported to offer minimal invasiveness and better cosmetic effects for CEA. Most surgeons currently use microscopy for dissection of the artery and plaque. Although no monitoring technique during CEA has been proven superior, multiple monitors offer better sensitivity for predicting postoperative neurological deficit. To date, data are lacking regarding whether routine shunt or selective shunt is better. Individual surgeons thus need to select the method with which they are more comfortable. Many surgical techniques have been reported to obtain distal control of the internal carotid artery in patients with high cervical carotid bifurcation or high plaque, and minimally invasive techniques should be considered. Multiple studies have shown that patch angioplasty reduces the risks of stroke and restenosis compared with primary closure, but few surgeons in Japan have been performing patch angioplasty. Most surgeons thus experience only a small volume of CEAs in Japan, so training programs and development of in vivo training models are important.

Ramucirumab after prior sorafenib in patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein: Japanese subgroup analysis of the REACH-2 trial.

BACKGROUND: The global, randomized, phase 3 REACH-2 study (ClinicalTrials.gov identifier: NCT02435433) found significantly longer overall survival (OS) for second-line ramucirumab versus placebo (hazard ratio [HR]: 0.710, 95% confidence interval [CI] 0.531-0.949, P = 0.0199) in patients with advanced hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) ≥ 400 ng/mL. This prespecified subgroup analysis evaluated the efficacy and safety of ramucirumab in the Japanese patients enrolled in the study. METHODS: Patients with advanced HCC and AFP ≥ 400 ng/mL after first-line sorafenib were randomized 2:1 to ramucirumab (8 mg/kg intravenously) or placebo every 2 weeks. Hazard ratios for progression-free survival (PFS) and OS (primary endpoint of the overall study) were estimated using the stratified Cox regression model. We also pooled individual patient data from REACH-2 with data from REACH (NCT01140347) for patients with AFP ≥ 400 ng/mL. RESULTS: In the Japanese REACH-2 subpopulation, there were improvements for ramucirumab (n = 41) versus placebo (n = 18) in PFS (HR 0.282, 95% CI 0.144-0.553) and OS was numerically prolonged (HR 0.599, 95% CI 0.303-1.187), consistent with the significant benefit seen in the overall REACH-2 study population. In the ramucirumab and placebo arms, respectively, the objective response rate was 7.3% and 0%, and the disease control rate was 70.7% and 33.3%. The most frequently reported grade ≥ 3 treatment-emergent adverse event was hypertension (ramucirumab: 15%; placebo: 11%). CONCLUSIONS: Ramucirumab after prior sorafenib improved PFS and OS compared with placebo, with a manageable safety profile, in the Japanese REACH-2 subpopulation, consistent with the overall REACH-2 study results. Ramucirumab is the first agent to demonstrate clinical benefit for Japanese patients with HCC in the second-line setting.