Faculty Bibliography

BACKGROUND AND OBJECTIVE/UNASSIGNED:Thyroid nodules are frequently incidentally found on physical exam or imaging for an unrelated work-up. Although surgery remains the gold standard for treating symptomatic benign and/or malignant thyroid nodules, radiofrequency ablation (RFA) has emerged as a minimally invasive treatment option for high risk patients and those who decline surgery. The novel application of RFA to treat thyroid disease was originally described for symptomatic, benign thyroid nodules. Since then, several studies have tried to expand its indication to treat primary and recurrent well-differentiated thyroid cancer. The high success rates and the low complication profile, has allowed for quick adoption of RFA as a treatment option for well-selected patients with benign thyroid nodules and locoregional recurrent thyroid malignancy. As such, multidisciplinary guidelines and consensus statements were developed to standardize indications, techniques, outcome measures, and follow-up to ensure the best patient care. This article summarizes the current indications and recommendations to help guide clinicians on how best to effectively and safely utilize RFA to treat thyroid disease. METHODS/UNASSIGNED:A PubMed/MEDLINE search between 2000-2022 using a combination of "radiofrequency ablation", "RFA", "thyroid nodule", and "guidelines" was conducted. The inclusion criteria were articles published in English which offered recommendations on RFA use for thyroid nodules. KEY CONTENT AND FINDINGS/UNASSIGNED:For symptomatic, benign thyroid nodules, RFA is effective at significantly reducing nodule volume. For large nodules, multiple RFA sessions may be needed to achieve clinically significant volume reduction. Patients undergoing RFA for autonomously functioning thyroid nodules may see symptomatic relief but success rates are variable. RFA may serve a curative or palliative role in recurrent well-differentiated thyroid cancers. There is little data describing the use of RFA for primary well-differentiated thyroid cancer >1 cm and the role of RFA for thyroid microcarcinomas remains controversial. CONCLUSIONS/UNASSIGNED:RFA is a safe minimally invasive technique and may be considered, in appropriate circumstances, a first-line treatment option for benign thyroid nodules. Practices adopting RFA will likely increase as more clinicians become familiar with this technique, highlighting the importance of developing standardized guidelines.

OBJECTIVES/OBJECTIVE:Single-sided deafness (SSD) can have consequences for a child's language, educational, and social development. A cochlear implant (CI) is the only device which can restore true binaural hearing, yet they are only approved for children with (SSD) over the age of five in the United States. Reports on speech perception outcomes for children implanted at a younger age are limited. The present study aims to examine the effects of age at implantation, duration of deafness, hearing loss etiology, and presence of additional disabilities on device usage and speech perception outcomes. METHODS:A retrospective chart review was used to examine demographics and speech perception outcomes for 18 children implanted at age five or younger. RESULTS:Speech perception results were highly variable, with some children deriving significant benefit and others demonstrating no sound awareness through the implant alone. Age at implantation and duration of deafness did not have a clear impact on outcomes. Device usage was low in many children, often those with anatomical abnormalities such as a hypoplastic cochlear nerve. There are challenges to assessing speech perception in young children with SSD, leading to a lack of standardized outcome measures. CONCLUSIONS:Early CI for children with SSD may improve speech perception, but benefit is not guaranteed. Candidacy evaluation should consider both medical and audiological factors, in addition to the degree of family support and realistic expectations. Caution is especially warranted in children with significant anatomical anomalies.

Astrocytes play crucial roles in regulating neural circuit function by forming a dense network of synapse-associated membrane specializations, but signaling pathways regulating astrocyte morphogenesis remain poorly defined. Here, we show the Drosophila lipid-binding G protein-coupled receptor (GPCR) Tre1 is required for astrocytes to establish their intricate morphology in vivo. The lipid phosphate phosphatases Wunen/Wunen2 also regulate astrocyte morphology and, via Tre1, mediate astrocyte-astrocyte competition for growth-promoting lipids. Loss of s1pr1, the functional analog of Tre1 in zebrafish, disrupts astrocyte process elaboration, and live imaging and pharmacology demonstrate that S1pr1 balances proper astrocyte process extension/retraction dynamics during growth. Loss of Tre1 in flies or S1pr1 in zebrafish results in defects in simple assays of motor behavior. Tre1 and S1pr1 are thus potent evolutionarily conserved regulators of the elaboration of astrocyte morphological complexity and, ultimately, astrocyte control of behavior.

UNLABELLED:DNA methylation is an essential molecular assay for central nervous system (CNS) tumor diagnostics. While some fusions define specific brain tumors, others occur across many different diagnoses. We performed a retrospective analysis of 219 primary CNS tumors with whole genome DNA methylation and RNA next-generation sequencing. DNA methylation profiling results were compared with RNAseq detected gene fusions. We detected 105 rare fusions involving 31 driver genes, including 23 fusions previously not implicated in brain tumors. In addition, we identified 6 multi-fusion tumors. Rare fusions and multi-fusion events can impact the diagnostic accuracy of DNA methylation by decreasing confidence in the result, such as BRAF, RAF, or FGFR1 fusions, or result in a complete mismatch, such as NTRK, EWSR1, FGFR, and ALK fusions. IMPLICATIONS/UNASSIGNED:DNA methylation signatures need to be interpreted in the context of pathology and discordant results warrant testing for novel and rare gene fusions.

Objective: To describe the phenotypic characteristics of the epiglottis at rest and their impact on vallecular residue. Methods: Videofluoroscopic studies (VFSS) were pooled from 2 Laryngology practices, and Image J was used to measure epiglottic anatomic features at rest. Studies were rated by the MBSImp and presence of vallecular residue following swallow of thin and puree boluses. A conditional inference tree analysis was performed to isolate which epiglottic parameters were risk factors for presence of vallecular reside followed by logistic regression. Results: The majority of patients had a normal shaped epiglottis, followed by omega shape. The mean angle of the epiglottis from the hyoid was approximately 90°. Only abnormal epiglottic movement was associated with increased risk of residue for thin boluses (OR 35.09, CI 10.93-158.66, P <.001). However, in those with normal epiglottic movement, age >70 years old was associated with increased risk of residue (OR 3.98, CI 1.73-9.23, P =.001). For puree boluses, a normal or omega shaped epiglottis was associated with residue (OR 5.19, CI 2.41-11.51, P <.001), and this relationship was further modulated by increased distance of the epiglottic tip from the posterior pharyngeal wall. No other anatomic features of the resting epiglottis were associated with residue. Comorbidities potentially affecting swallow were infrequent in the cohort and were not associated with residue. Conclusion: Abnormal epiglottic movement is associated with aspiration, and in this study we find that abnormal epiglottic movement increases the risk of vallecular residue and that older age is a risk factor for residue. The resting properties of the epiglottis do not appear to be associated with abnormal epiglottic movement or residue.

Introduction: Pediatric-type follicular lymphoma (PTFL) is a rare B-cell lymphoma that primarily affects the head and neck, accounting for approximately 1.5"“2% of childhood lymphomas. Distinguishing between follicular lymphoma and PTFL is critical due to their distinct clinical characteristics, which influence prognosis and treatment. Case presentation: Two patients, a 14-year-old male (Case 1) and a 17-year-old male (Case 2), presented to the pediatric otolaryngology clinic with complaints of an isolated neck and parotid masses, respectively. In Case 1, physical examination revealed a 5 cm upward-growing neck mass without accompanying B symptoms or discomfort. CT scan, needle biopsy, and MRI with contrast confirmed the presence of the mass, which was subsequently surgically excised. In Case 2, the patient had an enlarging left-sided parotid mass, along with night sweats, fatigue, and arthralgias. Ultrasound and contrast-enhanced MRI confirmed a well-defined solid vascular mass within the left parotid gland, which was subsequently surgically excised. Pathological examination confirmed PTFL in both cases, leading to a positron emission tomography (PET)/CT scan for further evaluation and staging. Conclusion: This case series underscores the importance of pediatric surgeons to consider PTFL in the differential diagnosis of head and neck masses, as it can be effectively cured through surgical excision.

Purpose: The expression of PD-L1 in high-grade meningiomas made it a potential target for immunotherapy research in refractory cases. Several prospective studies in this field are still on going. We sought to retrospectively investigate the effects of check-point inhibitors (CI) on meningiomas that had been naïve to either surgical or radiation approaches by following incidental meningiomas found during treatment with CI for various primary metastatic cancers. Methods: We used the NYU Perlmutter Cancer Center Data Hub to find patients treated by CI for various cancers, who also had serial computerized-tomography (CT) or magnetic-resonance imaging (MRI) reports of intracranial meningiomas. Meningioma volumetric measurements were compared between the beginning and end of the CI treatment period. Patients treated with chemotherapy during this period were excluded. Results: Twenty-five patients were included in our study, of which 14 (56%) were on CI for melanoma, 5 (20%) for non-small-cell lung cancer and others. CI therapies included nivolumab (n = 15, 60%), ipilimumab (n = 11, 44%) and pembrolizumab (n = 9, %36), while 9 (36%) were on ipilimumab/nivolumab combination. We did not find any significant difference between tumor volumes before and after treatment with CI (1.31 ± 0.46 vs. 1.34 ± 0.46, p=0.8, respectively). Among patients beyond 1 year of follow-up (n = 13), annual growth was 0.011 ± 0.011 cm³/year. Five patients showed minor volume reduction of 0.12 ± 0.10 cm³ (21 ± 6% from baseline). We did not find significant predictors of tumor volume reduction. Conclusion: Check-point inhibitors may impact the natural history of meningiomas. Additional research is needed to define potential clinical indications and treatment goals.

BACKGROUND AND OBJECTIVES/OBJECTIVE:An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS:Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS:The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION/CONCLUSIONS:SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Median survival for all patients with breast cancer with brain metastases (BCBMs) has increased in the era of targeted therapy (TT) and with improved local control of intracranial tumors using stereotactic radiosurgery (SRS) and surgical resection. However, detailed characterization of the patients with long-term survival in the past 5 years remains sparse. The aim of this article is to characterize patients with BCBM who achieved long-term survival and identify factors associated with the uniquely better outcomes and to find predictors of mortality for patients with BCBM. METHODS:We reviewed 190 patients with breast cancer with 931 brain tumors receiving SRS who were followed at our institution with prospective data collection between 2012 and 2022. We analyzed clinical, molecular, and imaging data to assess relationship to outcomes and tumor control. RESULTS:The median overall survival from initial SRS and from breast cancer diagnosis was 25 months (95% CI 19-31 months) and 130 months (95% CI 100-160 months), respectively. Sixteen patients (17%) achieved long-term survival (survival ≥5 years from SRS), 9 of whom are still alive. Predictors of long-term survival included HER2+ status ( P = .041) and treatment with TT ( P = .046). A limited number of patients (11%) died of central nervous system (CNS) causes. A predictor of CNS-related death was the development of leptomeningeal disease after SRS ( P = .025), whereas predictors of non-CNS death included extracranial metastases at first SRS ( P = .017), triple-negative breast cancer ( P = .002), a Karnofsky Performance Status of <80 at first SRS ( P = .002), and active systemic disease at last follow-up ( P = .001). Only 13% of patients eventually needed whole brain radiotherapy. Among the long-term survivors, none died of CNS progression. CONCLUSION/CONCLUSIONS:Patients with BCBM can achieve long-term survival. The use of TT and HER2+ disease are associated with long-term survival. The primary cause of death was extracranial disease progression, and none of the patients living ≥5 years died of CNS-related disease.

Objectives: For transwomen undergoing voice feminization interventions, fundamental frequency (F0; vocal pitch) is a commonly reported functional outcome measure in the literature. However, F0may not correlate well with improvement in quality of life (QoL). Several validated voice-related QoL instruments have been used to assess QoL improvement in these patients, yet there is no consensus on the most appropriate instrument. This systematic review and meta-analysis aimed to assess the relationship between change in F0and QoL improvement following voice feminization, and to compare validated QoL instruments commonly used in this population. Data Sources: PubMed, Cochrane, and Embase. Review Methods: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Primary studies of transwomen undergoing voice feminization, reporting validated QoL outcomes were included. Meta-analyses for associations between mean change in QoL score and mean change in F0, as well as variations in mean change in QoL score by QoL instrument, were performed using a multilevel mixed effects model. Results: No statistically significant correlation was found between change in F0and QoL score improvement post-intervention. Different validated instruments showed statistically significant variation in QoL score change, with the Trans Women Voice Questionnaire (TWVQ) capturing a greater improvement in QoL score relative to other instruments. Conclusions: Lack of correlation between changes in F0and QoL improvement further supports that F0alone is insufficient to assess the efficacy of voice feminizing interventions. Validated QoL measures are useful adjuncts. Of these, the TWVQ appears to be the most sensitive for measurement of QoL improvement following voice feminization.