[Show abstract][Hide abstract] ABSTRACT: The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
[Show abstract][Hide abstract] ABSTRACT: Medical treatment for asymptomatic carotid artery stenosis (ACAS) has advanced recently. The outcomes of medical treatment and surgical treatment were evaluated to clarify the optimal treatment for ACAS.Patients with ACAS of ≥ 50% luminal narrowing underwent serial follow-up carotid artery ultrasonography for one year or more at the Center for Cardiovascular Disease Prevention between November 2006 and October 2013. The incidence of cardiovascular events (stroke, myocardial infarction, cardiovascular death) was examined in 64 patients (medical treatment group), and in 47 patients (surgical group) who underwent surgical treatment (carotid endarterectomy or carotid artery stenting) during this same period at the Department of Neurosurgery.Annual cardiovascular event rate was 0.91% (2/219 person-year) in the group of guideline-oriented medical treatment with an annual check-up for disease management and 5.6% (6/107 person-year) in the surgical group (log-rank P = 0.027; HR in the medical treatment group, 0.19 [medical treatment/surgical]; 95% confidence interval [CI], 0.028 to 0.87). Annual stroke event rate was 0.46% (1/219 person-year) in the medical treatment group and 4.7% (5/107 personyear) in the surgical group (log-rank P = 0.016; HR in the medical treatment group, 0.11 [medical treatment/surgical]; 95% CI, 0.0057 to 0.70). Multivariate logistic analysis showed that the surgical group was an independent variable associated with cardiovascular events (P = 0.049).Annual cardiovascular and stroke event rates were low in patients receiving medical treatment for ACAS and better than surgical treatment. The present study shows that medical treatment is an important option for ACAS.
Full-text · Article · Dec 2015 · International Heart Journal
[Show abstract][Hide abstract] ABSTRACT: Carmustine wafers improve the survival of patients with high-grade gliomas, but several adverse events have been reported. A 42-year-old man with left insulo-opercular anaplastic astrocytoma developed a massive intra-cavital hematoma with subarachnoid hemorrhage caused by ruptured pseudoaneurysm of the left middle cerebral artery (MCA) adjacent to the site of carmustine wafers implanted 6 months previously. Intraoperative finding demonstrated a dissection of the insular portion of the MCA, and pathological examination identified the resected pseudoaneurysm. This case demonstrates that carmustine wafers can cause changes in local vessels. Therefore, implantation of carmustine wafers near to important vessels passing close to the resection cavity should be considered with great caution.
No preview · Article · Oct 2015 · Neurologia medico-chirurgica
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
Radiation-induced cerebral cavernous malformation reflects post-irradiation impairment of cerebral microcirculation. Our purpose was to determine effects of radiation field size and dose on the extent of developing cavernous malformations in long-term survivors of intracranial germ cell tumors (GCTs).
The study involved 34 patients with a history of intracranial GCTs treated with either whole-brain or reduced-field irradiation and undergoing magnetic resonance (MR) imaging with a mean follow-up of 18.5years. The number of cavernous malformations on T2*-weighted MR images between whole-brain and reduced-field irradiation groups as well as between high- (50.2Gy) and low-dose (24.4Gy) fields were compared.
A total of 235 cavernous malformation lesions were observed in 32 of 34 patients (94.1%). The mean number of lesions was 2.3 times as high in the whole-brain group as in the reduced-field group (P=0.00296). The number of lesions in high-dose fields was significantly larger than in low-dose (P<0.000001) or untreated fields (P<0.001).
Radiation field size and dose were positively associated with the number of cavernous malformations developed. Cavernous malformations detected on MR imaging can be used as a surrogate marker for microvascular injury following intracranial irradiation in long-term cancer survivors.
Full-text · Article · Sep 2015 · Radiotherapy and Oncology
[Show abstract][Hide abstract] ABSTRACT: We described clinical course of a 24-year-old woman with 3p deletion syndrome associated with cerebellar hemangioblastoma at the age of 16years old. She presented dysmorphic facial features, growth retardation and severe psychomotor retardation associated with 3p deletion syndrome. We identified de novo 3p deletion encompassing p25 by using array-based comparative genomic hybridization, where causative gene of von Hippel-Lindau (VHL) disease located. Surgical therapy for cerebellar hemangioblastoma was performed, and histological examination was consistent in cerebellar hemangioblastoma. She showed no other tumors associated VHL disease till 24years old. This is the first case report of a patient with 3p deletion syndrome whose cerebellar hemangioblastoma may be associated with VHL disease. Repeat imaging studies were recommended for the patients with 3p deletion syndrome.
No preview · Article · Sep 2015 · Brain & development
[Show abstract][Hide abstract] ABSTRACT: After the drainage of chronic subdural hematomas (CSDHs), residual isolated deep-seated hematomas (IDHs) may recur. We introduce intraoperative ultrasonography to detect and remove such IDHs. Intraoperative ultrasonography is performed with fine transducers introduced via burr holes. Images obtained before dural opening show the CSDHs, hyper- and/or hypoechoic content, and mono- or multilayers. Images are also acquired after irrigation of the hematoma under the dura. Floating hyperechoic spots (cavitations) on the brain cortex created by irrigation confirm the release of all hematoma layers; areas without spots represent IDHs. Their overlying thin membranes are fenestrated with a dural hook for irrigation. Ultrasonographs were evaluated in 43 CSDHs (37 patients); 9 (21%) required IDH fenestration. On computed tomography scans, 17 were homogeneous-, 6 were laminar-, 16 were separated-, and 4 were trabecular type lesions. Of these, 2 (11.8%), 3 (50%), 4 (25%), and 0, respectively, manifested IDHs requiring fenestration. There were no technique-related complications. Patients subjected to IDH fenestration had lower recurrence rates (11.1% vs. 50%, p = 0.095) and required significantly less time for brain re-expansion (mean 3.78 ± 1.62 vs. 18 ± 5.54 weeks, p = 0.0009) than did 6 patients whose IDHs remained after 48 conventional irrigation and drainage procedures. Intraoperative ultrasonography in patients with CSDHs facilitates the safe release of hidden IDHs. It can be expected to reduce the risk of postoperative hematoma recurrence and to shorten the brain re-expansion time.
[Show abstract][Hide abstract] ABSTRACT: Background:
Facial nerve schwannomas are rare lesions that constitute only 0.8% of all intrapetrous mass lesions. The least frequent lesions are tumors originating in the greater petrosal nerve (GPN). We present a case of a GPN schwannoma with temporal lobe edema in which the patient was operated on using an extradural and intradural approach to prevent complications.
A 66-year-old woman with vertigo and abnormal magnetic resonance imaging findings was referred to our department. Computed tomography scan revealed an isodense subtemporal mass with partial rim calcification and petrosal bone apex erosion. Magnetic resonance imaging confirmed a 22-mm left middle fossa lesion with heterogeneous enhancement and edema of the temporal lobe. A left temporal craniotomy to the middle fossa was performed. The initial extradural exploration revealed the tumor to be in the Glasscock triangle, mainly involving the location of the GPN. The tumor was removed through an intradural approach in piecemeal fashion. Finally, using an extradural and intradural middle fossa approach, the tumor was totally removed, leaving the capsule on the middle fossa floor with continuous facial nerve monitoring. The postoperative course was uneventful without complications of xerophthalmia and facial palsy.
GPN schwannomas are very rare lesions. The extradural and intradural middle fossa approach was used to preserve the tumor capsule around the GPN. Using this technique, one can safely protect the geniculate ganglion and the GPN.
No preview · Article · Sep 2015 · World Neurosurgery
[Show abstract][Hide abstract] ABSTRACT: i>Objective :When employing the lateral suboccipital approach, the thin dura shrinks due to the drying effect of illumination and air exposure, and dural substitutes are often needed for closure. We developed a new technique involving dural moisturizing with fibrin glue coating that facilitates primary dural closure. Patients and Methods :We used this technique in 12 adults who underwent the lateral suboccipital approach for 5 hemifacial spasms, 3 trigeminal neuralgias, 2 cerebellopontine meningiomas, 1 vestibular schwannoma, and 1 vertebral artery aneurysm. Fibrin glue was sprayed on the outer surface before opening the dura, and additionally sprayed on the inner surface of the reflected dural flap after opening the dura. After the intradural procedures the dura was closed with the usual knotted sutures. Results :Dural closure was performed 65-340 minutes(mean:161.9 minutes)post-durotomy. This technique resulted in primary dural closure with a sufficient area of preserved dura in all but one patient. In this patient, the dura shrank due to coagulation of the dural attachment to the meningioma for which a small autologous substitute was required. There were no procedure-related complications such as cerebrospinal fluid leakage and meningitis. Conclusions :Dural moisturizing with fibrin glue coating is simple, protects the dura from drying and shrinkage, and facilitates primary dural closure in patients undergoing the lateral suboccipital approach.
No preview · Article · Aug 2015 · No shinkei geka. Neurological surgery
[Show abstract][Hide abstract] ABSTRACT: As cerebrovascular anastomosis is performed in moist conditions that may impede precise manipulations, surgeons must undergo extensive preoperative training. We developed a simple moist-condition training method. It involves placing a free-floating inner platform hosting an artery from a chicken wing in an outer container filled with tap water to just below the specimen. Trainees performed anastomosis under magnification. Training sessions mimicked difficulties encountered during operations such as poor visibility of the lumen and problems handling the sutures. A retrospective comparison of 100 wet- and 100 dry-condition training sessions for end-to-side anastomoses with 8 stitches showed that under moist condition the time required for the entire procedure was significantly longer (17.8 ± 2.1 vs. 15.3 ± 2.1 min, p < 0.01) and the incidence of wrong stitching was greater (0.38 vs. 0%, p = 0.04). In 8 cases after introducing moist-condition training, the time required in superficial temporal artery to middle cerebral artery bypass surgery was significantly shorter than 8 cases before introducing the training (32.3 ± 5.6 min vs. 48.3 ± 15.9 min, p = 0.01). Incidence of wrong stitches was less in cases after introducing moist-condition training (2.7 vs. 7.4%, p = 0.10). Those indicate that moist-condition training is a useful and practical step and a bridge between training for basic manipulations under dry conditions and actual surgery.
[Show abstract][Hide abstract] ABSTRACT: Objectives The one-piece supraorbital approach is a rational approach for the removal of orbital tumors. However, cutting the roof through the orbit is often difficult. We modified the technique to facilitate the osteotomy and improve the cosmetic effect. Design Three burr holes are made: the first, the MacCarty keyhole (burr hole 1), exposes the anterior cranial fossa and orbit; the second is placed above the supraorbital nerve (burr hole 2); and the third on the superior temporal line. Through burr hole 2, a small hole is created on the roof, 10 mm in depth. Next the roof is rongeured through burr hole 1 toward the preexisting small hole. Seamless osteotomies using a diamond-coated threadwire saw and the preexisting four holes are performed. Lastly the flap is removed. On closure, sutures are passed through holes in the cuts made with the threadwire saw, and tied. Results We applied our technique to address orbital tumors in two adult patients. The osteotomies in the roof were easy, and most parts of the roof were repositioned. Conclusions Our modification results in orbital osteotomies with greater preservation of the roof. Because the self-fitting flap does not require the use of fixation devices, the reconstruction is cosmetically satisfactory.
No preview · Article · Jun 2015 · Journal of Neurological Surgery, Part B: Skull Base
[Show abstract][Hide abstract] ABSTRACT: Human chorionic gonadotropin (hCG) production has been utilized as a diagnostic marker for germinoma with syncytiotrophoblastic giant cells (STGC) and choriocarcinoma. Elevated hCG in germinoma is considered to predict less favorable prognosis, and an intensive treatment strategy may accordingly be applied. However, there is some evidence that any germinoma may produce hCG to varying extent. We investigated mRNA expression of the hCG β subunit (hCGβ) using real time quantitative polymerase chain reaction in 94 germ cell tumors (GCTs). Most (93.3 %) GCTs showed higher expression levels compared with that of normal brain tissue (1.09 × 10(0)-1.40 × 10(5) fold). The expression was the highest in GCTs which harbor choriocarcinoma or STGC components. The expression level of hCGβ in germinoma was highly variable (1.09 × 10(0)-5.88 × 10(4) fold) in linear but not bimodal distribution. hCG concentrations in serum and CSF correlated with gene expression, especially when GCTs with single histological component were analyzed separately. The expression was not significantly associated with recurrence in pure germinoma. These results suggest that the serum/CSF hCG levels may need to be interpreted with caution as most GCTs appear to have the capacity of producing hCG irrespective of their histology. The clinical significance of ubiquitous hCG expression in GCTs needs further investigation.
No preview · Article · May 2015 · Journal of Neuro-Oncology
[Show abstract][Hide abstract] ABSTRACT: Monitoring of the intraoperative auditory brainstem response (ABR) is a less invasive, easy, and useful method for hearing preservation in patient undergoing cerebellopontine angle surgery such as microvascular decompression (MVD) and excision of an acoustic neurinoma The ABR is tolerant of both inhalation and intravenous anesthesia However, ABR recordings are highly susceptible to electrical noise from surgical devices. Therefore, for ABR recordings to be reliable, noise must be minimized and appropriate evaluation of waveform changes is critical. Electrode setting with low contact impedance and bilateral derivation effectively address these issues. Prolongation of the wave V latency alerts to surgical stress on the cochlear nerve due to nerve stretching from cerebellar retraction. According to Sekiya the surgeon performing MVD or acoustic neurinoma excision should be warned as soon as latency prolongation exceeds 1.5 msec or even less than 0.5 msec, respectively. However, hearing was preserved in some patients with false-positive results with respect to intraoperative wave V diminution. To use it as a useful intraoperative modality, the characteristics of ABR must be understood.
No preview · Article · May 2015 · Masui. The Japanese journal of anesthesiology
[Show abstract][Hide abstract] ABSTRACT: Background: The aim of this study was to clarify the degree of information provision to children with brain tumors, factors influencing this provision, and the relationship between this provision and psychosocial consequences. Methods: A total of 157 parents completed a questionnaire on the degree of information provision to their children and sociodemographic and medical characteristics. Parents and their children completed subscales of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module. Relevant factors were investigated using ordinal logistic regression analysis and compared with PedsQL scores by degree of information provision with adjustment for age. Results: The majority of children aged 2-4 years received a low level of information only in regard to medical procedure and preparation. The majority of children aged 5-11 years were I. Sato et al. 452 provided information regarding disease symptoms and treatment, but not actual diagnosis. Approximately half of children aged 12-18 years were provided detailed information including their actual diagnosis. Older children generally received more information regarding their disease (odds ratio [OR] = 1.3 per 1 year old, P < 0.001), while children with intellectual disability received less (OR = 0.2, P = 0.006). The provision of information did not worsen scores for Procedural Anxiety , Treatment Anxiety, Worry, or Communication. Conclusions: To our knowledge, this is the first report on the degree of information provision to children with brain tumors. Parents of children with brain tumors in Japan provide information dependent on age and intellectual level. The disclosure of information to children regarding their disease might affect their trust of medical and health care professionals.
Full-text · Article · Apr 2015 · Open Journal of Nursing
[Show abstract][Hide abstract] ABSTRACT: This retrospective study was aimed to compare the perioperative complications for internal carotid artery stenosis (ICS) in a Japanese single institute between the use of carotid artery stenting (CAS) alone or the use of an appropriate individualized treatment method allowing either carotid endarterectomy (CEA) or CAS based on patient risk factors. Based on the policy at our hospital, only CAS was performed on patients (n = 33) between January 2005 and November 2009. From December 2009 to December 2012, either CEA or CAS (tailored treatment) was selected for patients (n = 61) based on individual patient risk factors. CEA was considered the first-line treatment in all cases. In high-risk CEA cases, CAS was performed instead (n = 11), whereas in low-risk CEA cases, CEA was performed (n = 19). Further, in moderate-risk CEA cases based on own criteria, CAS was considered first, whereas for high-risk CAS cases, CEA was performed (n = 17). For low-risk CAS cases, CAS was performed (n = 9). Perioperative clinical complications (any stroke, myocardial infarction, or death within 30 days) were compared between both periods. Significantly reduced perioperative complications were observed during the tailored period (4/61 sites, 6.6%) as compared with the CAS period (8/33 sites, 24.2%) [Fisher's exact test p = 0.022; odds ratio, 4.56 (CAS/tailored); 95% confidence interval, 1.26-16.5]. Selecting an appropriate individualized treatment method according to patient risk factors, as opposed to adhering to a single treatment approach such as CAS, may contribute to improved overall outcomes in patients with ICS.
Full-text · Article · Feb 2015 · Neurologia medico-chirurgica
[Show abstract][Hide abstract] ABSTRACT: Glioblastoma is the most malignant human brain tumor and has a dismal prognosis; however, some patients show long-term survival. The interaction between the costimulatory molecule OX40 and its ligand OX40L generates key signals for T-cell activation. The augmentation of this interaction enhances antitumor immunity. In this present study, we explored whether OX40 signaling is responsible for antitumor adaptive immunity against glioblastoma and also established therapeutic antiglioma vaccination therapy.
Tumor specimens were obtained from patients with primary glioblastoma (n = 110) and grade III glioma (n = 34). Quantitative polymerase chain reaction (PCR), flow cytometry, and immunohistochemistry were used to analyze OX40L expression in human glioblastoma specimens. Functional consequences of OX40 signaling were studied using glioblastoma cell lines, mouse models of glioma, and T cells isolated from human subjects and mice. Cytokine production assay with mouse regulatory T cells was conducted under hypoxic conditions (1.5% O2).
OX40L mRNA was expressed in glioblastoma specimens and higher levels were associated with prolonged progression-free survival of patients with glioblastoma, who had undergone gross total resection. In this regard, OX40L protein was expressed in A172 human glioblastoma cells and its expression was induced under hypoxia, which mimics the microenvironment of glioblastoma. Notably, human CD4 T cells were activated when cocultured in anti-CD3-coated plates with A172 cells expressing OX40L, as judged by the increased production of interferon-γ. To confirm the survival advantage of OX40L expression, we then used mouse glioma models. Mice bearing glioma cells forced to express OX40L did not die during the observed period after intracranial transplantation, whereas all mice bearing glioma cells lacking OX40L died. Such a survival benefit of OX40L was not detected in nude mice with an impaired immune system. Moreover, compared with systemic intraperitoneal injection, the subcutaneous injection of the OX40 agonist antibody together with glioma cell lysates elicited stronger antitumor immunity and prolonged the survival of mice bearing glioma or glioma-initiating cell-like cells. Finally, OX40 triggering activated regulatory T cells cultured under hypoxia led to the induction of the immunosuppressive cytokine IL10.
Glioblastoma directs immunostimulation or immunosuppression through OX40 signaling, depending on its microenvironment.
[Show abstract][Hide abstract] ABSTRACT: Transdural anastomosis (TA) from the middle meningeal arteries (MMAs) to the brain is important in maintaining cerebral blood flow in patients with Moyamoya disease. A 16-year-old adolescent girl presented with a transient ischemic attack. Preoperative cerebral angiography revealed TA from the MMA. During surgery, the MMA was exposed on the dural surface directly under the burr hole. Measurement of flow velocity in the MMA with an ultrasonic blood flowmeter revealed increased diastolic flow velocity. As the MMA was assumed to contribute to TA, a new burr hole was made to preserve the MMA, and a bone flap was prepared. Direct and indirect bypass surgeries were performed. Electrocoagulation was not applied to the MMA associated with TA, but the artery was compressed with gelfoam containing fibrin glue to achieve hemostasis. Postoperatively, no evidence of cerebral infarction was detected. Determining which of several MMAs exposed in the surgical field is associated with TA can be difficult. However, measurement of flow velocity with an ultrasonic blood flowmeter to confirm increased flow velocity in the diastolic phase is useful for confirming the presence or absence of TA from the extracranial arteries including the MMA.