Long-Term Hearing Outcome For Vestibular Schwannomas After Microsurgery And Radiotherapy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Hearing loss is a common symptom associated with vestibular schwannoma (VS), either because of the tumor's effects on the cochlear nerve or due to active treatments such as surgery or stereotactic radiosurgery (SRS). Treatment decisions for VS are based on factors including tumor size, hearing status, patient symptoms, and institutional preference. The study aimed to investigate long-term auditory outcomes in VS patients undergoing active treatments with a hearing preservation intent. DATA SOURCES: A systematic literature review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching Scopus, Pubmed, and Web of Science databases from inception to January 2024. REVIEW METHODS: Studies meeting inclusion criteria, including a minimum 5-year follow-up and assessment of pre- and posttreatment hearing outcomes, were included. Pooled prevalence estimates for serviceable hearing after SRS and microsurgery were calculated using MetaXL software. Risk of bias assessment was performed with the Risk of Bias in Non-randomized Studies of Interventions tool. RESULTS: Nine studies met the inclusion criteria, with 356 patients included for analysis. The pooled prevalence of maintaining serviceable hearing after SRS at 10 years was 18.1% (95% confidence interval [CI]: 1.7%-43.3%), with wide prediction intervals indicating variability in outcomes. Microsurgery demonstrated a higher prevalence of maintaining long-term serviceable hearing, with a pooled estimate of 74.5% (95% CI: 63.5%-84.1%). CONCLUSION: This systematic review underscores the importance of long-term follow-up in evaluating auditory outcomes in VS treatment. Despite the biases inherent to pretreatment patients selection, hearing preservation microsurgery for sporadic VS removal demonstrated favorable and stable long-term serviceable hearing.

Tumor Budding, p53, and DNA Mismatch Repair Markers in Sinonasal Intestinal-Type Adenocarcinoma: A Retrospective Study Supports the Adverse Prognostic Impact of Tumor Budding.

Sinonasal intestinal-type adenocarcinoma (ITAC) is a very rare, closely occupational-related tumor with strong histological similarities to colorectal cancer (CRC). In the latter, tumor budding (TB) is widely recognized as a negative prognostic parameter. The aim of this study was to evaluate the prognostic role of TB in ITAC and to correlate it with other established or emerging biomarkers of the disease, such as p53 and deficient DNA mismatch repair (MMR) system status/microsatellite instability (MSI). We retrospectively analyzed 32 consecutive specimens of patients with ITAC diagnosis treated in two institutions in Northern Italy. We reviewed surgical specimens for TB evaluation (low-intermediate/high); p53 expression and MMR proteins were evaluated via immunohistochemistry. Results were retrospectively stratified using clinical data and patients' outcomes. According to bud counts, patients were stratified into two groups: intermediate/high budding (>4 TB) and low budding (≤4 TB). Patients with high TB (>4) have an increased risk of recurrence and death compared to those with low TB, with a median survival of 13 and 54 months, respectively. On multivariate analysis, considering TB, therapy, and stage as covariates, TB emerged as an independent prognostic factor net of the stage of disease or type of therapy received. No impact of p53 status as a biomarker of prognosis was observed and no alterations regarding MMR proteins were identified. The results of the present work provide further significant evidence on the prognostic role of TB in ITAC and underline the need for larger multicenter studies to implement the use of TB in clinical practice.

Post-traumatic Delayed Facial Nerve Palsy: Report of 2 Cases and Systematic Review.

OBJECTIVE: Delayed facial nerve palsy (dFNP) secondary to head injury is definitely uncommon. Although the mechanism of immediate facial nerve paralysis is well-studied, its delayed presentation remains debated. Given the dearth of available information, we reported herein our experience with 2 cases of posttraumatic dFNP. This systematic review aimed to evaluate all available information on dFNP and to assess treatment outcome also comparing conservatively and surgically approaches. DATA SOURCES: Pubmed, Scopus, and Web of Science databases were systematically screened. REVIEW METHODS: The protocol of this investigation was registered on PROSPERO in April 2023 and the systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. RESULTS: Both patients in the case studies showed a complete recovery within 2 to 3 months after the head trauma. One of them still reported a subjective taste alteration at last control. After the application of the inclusion-exclusion criteria, 9 manuscripts with adequate relevance to this topic were included in the systematic review. The study population consisted of 1971 patients with a diagnosis of posttraumatic facial nerve palsy, of which 128 with a dFNP. CONCLUSIONS: dFNP due to head trauma is a rarely encountered clinical entity, and optimal treatment still remains to be elucidated. Based on the reported data, it seems rational to propose a conservative approach for dFNP with steroid administration as a first line in most cases, indicating surgery in severe and/or refractory cases.

Remote Check as a tele-health instrument for cochlear implant recipients: Analysis of impact and feasibility of application.

PURPOSE: The number of cochlear implant (CI) surgeries is growing over time, with the risk of overloading CI centers in the post-surgical management. Telemedicine is a possible solution to address this phenomenon. Remote Check (RC) is an application that is specific for CI recipients monitoring. The aim of this study is to evaluate the feasibility of application, potential economic impact and patients' acceptance of RC. METHODS: The study is retrospective investigation, data on clinical, audiological features (from remote and on-site evaluation), and satisfaction surveys of 66 consecutive patients were collected; costs required for RC and for on-site evaluations were recorded as well. RESULTS: One hundred and ninety RC sessions were completed by the patients (2.88 sessions per patient). RC and on-site audiometry significantly correlated except for the 500 Hz frequency. Estimated costs for the Italian National Health System for RC review and on-site evaluations were 1.32€ and 3.49€ per minute, respectively. High satisfaction for RC was reached in 91 % of patients. CONCLUSION: RC revealed to be a reliable, cost-effective and well accepted tool in CI monitoring. This study preliminarily supports the hypothesis that RC could be a valid instrument to reduce CI management overload in the outpatient clinic.

Facial Surface Electromyography: A Novel Approach to Facial Nerve Functional Evaluation after Vestibular Schwannoma Surgery.

BACKGROUND: Vestibular schwannoma (VS) surgery may cause facial nerve damage. However, a comprehensive evaluation of post-operative facial outcomes may be difficult to achieve. Surface electromyography (sEMG) is a promising non-invasive evaluation tool. However, its use in the follow-up after VS surgery has not been reported yet. The main objective was to develop and validate a new sEMG application specifically for the post-VS surgery setting. Secondary goals were to provide a systematic description of facial muscle activity after VS surgery and assess the association between sEMG parameters and Sunnybrook scale scores. METHODS: Thirty-three patients with facial palsy following VS surgery were included. The clinical outcomes (Sunnybrook symmetry, movement, and synkinesis scores) and sEMG parameters (signal amplitude normalized by the maximal voluntary contraction (NEMG) and sEMG synkinesis score (ESS, number of synkinesis per movement sequence)) were evaluated at the end of the follow-up. RESULTS: In all tested muscles, NEMG variance was significantly higher on the affected side than the contralateral (variance ratio test, p < 0.00001 for each muscle). In total, 30 out of 33 patients (90.9%) showed an ESS ≥ 1 (median: 2.5, IQR: 1.5-3.0). On the affected side, NEMG values positively correlated with both dynamic and overall Sunnybrook scores (Spearman's model, p < 0.05 for each muscle, except orbicularis oculi). ESS significantly correlated with the Sunnybrook synkinesis score (Spearman's rho: 0.8268, p < 0.0001). CONCLUSIONS: We described and preliminarily validated a novel multiparametric sEMG approach based on both signal amplitude and synkinesis evaluation specifically for oto-neurosurgery. Large-scale studies are mandatory to further characterize the semiological and prognostic value of facial sEMG.

Tumor budding to investigate local invasion, metastasis, and prognosis of head and neck carcinoma: A systematic review.

The aim of this systematic review is to shed light on the role of tumor budding (TB) in the biology, behavior, and prognosis of head and neck squamous cell carcinoma (HNSCC). A search was run in PubMed, Scopus, and Embase databases following PRISMA guidelines. After full-text screening and application of inclusion/exclusion criteria, 36 articles were included. Several investigations support the prognostic role of TB, which might play a role in selecting rational treatment strategies. To achieve this goal, further research is needed for greater standardization in TB quantification. Although TB is not included as a negative prognostic factor in the current management guidelines, it might be reasonable to consider a closer follow-up for HNSCC cases with high histopathological evidence of TB.

Facial surface electromyography: A systematic review on the state of the art and current perspectives.

PURPOSE: Peripheral facial nerve palsy is a severely disabling condition. In current clinical practice, the commonest tools to assess facial palsy are grading scales, digital face image analyses or facial muscle electrophysiology. However, these techniques suffer from subjectivity or invasiveness and cannot be applied as part of a routine clinical assessment. Therefore, novel non-invasive office-based tools are needed. Surface electromyography (sEMG) may potentially fulfill the requirements of objectivity, low examiner-dependence, and minimal invasiveness. The aim of this systematic review is to define the state of the art on the use of sEMG for facial nerve functional assessment. MATERIALS AND METHODS: Pubmed, Scopus and Web of Science databases were systematically searched. The study protocol was registered on PROSPERO in January 2023. The review was conducted according to the PRISMA guidelines. RESULTS: After the application of inclusion-exclusion criteria, 15 manuscripts with adequate relevance to this topic were included in the review. CONCLUSIONS: Facial sEMG represents a potentially useful tool to implement objective quantification of facial nerve function in clinical practice. Given the heterogeneity of methods and analysis in the available studies, sEMG results are hardly comparable. The introduction of methodological guidelines, followed by large prospective studies on well-defined subsets of patients with facial nerve impairment, is advocated.

The Prognostic Role of the Immune Microenvironment in Sinonasal Intestinal-Type Adenocarcinoma: A Computer-Assisted Image Analysis of CD3+ and CD8+ Tumor-Infiltrating Lymphocytes.

The prognostic value of conventional histopathological parameters in the sinonasal intestinal-type adenocarcinoma (ITAC) has been debated and novel variables should be investigated. Increasing evidence demonstrated that the evolution of cancer is strongly dependent upon the complex interactions within tumor microenvironment. The aim of this retrospective study was to assess the features of immune microenvironment in terms of CD3+ and CD8+ cells in a series of ITAC and explore their prognostic role, as well as their relations with clinicopathological variables. A computer-assisted image analysis of CD3+ and CD8+ tumor-infiltrating lymphocytes (TIL) density was conducted on surgical specimens of 51 patients with ITAC that underwent a curative treatment including surgery. ITAC displays variable TIL density, which is associated with OS. In a univariate model, the density of CD3+ TIL was significantly related to OS (p = 0.012), whereas the association with CD8+ TIL density resulted in being non-significant (p = 0.056). Patients with intermediate CD3+ TIL density were associated with the best outcome, whereas 5-year OS was the lowest for intermediate CD8+ TIL density. CD3+ TIL density maintained a significant association with OS in the multivariable analysis. TIL density was not significantly related to demographic and clinicopathological variables. CD3+ TIL density was independently associated with OS in a non-linear fashion and patients with intermediate CD3+ TIL density had the best outcome. Though based on a preliminary analysis on a relatively small series of patients, this finding makes TIL density a potential independent prognostic factor of ITAC.

Benefits of bone conduction hearing aid in children with unilateral aural atresia.

Objective: To assess the hearing benefit with a unilateral bone conduction hearing aid in a cohort of children with unilateral aural atresia. Methods: Cross-sectional case series pilot study involving 7 children (median age: 10 years, range 6-11). All patients underwent pure-tone, speech, aided sound field and aided speech audiometry and Simplified Italian Matrix Test (SIMT) with and without bone conduction hearing aid (Baha 5® CochlearTM). Cognitive abilities were assessed in 5 patients. Results: The mean air conduction pure-tone average (PTA) of the atretic ear was 63.2 ± 6.9 dB, while the bone conduction PTA was 12.6 ± 4.7 dB. Speech discrimination score of the atretic ear was 88.6 ± 3.8 dB, while with the hearing aid it was 52.8 ± 1.9 dB. In the contralateral ear, there was no significant air-bone gap, and PTAs for air and bone conduction thresholds were within normal range (PTA ≤ 25 dB). The mean aided air conduction hearing threshold was 26.2 ± 7.97. Mean speech recognition threshold without the hearing aid was -5.1 ± 1.9 dB, and -6.0 ± 1.7 dB with the hearing aid tested with the SIMT. The mean score of the cognitive test was 46.8 ± 42.8. Conclusions: These preliminary findings should encourage clinicians in proposing a unilateral bone conduction hearing aid in children with unilateral atresia.

Survival Outcomes in Squamous Cell Carcinoma of the External Auditory Canal: A Systematic Review and Meta-Analysis.

Squamous cell carcinomas (SCC) of the external auditory canal (EAC) are rare tumors representing a surgical challenge. Current knowledge is based largely on case series; thus, the level of evidence is weak. This study sought to systematically review the available SCC of the EAC literature and to identify risk factors for overall survival (OS) and disease-specific survival (DSS). A systematic review and meta-analysis of papers searched up to December 2022 through PubMed, Scopus, Web of Science, and Cochrane Library databases was conducted. Quality assessment of the eligible studies was done according to the Newcastle-Ottawa Scale. Pooled univariate and multivariable analyses and meta-analysis using a random-effects or fixed-effects Mantel-Haenszel model were performed. Fifteen articles (282 patients) met the inclusion criteria and were included in the quantitative analysis. The pooled multivariable analysis revealed cT3 and cT4 as independent prognostic factors for OS (p = 0.005, and p < 0.001, respectively) and DSS (p = 0.002, and p < 0.001, respectively). Local recurrence rate was 32.3%. The meta-analysis estimated significantly higher odds ratios for advanced T categories, than cT1-T2 tumors for OS and DSS (OR = 3.55; 95% CI, 1.93-6.52, and OR = 3.73; 95% CI, 2.00-6.97, respectively). In conclusion, locally advanced tumors were associated with poor prognosis. Poor outcomes mostly occurred due to local recurrence.

Tumor Microenvironment in Sporadic Vestibular Schwannoma: A Systematic, Narrative Review.

Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome. The aim of this systematic, narrative review was to assess the level of knowledge on TME implicated in the biology, behavior, and prognosis of sporadic VSs. A search (updated to November 2022) was run in Scopus, PubMed, and Web of Science electronic databases according to the PRISMA guidelines, retrieving 624 titles. After full-text evaluation and application of inclusion/exclusion criteria, 37 articles were included. VS microenvironment is determined by the interplay of a dynamic ecosystem of stromal and immune cells which produce and remodel extracellular matrix, vascular networks, and promote tumor growth. However, evidence is still conflicting. Further studies will enhance our understanding of VS biology by investigating TME-related biomarkers able to predict tumor growth and recognize immunological and molecular factors that could be potential therapeutic targets for medical treatment.

Does social distancing impact pediatric upper airway infections? An observational controlled study and a brief literature review.

PURPOSE: SARS-CoV-2 pandemic has reduced social interaction even among children. The objective of the study was to assess the role of social distancing in the course of common pediatric upper airway recurrent diseases. MATERIALS AND METHODS: Patients aged ≤14 years with at least one ENT-related clinical condition were retrospectively recruited. All patients had two outpatient evaluations in the same period (April - September): the control group had the first evaluation in 2018 and second in 2019, whereas the case group had the first evaluation in 2019 and second in 2020. Patients of each group were individually compared between their two visits and deemed improved/unchanged/worsened for each specific ENT condition. The percentage of children improved/unchanged/worsened were then collectively compared between the two groups for each condition. RESULTS: Patients who experienced social distancing presented a significantly higher improvement rate than controls for recurrent acute otitis media episodes (35.1 % vs. 10.8 %; Fisher's exact test p = 0.033) and for tympanogram type (54.5 % vs. 11.1 %, Fisher's exact test p = 0.009). CONCLUSIONS: The anti-contagion social restrictions decreased the prevalence of middle ear infections and effusion in children. Further studies on larger cohorts are required to better elucidate these findings.

Validity and reliability of the Italian translation of the Yale Pharyngeal Residue Severity Rating Scale.

Objective: In the dysphagic patient, pharyngeal residues (PR) are associated with aspiration and poor quality of life. The assessment of PR using validated scales during flexible endoscopic evaluation of swallowing (FEES) is crucial for rehabilitation. This study aims to validate and test the reliability of the Italian version of the Yale Pharyngeal Residue Severity Rating Scale (IT-YPRSRS). The effects of training and experience in FEES on the scale were also determined. Methods: The original YPRSRS was translated into Italian according to standardised guidelines. Thirty FEES images were selected after consensus and proposed to 22 naive raters who were asked to assess the severity of PR in each image. Raters were divided into two subgroups by years of experience at FEES, and randomly by training. Construct validity, inter-rater, and intra-rater reliability were assessed by kappa statistics. Results: IT-YPRSRS showed substantial to almost perfect agreement (kappa > 0.75) in validity and reliability for both the overall sample (660 ratings), and valleculae/pyriform sinus sites (330 ratings each). No significant differences emerged between groups considering years of experience, and variable differences were observed by training. Conclusions: The IT-YPRSRS demonstrated excellent validity and reliability in identifying location and severity of PR.

Early surgery and definitive cure in small sporadic vestibular schwannoma.

Objective: To report surgical outcomes of a cohort of small sporadic vestibular schwannoma and discuss the role of early surgery. Methods: Retrospective descriptive analysis of 234 consecutive patients with small vestibular schwannoma operated on with translabyrinthine or hearing preservation surgical approaches. Outcome measures were control of disease, postoperative facial nerve function, complications and hearing outcome. Results: A translabyrinthine approach was performed in 59% of cases, hearing preservation surgery in 40% and transmeatal approach in 1%, respectively. Complete resection was achieved in 100% of cases. Overall, postoperative major and minor complications were 8.5% in the series, with complete recovery and no sequalae. Facial nerve function at one year postoperatively was House-Brackmann scale (HB) 1-2 in 95% of cases. The rate of hearing preservation was 70% A-B-C classes of Tokyo classification and 77% AB classes of AAOHNS classification. Conclusions: Early surgery in small vestibular schwannoma is a valid option, due to good functional outcomes, low morbidity and definitive cure. Early surgery is associated with better outcomes when considered in relation to non-surgical treatments reported in the literature.

Early Translabyrinthine Surgery for Small- and Medium-Sized Vestibular Schwannomas: Consecutive Cohort Analysis of Outcomes.

OBJECTIVE: Reappraisal of the role of translabyrinthine (TLAB) surgery in small- and medium-sized vestibular schwannomas (VSs). STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A total of 330 consecutive patients diagnosed between 1973 and 2019 with small- and medium-sized VS up to 20 mm in the extrameatal portion submitted to surgical treatment. INTERVENTIONS: VS removal through microscopic TLAB approach. MAIN OUTCOME MEASURES: Facial nerve function according to the House-Brackmann scale at 12-month follow-up, postoperative complications and entity of tumor resection assessed with postoperative MRI. A comparative analysis of outcomes between two groups of patients was further conducted, according to tumor size: Group A, small-sized (intrameatal or ≤10 mm extrameatal tumors) and Group B, medium-sized VSs (extrameatal between 11 and 20 mm). RESULTS: Complete tumor removal was achieved in all cases. The overall complication rate was 5.5%, being cerebrospinal fluid leak the most frequent. Patients with small-sized VS (n = 121) presented a significantly better facial nerve function than patients with medium-sized tumors (n = 209), showing House-Brackmann Grades I to II in 92.6% versus 73.6% of cases, respectively ( p < 0.001). A nearly 4.5-fold higher risk of poor facial nerve function at 12 months affects patients with medium-sized tumors (odds ratio, 4.473; 95% confidence interval, 2.122-9.430; p < 0.001). CONCLUSION: In the current scenario of multioptional VS management, when hearing preservation is not feasible, early TLAB approach as first-line treatment for small-sized VSs showed favorable results. Factors supporting such proactive surgical treatment include long-term definitive cure, no major complications, good facial nerve outcomes, and the possibility of simultaneous hearing rehabilitation with a cochlear implant.

Treatment of advanced squamous cell carcinoma of the external auditory canal: Critical analysis of persistent failures in diagnosis and surgery with a competing-risk model.

BACKGROUND: A series of temporal bone squamous cell carcinomas (TBSCCs) was analyzed with the aim of (i) better understanding the causes for the persistent high failure rate in advanced SCCs and (ii) discussing a possible way out from this stalemate in treatment. METHODS: Forty-five TBSCCs consecutively treated surgically were reviewed. RESULTS: The 5-year cumulative incidence for postoperative local recurrence was 41.8%. At multivariable analysis, pT3-4 stages were associated with eightfold relative incidence of developing local recurrence during follow-up (sHR = 9.06, 95% confidence interval [CI] = 1.18-69.46, p = 0.034) and cause-specific death (sHR = 7.95, 95%CI = 1.01-62.27, p = 0.048). CONCLUSIONS: The poor outcome in advanced TBSCC occurred because of local recurrence due to defective resection. The fundamental pitfall of surgery on advanced TBSCC appeared to be the insufficient knowledge of microscopic tumor growth in the different sites and subsites of the temporal bone. The serial histopathological study of the en bloc surgical specimen and autopsy temporal bones seems to represent a way to enhance our understanding of these tumors.

Different inflammatory blood markers correlate with specific outcomes in incident HPV-negative head and neck squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Inflammatory blood markers have been associated with oncological outcomes in several cancers, but evidence for head and neck squamous cell carcinoma (HNSCC) is scanty. Therefore, this study aims at investigating the association between five different inflammatory blood markers and several oncological outcomes. METHODS: This multi-centre retrospective analysis included 925 consecutive patients with primary HPV-negative HNSCC (median age: 68 years) diagnosed between April 2004 and June 2018, whose pre-treatment blood parameters were available. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated; their associations with local, regional, and distant failure, disease-free survival (DFS), and overall survival (OS) was calculated. RESULTS: The median follow-up was 53 months. All five indexes were significantly associated with OS; the highest accuracy in predicting patients' survival was found for SIM (10-year OS = 53.2% for SIM < 1.40 and 40.9% for SIM ≥ 2.46; c-index = 0.569) and LMR (10-year OS = 60.4% for LMR ≥ 3.76 and 40.5% for LMR < 2.92; c-index = 0.568). While LMR showed the strongest association with local failure (HR = 2.16; 95% CI:1.22-3.84), PLR showed the strongest association with regional (HR = 1.98; 95% CI:1.24-3.15) and distant failure (HR = 1.67; 95% CI:1.08-2.58). CONCLUSION: Different inflammatory blood markers may be useful to identify patients at risk of local, regional, or distant recurrences who may benefit from treatment intensification or intensive surveillance programs.