Extraprimary Local Recurrence of Esthesioneuroblastoma: Case Series and Literature Review.

OBJECTIVES: Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy arising from olfactory neuroepithelium. Recurrence typically occurs locoregionally at the primary site or in the form of cervical metastasis. Delayed local recurrence away from the initial primary site is exceedingly rare. METHODS: Retrospective review of 4 patients with histologically confirmed extraprimary local recurrence of ENB was performed with review of the literature. RESULTS: All cases initially presented with ENB isolated to the cribriform plate(s) treated with primary surgical resection and adjuvant radiotherapy. The first patient had ENB recurrence 8 years posttreatment involving the right orbit. She later developed metastases to the spine, neck, and mandible requiring composite resection and 4 courses of radiotherapy. The second patient had ENB recurrence of the dorsal septum 9 years posttreatment with cervical metastases requiring septectomy, bilateral neck dissection, and radiotherapy. The third patient had ENB recurrence 7 years posttreatment in the posterior nasopharynx requiring endonasal nasopharyngectomy. Finally, the fourth patient had ENB recurrence 12 years posttreatment in the sphenopalatine foramen, which was endoscopically resected. At the time of this review, all 4 patients were disease free at 32, 21, 4, and 24 months posttreatment follow-ups, respectively. CONCLUSIONS: This case series describes the rare phenomenon of delayed extraprimary local recurrence of histologically confirmed ENB. Treatment of extraprimary recurrences, analogous to other forms of ENB, should include primary surgical resection with adjuvant radiotherapy for generally favorable outcomes. Long-term close follow-up based on symptoms, endoscopy, and imaging is essential because of the risk of delayed recurrence.

An Algorithm for Sellar Reconstruction Following the Endoscopic Endonasal Approach: A Review of 300 Consecutive Cases.

Objectives/Hypotheses The endoscopic endonasal approach (EEA) is the workhorse endoscopic procedure for sellar and parasellar pathology. Various reconstruction techniques have been reported following EEA surgery, ranging from no reconstruction to vascularized flaps. We review our institution's experience with sellar reconstruction following EEA and propose an evidence-based algorithm. Design Retrospective review. Setting Tertiary academic medical center. Participants Patients who underwent endoscopic EEA surgery for sellar or parasellar pathology between March 1, 2013 and August 31, 2016. Main Outcome Measures Patient demographic and clinicopathologic data were collected. Outcome measures included intraoperative and postoperative cerebrospinal fluid (CSF) leak rates and extent of resection (gross or subtotal). Results Three hundred consecutive patients were included. Depending on the presence and grade of intraoperative CSF leak, cases were reconstructed using either a free mucosal graft (FMG) or nasoseptal flap (NSF). Intraoperative and postoperative CSF leak rates were 30.7% and 2.3%, respectively. Multivariable logistic regression found that intraoperative CSF leak was associated with recurrent disease (odds ratio [OR] 2.47, p = 0.004), with no apparent predictors of postoperative CSF leak. Conclusions Based on this large series, we propose the following algorithm for sellar reconstruction: FMG for no CSF leak; fat graft + FMG ± rigid fixation for low-grade leaks; and fat graft + NSF ± rigid fixation for high-grade leaks.

The value of frontal sinusotomy for chronic rhinosinusitis with nasal polyps-A cost utility analysis.

OBJECTIVES/HYPOTHESIS: The number of surgical procedures performed for frontal sinusitis and the associated costs have increased dramatically over the past decade. The purpose of this study was to evaluate the cost-effectiveness of endoscopic frontal sinusotomy (EFS) in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). STUDY DESIGN: Cohort-style Markov decision-tree economic model with a 36-year time horizon. METHODS: Matched cohorts of CRSwNP patients who underwent endoscopic sinus surgery (ESS) with (n = 139) and without (n = 49) EFS were compared to each other and to patients (n = 139) from the Medical Expenditures Survey Panel database who underwent medical management for chronic rhinosinusitis. Multi-year health utility values were calculated from responses to the EuroQol 5-Dimension instrument. The primary outcome measure was the incremental cost-effectiveness ratio (ICER). RESULTS: Decision analysis showed that ESS without EFS proved more cost-effective than ESS with EFS or medical management. ESS without EFS compared to medical management yielded an ICER of $9,004/quality-adjusted life year (QALY). ESS with EFS compared to ESS without EFS yielded an ICER of $62,310/QALY. At a willingness-to-pay (WTP) threshold of $50,000/QALY, ESS without EFS was more cost-effective than ESS with EFS with 52.1% certainty. These results were robust to one-way analysis and probabilistic sensitivity analysis. CONCLUSIONS: ESS remains a cost-effective intervention compared to medical therapy alone for patients with CRSwNP. In this study, the addition of frontal sinusotomy during ESS for patients with CRSwNP was not found to be cost-effective at a WTP threshold of $50,000/QALY, but may be cost effective at a higher threshold of $100,000/QALY. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:43-51, 2018.

The impact of asthma on the cost effectiveness of surgery for chronic rhinosinusitis with nasal polyps.

BACKGROUND: The objective of this work was to evaluate the impact of asthma on the cost-effectiveness profile of endoscopic sinus surgery (ESS) compared to medical therapy for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: The study design consisted of a cohort-style Markov decision-tree cost utility analysis with a 35-year time horizon. Matched cohorts of CRSwNP patients with (n = 95) and without (n = 95) asthma who underwent ESS were compared with cohorts of patients from the national Medical Expenditures Survey Panel (MEPS) database who underwent medical management for chronic rhinosinusitis (CRS). Baseline, 1-year, and 2-year health utility values were calculated from responses to the EuroQol-5 Dimension (EQ-5D) instrument in both cohorts. The primary outcome measure was the incremental cost effectiveness ratio (ICER) for each cohort. RESULTS: The reference cases for CRSwNP patients with and without asthma yielded ICERs for ESS vs medical therapy alone of $12,066 per quality-adjusted life year (QALY) and $7,369 per QALY, respectively. At a willingness-to-pay threshold of $50,000/QALY, the ICER scatter plots demonstrated 86% and 99% certainty that the ESS strategy was the most cost-effective option for CRSwNP patients with and without asthma, respectively. ESS was not significantly more cost effective for CRSwNP patients without asthma (p = 0.494). CONCLUSION: ESS remains cost effective compared to medical therapy for patients both with and without asthma. While the comorbidity of asthma results in an inferior ICER result, it does not result in a statistically significant negative impact on the overall cost effectiveness of ESS.

Impact of Primary Language and Insurance on Pediatric Hearing Health Care in a Multidisciplinary Clinic.

Objective This study aims to describe the effects of primary language and insurance status on care utilization among deaf or hard-of-hearing children under active otolaryngologic and audiologic care. Study Design Cross-sectional analysis. Setting Multidisciplinary hearing loss clinic at a tertiary center. Subjects and Methods Demographics, hearing loss data, and validated survey responses were collected from 206 patients aged 0 to 19 years. Two-sided t tests and χ2 tests were used to obtain descriptive statistics and hypothesis testing. Results Of the sample, 52.4% spoke primarily English at home. Non-English-speaking children and families were less likely to receive psychiatric counseling (12.2% vs 35.2% in the English group, P < .001) and reported more difficulty obtaining educational interventions ( P = .016), and 68.9% had public insurance. Parents of publicly insured children were less likely to know the type or degree of their child's hearing loss (56.9% vs 75.4%, P = .022), and these children were older on presentation to the clinic (8.5 vs 6.5 years of age, P = .01) compared to privately insured children. Publicly insured children were less likely to receive cochlear implants ( P = .046) and reported increased difficulty obtaining hearing aids ( P = .047). While all patients reported impairment in hearing-related quality of life, publicly insured children aged 2 to 7 years were more likely to perform below minimum thresholds on measures of auditory/oral functioning. Conclusion Even when under active care, deaf or hard-of-hearing children from families who do not speak English at home or with public insurance face more difficulty obtaining educational services, cochlear implants, and hearing aids. These findings represent significant disparities in access to necessary interventions.

Prevalence of Hearing Loss in US Children and Adolescents: Findings From NHANES 1988-2010.

Importance: There have been concerns about increasing levels of hearing impairment in children and adolescents, especially in relation to noise exposure, because even mild levels of hearing loss can affect educational outcomes. Objective: To further characterize changes in prevalence of hearing loss and noise exposures in the US pediatric population over time. Design, Setting, and Participants: This is a retrospective analysis of demographic and audiometric data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), NHANES 2005-2006, NHANES 2007-2008, and NHANES 2009-2010. The NHANES are nationally representative survey data sets collected and managed by the US National Center for Health Statistics, and this study includes a total of 7036 survey participants ages 12 to 19 years with available audiometric measurements. Exposures: Hearing-related behaviors and risk factors such as history of ear infections, noise exposures, firearm use, and hearing protection use. Main Outcomes and Measures: Level of hearing loss measured by pure-tone audiometry, as well as high-frequency and low-frequency hearing loss and noise-induced threshold shifts. Results: Overall, data from 7036 survey participants ages 12 to 19 years with available audiometric measurements were analyzed. The prevalence of hearing loss increased from NHANES III to NHANES 2007-2008 (17.0% to 22.5% for >15 dB hearing loss; absolute difference, 5.5%; 95% CI, 6.1%-10.3%) but decreased in the NHANES 2009-2010 to 15.2% (absolute difference, 7.2%; 95% CI, 2.0%-12.4%) with no significant overall secular trend identified. There was an overall rise in exposure to loud noise or music through headphones 24 hours prior to audiometric testing from NHANES III to NHANES 2009-2010. However, noise exposure, either prolonged or recent, was not consistently associated with an increased risk of hearing loss across all surveys. The most recent survey cycle showed that nonwhite race/ethnicity and low socioeconomic status are independent risk factors for hearing loss. Conclusions and Relevance: This analysis did not identify significant changes in prevalence of hearing loss in US youth ages 12 to 19 years over this time period despite increases in reported noise exposures. No consistent associations were shown between noise exposure and hearing loss, though there was an association between racial/ethnic minority status and low socioeconomic status and increased risk of hearing loss. Ongoing monitoring of hearing loss in this population is necessary to elucidate long-term trends and identify targets for intervention.

Cost utility analysis of endoscopic sinus surgery for chronic rhinosinusitis with and without nasal polyposis.

OBJECTIVE: To evaluate the cost-effectiveness of endoscopic sinus surgery (ESS) compared to medical therapy for patients with chronic rhinosinusitis (CRS) with and without nasal polyposis (NP). STUDY DESIGN: Cohort-style Markov decision-tree economic model with a 36-year time horizon. METHODS: Two cohorts of 229 CRS patients with and without NP who underwent ESS were compared with a matched cohort of 229 CRS patients from the Medical Expenditures Survey Panel database (Agency for Healthcare Research and Quality, Rockville, MD) who underwent medical management. Utility scores were calculated from sequential patient responses to the EuroQol five-dimensions questionnaire. Decision-tree analysis and a 10-state Markov model utilized published event probabilities and primary data to calculate long-term costs and utility. The primary outcome was the incremental cost per quality-adjusted life year (QALY). Thorough sensitivity analyses were performed. RESULTS: The reference case for CRS with NP yielded an incremental cost-effectiveness ratio (ICER) for ESS versus medical therapy of $5,687.41/QALY. The reference case for CRS without NP yielded an ICER of $5,405.44/QALY. The cost-effectiveness acceptability curve in both cases demonstrated 95% certainty that the ESS strategy was the most cost-effective option at a willingness-to-pay threshold of $20,000/QALY or higher. These results were robust to one-way and probabilistic sensitivity analysis. CONCLUSION: This study demonstrates the cost-effectiveness of ESS compared to medical therapy alone for the management of CRS patients both with and without NP. The presence of nasal polyps was not found to affect the overall cost-effectiveness of ESS. LEVEL OF EVIDENCE: 2C. Laryngoscope, 127:29-37, 2017.

Cost utility analysis of endoscopic sinus surgery for chronic rhinosinusitis.

BACKGROUND: The purpose of this work was to evaluate the cost-effectiveness of endoscopic sinus surgery (ESS) compared to medical therapy for patients with chronic rhinosinusitis (CRS). METHODS: The study design consisted of a microsimulation Markov decision-tree economic model with a 31-year time horizon. A cohort of 489 patients who underwent ESS for CRS were matched 1 to 1 with a cohort of 489 patients from the national Medical Expenditures Panel Survey database who underwent medical management for CRS. Utility scores were calculated from responses to the EuroQol 5-Dimension instrument in both cohorts. Decision-tree analysis and a subsequent 10-state Markov model utilized published event probabilities as well as primary data from a large multisurgeon prospective outcomes study to calculate long-term costs and utility. The primary outcome measure was incremental cost per quality-adjusted life year (QALY). Multiple sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratio (ICER) for ESS vs medical therapy alone was $13,851.26 per QALY. The cost effectiveness acceptability curve demonstrated 85.84% and 98.69% certainty that the ESS strategy was the most cost-effective option at willingness-to-pay thresholds of $25,000 and $50,000 per QALY, respectively. CONCLUSION: This study shows ESS to be a cost-effective intervention compared to medical therapy alone for the management of patients with CRS.

Protein kinase Gin4 negatively regulates flippase function and controls plasma membrane asymmetry.

Plasma membrane function requires distinct leaflet lipid compositions. Two of the P-type ATPases (flippases) in yeast, Dnf1 and Dnf2, translocate aminoglycerophospholipids from the outer to the inner leaflet, stimulated via phosphorylation by cortically localized protein kinase Fpk1. By monitoring Fpk1 activity in vivo, we found that Fpk1 was hyperactive in cells lacking Gin4, a protein kinase previously implicated in septin collar assembly. Gin4 colocalized with Fpk1 at the cortical site of future bud emergence and phosphorylated Fpk1 at multiple sites, which we mapped. As judged by biochemical and phenotypic criteria, a mutant (Fpk1(11A)), in which 11 sites were mutated to Ala, was hyperactive, causing increased inward transport of phosphatidylethanolamine. Thus, Gin4 is a negative regulator of Fpk1 and therefore an indirect negative regulator of flippase function. Moreover, we found that decreasing flippase function rescued the growth deficiency of four different cytokinesis mutants, which suggests that the primary function of Gin4 is highly localized control of membrane lipid asymmetry and is necessary for optimal cytokinesis.