Sporadic Vestibular Schwannoma Research Articles

The Role of Endoscopy in the Resection of Sporadic Vestibular Schwannomas: A Systematic Review of Surgical Outcomes.

Vestibular schwannomas (VS) are benign intracranial tumors originating from the vestibular division of the eighth cranial nerve. Treatment options include microsurgery, radiotherapy, and surveillance. Endoscopy is becoming more widely used as an adjunct in skull base surgery and may influence outcomes in surgically managed VS. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies involving endoscope-assisted and fully endoscopic procedures for sporadic VS resection were identified. Facial nerve function, hearing preservation, extent of resection, and complications were analyzed. Thirty-one studies were included (27 endoscope-assisted, four fully endoscopic). Subgroup analyses were performed to assess outcomes according to tumor size and surgical approach. Overall, endoscopic facial nerve preservation rates were comparable to microsurgical treatment. A subgroup analysis suggested that functional facial nerve preservation rates may be higher when endoscopic assistance is used for smaller (Koos I-II) tumors using the retrosigmoid or translabyrinthine approach. The gross total resection rate for small tumors was higher in retrosigmoid ES-assisted microsurgery (96.2%) compared to rates in the literature for the standard, open retrosigmoid approach. Hearing outcomes were more variable and were under-reported. Current data suggest that ES-assisted resection of sporadic VS is not inferior to microsurgical resection with respect to facial nerve outcomes and extent of resection. However, some ES series report poor hearing outcomes, which are under-reported in the literature. Further prospective studies are required to ascertain if endoscopic assistance can improve outcomes for VS resection, particularly for smaller (Koos I-II) tumors.

Typical 22q11.2 deletion syndrome appears to confer a reduced risk of schwannoma

PurposeThe LZTR1 gene has been associated with schwannomatosis tumor predisposition and is located in a region that is deleted in the great majority (89%) of patients with 22q11.2 deletion syndrome (22q11.2DS). Since it is known that approximately 1 in 500 people in the general population will develop a sporadic schwannoma and there are no reports of the occurrence of schwannoma in 22q11.2DS, we investigated whether whole-gene deletion of LZTR1 occurs in schwannomatosis and assessed the risk of schwannoma in 22q11.2DS. MethodsWe assessed the genetic testing results for LZTR1-associated schwannomatosis and the clinical phenotypes of patients with 22q11.2DS. ResultsThere were no reports of schwannoma in over 1,500 patients with 22q11.2DS. In addition, no patients meeting clinical diagnostic criteria for schwannomatosis had a whole-gene deletion in LZTR1. Only 1 patient in 110 with an apparently sporadic vestibular schwannoma had a constitutional whole-gene deletion of LZTR1. ConclusionPeople with a large 22q11.2 deletion may have a reduced risk of developing a schwannoma compared to the general population. [Display omitted]

Global Incidence of Sporadic Vestibular Schwannoma: A Systematic Review

Ubiquitous throughout the literature and during patient counseling, vestibular schwannoma is often quoted to affect about 1 per 100,000 people. Yet, reports from distinct international populations suggest that the incidence is likely much higher. The objective of the current work was to systematically characterize the global incidence of sporadic vestibular schwannoma. Scopus, Embase, and PubMed. Population-based studies reporting incidence rates of sporadic vestibular schwannoma between January 2010 and August 2020 were searched with language restrictions requiring reports to be published in Chinese, English, German, Italian, or Spanish. The protocol was registered with PROSPERO (CRD42021228208) prior to commencement of data collection. PRISMA guidelines for transparent reporting of systematic reviews were followed. Among 424 citations, 6 publications covering 4 distinct populations from Denmark, the Netherlands, Taiwan, and the United States met inclusion criteria. Most recent incidence rates of among all ages ranged between 3.0 and 5.2 per 100,000 person-years. Highest incidence rates were reported among patients aged ≥70 years, peaking at 20.6 per 100,000 person-years. One study from the United States reported the incidence of asymptomatic, incidentally diagnosed tumors at a rate of 1.3 per 100,000 person-years from 2012 to 2016. Recent international incidence rates of sporadic vestibular schwannoma exceed the commonly quoted "1 per 100,000" figure by up to 5-fold among all ages and by up to 20-fold among age groups at highest risk. Based on modern incidence rates, the lifetime prevalence of developing sporadic vestibular schwannoma likely exceeds 1 per 500 persons.

Is Cochlear Implantation Effective for Auditory Rehabilitation Following Vestibular Schwannoma Treatment?

Is Cochlear Implantation Effective for Auditory Rehabilitation Following Vestibular Schwannoma Treatment?

Early phase clinical studies of AR-42, a histone deacetylase inhibitor, for neurofibromatosis type 2-associated vestibular schwannomas and meningiomas.

ObjectivesTwo pilot studies of AR‐42, a pan‐histone deacetylase inhibitor, in human neurofibromatosis type 2 (NF2), vestibular schwannomas (VS), and meningiomas are presented. Primary endpoints included safety, and intra‐tumoral pharmacokinetics (PK) and pharmacodynamics (PD).MethodsPilot 1 is a subset analysis of a phase 1 study of AR‐42 in solid tumors, which included NF2 or sporadic meningiomas. Tumor volumes and treatment‐related adverse events (TRAEs) are reported (NCT01129193).Pilot 2 is a phase 0 surgical study of AR‐42 assessing intra‐tumoral PK and PD. AR‐42 was administered for 3 weeks pre‐operatively. Plasma and tumor drug concentrations and p‐AKT expression were measured (NCT02282917).ResultsPilot 1: Five patients with NF2 and two with sporadic meningiomas experienced a similar incidence of TRAEs to the overall phase I trial. The six evaluable patients had 15 tumors (8 VS, 7 meningiomas). On AR‐42, tumor volume increased in six, remained stable in eight, and decreased in one tumor. The annual percent growth rate decreased in eight, remained stable in three, and increased in four tumors. Pilot 2: Four patients with sporadic VS and one patient with meningioma experienced no grade 3/4 toxicities. Expression of p‐AKT decreased in three of four VS. All tumors had higher AR‐42 concentrations than plasma.ConclusionsAR‐42 is safe. Tumor volumes showed a mixed response, but most slowed growth. On a 40‐mg regimen, drug concentrated in tumors and growth pathways were suppressed in most tumors, suggesting this may be a well‐tolerated and effective dose. A phase 2 study of AR‐42 for NF2‐associated tumors appears warranted.Level of Evidence1b, 4.

Microsurgical treatment of symptomatic vestibular schwannomas in patients under 40: different results before and after age of 30.

In 10-15% of cases of vestibular schwannoma (VS), age at diagnosis is 40years or less. Little is known about the differences in natural history, surgical findings, and postoperative outcomes of such younger patients as compared to those of greater age. To analyze clinical and surgical and imaging data of a consecutive series of n = 50 patients with unilateral sporadic VS, aged 40years or younger - separated in a very young group (15-30years) and a moderately young group (31-40years). Retrospective case series. Fifty consecutive patients under 40years of age underwent microsurgical resection of unilateral sporadic VS via the retrosigmoid approach. The study cohort was subdivided into two groups according to the age range: group A, age range 15-30years (n = 23 patients), and group B, age range 31-40years (n = 27 patients). The adherence of VS capsule to surrounding nervous structures and the tendency of the tumors to bleed were evaluated by reviewing video records; the course of the FN in relation to the tumor's surface was assessed in each case. Microsurgical removal of tumor was classified as total (T), near total (residual tumor volume < 5%), subtotal (residual tumor volume 5-10%), or partial (residual tumor volume > 10%). Mean tumor size of entire cohort was 2.53 (range: 0.6-5.8) cm: 2.84cm in group A and 2.36cm in group B (p = NS). Facial nerve course and position within the cerebellopontine angle did not differ significantly between the two groups. At 6-month follow-up, FN functional outcome was HBI-II in 69.5% in group A, versus 96.3% in group B (p < .001). Hearing preservation was achieved in 60.0% of patients of group A and in 58.3% of group B (p = NS). Total and near-total resection was feasible in 95.6% of cases of group A and in 88.9% of group B (p = NS). Tumor capsule was tightly adherent to nervous structures in 69.6% patients of group A and in 22.2% of group B (p < .05). Significant bleeding was encountered in 56.5% of group A tumors, and in 29.6% of group B tumors (p < .01). Microsurgery of VS in patients aged 40 or less is associated with good functional results, and with high rates of total and near total tumor removal. Patients < 30years of age have more adherent tumor capsules. Furthermore, their tumors exhibit a tendency to larger sizes, to hypervascularization, to profuse intraoperative bleeding and they present worse long-term functional FN results when compared to patients in their fourth decade of life. Our limited experience seems to suggest that a near total resection in very young VS patients with large tumors should be preferred in adherent and hypervascularized cases, in order to maximize resection and preserve function.

Simultaneous Cochlear Implantation After Translabyrinthine Vestibular Schwannoma Resection: A Report of 41 Cases.

To study the auditory outcome of simultaneous translabyrinthine vestibular schwannoma (VS) resection and cochlear implantation (CI) after successful cochlear nerve preservation. A retrospective case series and patient questionnaire. Quaternary referral center for skull base pathologies. Patients with small (<2 cm) sporadic or neurofibromatosis 2 related tumors were included in this study. Vestibular schwannoma resection + simultaneous cochlear implantation. Audiological performance postimplantation and perceived patients' benefits. Forty-one patients were included. Thirty-three were sporadic VS and eight were neurofibromatosis 2. Auditory perception postimplantation was achieved in 33 patients (80.5%). At the last follow-up, 20 patients (48.8%) were users and 21 (51.2%) were nonusers. In the users' group, and after 1 year of implant activation, vowel identification was 75.3%, disyllabic word recognition 54%, sentence recognition 60.7%, and common phrase comprehension 61%, whereas in the nonusers' group and after 1 year of implant activation, vowel identification was 22.9%, disyllabic word recognition 14.8%, sentence recognition 15.3%, and common phrase comprehension 14%. Sixteen users were classified into 10 high performers, three intermediate performers, and three poor performers. In the user' group, the mean postimplantation pure tone average was 63.4 dB and the mean speech discrimination score was 63.7%. Simultaneous CI and VS resection is a viable option with many patients achieving auditory perception and nearly half the patients are CI users at long follow-up.

Retrospective Investigation of Contralateral Hearing Thresholds of Patients With Sporadic Vestibular Schwannoma.

The aim of this study was to investigate the contralateral hearing of patients with sporadic vestibular schwannoma (VS). Retrospective cohort study. Pure-tone audiograms of the contralateral ear from patients with a wait-and-scan strategy were compared to the ones who received therapy. Due to a possible bias caused by the therapy, hearing thresholds before and after radiotherapy or surgery were compared separately with the wait-and-scan group. From 1979 to 2017, 508 patients with sporadic VS could be included in the study. Of these, 240 received regular controls in the sense of wait-and-scan, 72 underwent radiotherapy (63 audiograms before and 43 after radiotherapy), and 196 had a surgery (186 audiograms before and 146 after surgery). Age-normalized hearing thresholds of the contralateral ear from patients with a wait-and-scan strategy were compared to ones who received therapy. In addition, hearing thresholds were compared to norm values. There was no evidence for a difference in the contralateral hearing of patients with sporadic VS between the wait-and-scan and therapy groups. The mean difference of hearing thresholds in our sample to norm values was found to be larger for the high frequencies and more pronounced in male patients. There was no evidence for a difference in the contralateral hearing loss of patients with sporadic VS between the wait-and-scan and therapy groups. However, there was some indirect indication of poorer contralateral hearing in all patients with sporadic VS compared to normative values.

Detection of early changes in the post-radiosurgery vestibular schwannoma microenvironment using multinuclear MRI

Stereotactic radiosurgery (SRS) is an established, effective therapy against vestibular schwannoma (VS). The mechanisms of tumour response are, however, unknown and in this study we sought to evaluate changes in the irradiated VS tumour microenvironment through a multinuclear MRI approach. Five patients with growing sporadic VS underwent a multi-timepoint comprehensive MRI protocol, which included diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE) MRI and a spiral 23Na-MRI acquisition for total sodium concentration (TSC) quantification. Post-treatment voxelwise changes in TSC, DTI metrics and DCE-MRI derived microvascular biomarkers (Ktrans, ve and vp) were evaluated and compared against pre-treatment values. Changes in tumour TSC and microvascular parameters were observable as early as 2 weeks post-treatment, preceding changes in structural imaging. At 6 months post-treatment there were significant voxelwise increases in tumour TSC (p < 0.001) and mean diffusivity (p < 0.001, repeated-measures ANOVA) with marked decreases in tumour microvascular parameters (p < 0.001, repeated-measures ANOVA). This study presents the first in vivo evaluation of alterations in the VS tumour microenvironment following SRS, demonstrating that changes in tumour sodium homeostasis and microvascular parameters can be imaged as early as 2 weeks following treatment. Future studies should seek to investigate these clinically relevant MRI metrics as early biomarkers of SRS response.

Outcomes of stereotactic radiosurgery in young adults with vestibular schwannomas.

Vestibular schwannomas (VSs) are comparatively rare in younger patients, and stereotactic radiosurgery (SRS) outcome data are limited. We aimed to evaluate long-term SRS outcomes concerning sporadic VSs in patients aged ≤ 40years. Of 383 patients with VS who had undergone SRS at our institution between 1990 and 2017, we retrospectively compared younger and older patients' tumor control and radiation-induced complication rates using case-control propensity score (PS) matching. The mean follow-up was 83 and 92months in older and younger patients, respectively. Compared with older patients, younger patients were more likely to have a history of resection (20% vs. 39%, p = 0.006) and be treated with higher marginal doses (median, 12Gy vs. 14Gy; p = 0.014). Cumulative 5- and 10-year tumor control rates were higher in older patients (97.7% and 93.9%, respectively) than in younger patients (90.2% and 85.4%, respectively, p = 0.024). After PS matching, younger patients' cumulative tumor control rates (93.6%, 85.4%, and 85.4% at 5, 10, and 15years, respectively) were similar to those of older patients (p = 0.411). No significant between-cohort differences in hearing preservation rates or other cranial nerve complications were observed. Two younger patients had malignant tumors several years post-SRS, with one patient having confirmed histological transformation. SRS is equally effective for younger and older patients. Complications other than hearing deterioration are uncommon. However, malignant transformation is possible, and long-term post-SRS surveillance MRI is important. These data are useful for decision-making involving young adults with VSs.

The SH3PXD2A-HTRA1 fusion transcript is extremely rare in Norwegian sporadic vestibular schwannoma patients

IntroductionVestibular schwannoma (VS) is a benign intracranial tumor in which the underlying genetics is largely uncertain, apart from mutations in the tumor suppressor gene NF2. Alternative tumorigenic mechanisms have been proposed, including a recurrent in-frame fusion transcript of the HTRA1 and SH3PXD2A genes. The gene product of the SH3PXD2A-HTRA1 fusion has been shown to promote proliferation, invasion and resistance to cell death in vitro and tumor growth in vivo. The aim of this study was to replicate the findings and to investigate the frequency of this fusion gene in another cohort of vestibular schwannoma patients.MethodsThe SH3PXD2A-HTRA1 transcript was synthesized in vitro using PCR and used as a positive control to assess the sensitivity of a real-time PCR assay. This real-time PCR assay was used to search for the presence of the fusion transcript in 121 Norwegian sporadic VS patients.ResultsThe real-time PCR assay showed a high sensitivity and was able to detect as low as ~ 5 copies of the fusion transcript. Out of the 121 investigated tumors, only 1 harbored the SH3PXD2A-HTRA1 fusion.ConclusionEven though the SH3PXD2A-HTRA1 fusion has been shown to be a driver of tumorigenesis, our results suggest that it is a rare event in our VS patients. Further investigation is warranted in order to elucidate whether our results represent an extreme, and if the fusion is present also in other neoplasms.

Adherence to Long-Term Follow-up in Patients With Sporadic Vestibular Schwannomas Managed With Serial Observation.

ObjectivesTo examine the long-term adherence to serial imaging of patients with sporadic vestibular schwannoma and analyze factors associated with being lost to follow-up.Study DesignRetrospective chart review with telephone interview.SettingSingle tertiary care center.MethodsPatients with a sporadic vestibular schwannoma and started on observational surveillance management between January 2005 and December 2010 were included. Demographic data, tumor size, hearing and vestibular changes, and follow-up length were recorded. Patient factors were analyzed for association with being lost to follow-up.ResultsIn total, 122 patients were included with a median length of follow-up of 5 months (range, 0-146). After initial surveillance, 22.1% (n = 27) of patients had a change in management to either microsurgery or radiosurgery. Of the remaining 77.9% (n = 95), nearly half (44.2%, n = 42) never returned for a second visit, and all but 3 were eventually lost to follow-up. There was no association between sex, race, age at diagnosis, initial tumor size, insurance status, household income, or driving distance to hospital and being lost to follow-up. Of 26 interviewed patients initially lost to follow-up, 11 (42.3%) sought care at another institution, 5 (19.2%) chose to no longer receive care, 1 (3.8%) had transportation difficulties, and 9 (36.4%) had poor understanding of their diagnosis or instructions.ConclusionsThe length of follow-up for patients undergoing surveillance of sporadic vestibular schwannoma varies widely, and patients are commonly lost to follow-up. Further efforts should be made to identify at-risk patients and provide adequate education to improve long-term surveillance.

A novel scoring system based on small vestibular schwannomas to determine consideration for cochlear implantation.

Simultaneous translabyrinthine tumor resection and cochlear implantation is a promising treatment method with hearing rehabilitation for sporadic vestibular schwannomas. Size of vestibular schwanomma, distance to modiolus, residual hearing and promontory stimulation electrical brainstem response audiometry are important preoperative predictive factors for determining a positive post tumour resection electrically evoked auditory brain stem response. The presence of an electrically evoked auditory brain stem response with an intracochlear test electrode after tumour resection was used to determine whether a patient received a cochlear implant Positive electrically evoked auditory brain stem responses measured with an intracochlear test electrode after tumour resection seem to correlate well with auditory perception with a cochlear implant.

Natural History of Growing Sporadic Vestibular Schwannomas During Observation: An International Multi-Institutional Study.

Active treatment of small- or medium-sized vestibular schwannoma during wait-and-scan management is currently recommended at most centers globally once growth is detected. The primary aim of the current study was to characterize the natural history of growing sporadic vestibular schwannoma during observation. Cohort study. Four tertiary referral centers across the United States and Denmark. Patients with two prior MRI scans demonstrating ≥2 mm of linear growth who continued observational management. Observation with serial imaging. Subsequent linear growth-free survival (i.e., an additional ≥2 mm of growth) following initial growth of ≥2 mm from tumor size at diagnosis. Among 3,402 patients undergoing observation, 592 met inclusion criteria. Median age at initial growth was 66 years (IQR 59-73) for intracanalicular tumors (N = 65) and 62 years (IQR 54-70) for tumors with cerebellopontine angle extension (N = 527). The median duration of MRI surveillance following initial detection of tumor growth was 5.2 years (IQR 2.4-6.9) for intracanalicular tumors and 1.0 year (IQR 1.0-3.3) for cerebellopontine angle tumors. For intracanalicular tumors, subsequent growth-free survival rates (95% CI; number still at risk) at 1, 2, 3, 4, and 5 years following the initial MRI that demonstrated growth were 77% (67-88; 49), 53% (42-67; 31), 46% (35-60; 23), 34% (24-49; 17), and 32% (22-47; 13), respectively. For cerebellopontine angle tumors, subsequent growth-free survival rates were 72% (68-76; 450), 47% (42-52; 258), 32% (28-38; 139), 26% (21-31; 82), and 22% (18-28; 57), respectively. For every 1 mm increase in magnitude of growth from diagnosis to tumor size at detection of initial growth, the HRs associated with subsequent growth were 1.64 (95% CI 1.25-2.15; p < 0.001) for intracanalicular tumors and 1.08 (95% CI 1.01-1.15; p = 0.02) for cerebellopontine angle tumors. Growth detected during observation does not necessarily portend future growth, especially for slowly growing tumors. Because early treatment does not confer improved long-term quality of life outcomes, toleration of some growth during observation is justifiable in appropriately selected cases.

Cochlear Implantation in Vestibular Schwannoma: A Systematic Literature Review.

Objective Ipsilateral cochlear implantation (CI) in vestibular schwannoma (VS) has been an emerging trend over the last two decades. We conducted the first systematic review of hearing outcomes comparing neurofibromatosis 2 (NF2) and sporadic VS undergoing CI. A comparison of the two populations and predictor of outcome was assessed. This is an update to a previously presented study. Data Sources Systemic data searches were performed in PubMed NCBI and Scopus by an academic librarian. No restrictions based on the year of publication were used. Study Selection Studies were selected if patients had a diagnosis of NF2 and a CI placed in the affected side with reports of hearing outcome. Two independent reviewers screened each abstract and full-text article. Data Extraction Studies were extracted at the patient level, and the assessment of quality and bias was evaluated according to the National Institutes of Health Quality Assessment Tool. Main Outcome Measures Outcome predictors were determined by using the chi-square test and Student's t -test. Results Overall, most CI recipients functioned in the high-to-intermediate performer category for both sporadic and NF2-related VS. Median AzBio (Arizona Biomedical Institute Sentence Test) was 72% (interquartile range [IQR]: 50) in NF2 patients and 70% (IQR: 7.25) in sporadic patients. Larger tumor size predicted a poorer final audiometric outcome. Conclusions Categorization of hearing outcome into superior performance and inferior performance based on sentence recognition revealed a generally good hearing outcome regardless of treatment or patient population. Select patients with sporadic and NF2 VS may benefit from CI.

The proteome of the human endolymphatic sac endolymph

The endolymphatic sac (ES) is the third part of the inner ear, along with the cochlea and vestibular apparatus. A refined sampling technique was developed to analyse the proteomics of ES endolymph. With a tailored solid phase micro-extraction probe, five ES endolymph samples were collected, and six sac tissue biopsies were obtained in patients undergoing trans-labyrinthine surgery for sporadic vestibular schwannoma. The samples were analysed using nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) to identify the total number of proteins. Pathway identification regarding molecular function and protein class was presented. A total of 1656 non-redundant proteins were identified, with 1211 proteins detected in the ES endolymph. A total of 110 proteins were unique to the ES endolymph. The results from the study both validate a strategy for in vivo and in situ human sampling during surgery and may also form a platform for further investigations to better understand the function of this intriguing part of the inner ear.

766 Endoscopic Surgery for Sporadic Vestibular Schwannoma Resection: A Systematic Review of Surgical Outcomes

Abstract Introduction Vestibular schwannomas (VS) are benign intracranial tumours originating from the vestibular division of the eighth cranial nerve. The mainstay of their surgical management is microsurgery, other options are radiotherapy or radiological monitoring. Endoscopy (ES) is becoming widely used in neurosurgery and may have a role in improving visualisation and outcomes by enhancing extent of resection, facial nerve, and hearing preservation in VS resection and describe the postoperative outcomes. Method The review was conducted according to the PRISMA guidelines and yielded 31 studies for inclusion. Systematic searches of literature databases were done for studies where endoscopic-assisted and/or endoscopic resection of VS were reported. Results ES facial nerve preservation rates (median 91.3%, range 39.0 - 100%) were comparable to microsurgical treatment. Hearing outcomes were more variable in ES series and were under-reported. A median gross total resection rate of 97.4% (61.0 - 100%) was achieved in the ES series. Conclusions Current data suggest that ES-assisted resection of sporadic VS is not inferior to microsurgical resection with respect to facial nerve outcomes and extent of resection. However, some ES series report poor hearing outcomes, which are under-reported in the literature.

Association of Metformin With Volumetric Tumor Growth of Sporadic Vestibular Schwannomas.

Recent research demonstrates a potential association between metformin use and reduced sporadic vestibular schwannoma (VS) growth in patients undergoing conservative observation. The current study was designed to elucidate the effect of metformin on tumor growth in sporadic VS using volumetric analyses. Retrospective cohort. Tertiary referral center. Patients with sporadic VS who elected initial conservative treatment with at least two serial magnetic resonance imaging (MRI) scans were included. Metformin use among patients with observed sporadic VS. Tumor growth, defined as an increase in volume of at least 20% from the initial MRI. A total of 361 patients were evaluated. Thirty-four patients (9%) had a diagnosis of diabetes at baseline. Nineteen patients (5%) were taking metformin at the time of the initial MRI. Metformin use was not significantly associated with a reduced risk of volumetric tumor growth in a univariable analysis in all patients undergoing observation for VS (hazard ratio [HR] 0.75; 95% confidence intervals [CI] 0.40-1.42; p = 0.38) or within the diabetic subset (HR 0.79; 95% CI 0.34-1.83; p = 0.58). Additionally, diabetes status, insulin dependence, hemoglobin A1c value, and metformin dose were not significantly associated with volumetric tumor growth. Despite promising initial results in several previous studies, our data suggest that metformin use does not significantly reduce the risk of volumetric tumor growth in sporadic VS.

Intraoperative facial nerve electromyography parameters to optimize postoperative facial nerve outcome in patients with large unilateral vestibular schwannoma.

Decision-making for large sporadic vestibular schwannomas (VS) resection guided by the intraoperative change in supramaximal facial nerve (FN) amplitude and latency response to optimize post-operative FN outcome. Prospectively study of 43 patients, from January to December 2018, of large sporadic VS with preoperative normal FN function at our center. Tumors were removed through retrosigmoid (81%) or translabyrinthine (19%) approaches with FN monitoring. Intraoperative pre- and post-VS resection supramaximal (2 mA) amplitude and latency responses at the proximal FN root were recorded. Total, near-/subtotal VS resections (TR, NTR, STR) were achieved in 51%, 38%, and 11% of tumors, respectively, guided by no more than 40% decrease in supramaximal amplitude. Pre- and post-resection supramaximal amplitude and latency responses were lower and longer, respectively, in NTR+STR than in TR. At day 8, FN function was grade I-II in 77% of patients and grade III-V in 23%, and after 6 months, it was in grade I-II in 95% and grade III in 5%, and there was no significant difference between TR and NTR+STR. Facial palsy occurred in older patients and in the case of severe FN adhesion. At day 8, pre- and post-resection supramaximal amplitude but not latency responses were different between FN grade III-V and grade I-II. Serviceable hearing was preserved in 28% of large VS. Intraoperative FN monitoring guided VS resection in large VS so that 49% retained some residual tumor. Accordingly, 95% good postoperative FN function and significant hearing preservation were achieved after 6 months.

COX2 expression is associated with preoperative tumor volume but not with volumetric tumor growth in vestibular schwannoma

ObjectiveVestibular schwannomas (VS) are benign slow growing tumors arising from the vestibular nerve. The role of cyclooxygenase 2 (COX2) in tumor development of growth has been addressed in a few studies with contradictory results and suggestions. We recently analyzed the immunohistochemical expression of COX2 in 1044 VS samples and described an association of higher COX2 expression with proliferation but found no influence by regular intake of acetylsalicylic acid. We now collected volumetric radiographic data of the preoperative tumor volume and growth to further test the role of COX2 in VS growth.MethodsPreoperative images of 898 primary sporadic vestibular schwannomas were assessed, and sufficient preoperative imaging was used for the volumetric measurement preoperative tumor volume (n = 747) and preoperative relative tumor growth (n = 171). Clinical parameters and results of the immunohistochemical expression of COX2 and MIB1 in resected tumor tissue samples were obtained from our prior study. ANOVA, CART-analysis and multivariate nominal logistic regression were used for statistical analysis.ResultsLarger preoperative tumor volumes were observed with tumors of younger patients (p = 0.0288) and with higher COX2 expression scores (p < 0.0001). Higher MIB1 expression was associated with smaller tumors (p = 0.0149) but with increased radiographic tumor growth (p = 0.0003). Patients of older age had tumors with slower growth rates (p = 0.0311). In the multivariate analysis only MIB1 expression was an independent significant factor regarding tumor growth (p = 0.0002).ConclusionsHigher expression of COX2 in schwannoma is associated with an increased preoperative tumor volume but not with radiographic tumor growth over time.