Faculty Bibliography

BACKGROUND:Oral and oropharyngeal cancers are among the most common cancers globally. This study aimed to assess the incidence and mortality trends of oral and oropharyngeal cancers in China between 2005 and 2013. METHODS:Estimates of national trends of oral and oropharyngeal cancers were based on the data from Chinese Cancer Registry Annual Reports. The crude incidence rates of oral and oropharyngeal cancers between 2015 and 2035 were evaluated. The age-standardized rate was based on the world standard population. RESULTS:It was estimated that 285,857 new cases and 132,698 deaths were related to oral and oropharyngeal cancers in China between 2005 and 2013, with mouth and tongue cancers being the most frequently diagnosed and the leading causes of death among all oral and oropharyngeal cancers. The incidence rates of oral and oropharyngeal cancer fluctuated from 1.69 to 1.89 per 100,000 person-years, and the mortality rate showed an increasing trend, ranging from 0.77 and 0.84 per 100,000 person-years. Males were more susceptible than females to oral and oropharyngeal cancers. The incidence and mortality rates of oral and oropharyngeal cancers were significantly higher in urban regions. The crude incidence rates of oral cancers are projected to increase from 2.26 to 3.21 per 100,000 person-years over the next 20 years in China. CONCLUSION/CONCLUSIONS:The incidence of oral and oropharyngeal cancers fluctuated, whereas the mortality rate showed an upward trend from 2005 to 2013. A heavier burden from oral and oropharyngeal cancers is predicted in the next two decades in China.

The auditory system can theoretically encode frequencies by either the rate or place of stimulation within the cochlea. Previous work with cochlear implants has demonstrated that both changes in timing and place can be described as pitch changes but are perceptually orthogonal. Using multidimensional scaling, the present experiment extends the previous findings that timing and place changes are perceptually orthogonal into the cochlear apex using long 31-mm electrode arrays. However, temporal cues seem to be more reliable across subjects at the apex while place cues seem to be more reliable at the middle of the cochlea.

Chronic flaccid facial paralysis (FFP>2 years) may be approached with static and dynamic techniques. A horizontal zonal assessment evaluates the upper, middle, and lower thirds of the face. Surgery is tailored to an individual's deficits, goals, and health status. While dynamic reanimation is the gold standard for rehabilitation, there are cases in which static approaches are more appropriate or may be used as an adjunct to dynamic techniques. This article focuses on the surgical management of FFP primarily using static approaches to the individual zones of the face to create resting symmetry.

OBJECTIVES:Human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is a unique form of head and neck cancer with improved prognosis. We assessed survival for stage I patients with low- or intermediate-risk pathologic features with surgery alone compared with surgery with adjuvant radiation (RT) or chemoradiation (CRT). MATERIALS AND METHODS:We identified patients with stage I HPV+ OPSCC (after restaging with 8th edition staging system) treated with surgery alone, adjuvant RT or CRT in the National Cancer Data Base from 2010 to 2013. We compared survival for low-risk patients (≤1 metastatic lymph nodes with no adverse features) and intermediate-risk patients (2-4 metastatic lymph nodes, microscopic extranodal extension (ENE) or lymphovascular invasion). RESULTS:We examined 1677 patients with median follow-up of 43.9 months. In the intermediate-risk group, 4-year overall survival was 94.0% with surgery alone, 91.5% with adjuvant RT and 92.0% with adjuvant CRT (p = 0.72). There were similar rates of overall survival in the low-risk group. In multivariable models accounting for clinicopathologic differences the dose of adjuvant RT was not associated with mortality. On Cox proportional hazard modeling, adjuvant RT (HR 0.94; CI 0.43-2.08) or CRT (HR 0.96; CI 0.45-2.11) did not significantly improved survival compared with surgery alone in the intermediate-risk group (reference). Similar results were seen in the low-risk group. The composite number of pathologic risk features significantly improved risk stratification. CONCLUSION:We provide observational evidence that adjuvant RT or CRT does not provide a survival benefit for stage I HPV+ OPSCC with low- or intermediate-risk pathologic features.

Most animals orient their bodies with respect to gravity to facilitate locomotion and perception. The neural circuits responsible for these orienting movements have long served as a model to address fundamental questions in systems neuroscience. Though postural control is vital, we know little about development of either balance reflexes or the neural circuitry that produces them. Recent work in a genetically and optically accessible vertebrate, the larval zebrafish, has begun to reveal the mechanisms by which such vestibular behaviors and circuits come to function. Here we highlight recent work that leverages the particular advantages of the larval zebrafish to illuminate mechanisms of postural development, the role of sensation for balance circuit development, and the organization of developing vestibular circuits. Further, we frame open questions regarding the developmental mechanisms for functional circuit assembly and maturation where studying the zebrafish vestibular system is likely to open new frontiers.

BACKGROUND:Trigeminal neuralgia (TN) is a chronic orofacial pain syndrome, which manifests as severe pain in the distribution of any trigeminal nerve branch. Though traditionally responsive to anticonvulsant therapy, TN can become refractory to medications and require surgical intervention. CASE DESCRIPTION/METHODS:We present a case of V2 TN that was treated with minimally invasive trigeminal ablation. The patient presented with a 6-year history of type 1 TN and had failed the maximum tolerated doses of carbamazepine and gabapentin. There was no evidence of vascular compression on neuroimaging. After the patient refused stereotactic radiosurgery, she was offered minimally invasive trigeminal ablation. At 5 months postoperatively the patient reported complete alleviation of pain with tolerable sensorineural numbness. CONCLUSIONS:The endoscopic approach allows for precise targeting of V2, which is ideal in patients undergoing targeted neuroablation for pain. This is the first documented case of a transoral endoscopic approach toward ablative V2 TN management.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Our laboratory recently described NR4A1 as an endogenous inhibitor of TGF-β-induced vocal fold (VF) fibrosis. Our prior report described the temporal expression of NR4A1 during VF healing in vivo and the effects of NR4A1 knockdown on fibroplastic cell activities in vitro. Based on these findings, we hypothesized that cytosporone-B (Csn-B), an NR4A1 agonist, may hold significant therapeutic potential. STUDY DESIGN/METHODS:In vitro. METHODS:Human VF fibroblasts were exposed to TGF-β1+/-Csn-B. Expression of genes related to fibrosis were quantified. In addition, contraction was assayed as a surrogate for the fibrotic phenotype in our cell line. RESULTS:TGF-B1 stimulated COL1A1 and ACTA2, as expected. Csn-B significantly downregulated TGF-β1-mediated upregulation of these genes (P = .009, P = .03, respectively). Csn-B had no effect on genes related to TGF-β/Smad signaling. Csn-B also decreased the TGF-β1-mediated contractile phenotype in our cells (P = .004). CONCLUSIONS:NR4A1 is an endogenous inhibitor of fibrosis in the vocal folds and Csn-B, as an NR4A1 agonist, may evolve as an ideal, therapeutic candidate for this challenging condition. LEVEL OF EVIDENCE/METHODS:NA Laryngoscope, 2018.

OBJECTIVE:The clinical use of microsignals recorded over broad cortical regions is largely limited by the chronic reliability of the implanted interfaces. APPROACH/METHODS:We evaluated the chronic reliability of novel 61-channel micro-electrocorticographic (µECoG) arrays in rats chronically implanted for over one year and using accelerated aging. Devices were encapsulated with polyimide (PI) or liquid crystal polymer (LCP), and fabricated using commercial manufacturing processes. In vitro failure modes and predicted lifetimes were determined from accelerated soak testing. Successful designs were implanted epidurally over the rodent auditory cortex. Trends in baseline signal level, evoked responses and decoding performance were reported for over one year of implantation. MAIN RESULTS/RESULTS:Devices fabricated with LCP consistently had longer in vitro lifetimes than PI encapsulation. Our accelerated aging results predicted device integrity beyond 3.4 years. Five implanted arrays showed stable performance over the entire implantation period (247-435 days). Our regression analysis showed that impedance predicted signal quality and information content only in the first 31 days of recordings and had little predictive value in the chronic phase (> 31 days). In the chronic phase, site impedances slightly decreased yet decoding performance became statistically uncorrelated with impedance. We also employed an improved statistical model of spatial variation to measure sensitivity to locally varying fields, which is typically concealed in standard signal power calculations. SIGNIFICANCE/CONCLUSIONS:These findings show that µECoG arrays can reliably perform in chronic applications in vivo for over one year, which facilitates the development of a high-density, clinically viable interface.

BACKGROUND:Quality improvement (QI) in the management of chronic rhinosinusitis (CRS) is garnering increasing attention. Defining frameworks and metrics to assess the quality of key components in CRS management could assist in reducing unwarranted practice variation and increase high-quality care. METHODS:A panel of the American Rhinologic Society (ARS) QI committee reviewed the literature to determine important presurgical components of CRS care that warrant QI. The evidence was organized into 4 categories: (1) diagnosis, (2) medical management, (3) appropriate patient selection for surgery, and (4) patient-centered discussion. The combination of these categories was used to develop a framework termed the CRS Appropriate Presurgical Algorithm (CAPA). RESULTS:Prior to offering surgery for CRS, the best available evidence support the following quality metrics: (1) a guideline-based diagnosis should be confirmed; (2) appropriate medical management, including a minimum of topical corticosteroid therapy and saline irrigations, should have been attempted (assuming patient tolerance); (3) a computed tomography (CT) scan should be obtained (to confirm the presence of sinus inflammation and for surgical planning); and (4) a patient-centered discussion regarding treatment options for refractory CRS (ie, alternative medical therapies vs surgery vs observation) while focusing on risks and benefits, the need for long-term medical compliance, and understanding of patient preferences and expectations. CONCLUSION/CONCLUSIONS:Defining metrics that assess key components to CRS care prior to offering surgery has the potential to further improve upon an already successful treatment paradigm, reduce unwarranted practice variation, and to ensure that patients are receiving a similar level of high-quality care.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To assess patterns of care and outcomes with the use of neoadjuvant chemotherapy followed by definitive radiation in local-regionally advanced nasopharyngeal carcinoma. STUDY DESIGN/METHODS:Retrospective database analysis. METHODS:We queried the National Cancer Database for patients with T3-4N2 or T1-4N3 nasopharyngeal carcinoma who received concurrent chemoradiotherapy or neoadjuvant chemotherapy followed by radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method, propensity-score matching, and a Cox proportional hazards model adjusting for demographic and disease-specific prognostic factors. RESULTS:P = .001). At a median follow-up of 36.6 months, patients had 3-year OS of 66% in the neoadjuvant group compared with 70% in those who received concurrent chemoradiotherapy (log rank P = .29). On subgroup analysis by histology, T stage, and N stage, there remained no differences in OS between the two groups. On multivariable analysis, there was no significant survival difference associated with neoadjuvant chemotherapy (adjusted hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 0.89-1.25, P = .54). In a propensity score-matched population of 1,008 patients (504 with neoadjuvant therapy and 504 without), there was no significant survival difference associated with neoadjuvant chemotherapy (H: 1.13, 95% CI: 0.93-1.38, P = .22). CONCLUSIONS:Neoadjuvant chemotherapy was used in over 25% of patients, and its use is increasing. However, neoadjuvant chemotherapy was not associated with any differences in survival compared to concurrent chemoradiotherapy. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2018.