Hiroaki Motegi

Type 1 collagen as a potential niche component for CD133‐positive glioblastoma cells

Cancer stem cells are thought to be closely related to tumor progression and recurrence, making them attractive therapeutic targets. Stem cells of various tissues exist within niches maintaining their stemness. Glioblastoma stem cells (GSCs) are located at tumor capillaries and the perivascular niche, which are considered to have an important role in maintaining GSCs. There were some extracellular matrices (ECM) on the perivascular connective tissue, including type 1 collagen. We here evaluated whether type 1 collagen has a potential niche for GSCs. Imunohistochemical staining of type 1 collagen and CD133, one of the GSCs markers, on glioblastoma (GBM) tissues showed CD133‐positive cells were located in immediate proximity to type 1 collagen around tumor vessels. We cultured human GBM cell lines, U87MG and GBM cells obtained from fresh surgical tissues, T472 and T555, with serum‐containing medium (SCM) or serum‐free medium with some growth factors (SFM) and in non‐coated (Non‐coat) or type 1 collagen‐coated plates (Col). The RNA expression levels of CD133 and Nestin as stem cell markers in each condition were examined. The Col condition not only with SFM but SCM made GBM cells more enhanced in RNA expression of CD133, compared to Non‐coat/SCM. Semi‐quantitative measurement of CD133‐positive cells by immunocytochemistry showed a statistically significant increase of CD133‐positive cells in Col/SFM. In addition, T472 cell line cultured in the Col/SFM had capabilities of sphere formation and tumorigenesis. Type 1 collagen was found in the perivascular area and showed a possibility to maintain GSCs. These findings suggest that type 1 collagen could be one important niche component for CD133‐positive GSCs and maintain GSCs in adherent culture.

Hemorrhagic Onset of Hemangioblastoma Located in the Dorsal Medulla Oblongata Presenting with Tako-Tsubo Cardiomyopathy and Neurogenic Pulmonary Edema: A Case Report

Here, we present a case of dorsal medulla oblongata hemangioblastoma with fourth ventricular hemorrhage. A 23-year-old female developed sudden consciousness disturbance, and CT revealed hemorrhage in all cerebral ventricles and a hyperdense mass in the cisterna magna. Although the reddish tumor located in the dorsal medulla oblongata was successfully removed, she suffered from severe tako-tsubo cardiomyopathy (TTC) and neurogenic pulmonary edema (NPE) because of baroreflex failure and damage to the solitary tract nuclei. After intensive care for 12 weeks following surgery, she was discharged without any neurological or radiological deficits. Pathogenesis of TTC/NPE is discussed in this paper.

Change in 18F-Fluoromisonidazole PET Is an Early Predictor of the Prognosis in the Patients with Recurrent High-Grade Glioma Receiving Bevacizumab Treatment.

Background Bevacizumab (BEV), a humanized monoclonal antibody, become a currently important chemotherapeutic option for the patients with recurrent glioma. The aim of this retrospective study is to investigate whether 18F-Fluoromisonidazole (FMISO) PET have the potential to detect BEV-resistant gliomas in the early-stage. Methods We reviewed the FMISO PET and MRI appearances before and 3 to 4 courses after BEV treatment on 18 recurrent glioma patients. FMISO accumulation was assessed by visual inspection and semi-quantitative values which were tumor-to-normal (T/N) ratio and hypoxic volume. MRI responses were evaluated based on RANO (Response Assessment in Neuro-Oncology) criteria. The prognostic analysis was performed in relation to the response assessment by FMISO PET and MRI using overall survival (OS) after BEV application. Results After BEV application, MRI revealed partial response in 14 of 18 patients (78%), of which 9 patients also demonstrated decreased FMISO accumulation. These 9 patients (50%) were classified as “MRI-FMISO double responder”. As for the other 5 patients (28%), FMISO accumulation volumes increased or remained stable after BEV treatment although partial responses were achieved on MRI. Therefore, these cases were classified as “MRI-only responder”. The remaining 4 patients (22%) did not show treatment response on FMISO PET or MRI (“non-responder”). MRI-FMISO double responders showed significantly longer OS than that in other groups (median 12.4 vs 5.7 months; P < 0.001), whereas there were no overall survival difference between MRI-only responders and non-responders (median OS, 5.7 and 4.8 months; P = 0.58). Among the pre-treatment clinical factors, high FMISO T/N ratio was a significant prognostic factor of overall survival in these patients under the assessment of Cox proportional hazard model. Conclusions Recurrent gliomas with decreasing FMISO accumulation after short-term BEV application could derive a survival benefit from BEV treatment. Change in FMISO PET appearance can identify BEV-resistant gliomas in early-stage regardless of MRI findings in a comprehensible way.

Prognostic Factors for Survival in Patients with High- Grade Meningioma and Recurrence-Risk Stratification for Application of Radiotherapy

Background Radiotherapy for high-grade meningioma (HGM) is one of the essential treatment options for disease control. However, appropriate irradiation timing remains under debate. The object of this study is to discern which prognostic factors impact recurrence in HGM patients and to propose a risk-stratification system for the application of postoperative radiotherapy. Methods We retrospectively reviewed 55 adult patients who were diagnosed with Grade II and III intracranial meningioma. Cox regression models were applied to the analysis for impact on early recurrence in HGM patients without postoperative radiotherapy. Results Grade III malignancy (P = 0.0073) and transformed histology (P = 0.047) proved to be significantly poor prognostic factors of early recurrence by multivariate analysis. The other candidates for recurrence factors were Simpson Grade 3–5 resection, preoperative Karnofsky Performance status < = 70%, and MIB-1 labeling index > = 15%. According to these prognostic factors, postoperative HGM patients could be stratified into three recurrence-risk groups. The prognoses were significantly different between each group, as the 3-year actual recurrence-free rates were 90% in low-risk group, 31% in intermediate-risk group, and 15% in high-risk group. Conclusion We propose recurrence-risk stratification for postoperative HGM patients using clinically available factors. Our results suggest that the prognosis for patients with high-risk HGMs is dismal, whereas HGM patients belonging to the low-risk group could have favorable prognoses. This stratification provides us with the criteria necessary to determine whether to apply adjuvant radiotherapy to postoperative HGM patients, and to also help identify potentially curable HGMs without adjuvant radiotherapy.

Regression of Dural Arteriovenous Fistulae after Venous Flow Reconstructive Surgery in a Case with Hemangiopericytoma at the Confluence of Sinuses

Background: The mechanism by which acquired dural arteriovenous fistula (dAVF) develops is still unclear. Few cases have been reported with both dAVF and intracranial tumors, and in these few cases the authors have proposed that induced venous hypertension may lead to the pathogenesis of dAVF. We experienced a case of intrasinusoidal hemangiopericytoma (HPC) with dAVF development. In addition to its rare pathology and tumor location, this case showed regression of dAVF immediately after tumor removal. Case Report: The patient was a 23-year-old man who developed progressively worse headaches and papilledema. The HPC was located entirely inside the confluence of the sinuses (CoS) and resulted in venous sinus occlusion. Cerebral angiography demonstrated a dAVF located in the straight sinus, upstream of the occluded CoS, which was fed by the dural branch of the posterior cerebral artery. After the endovascular embolization of the tumor feeders, subsequent surgery included venous reconstruction in addition to tumor excision. Although the dAVF was not treated with an endovascular procedure or surgery, postoperative angiography revealed complete disappearance of the dAVF. Conclusion: We conclude that venous reconstructive surgery greatly contributed to the immediate regression of the dAVF. When planning the treatment strategy for such cases, it should be remembered that acquired dAVF may regress due to the normalization of venous hypertension.

[Risk Factors for Adverse Events after Implantation of BCNU Wafers in High-grade Gliomas].

BACKGROUND In Japan, patients with malignant glioma have been treated with BCNU wafers (Gliadel®) since January 2013. Several adverse events(AEs)associated with implantation of BCNU wafers, including cerebral edema or cyst formation, are recognized. Here, we report a retrospective review of the experience with implantation of BCNU wafers in our institutions and our findings regarding the risk factors for the AEs. METHODS We reviewed the records of patients with malignant glioma who were implanted with BCNU wafers between April 2013 and September 2014. Their AEs were examined clinically and radiologically and evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) grading. For investigating the association between risk factors and incidence of AEs, histological diagnosis, extent of resection, and period of BCNU wafers implantation surgery were selected as possible risk factors. RESULTS Twenty-one patients were included in this investigation. There were no associations among incidence of AEs and histological diagnosis or extent of tumor resection. However, regarding the period of BCNU wafers implantation, additional resection for newly diagnosed tumors and resection for recurrent tumors tended to increase the rate and severity of AEs, especially cerebral edema, compared to primary resection. CONCLUSION In cases of BCNU wafers implantation, the incidence and degree of AEs might increase if additional resection for newly diagnosed tumors or resection for recurrent tumors is performed. Our investigation revealed that AEs associated with implantation of BCNU wafers tend to occur in the repeated glioma surgery.

Endoscopic transsphenoidal surgery using pedicle vascularized nasoseptal flap for cholesterol granuloma in petrous apex: A technical note

BACKGROUND Compared with surgical resection, endoscopic transsphenoidal surgery (TSS) for cholesterol granuloma (CG) in the petrous apex (PA) is associated with local recurrence due to obstruction of the drainage route. We present a detailed procedure of an endoscopic TSS using pedicle vascularized nasoseptal flap (PVNF). METHODS A 40-year-old woman with a history of repeated surgery for left tympanitis was referred to our institution. Neurological examination revealed severe hearing loss in the left ear. Radiologic examination presented a round mass in the left PA and significant fluid collection in the mastoid air cells of the left temporal bone. CG was strongly suspected, and endoscopic TSS using PVNF was performed. Prior to endoscopic drainage, a PVNF was harvested from the mucosa of the ipsilateral nasal septum, with an attempt to preserve the sphenopalatine artery in the flap. Following this, puncture and adequate irrigation of the lesion was performed by endoscopic TSS, with neuro-navigation system assistance; the apex of PVNF was then placed into the lesion to prevent the obstruction of the drainage route. An absorbable polyglycolic acid sheet and fibrin glue were applied on the flap to prevent spontaneous deviation from the lesion. RESULTS The patient was discharged without any further neurological complications. Eight-month postoperative computed tomography images showed no recurrence; the drainage route was patent and the fluid collection in the left mastoid air cells was resolved. Moreover, hearing loss was improved. CONCLUSIONS Endoscopic TSS using PVNF may be one of available surgical options for PACG.

Postoperative Acute Submandibular Sialadenitis after Neurosurgery: Two Case Reports and a Review of the Literature

This article details two case reports and reviews the extant literature concerning acute postoperative submandibular sialadenitis occurring in the side contralateral to the operated site after neurosurgery. Although its precise pathogenesis remains to be elucidated, it is likely related to intraoperative compression of the submandibular gland and surrounding tissues, caused by head positioning and the endotracheal tube. Submandibular swelling rapidly deteriorates after surgery, and emergent airway protection is required in most cases in order to avoid fatal airway obstruction. To avoid serious sequelae, we should be aware of acute submandibular sialadenitis that occurs contralateral to the surgical side, which, although rare, is more probable after posterior fossa surgery. When it occurs, early airway protection is crucial, and the following conservative treatment could provide a good prognosis.

Application of endoscopic ultrasonography to intraventricular lesions

BackgroundAnatomical landmarks such as choroid plexus and foramen of Monro are very important to undergo intraventricular surgery safely and effectually. These landmarks would be unclear in cases with a huge cyst or repeat surgery. We report the usability and precautions to apply a bronchoscope with an ultrasonic convex probe to intraventricular surgery.MethodsTwo patients diagnosed with obstructive hydrocephalus, one with a large cyst and the other with recurrent craniopharyngioma in the third ventricle, were applied to the EBUS system.ResultsIn both patients, the EBUS system was applied safely, and lesions beyond the wall of ventricles or the cyst were visible. Color Doppler ultrasonography detected choroid plexus and internal cerebral veins. Furthermore, we performed real-time ultrasound-guided cyst puncture safely on the case with a large cyst. The most important precaution is that the curved portion of the EBUS system is too long to be bent within cerebral ventricles.ConclusionsThe new EBUS system with an ultrasonic convex probe is a novel and effectual device to perform intraventricular surgery.