Faculty Bibliography

BACKGROUND:Frailty is defined as a disability in those of advanced age, often with comorbidities, poor nutritional status, cognitive decline, and reduced functional status. OBJECTIVES/OBJECTIVE:The purpose of this article is to discuss the concept of frailty, assess the use of a comprehensive geriatric assessment (CGA), and understand the implications for treatment to maintain or enhance physical, functional, and cognitive health of older adult patients with cancer. METHODS:Literature about frailty in older adult patients diagnosed with cancer was reviewed to determine evidence-based assessment and treatment options. FINDINGS/RESULTS:About half of all older adult patients with cancer experience some degree of frailty. CGA is a useful way to evaluate frailty and the extent of limitations. Many frailty-specific tools have been developed. Evidence-based strategies are available to address limitations associated with frailty in older adult patients with cancer.

A potential bottleneck to improving speech perception performance in cochlear implant (CI) users is that some of their electrodes may poorly encode speech information. Several studies have examined the effect of deactivating poorly encoding electrodes on speech perception with mixed results. Many of these studies focused on identifying poorly encoding electrodes by some measure (e.g. electrode discrimination, pitch ordering, threshold, CT-guided, masked modulation detection), but provide inconsistent criteria about which electrodes, and how many, should be deactivated, and without considering how speech information becomes distributed across the electrode array. The present simulation study addresses this issue using computational approaches. Previously validated models were used to generate predictions of speech scores as a function of all possible combinations of active electrodes in a 22-electrode array in three groups of hypothetical subjects representative of relatively better, moderate, and poorer performing CI users. Using high-performance computing, over 500 million predictions were generated. Although deactivation of the poorest encoding electrodes sometimes resulted in predicted benefit, this benefit was significantly less relative to predictions resulting from model-optimized deactivations. This trend persisted when using novel stimuli (i.e. other than those used for optimization) and when using different processing strategies. Optimum electrode deactivation patterns produced an average predicted increase in word scores of 10% with some scores increasing by more than 20%. Optimum electrode deactivation patterns typically included 11 to 19 (out of 22) active electrodes, depending on the performance group. Optimal active electrode combinations were those that maximized discrimination of speech cues, maintaining 80%-100% of the physical span of the array. The present study demonstrates the potential for further improving CI users' speech scores with appropriate selection of active electrodes.

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.

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.

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.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To determine if a long segment of trachea can be transplanted as a vascularized organ and to determine if a tracheal transplant is a potential surgical option for a long-segment circumferential tracheal defect. STUDY DESIGN/METHODS:Animal model. METHODS:Four (two donors and two recipients) adult domestic Yorkshire swine were used. Two sets of transplants were performed from a donor to recipient pig. The transplant was placed heterotopically (not in continuity with the airway), and the recipient animals were monitored for 14 days to ensure the transplants were well vascularized. Immunosuppressive therapies included methylprednisolone, cyclosporine, and azathioprine. Gross as well as histological examination of multiple tissues types including mucosa, cartilage, muscle, and blood vessels were performed postsacrifice on day 14. RESULTS:Recipient animal weights ranged from 40 to 42 kilograms. Both recipient pigs survived the full 14 days of study and exhibited normal activity and appetite. Ischemia time of transplanted grafts ranged from 63 to 72 minutes. Transplanted tracheas included a minimum of 15 cartilaginous rings and measured greater than 10 cm in length. Both grafts maintained a robust blood supply throughout the duration of study. CONCLUSIONS:The entire visceral compartment can be reliably transplanted, either as a single component (trachea) or as a chimeric flap with multiple components (trachea, esophagus, larynx, and pharynx). Further studies in the swine model should be considered to study the effects of transplanting the trachea orthotopically into the native airway. Further studies are needed into the reliability of this technique of transplantation in humans. LEVEL OF EVIDENCE/METHODS:NA Laryngoscope, 128:S1-S9, 2018.

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.

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.

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.