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BACKGROUND: In the cochlea, auditory development depends on precise patterns of innervation by afferent and efferent nerve fibers, as well as a stereotyped arrangement of hair and supporting cells. Neuronal cell adhesion molecule (NrCAM) is a homophilic cell adhesion molecule that controls diverse aspects of nervous system development, but the function of NrCAM in cochlear development is not well understood. RESULTS: Throughout cochlear innervation, NrCAM is detectable on spiral ganglion neuron (SGN) afferent and olivocochlear efferent fibers, and on the membranes of developing hair and supporting cells. Neonatal Nrcam-null cochleae show errors in type II SGN fasciculation, reduced efferent innervation, and defects in the stereotyped packing of hair and supporting cells. Nrcam loss also leads to dramatic changes in the profiles of presynaptic afferent and efferent synaptic markers at the time of hearing onset. Despite these numerous developmental defects, Nrcam-null adults do not show defects in auditory acuity, and by postnatal day 21, the developmental deficits in ribbon synapse distribution and sensory domain structure appear to have been corrected. CONCLUSIONS: NrCAM is expressed by several neural and sensory epithelial subtypes within the developing cochlea, and the loss of Nrcam confers numerous, but nonpermanent, developmental defects in innervation and sensory domain patterning. Developmental Dynamics 247:934-950, 2018. © 2018 Wiley Periodicals, Inc.
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Tipificación del Cuerpo/fisiología , Moléculas de Adhesión Celular Neuronal/fisiología , Moléculas de Adhesión Celular/metabolismo , Cóclea/inervación , Células Receptoras Sensoriales/química , Animales , Orientación del Axón , Moléculas de Adhesión Celular/deficiencia , Moléculas de Adhesión Celular/fisiología , Cóclea/citología , Cóclea/crecimiento & desarrollo , Células Ciliadas Auditivas , Ratones , Ganglio Espiral de la CócleaRESUMEN
BACKGROUND: We used electromyography to characterize hypoglossal nerve function among radiation-treated head and neck cancer survivors with later onset unilateral tongue immobility. METHODS: Patients with unilateral tongue immobility without evidence of recurrent cancer were seen at a tertiary academic institution between February and September 2021. All patients were at least 2 years post-treatment with radiation therapy for head and neck squamous cell carcinoma. Participants were under annual surveillance and displayed no evidence of operative injury to the hypoglossal nerve. RESULTS: The median symptom-free interval for the 10 patients included in this study was 13.2 years (range 2-25 years). Myokymia alone was present in 3 of 10 patients, fibrillation potentials alone were present in 3 of 10 patients, and 1 subject displayed both fibrillation and myokymia. Three out of 10 patients had normal hypoglossal nerve function. DISCUSSION: These findings highlight how disparate mechanisms may underlie similar clinical presentations of radiation-induced neuromuscular dysfunction.
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Electromiografía , Traumatismos por Radiación , Humanos , Masculino , Femenino , Persona de Mediana Edad , Traumatismos por Radiación/fisiopatología , Anciano , Neoplasias de Cabeza y Cuello/radioterapia , Nervio Hipogloso/efectos de la radiación , Adulto , Lengua/efectos de la radiación , Lengua/inervación , Lengua/fisiopatología , Enfermedades de la Lengua/etiología , Enfermedades de la Lengua/fisiopatología , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapiaRESUMEN
OBJECTIVE: To evaluate whether postoperative radiotherapy (PORT) improves survival among patients who received maxillectomy for pT4aN0 maxillary gingival or hard palate squamous cell carcinoma (SCC) with respect to tumor size. STUDY DESIGN: Retrospective analysis. SETTING: National Cancer Database from 2004 to 2019. METHODS: Included adult patients who received maxillectomy (partial, subtotal, or total) and neck dissection for treatment-naive margin negative pT4aN0 SCC of the maxillary gingiva or hard palate. Adjusted for age, gender, race, insurance status, income, education, urban/rural, facility type, region, comorbidity index, tumor grade, and tumor extension. Inverse probability weights were incorporated into a multivariable Cox proportional hazards model. A priori post hoc subgroup analysis was performed according to tumor size. RESULTS: We included 416 patients who underwent maxillectomy for pT4aN0 SCC of the maxillary gingiva or hard palate (mean [standard deviation] age, 71.5 [11.3] years; male, 190 [45.7%]; tumor size 2 cm, 362 [87%]). Overall, 49.3% of patients received PORT (205 patients). PORT was associated with a 50% improvement in survival compared to surgery alone (adjusted hazard ratio [aHR], 0.50; 95% confidence interval [95% CI], 0.32-0.81). On subgroup analysis, PORT was associated with improved survival for tumors 2 cm (aHR, 0.47; 95% CI, 0.29-0.77), but not for tumors < 2 cm (aHR, 1.15; 95% CI, 0.33-4.08). CONCLUSION: The vast majority of patients with pT4aN0 bone-invading SCC of the maxillary gingiva and hard palate benefit from PORT. Patients with tumors < 2 cm did not demonstrate a survival benefit from adjuvant treatment, suggesting that bony invasion alone may not be sufficient criteria for treatment escalation.
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OBJECTIVES: To evaluate the therapeutic effect of post-operative radiotherapy (PORT) with respect to nodal status among patients with head and neck Merkel cell carcinoma (HNMCC). METHODS: In this retrospective study, we queried Surveillance, Epidemiology, and End Results (SEER) dataset from 2000 through 2019. We included all adult patients who received primary surgical resection for histologically confirmed treatment naive HNMCC. Entropy balancing was used to reweight observations such that there was covariate balance between patients who received PORT and patients who received surgical resection alone. Doubly robust estimation was achieved by incorporating weights into a multivariable cox proportional hazards model. Planned post hoc subgroup analysis was performed to evaluate the impact of PORT by pathological node status. RESULTS: Among 752 patients (mean age, 73.3 years [SD 10.8]; 64.2% male; 91.2% White; 41.9% node-positive), 60.4% received PORT. Among node-positive patients, we found that PORT was associated with improved overall survival (OS) (aHR, 0.55; 95% CI, 0.37-0.81; p = 0.003) and improved disease-specific survival (DSS) (aHR, 0.57; 95% CI, 0.35-0.92; p = 0.022). Among node-negative patients, we found that PORT was not associated with OS and was associated with worse DSS (aHR, 2.34; 95% CI, 1.30-4.23; p = 0.005). CONCLUSIONS: We found that PORT was associated with improved OS and DSS for node-positive patients and worse DSS for node-negative patients. For HNMCC treated with primary surgical resection, these data confirm the value of PORT for pathologically node-positive patients and support the use of single modality surgical therapy for pathologically node-negative patients without other adverse risk factors. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3587-3594, 2024.
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Carcinoma de Células de Merkel , Neoplasias de Cabeza y Cuello , Programa de VERF , Humanos , Carcinoma de Células de Merkel/radioterapia , Carcinoma de Células de Merkel/mortalidad , Carcinoma de Células de Merkel/cirugía , Carcinoma de Células de Merkel/patología , Masculino , Femenino , Anciano , Estudios Retrospectivos , Radioterapia Adyuvante , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias de Cabeza y Cuello/patología , Metástasis Linfática , Anciano de 80 o más Años , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/cirugía , Persona de Mediana Edad , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugíaRESUMEN
OBJECTIVE: To evaluate whether subcategorization of perineural invasion (PNI) improves the prognostic resolution of the American Joint Committee on Cancer, Eighth Edition (AJCC8) staging system in oral cavity squamous cell carcinoma (OCSCC). METHODS: OCSCC tumor specimens from patients seen at a tertiary care institution who underwent primary surgical resection between January 2019 and June 2021 were sorted into four PNI categories: negative, intratumoral, peripheral, and extratumoral. The prognostic effect of these PNI categories were assessed through Kaplan-Meier, Cox regression, and log-rank testing using recurrence-free survival (RFS) and overall survival (OS) as primary and secondary outcomes respectively. RESULTS: A total of 158 patients were examined. The median follow-up time was 21 months. PNI subcategorization further stratified RFS (p = 0.007) and OS (p = 0.002). Extratumoral PNI was associated with a 4.5-fold increase in recurrence risk (adjusted hazards ratio [aHR]: 4.53; 95% confidence interval [CI]: 1.1-18.66) and worse OS when compared with PNI negative disease (aHR: 5.71; 95% CI: 1.0-32.67). Peripheral PNI was associated with worse OS (aHR: 5.7; 95% CI: 1.35-24.08) but not worse RFS (p = 0.18) when compared with PNI negative disease. Interestingly, intratumoral PNI was not associated with significant differences in RFS (p = 0.087) or OS (p = 0.22) when compared with PNI negative disease. CONCLUSIONS: Subcategorization of OCSCC tumors into extratumoral, peripheral, and intratumoral PNI stratifies RFS and OS when compared with patients with PNI negative disease in an incremental fashion. This pilot study suggests that there may be added benefit in subcategorization of PNI in the prognostic evaluation of OCSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1656-1662, 2024.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Proyectos Piloto , Estadificación de Neoplasias , Estudios Retrospectivos , Nervios Periféricos/patología , Pronóstico , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Neoplasias de Cabeza y Cuello/patología , Invasividad Neoplásica/patologíaRESUMEN
Importance: Oral cavity squamous cell carcinoma (SCC) tumors with mandibular invasion are upstaged to pT4a regardless of their size. Even small tumors with boney invasion, which would otherwise be classified as pT1-2, are recommended for the locally advanced treatment pathway to receive administration of postoperative radiotherapy (PORT). Objective: To evaluate the association of PORT with overall survival according to tumor size among patients who received mandibulectomy for pT4aN0 oral cavity SCC. Design, Setting, and Participants: This was a retrospective analysis using data from the US National Cancer Database from January 1, 2004, through December 31, 2019. All patients who received mandibulectomy for treatment-naive pT4aN0 oral cavity SCC with negative surgical margins were included. Data analyses were performed in January 2023 and finalized in July 2023. Exposure: PORT vs no PORT. Main Outcomes and Measures: Entropy balancing was used to balance covariate moments between treatment groups. Weighted multivariable Cox proportional hazards regression was used to measure the association of PORT with overall survival associated with tumor size. Results: Among 3268 patients with pT4aN0 oral cavity SCC (mean [SD] age, 65.9 [12.1] years; 2024 [61.9%] male and 1244 [38.1%] female), 1851 (56.6%) received PORT and 1417 (43.4%) did not receive PORT. On multivariable analysis was adjusted for age, insurance status, Charlson Comorbidity Index score, tumor site, tumor grade, tumor size, and PORT. Findings indicated that PORT was associated with improved overall survival and that this relative survival advantage trended upwards with increasing tumor size. That is, the larger the tumor, the greater the survival advantage associated with the use of PORT. For the 1068 patients with tumors greater than 4 cm, the adjusted hazard ratio (aHR) in favor of PORT was 0.63 (95% CI, 0.48-0.82); for the 1774 patients with tumors greater than 2 cm but less than or equal to 4 cm, the aHR was 0.76 (95% CI, 0.62-0.93); and for 426 patients with tumors less than 2 cm, the aHR was 0.81 (95% CI, 0.57-1.15). Conclusions and Relevance: In this retrospective analysis of patients who received mandibulectomy for pT4aN0 oral cavity SCC, PORT was associated with improved overall survival, the benefit of which improved relatively with increasing tumor size. These findings suggest that tumor size should be considered in guidelines for PORT administration in this patient population.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Masculino , Femenino , Anciano , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Estudios Retrospectivos , Osteotomía Mandibular , Radioterapia Adyuvante , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/cirugía , Neoplasias de Cabeza y Cuello/patología , Estadificación de NeoplasiasRESUMEN
Objective: To evaluate how pediatric indications for tonsillectomy or adenotonsillectomy relate to gender, race/ethnicity, and age. Methods: Included consecutive pediatric patients who underwent tonsillectomy or adenotonsillectomy from a single tertiary academic institution between 2012 and 2019. Logistic regression analysis was used to measure association between the indication for tonsillectomy and the demographic variables gender, race/ethnicity, and age. Results: Of the 1106 children included in this study, 53% were male and 47% were female. Half of the children were White, 40% were African American, 6% were Hispanic and 4% were other. The most common indication for surgery was upper airway obstruction alone (66%), followed by obstruction and infection (22%), and recurrent infections (12%). We found that male gender (OR 1.59, 95% CI 1.24-2.04), African American race (OR 2.76, 95% CI 2.08-3.65), and younger age were associated with greater odds of presenting with upper airway obstruction as the indication for tonsillectomy. Conversely, male gender (OR 0.63, 95% CI 0.44-0.92), African American race (OR 0.4, 95% CI 0.26-0.61), and younger age were associated with lower odds of presenting with recurrent infection as the indication for tonsillectomy. Conclusions: Male gender, African American race, and young age are risk factors for tonsillar surgery due to airway obstruction. Female gender, White race, and older age are risk factors for tonsillar surgery due to recurrent throat infections. Level of Evidence: 3.
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OBJECTIVE: To investigate how the internet presence of Otolaryngology residency programs influences recruitment of diverse applicants. STUDY DESIGN: Retrospective cohort study. SETTING: Website, Instagram, and AAMC Residency Explorer data from all US, non-military, allopathic otolaryngology residency programs. METHODS: We identified 10 common ways in which residency programs communicate their commitment to diversity through web-based platforms. We then analyzed program websites and Instagram pages for the presence of these 10 diversity elements. Univariate and multivariate linear regression were used to evaluate the association between presence of a diversity elements and the proportion of underrepresented minority residents in the program. RESULTS: Review of 106 Otolaryngology residency program websites and Instagram pages was completed from February to May 2021. Most programs (69.8%) satisfied at least one diversity element. Of the programs reviewed, 83 had demographic information available for comparison. After adjusting for Doximity ranking, multivariate linear regression demonstrated that several elements were positive predictors of program diversity. Diversity and inclusion message (p < 0.0001), statement encouraging URM applicants (p < 0.0001), dedicated diversity chair/committee (pâ¯=â¯0.005), and diversity related articles/blog posts (pâ¯=â¯0.006) were independently associated with a greater proportion of URM residents in a given program. CONCLUSION: These data demonstrate that providing diversity related information on residency program websites may play a role in improving program diversity. The large percentage of programs that lack the presence of any diversity element (30.2%) demonstrates that there is significant room for improvement. This study presents a promising strategy through which programs can improve recruitment of diverse residents.
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Internado y Residencia , Otolaringología , Humanos , Estudios Retrospectivos , Grupos Minoritarios , Otolaringología/educaciónRESUMEN
BACKGROUND: After definitive cancer treatment, survivors of head and neck cancer (HNC) are commonly recommended to participate in therapies aimed at reducing the burden of treatment-related side effects. OBJECTIVE: In this study, we evaluated whether adherence to referral to physical therapy (PT) and speech-language pathology therapy (SLPT) is related to patient health literacy (HL). METHODS: This is a retrospective cohort analysis of patients attending a multidisciplinary HNC survivorship clinic between 2017 and 2019. HL was measured using the Brief Health Literacy Screen, with scores below 10 indicating inadequate HL. Chi-square and logistic regression were used to evaluate the association between HL and adherence to PT or SLPT referral. KEY RESULTS: From the overall cohort (N = 454), 80 patients (18%) had inadequate HL. Compared to those with adequate HL, patients with inadequate HL were significantly less likely to complete initial PT evaluation (74% vs. 58%, p = .034) but were not significantly less likely to complete initial SLPT evaluation (70% vs. 61%, p = .37). After adjusting for age, primary tumor site, and treatment stage, we found that patients with inadequate HL were half as likely to follow up for initial PT evaluation (odds ratio 0.45, p = .032). CONCLUSION: Overall, inadequate HL is associated with reduced adherence to PT but is not associated with adherence to SLPT among HNC survivors. These results highlight the clinical importance of HL and underscore the need for interventions to facilitate adherence to treatment for patients with inadequate HL. [HLRP: Health Literacy Research and Practice. 2023;7(1):e52-e60.].
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Neoplasias de Cabeza y Cuello , Alfabetización en Salud , Humanos , Estudios Retrospectivos , Neoplasias de Cabeza y Cuello/terapia , Estudios de Cohortes , SobrevivientesRESUMEN
Objective: The purpose of this study was to evaluate the utility of ICD-O-3-classified local tumor behavior as a prognosticator of head and neck paraganglioma (HNP) outcomes. Study Design: Retrospective cohort study. Setting: National Cancer Database between 2004 and 2016. Methods: This study included patients aged ≥18 years who were diagnosed with HNP. Clinical outcomes and clinicopathologic features were compared with regard to local tumor behavior. Results: Our study included 525 patients, of which the majority had HNP classified as locally invasive (45.9%) or borderline (37.9%). The most common anatomic sites involved were the carotid body (33.7%), intracranial regions (29.0%), or cranial nerves (25.5%). Carotid body tumors were exclusively locally invasive, whereas intracranial and cranial nerve HNP were overwhelmingly benign or borderline (94% and 91%, respectively). One-fourth of patients underwent pathologic analysis of regional lymph nodes, of which the majority were positive for metastasis (80.6%). Metastasis to distant organs was twice as common in patients with locally invasive tumors vs benign (15% vs 7.1). For benign disease, surgery with radiotherapy (adjusted hazard ratio [aHR], 40.45; P = .006) and active surveillance (aHR, 24.23; P = .008) were associated with worse survival when compared with surgery alone. For locally invasive tumors, greater age (aHR, 1.07; P < .0001) and positive surgical margins (aHR, 4.13; P = .010) were predictors of worse survival, while combined surgery and radiotherapy were predictors of improved survival vs surgery alone (aHR, 0.31; P = .027). Conclusion: While criteria for tumor behavior could not be defined, our results suggest that such a classification system could be used to enhance HNP risk stratification and guide clinical management decisions.