The Clinical Implications of Spontaneous Hemorrhage in Vestibular Schwannomas.
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ABSTRACT:
SUBMITTER: Hong CS
PROVIDER: S-EPMC8289498 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them. In order to find target to fight against vestibular schwannoma, we performed an analysis of gene expression by microarrays.
2013-03-01 | E-GEOD-39645 | biostudies-arrayexpress
Project description:Vestibular schwannomas show a large variation in growth rate, making prediction and anticipation of tumor growth difficult. More accurate prediction of clinical behavior requires better understanding of tumor biological factors influencing tumor progression. Biological processes like intratumoral hemorrhage, cell proliferation, microvessel density, and inflammation were analyzed in order to determine their role in vestibular schwannoma development. Tumor specimens of 67 patients surgically treated for a histologically proven unilateral vestibular schwannoma were studied. Preoperative magnetic resonance imaging (MRI) scans were used to determine tumor size and to classify tumors as homogeneous, inhomogeneous, and cystic. Immunohistochemical studies evaluated cell proliferation (histone H3 and Ki-67), microvessel density (CD31), and inflammation (CD45 and CD68). Intratumoral hemorrhage was assessed by hemosiderin deposition. The expression patterns of these markers were compared with tumor size, tumor growth index, MRI appearance, patients' age, and duration of symptoms. No relation between cell proliferation and clinical signs of tumor volume increase or MRI appearance was found. Intratumoral hemosiderin, microvessel density, and inflammation were significantly positively correlated with tumor size and the tumor growth index. Cystic and inhomogeneous tumors showed significantly more hemosiderin deposition than homogeneous tumors. The microvessel density was significantly higher in tumors with a high number of CD68-positive cells. The volume increase of vestibular schwannomas is not based on cell proliferation alone. Factors like intratumoral bleeding, (neo)vascularization, and intensity of the inflammatory reaction also influence tumor volume.
| S-EPMC3371334 | biostudies-literature
Project description:Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them.
2013-03-01 | GSE39645 | GEO
Project description:Vestibular schwannomas (VSs) grow in the region where the energy from mobile phone use is absorbed. We examined the associations of VSs with mobile phone use. This study included 119 patients who had undergone surgical tumor removal. We used two approaches in this investigation. First, a case-control study for the association of mobile phone use and incidence of VSs was conducted. Both cases and controls were investigated with questions based on INTERPHONE guidelines. Amount of mobile phone use according to duration, daily amount, and cumulative hours were compared between two groups. We also conducted a case-case study. The location and volume of the tumors were investigated by MRI. Associations between the estimated amount of mobile phone use and tumor volume and between the laterality of phone use and tumor location were analyzed. In a case-control study, the odds ratio (OR) of tumor incidence according to mobile phone use was 0.956. In the case-case study, tumor volume and estimated cumulative hours showed a strong correlation (r(2)?=?0.144, p?=?0.002), and regular mobile phone users showed tumors of a markedly larger volume than those of non-regular users (p?<?0.001). When the analysis was limited to regular users who had serviceable hearing, laterality showed a strong correlation with tumor side (OR?=?4.5). We found that tumors may coincide with the more frequently used ear of mobile phones and tumor volume that showed strong correlation with amount of mobile phone use, thus there is a possibility that mobile phone use may affect tumor growth.
| S-EPMC3907669 | biostudies-literature
Project description:The study was conducted to analyze outcomes following surgical management of large and giant vestibular schwannomas and management options for residual disease. This retrospective case note study includes patients who had undergone microsurgical resection of sporadic, large, or giant vestibular schwannomas from 1986 to 2008. Tumors are classified as large if the largest extracanalicular diameter was 3.5 cm or greater and giant if 4.5 cm or greater. The study included 45 patients (33 large, 12 giant tumors), mean tumor size 4.1 cm. Total excision was achieved in 14 cases (31.1%), near-total in 26 (57.8%), and subtotal in 5 (11.1%). Facial nerve outcome was House-Brackmann Grade I/II in 25 cases (55.6%), III/IV in 16 (35.6%), and V/VI in 4 (8.9%). No recurrence has been detected in those undergoing a complete resection. No residual tumor growth been observed in 15 of 26 who underwent near-total resection (57.7%). Of 11 patients, 10 received further treatment as their residual tumors showed growth. In the subtotal excision group, one patient died, three have demonstrated no growth, and one residual tumor has grown slightly but not required intervention. Optimal management for patients with large or giant vestibular schwannomas has yet to be determined. Management decisions must balance long term function with tumor control.
| S-EPMC3312131 | biostudies-other
Project description:Vestibular schwannomas (VSs) are the most common tumours of the cerebellopontine angle. Ninety-five percent of people with VS present with sensorineural hearing loss (SNHL); the mechanism of this SNHL is currently unknown. To establish the first model to study the role of VS-secreted factors in causing SNHL, murine cochlear explant cultures were treated with human tumour secretions from thirteen different unilateral, sporadic VSs of subjects demonstrating varied degrees of ipsilateral SNHL. The extent of cochlear explant damage due to secretion application roughly correlated with the subjects' degree of SNHL. Secretions from tumours associated with most substantial SNHL resulted in most significant hair cell loss and neuronal fibre disorganization. Secretions from VSs associated with good hearing or from healthy human nerves led to either no effect or solely fibre disorganization. Our results are the first to demonstrate that secreted factors from VSs can lead to cochlear damage. Further, we identified tumour necrosis factor alpha (TNFα) as an ototoxic molecule and fibroblast growth factor 2 (FGF2) as an otoprotective molecule in VS secretions. Antibody-mediated TNFα neutralization in VS secretions partially prevented hair cell loss due to the secretions. Taken together, we have identified a new mechanism responsible for SNHL due to VSs.
| S-EPMC4686978 | biostudies-literature
Project description:Objective Large vestibular schwannomas rarely present in pregnant women. Diagnosis and management of these tumors during pregnancy present a therapeutic challenge. Methods A 20-year-old primigravida woman at 26 weeks' gestation was transferred to our facility with gait imbalance, left facial weakness, left ear hearing loss, and recent nausea and vomiting. Magnetic resonance imaging revealed a large left cerebellopontine angle mass with extension into the left internal auditory canal and compression of the fourth ventricle resulting in mild hydrocephalus. The patient was admitted with a plan for early delivery at 32 weeks followed by tumor resection. One week later, the patient's headache and neurologic symptoms worsened due to increased hydrocephalus; a ventriculoperitoneal shunt was placed. The next day, an emergent cesarean delivery was performed due to worsening respiratory status. Four days later, a tracheostomy and percutaneous endoscopic gastrostomy tube were placed due to dysphagia. Eight days after the delivery, the mass was resected with a left retrosigmoid approach without complications. Immunohistochemistry confirmed vestibular cellular schwannoma on cranial nerve VIII showing unusually high mitotic activity. Results The patient was discharged to inpatient rehabilitation on postoperative day 12 without new neurologic deficit. At 1 month, the patient was swallowing without aspiration. Her facial sensation had returned, her facial weakness remained stable, and her gait was significantly improved. Conclusion If the patient is neurologically stable, the best option is to delay resection until after delivery. If resection is necessary during pregnancy, the optimal time is during the second trimester.
| S-EPMC4078191 | biostudies-other
Project description:We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [68Ga]Pentixafor. Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [68Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients. Results: [68Ga]Pentixafor PET/CT was visually positive in all cases. SUVmean and SUVmax were 3.0 ± 0.3 and 3.8 ± 0.4 and TBRmean and TBRmax were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors. Conclusion: Non-invasive imaging of CXCR4 expression using [68Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.
| S-EPMC6581743 | biostudies-literature
Project description:BackgroundAlthough the natural history of vestibular schwannomas (VS) has been previously studied, few studies have investigated associated epidemiological factors, primarily because of the lack of large available cohorts.ObjectiveThe objective of this study was to perform a multi-scale geographical analysis of the period prevalence of VS in West Scotland from 2000 to 2015.MethodsAdults diagnosed with sporadic VS were identified through the National Health Services of West Scotland database and geocoded to the unit postcode. To assess whether the cohort of VS cases could be pooled into a period prevalence measure, the locations of VS cases were analyzed by sex using Cross-L and Difference-K functions. VS period prevalence was examined at two aggregate spatial scales: the postcode district and a coarser scale of NHS Health Boards. The spatial structure of period prevalence within each level of spatial aggregation was measured using univariate global and local Moran's I. Bivariate local Moran's I was used to examine the between-scale variability in period prevalence from the postcode district level to the NHS Health Boards levels. Prior to spatial autocorrelation analyses, the period prevalence at the postcode district was tested for stratified spatial heterogeneity within the NHS Health Boards using Wang's q-Statistic.ResultsA total of 512 sporadic VS were identified in a population of over 3.1 million. Between 2000 and 2015, VS period prevalence was highest within the NHS Health Boards of Greater Glasgow and Clyde, Ayrshire and Arran and the Western Isles. However, at the NHS scale, period prevalence exhibited no spatial autocorrelation globally or locally. At the district scale, Highland exhibited the most unusual local spatial autocorrelation. Bivariate local Moran's I results indicated general stability of period prevalence across the postcode district to Health Boards scales. However, locally, some postcode districts in Greater Glasgow and Clyde, Ayrshire and Arran exhibited unusually low district to zone spatial autocorrelation in period prevalence, as did the southern parts of the Western Isles. Some unusually high period prevalence values between the postcode district to Health Board scale were found in Tayside, Forth Valley and Dumfries and Galloway.ConclusionGeographic variability in VS in West Scotland was identified in this patient population, showing that there are areas, even remote, with unusually high or low period prevalence. This can be partially attributed to links between primary and tertiary care. Potential genetic or environmental risk factors that may contribute to geographic variation in this disease within Scotland are also a possibility but require further investigation.
| S-EPMC5426599 | biostudies-literature
Project description:The classical middle cranial fossa approach (MCFA) for vestibular schwannoma (VS) removal often requires a large incision and craniotomy, excessive temporal lobe manipulation, and a longer recovery. We describe a keyhole MCFA (KMCFA) with endoscopic assistance that allows for adequate access with minimal temporal lobe manipulation, resulting in a fast recovery and an invisible scar. Eight sides of four cadaveric heads were dissected through the endoscopic-assisted KMCFA to access the internal auditory canal (IAC). Furthermore, five patients with intracanalicular VS underwent tumor removal with the endoscopic-assisted KMCFA. During the endoscopic-assisted KMCFA with fine instruments, a 3-cm supra-auricular incision and a 2-cm diameter keyhole craniotomy achieved exposure of the entire length of the IAC in all cadaveric dissections without unintended violation of the cochlea, semicircular canal, and facial nerve. The gross tumor was totally removed in five patients with no major postoperative complications. The surgical time was reduced, the hearing outcomes were similar to those of the classical MCFA, and the scar was invisible 1 month after the surgery. The endoscopic-assisted KMCFA permits intracanalicular VS removal in a safe, efficient, and cosmetic way. For small intracanalicular VSs, this approach can replace the classical MCFA when indicated.
| S-EPMC9101160 | biostudies-literature