Angioarchitecture of the hemorrhagic developmental venous anomaly with stenosis of the collecting vein and cavernous malformation: a case report.

We herein report a case of developmental venous anomaly (DVA) with venous congestion caused by stenosis of the collecting vein that presented with intracerebral hemorrhage (ICH). A 74-year-old woman was referred to our hospital a few days after the onset of motor aphasia. Computed tomography (CT) and magnetic resonance imaging (MRI) showed ICH in the left frontal lobe. Angiography revealed DVA in the left frontal lobe in the late venous phase. Stenosis of the collecting vein of DVA at the entrance to the superior sagittal sinus was detected and accompanied by cavernous malformation (CM) beside DVA. Cone-beam CT revealed the absence of the left septal vein and hypoplastic transverse caudate veins. The patient was treated by blood pressure management and no additional neurological symptoms were detected. DVA develops to compensate for the absence of pial or deep venous systems, and generally benign and clinically asymptomatic. However, the outflow restriction of DVA causes chronic venous hypertension and the formation of CM. These abnormalities are considered to occur during post-natal life and may result in ICH. The risk of hemorrhage needs to be considered in cases of DVA with restricted venous outflow or CM.

Evaluation of a Webinar for Pharmacists Learning Basic Clinical-Oncology during COVID-19 Pandemic in Japan.

It is essential for oncology pharmacists to update their knowledge, skills, and ethical attitudes. The Japanese Society of Pharmaceutical Oncology is an academic society for healthcare professionals involved in cancer treatment. It has conducted in-person seminars every year to cultivate the knowledge necessary for practicing advanced cancer medicine. Owing to the coronavirus disease (COVID-19) pandemic, the society was obligated to conduct a web-based seminar this year. A questionnaire survey was conducted before and after the webinar to explain how it works and to assess the learning attitudes of beginner and moderately skilled pharmacists in the field of oncology. Questionnaire surveys were conducted with the participants before and after watching the webinar. The questionnaires sought to determine participants' perspectives on the webinar and their knowledge of the seven modules. Of the 1756 webinar attendees, 1661 (94.6%) answered the pre-webinar survey and 1586 (90.3%) answered the post-webinar survey. Results indicate that the median post-webinar knowledge score was significantly higher than the median pre-webinar score (p < 0.001) in all modules. Principal component analysis of the degree of knowledge of seven modules revealed that the improved score group consisted of those from younger age groups, with less experience as pharmacists, non-society members, and those with less experience in past society seminars. Moreover, the web-based seminar provided a uniform learning effect throughout the country without distinguishing between urban and rural learners. The web-based educational program was an acceptable educational tool for Japanese oncology pharmacists.

Evaluation of a web-based educational programme for pharmacists during the COVID-19 pandemic in Japan.

WHAT IS KNOWN AND OBJECTIVE: Continuing education is essential for pharmacists to acquire and maintain the knowledge, skills, and ethical attitudes necessary for clinical practice. However, with the emergence of COVID-19, the social circumstances and face-to-face learning environments have changed. The objectives of this study were to determine Japanese pharmacists' perception of a web-based educational programme in oncology, and assess changes in their understanding of pharmaceutical care in oncology before and after their participation in the webinar. METHODS: Questionnaire-based surveys were conducted for the participants of the web-based educational programme to determine their perspectives on the webinar, and their degree of comprehension of the five cancer types covered before and after watching the webinar. RESULTS AND DISCUSSION: Of the 1936 pharmacists taking the programme, all participated in the pre-webinar survey, and 1861 (96.1%) in the post-webinar survey. Compared with previous seminars that were held in the offline mode before the COVID-19 pandemic, 76.8% of respondents were significantly satisfied with the web-based educational programme. The median post-webinar comprehension scores in all modules were significantly higher than the median pre-webinar scores (p < 0.0001). A majority of the participants agreed that a web-based educational programme was satisfactory in acquiring knowledge. WHAT IS NEW AND CONCLUSION: This web-based educational programme was effective for Japanese pharmacists for postgraduate education in pharmaceutical care in oncology. To the best of our knowledge, our study is the first to report the effectiveness of a web-based educational programme for oncology pharmacists using a large population.

Contribution of Capsule Endoscopy Early in a Bleeding Episode to Treatment of Small Bowel Angioectasia: A Case Report.

Background: Recent advances in endoscopic devices such as small bowel capsule endoscopy and balloon-assisted endoscopy have improved the level of medical care for small bowel bleeding. However, treating small bowel angioectasia remains challenging because repeated intermittent bleeding can occur from the multiple minute lesions (about 1 mm in size) that develop in a synchronous and metachronous manner. Here, we report a case of small bowel angioectasia in which capsule endoscopy performed early in a bleeding episode contributed to treatment. Case Summary: A 66-year-old man with suspected small bowel bleeding underwent small bowel capsule endoscopy and balloon-assisted endoscopy with argon plasma coagulation hemostasis for a small intestinal angioectasia. Because small bowel bleeding recurred intermittently after the treatment, small bowel capsule endoscopy and balloon-assisted endoscopy were repeated when there was no bleeding, but no abnormalities were found. Subsequent small bowel capsule endoscopy during a bleeding episode revealed bloody intestinal fluid in the proximal small intestine. Peroral balloon-assisted endoscopy was performed 2 days after SBCE for detailed observation of the small intestinal mucosa at the suspected bleeding site, and there a 1-mm Dieulafoy's lesion with no active bleeding was identified. We performed argon plasma coagulation, and no bleeding was observed thereafter. Conclusions: Small bowel capsule endoscopy immediately after bleeding onset can identify the bleeding source of multiple minute lesions in small bowel angioectasia.

Intra-aneurysmal embolization of cellulose porous beads to regenerate vessel wall: an experimental study.

PURPOSE: Although the treatment of intracranial cerebral aneurysms with detachable coils is now widely accepted, the problem of coil compaction and recanalization remains unsolved. If the vessel wall can be regenerated at the neck orifice of an aneurysm, thereby reducing the blood flow into the aneurysm, the recurrence rate of the aneurysm would decrease. Accordingly, we aimed to insert cellulose porous beads (CPBs) into rat models of external carotid artery (ECA) aneurysm and study their efficacy in promoting vessel wall regeneration. METHODS: Using a rat aneurysm model, we examined the tissue response to CPBs that were inserted into the ligated ECA sac of rats. The sacs were removed on days 14, 42, 84, and 180 after insertion and subjected to conventional and immunohistochemical examination. We evaluated the tissue response in the ECA sacs and observed the vessel wall regeneration progress. RESULTS: At the neck orifice of the aneurysm in which the CPB was inserted, a layer of regenerating α-smooth muscle actin-positive spindle cells was observed on day 14. The regenerative cell layer gradually thickened until day 42 and, thereafter, the thickness remained unchanged until day 180. A monolayer of factor VIII-positive cells also appeared at the neck orifice on day 14 and covered the entire orifice until day 180. The CPBs were stably localized in the sac without degradation or signs of inflammation. CONCLUSION: CPBs may be promising as embolic materials that can induce stable vessel wall regeneration at the neck orifice of an aneurysm without surrounding inflammatory reactions.

Efficacy of cyst-cisternal shunt for refractory cyst regrowth of cystic vestibular schwannomas.

Vestibular schwannomas (VSs) are generally benign and slow-growing tumors, and microsurgical resection is the commonly recommended treatment. Some reports suggested that inserting a cystoperitoneal shunt was effective for treatment of cystic VSs; however, there was no report of a cyst-cisternal shunt which diverts cyst fluid into cistern. We report a case of cystic VS with repeated cyst regrowth within weeks after repeated surgeries. We prevented further recurrence using cyst-cisternal shunt. This technique may be a new treatment option for refractory cyst regrowth of cystic VSs.

Chemically assisted peroral endoscopic myotomy with submucosal mesna injection in a porcine model.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a less invasive alternative to standard surgery for the treatment of achalasia. Previous studies have demonstrated that submucosal injections of mesna soften tissues and facilitate endoscopic submucosal dissection. MATERIAL AND METHODS: We studied the technical feasibility of a chemically assisted POEM procedure with mesna injection (CA-POEM) in ten pigs compared with POEM with saline injection in five pigs. We also compared two dissection techniques in CA-POEM, diathermy needle knife dissection (n = 5) and balloon mechanical dissection (n = 5). A 10 cm esophageal submucosal tunnel was created with a needle knife or with balloon mechanical dissection following mesna or saline submucosal injection. Approximately 5 cm of inner circular muscle was then dissected within the tunnel. The tunnel was closed with endoclip application at the mucosal endoscopic entry point. Pigs were sacrificed one week post procedure. RESULTS: All procedures were successful and all pigs survived for one week. Submucosal tunneling time was significantly shorter in the mesna group (363.8 sec for needle knife dissection and 294.2 sec for balloon dissection) than in the saline group (640 sec), regardless of the dissection method (p < 0.05). CONCLUSIONS: Our study demonstrated the technical feasibility of CA-POEM.

Relationship between frequency of surveillance colonoscopy and colorectal cancer prevention.

BACKGROUND AND AIM: The impact of frequent colonoscopy on colorectal cancer (CRC) remains unclear. The present study aimed to determine the relationship between frequency of surveillance colonoscopy and CRC prevention. METHODS: From April 2010 to April 2011, patients who underwent surveillance colonoscopy after screening and polypectomy in four Japanese endoscopy centers were enrolled in this multicenter historical cohort study. Patients were classified into the following two groups according to the findings of past colonoscopy: a low-risk group (no neoplasia or 1-2 cumulative adenomas <10 mm) and an increased-risk group (advanced adenoma or ≥ 3 cumulative adenomas). The relationship between colonoscopy frequency within the previous 5 years and the prevalence of advanced neoplasia in each group was analyzed using multiple logistic regression. RESULTS: The final analysis included 2391 patients. In the low-risk group, the odds ratios for advanced adenoma in patients undergoing moderately frequent colonoscopy (2-3 times within the previous 5 years), and frequent colonoscopy (≥ 4 times within 5 years) were 0.33 (95% confidence interval [CI], 0.14-0.81) and 0.21 (95% CI, 0.02-1.60), respectively, compared with infrequent colonoscopy (once or not at all within 5 years). In the increased-risk group, the respective odds ratios were 0.48 (95% CI, 0.28-0.83) and 0.28 (95% CI, 0.12-0.64). CONCLUSIONS: Although frequent colonoscopy provides benefits against advanced adenoma, the optimal benefit was achieved at 2-3 times. With very frequent colonoscopy (i.e. ≥ 4 times within 5 years), the additional risk reduction for advanced adenoma was relatively small.

A randomized crossover open trial of the adenoma miss rate for narrow band imaging (NBI) versus flexible spectral imaging color enhancement (FICE).

PURPOSE: Narrow band imaging (NBI) and flexible spectral imaging color enhancement (FICE) allow improved contrasted evaluation of the mucosal surface. However, no study has compared the utility of these two modalities. Therefore, the aim of this study was to compare the adenoma miss rate (AMR) between NBI and FICE. METHODS: A total of 55 patients (38 men, 17 women) were enrolled in this study. Patients were randomly assigned to the NBI-FICE group (NBI followed by FICE) or the FICE-NBI group (FICE followed by NBI). NBI and FICE total colonic observations were tandemly performed for each patient during the scope withdrawal with white light following cecal intubation. All detected polyps with the NBI or FICE observation were categorized into three groups according to the size and number of polyps missed. RESULTS: Twenty-nine patients were assigned to the NBI-FICE group, and 26 patients were assigned to the FICE-NBI group. There was no significant difference in the overall AMR when comparing the image-enhanced endoscopy technologies (17.9 % for NBI, 26 % for FICE, p = 0.159). AMR was lower for NBI than for FICE for adenomas <5 mm in diameter (5.7 % for NBI, 12.6 % for FICE, p = 0.036). AMR was not significantly different when comparing NBI and FICE for lesions 5 to 10 mm (p = 0.967) or for lesions ≥10 mm (p = 0.269). CONCLUSIONS: This study demonstrated that overall AMR was not different when comparing NBI and FICE.

Percutaneous transjugular approach without arterial monitoring for the treatment of a direct carotid-cavernous fistula with vascular Ehlers-Danlos syndrome: illustrative case.

BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) because of COL3A1 mutations is a rare inherited collagen vascular disease associated with spontaneous arterial dissections, aneurysms, vessel rupture, and organ rupture. A direct carotid-cavernous fistula (CCF) is the most common central nervous system vascular anomaly in vEDS; however, its treatment is challenging due to extremely fragile arteries and veins. OBSERVATIONS: A 22-year-old woman presented with pulsatile tinnitus and mild diplopia. CCF formation without trauma, cervical dissecting aneurysms, thin skin, and multiple ligament tears, as well as a genetic analysis, led to a diagnosis of vEDS. To minimize the risk of vascular injury in the thoracoperitoneal cavity, the internal jugular vein was directly punctured and the CCF was embolized transvenously using the triple-overlay road-mapping technique without arterial monitoring. The CCF was completely occluded, and the patient showed an excellent clinical course without neurological or vascular complications. LESSONS: Physicians and neurosurgeons should consider vEDS when treating younger patients with spontaneous CCF without trauma and investigate the possibility of genetic abnormalities and systemic vascular pathology. Transvenous embolization of a CCF through the transjugular route using the triple-overlay road-mapping technique can minimize the risk of vascular injury in a patient with vEDS.

"The microcatheter contrast injection technique": A novel technique to detect the proximal end of a thrombus in mechanical thrombectomy.

Background: An aspiration catheter needs to attach to a thrombus in order to achieve first-pass recanalization by mechanical thrombectomy (MT) for acute ischemic stroke (AIS), particularly that using a direct aspiration first pass technique. The meniscus sign, which is defined as meniscoid contrast opacification indicating the proximal edge of a thrombus, has been suggested to contribute to successful recanalization. In some cases, the meniscus sign is not detected following an injection of contrast medium through a guiding catheter. To precisely identify the location of a thrombus, we use "the microcatheter contrast injection (MCI) technique," which accurately shows the proximal edge of a thrombus. We herein introduce this novel technique and discuss its efficacy in MT. Methods: In cases without the meniscus sign, a microcatheter was advanced to the distal end of contrast opacification, and contrast medium was injected through the microcatheter to detect the meniscus sign. An aspiration catheter was then advanced to the thrombus indicated by the meniscus sign and slowly withdrawn under aspiration. Results: 29 patients underwent MT for AIS using the MCI technique. Even in cases without the meniscus sign on initial angiography, the MCI technique accurately revealed the proximal edge of the thrombus. Moreover, middle cerebral artery occlusion due to atherosclerotic stenosis and displacement of the aspiration catheter and thrombus axis were detected using this technique. Conclusions: The MCI technique may effectively reveal the exact site of a thrombus and increase the success rate of first-pass recanalization.

Registry study of immune-related adverse events using electronic patient-reported outcome in patients with cancer receiving immune checkpoint inhibitors: protocol for a multicentre cohort study.

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) is rapidly expanding in cancer treatment. ICIs have a unique safety profile, characterised by immune-related adverse events (irAEs). The safety profile of ICIs lacks patient experience and perspectives. This study primarily aims to obtain a database for descriptive research on the status of irAEs using the Patient-Reported Outcomes version of the Common Terminology Criteria (PRO-CTCAE) in patients with gastrointestinal cancer, lung cancer and malignant pleural mesothelioma treated with regimens containing ICIs. METHODS AND ANALYSIS: This is an ongoing, multicentre, observational study in Japan. Eligible patients must be at least 20 years old and have been diagnosed with lung cancer, malignant pleural mesothelioma or gastrointestinal cancer and plan to use ICIs. Participants will install the electronic PRO (ePRO) application and report adverse events via ePRO using PRO-CTCAE once weekly for up to 48 weeks. A registry will be established using background information obtained from medical records. The sample size is determined by 1 year projection without using statistical methods. Statistical analyses will include point estimates and 95% CIs for the incidence of each adverse event by cancer type and regimen at each time point. ETHICS AND DISSEMINATION: This research will be conducted per the Declaration of Helsinki, the Ethical Guidelines for Life Science and Medical Research Involving Human Subjects issued by the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labor and Welfare, and the revised Personal Information Protection Law. The study protocol was approved by the Ethics Committee (approval ID T2021-0180) of Tokyo Medical University Hospital on 15 October 2021. REGISTRATION DETAILS: The study began enrolling patients in December 2021. The target enrolment is 260; as of October 2022, 141 have been enrolled, and the enrolment is scheduled to end on 30 June 2023. TRIAL REGISTRATION NUMBER: UMIN000046418.

Prediction of high-grade meningioma by preoperative MRI assessment.

High-grade (World Health Organization grades II and III) meningiomas grow aggressively and recur frequently, resulting in a poor prognosis. Assessment of tumor malignancy before treatment initiation is important. We attempted to determine predictive factors for high-grade meningioma on magnetic resonance (MR) imaging before surgery. We reviewed 65 meningiomas (39 cases, benign; 26 cases, high-grade) and assessed four factors: (1) tumor-brain interface (TBI) on T1-weighted imaging (T1WI), (2) capsular enhancement (CapE), i.e., the layer of the tumor-brain interface on gadolinium-enhanced T1WI (T1Gd), (3) heterogeneity on T1Gd, and (4) tumoral margin on T1Gd. All four factors were useful in distinguishing high-grade from benign meningiomas, according to univariate analysis. On multivariate regression analysis, unclear TBI and heterogeneous enhancement were independent predictive factors for high-grade meningioma. In meningiomas with an unclear TBI and heterogeneous enhancement, the probability of high-grade meningioma was 98%. Our data suggest that this combination of factors obtained from conventional sequences on MR imaging may be useful to predict high-grade meningioma.

Cerebral Infarction Due to Occlusion of Main Trunk of Middle Cerebral Artery in Patient with Accessory Middle Cerebral Artery.

The existence of an accessory middle cerebral artery (AMCA) usually has no pathological significance. Three patients developed cerebral infarction due to thromboembolic occlusion of the main trunk of the middle cerebral artery (MCA). In these patients, AMCA originating from the anterior cerebral artery was intact, and ran to the lateral side along the main MCA. Emergency endovascular treatment to remove the thrombus in the main MCA was performed, and MCA was recanalized. In one patient, the main MCA re-occluded and cerebral infarction developed on the next day. The diameter of AMCA is commonly smaller than that of the main MCA. Therefore, volume of ischemic region depends on the collateral blood flow to the left MCA territory by AMCA. Once an anomalous MCA is detected in a patient with cerebral infarction involving the MCA territory, close examinations to assess the anatomy of both the main and anomalous MCA are mandatory.

Characteristics and Management of Ruptured Aneurysms Originating from the Penetrating Artery of the Distal Middle Cerebral Artery.

We report a rare case of an aneurysm originating from the penetrating artery of the distal middle cerebral artery (MCA). A 76-year-old man without a notable past history presented with sudden-onset severe headache, left hemiparesis, and a decreased level of consciousness. Computed tomography (CT) revealed subarachnoid hemorrhage (SAH) with intracerebral hemorrhage (ICH) in the right temporal lobe extending into the ventricle. Contrast-enhanced CT (CE-CT) demonstrated a focus of contrast enhancement (CE) adjacent to the hematoma in the right frontal lobe. An aneurysm fed by a penetrating artery branching off from the right distal MCA was found on angiography. The patient underwent emergency resection of the aneurysm and hematoma evacuation. Histological analysis revealed that arterial dissection may be an associated factor in the pathogenesis of this peripheral aneurysm formation. A focus of CE within or adjacent to the hematoma may be useful for diagnosing this peripheral aneurysm. ICH can result in a life-threatening situation. Therefore, microsurgery may be the first treatment choice for aneurysms in this location.

Megaesophagus and Megaduodenum Found Incidentally on a Routine Chest Radiograph During a Health Examination.

Chronic idiopathic intestinal pseudo-obstruction (CIIP) caused by impaired intestinal peristalsis leads to intestinal obstructive symptoms. A 20-year-old man had marked esophageal dilatation that was found incidentally on chest radiography during a health examination. Chest/abdominal contrast-enhanced computed tomography and endoscopy showed marked esophageal and duodenal dilatation without mechanical obstruction. Upper gastrointestinal series and high-resolution esophageal manometry revealed absent peristalsis in the dilated part. CIIP was suspected in the patient's father, suggesting familial CIIP. The patient likely had signs of pre-onset CIIP. This is the first case of suspected CIIP in which detailed gastrointestinal tract examinations were performed before symptoms appeared.

Hemifacial spasm caused by vertebral artery aneurysm treated by endovascular coil embolization.

BACKGROUND: Hemifacial spasm (HFS) caused by vertebral artery (VA) aneurysms is rare. Several cases of HFS caused by VA aneurysms treated by endovascular parent artery occlusion (PAO) have been reported. Recently, we treated a rare case of HFS caused by a saccular VA aneurysm at the bifurcation of the posterior inferior cerebellar artery (PICA), which was successfully treated by endovascular coil embolization, preserving the parent artery, and PICA. We discuss endovascular treatment for HFS induced by VA aneurysms with a literature review. CASE DESCRIPTION: A 59-year-old man presented with the left HFS persisting for 2 months. Magnetic resonance imaging revealed a left saccular VA-PICA aneurysm and demonstrated that a left facial nerve was compressed by the aneurysm at the root exit zone. Angiography revealed that the PICA was branching from the aneurysm neck. Endovascular coil embolization was performed using the balloon remodeling technique to preserve the left VA and PICA. HFS disappeared after treatment. CONCLUSION: Although microvascular decompression was commonly accepted for the standard treatment of HFS, coil embolization of aneurysms without PAO may be an effective treatment for HFS caused by VA aneurysms.

Mesalazine formulation intolerance due to suspected excipient allergy in the treatment of ulcerative colitis: a case report.

Mesalazine formulations are essential for treating ulcerative colitis (UC), and intolerance to these formulations complicates the treatment of this condition. Some cases of mesalazine formulation intolerance are caused by the excipients rather than the active ingredient mesalazine. Therefore, mesalazine administration can be continued in such cases by changing the mesalazine formulation. This report describes a case of intolerance to mesalazine in which UC was effectively treated by switching mesalazine formulations. A drug-induced lymphocyte stimulation test suggested that allergy to the additive povidone was the cause of mesalazine formulation intolerance. This is the first case study to identify an additive that caused mesalazine formulation intolerance.

Best period to replace or change plastic stents with self-expandable metallic stents using multivariate competing risk regression analysis.

In endoscopic biliary drainage (EBD) for various benign and malignant biliary disorders, the appropriate timing to replace or change a plastic stent (PS) with a self-expandable metallic stent (SEMS) remains unclear. This study aimed to define the best period to replace or change a PS with a SEMS. Between January 1, 2012, and December 31, 2018, 1,887 consecutive EBD procedures, including 170 SEMS placements, were retrospectively identified. The period to recurrent biliary obstruction (PRBO) was estimated and compared between the malignant and benign groups and according to each disease using time to event analysis and competing risk analysis. Compared with the benign group, the malignant group had significantly shorter median PRBO with interquartile range (IQR) after PS placement [108 (39 - 270) vs. 613 (191 - 1,329) days, P < 0.001], even on multivariate analysis, with a subdistribution hazard ratio (SHR) of 3.58 (P < 0.001). The shortest PRBO distribution from the first quartile of the non-RBO period was seen in Mirizzi syndrome cases (25 days, P = 0.030, SHR = 3.32) in the benign group and in cases of pancreatic cancer (32 days, P = 0.041, SHR = 2.06); perihilar bile duct cancer (27 days, P = 0.006, SHR = 2.69); and ampullary cancer (22 days, P = 0.001, SHR = 3.78) in the malignant group. Our study supports that stent replacement for the benign group is feasible after 6 months, and the best period to replace or change a PS with a SEMS should be decided on the basis of the underlying disease to prevent RBO.

Ligand-dependent EphB4 activation serves as an anchoring signal in glioma cells.

Of the erythropoietin-producing human hepatocellular receptors (Ephs), EphB4 has recently emerged as a potential target in several cancers due to its roles in modified cell migration and invasion. As little is known about the roles of EphB4 in glioma, we sought to investigate its function in glioma by in vitro cell migration and invasion assays, immunoblotting and immunostaining. EphB4 was expressed in glioma cell lines and stem-like cell lines. The stimulation of glioma cells with ephrin-B2, the sole ligand of EphB4, conducted EphB4 phosphorylation and suppressed migration and invasion that downregulation of EphB4 using small interfering RNA abrogated. The stimulation also suppressed the phosphorylation of Akt. We confirmed by immunostaining that EphB4-positive cells existing only in the tumor core, whereas ephrin-B2-positive cells widespread in both the tumor core and the invasive area signifying that EphB4-ephrin-B2 reaction occurred only at the tumor core. Taken together, our data suggest that ephrin-B2-dependent EphB4 phosphorylation acts as an anchoring signal to reduce the malignancy by inhibiting Akt phosphorylation in the glioma core, whereas the scarcity of signaling in the tumor periphery promotes invasion into the surrounding brain.