Faculty Bibliography

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Various animal models have been employed to investigate vocal fold (VF) and phonatory function. However, biomechanical testing techniques to characterize vocal fold structural properties vary and have not compared critical properties across species. We adapted a nondestructive, automated indentation mapping technique to simultaneously quantify VF structural properties (VF cover layer and intact VF) in commonly used species based on the hypothesis that VF biomechanical properties are largely preserved across species. STUDY DESIGN/METHODS:Ex vivo animal model. METHODS:Canine, leporine, and swine larynges (n = 4 each) were sagittally bisected, measured, and subjected to normal indentation mapping (indentation at 0.3 mm; 1.2 mm/s) with a 2-mm spherical indenter to quantify normal force along the VF cover layer, structural stiffness, and displacement at 0.8 mN; two-dimensional maps of the free VF edge through the conus elasticus were created for these characterizations. RESULTS:Structural stiffness was 7.79 gf/mm (0.15-74.55) for leporine, 2.48 gf/mm (0.20-41.75) for canine, and 1.45 gf (0.56-4.56) for swine. For each species, the lowest values were along the free VF edge (mean ± standard deviation; leporine: 0.40 ± 0.21 gf/mm, canine: 1.14 ± 0.49 gf/mm, swine: 0.89 ± 0.28 gf/mm). Similar results were obtained for the cover layer normal force at 0.3 mm. On the free VF edge, mean (standard deviation) displacement at 0.08 gf was 0.14 mm (0.05) in leporine, 0.11 mm (0.03) in canine, and 0.10 mm (0.02) in swine. CONCLUSIONS:Automated indentation mapping yielded reproducible biomechanical property measurement of the VF cover and intact VF. Divergent VF structural properties across canine, swine, and leporine species were observed. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2018.

OBJECTIVES:/UNASSIGNED:Prognostic information about the return of vocal fold mobility in patients with iatrogenic unilateral vocal fold immobility (UVFI) can help with informed decisions about temporary and permanent treatment options. Although many variables can influence the likelihood of recovery, clinical experience suggests that cervical versus thoracic injury is a determining factor. The purpose of this study was to compare recovery rates from UVFI between cervical and thoracic injuries. METHODS:/UNASSIGNED:analyses. RESULTS:/UNASSIGNED:Overall, 15% of patients recovered vocal fold mobility at a median of 4.1 months. Patients with cervical injury (65 of 329 [20%]) were significantly more likely to recover mobility than patients with thoracic injury (11 of 173 [6.4%]) (odds ratio, 3.63). The cervical cohort contained more women (68% vs 31%) and was younger (mean age, 60.4 ± 13.8 vs 64.1 ± 16.1 years; Cohen's D = 0.25). CONCLUSIONS:/UNASSIGNED:Patients with cervical injuries resulting in UVFI are 4 times more likely to recover mobility than patients with thoracic injuries. This information can be valuable in counseling patients with UVFI and may affect clinical decision making.

OBJECTIVES:Sentinel lymph node biopsy (SLNB) has been shown to be an accurate technique for staging the neck in early-stage oral cavity squamous cell carcinoma (OCSCC) and has been incorporated in treatment guidelines as an option instead of elective neck dissection (END). However, utilization of SLNB in the United States remains unclear, and existing prospective studies did not directly compare survival between SLNB and END. METHODS:We conducted a retrospective cohort study of patients with stage I to II OCSCC (cT1-2cN0cM0) who underwent staging of the neck in the National Cancer Data Base from 2012 to 2015. We compared the practice patterns and outcomes of patients who underwent SLNB versus END. RESULTS:We identified 8,328 eligible patients with a median follow-up of 35.4 months. SLNB was used for 240 patients, or 2.9% of stage I to II OCSCC. Completion neck dissection was avoided in 63.8% of patients undergoing SLNB. SLNB was associated with reduced perioperative morbidity, with median length of hospital stay of 1.0 days versus 3.0 days after END (P < 0.001). Perioperative 30-day mortality was 0% after SLNB versus 0.7% after END (P = 0.42). Overall 3-year survival was 82.0% after SLNB and 77.5% after END (P = 0.40). After adjustment, overall survival was equivalent between patients who underwent SLNB versus END (adjusted hazard ratio 1.03, confidence interval 0.67-1.59). CONCLUSIONS:SLNB for stage I to II OCSCC is associated with reduced length of hospital stay and equivalent overall survival compared with END. Despite these attributes, SLNB remains rarely used in the United States. LEVEL OF EVIDENCE:NA Laryngoscope, 129:162-169, 2019.

OBJECTIVE:The aim of this study was to evaluate the prevalence of comorbidities among patients with head and neck squamous cell carcinoma (HNSCC) at the time of their cancer diagnosis and during their survivorship trajectory. The second aim was to evaluate the differences in comorbidities developed according to treatment type received. STUDY DESIGN:Retrospective cross-sectional. SETTING:SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database. SUBJECTS AND METHODS:Individuals with a first-incident primary diagnosis of HNSCC from 2004 to 2011 per the SEER-Medicare database were included in analysis. The presence or absence of 30 comorbid conditions of interest was identified during distinct periods and analyzed according to treatment with surgery alone, primary (chemo)radiation, or surgery with (chemo)radiation. RESULTS:The study population consisted of 10,524 individuals diagnosed with HNSCC, with a mean age of 74.8 years. At diagnosis, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and diabetes were the most prevalent comorbidities, and they increased over time. The probability of developing treatment-related comorbidities such as pneumonia, dysphagia, weight loss, malnutrition, and dental issues rose significantly in the short and long term following treatment ( P < .05). By 5 years from cancer diagnosis, patients were most likely to have newly diagnosed hypertension, dysphagia, anemia, and weight loss. Primary surgery alone was associated with a lower risk of diagnosis with these treatment-related comorbidities, as compared with treatments involving radiation therapy and/or chemotherapy in the primary or adjuvant settings ( P < .05). CONCLUSIONS:There is a large burden of comorbidities among patients following HNSCC treatment, which warrant clinical attention during surveillance.

BACKGROUND:A major concern of patients who have stereotactic radiosurgery is the long-term risk of having a secondary intracranial malignancy or, in the case of patients with benign tumours treated with the technique, the risk of malignant transformation. The incidence of stereotactic radiosurgery-associated intracranial malignancy remains unknown; therefore, our aim was to estimate it in a population-based study to assess the long-term safety of this technique. METHODS:We did a population-based, multicentre, cohort study at five international radiosurgery centres (Na Homolce Hospital, Prague, Czech Republic [n=2655 patients]; Ruber International Hospital, Madrid, Spain [n=1080], University of Pittsburgh Medical Center, Pittsburgh, PA, USA [n=1027]; University of Virginia, Charlottesville, VA, USA [n=80]; and NYU Langone Health System, New York, NY, USA [n=63]). Eligible patients were of any age, and had Gamma Knife radiosurgery for arteriovenous malformation, trigeminal neuralgia, or benign intracranial tumours, which included vestibular or other benign schwannomas, WHO grade 1 meningiomas, pituitary adenomas, and haemangioblastoma. Patients were excluded if they had previously had radiotherapy or did not have a minimum follow-up time of 5 years. The primary objective of the study was to estimate the incidence of stereotactic radiosurgery-associated intracranial malignancy, including malignant transformation of a benign lesion or development of radiation-associated secondary intracranial cancer, defined as within the 2 Gy isodose line. Estimates of age-adjusted incidence of primary CNS malignancies in the USA and European countries were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer (IARC) Global Cancer statistics. FINDINGS/RESULTS:Of 14 168 patients who had Gamma Knife stereotactic radiosurgery between Aug 14, 1987, and Dec 31, 2011, in the five contributing centres, 4905 patients were eligible for the analysis (had a minimum follow-up of 5 years and no history of previous radiation therapy). Diagnostic entities included vestibular schwannomas (1011 [20·6%] of 4905 patients), meningiomas (1490 [30·4%]), arteriovenous malformations (1089 [22·2%]), trigeminal neuralgia (565 [11·5%]), pituitary adenomas (641 [13·1%]), haemangioblastoma (29 [0·6%]), and other schwannomas (80 [1·6%]). With a median follow-up of 8·1 years (IQR 6·0-10·6), two (0·0006%) of 3251 patients with benign tumours were diagnosed with suspected malignant transformation and one (0·0002%) of 4905 patients was considered a case of radiosurgery-associated intracranial malignancy, resulting in an incidence of 6·87 per 100 000 patient-years (95% CI 1·15-22·71) for malignant transformation and 2·26 per 100 000 patient-years (0·11-11·17) for radiosurgery-associated intracranial malignancy. Two (0·0004%) of 4905 patients developed intracranial malignancies, which were judged unrelated to the radiation field. Overall incidence of radiosurgery-associated malignancy was 6·80 per 100 000 patients-years (95% CI 1·73-18·50), or a cumulative incidence of 0·00045% over 10 years (95% CI 0·00-0·0034). The overall incidence of 6·8 per 100 000, which includes institutions from Europe and the USA, after stereotactic radiosurgery was found to be similar to the risk of developing a malignant CNS tumour in the general population of the USA and some European countries as estimated by the CBTRUS and IARC data, respectively. INTERPRETATION/CONCLUSIONS:These data show that the estimated risk of an intracranial secondary malignancy or malignant transformation of a benign tumour in patients treated with stereotactic radiosurgery remains low at long-term follow-up, and is similar to the risk of the general population to have a primary CNS tumour. Although prospective cohort studies with longer follow-up are warranted to support the results of this study, the available evidence suggests the long-term safety of stereotactic radiosurgery and could support physicians counselling patients on Gamma Knife stereotactic radiosurgery. FUNDING/BACKGROUND:None.

Previous studies have shown that tumor necrosis factor alpha (TNFα) is significantly increased in complete Freund's adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFα in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNFα in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. Intra-TMJ injection of CFA (10 μl, 5 mg/ml) induced inflammatory pain in the trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present on day 1 after CFA and persisted for at least 10 days. TNFα in both TG and Sp5C of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was significantly inhibited in TNFα KO mice. The immunofluorescence staining showed that intra-TMJ CFA injection not only enhanced co-localization of TNFα with Iba1 (a marker for microglia) in both TG and Sp5C but also markedly increased the expression of TNFα in the Sp5C neurons. By the methylated DNA immunoprecipitation assay, we also found that DNA methylation at the TNF gene promoter region in the TG was dramatically diminished after CFA injection, indicating that epigenetic regulation may be involved in the CFA-enhanced TNFα expression in our model. Our results suggest that TNFα in the trigeminal nociceptive system plays a critical role in CFA-induced inflammatory TMJ pain.

Pain is a complex multidimensional experience encompassing sensory-discriminative, affective-motivational and cognitive-emotional components mediated by different neural mechanisms. Investigations of neurophysiological signals from simultaneous recordings of two or more cortical circuits may reveal important circuit mechanisms on cortical pain processing. The anterior cingulate cortex (ACC) and primary somatosensory cortex (S1) represent two most important cortical circuits related to sensory and affective processing of pain. Here, we recorded in vivo extracellular activity of the ACC and S1 simultaneously from male adult Sprague-Dale rats (n = 5), while repetitive noxious laser stimulations were delivered to animalÕs hindpaw during pain experiments. We identified spontaneous pain-like events based on stereotyped pain behaviors in rats. We further conducted systematic analyses of spike and local field potential (LFP) recordings from both ACC and S1 during evoked and spontaneous pain episodes. From LFP recordings, we found stronger phase-amplitude coupling (theta phase vs. gamma amplitude) in the S1 than the ACC (n = 10 sessions), in both evoked (p = 0.058) and spontaneous pain-like behaviors (p = 0.017, paired signed rank test). In addition, pain-modulated ACC and S1 neuronal firing correlated with the amplitude of stimulus-induced event-related potentials (ERPs) during evoked pain episodes. We further designed statistical and machine learning methods to detect pain signals by integrating ACC and S1 ensemble spikes and LFPs. Together, these results reveal differential coding roles between the ACC and S1 in cortical pain processing, as well as point to distinct neural mechanisms between evoked and putative spontaneous pain at both LFP and cellular levels.

Introduction The aims of this study are to investigate a possible correlation between the time point at which peak hydraulic pressure and peak force on the cochlear wall appears during insertion of a cochlear implant electrode and to investigate whether a difference exists in maximum hydraulic pressure and maximum force on the cochlear wall during a fast and slow insertion, a manual and automatic insertion and an electrode insertion into a narrow or wide round window (RW) opening. Material and methods Twenty fresh frozen human temporal bones were used. Intracochlear hydraulic pressure and force on the cochlear wall were recorded during round window insertions of a straight electrode array with different insertion speeds, different insertion methods and with different widths of the opening of the RW. Results A statistical signifcant correlation between the time point at which peak hydraulic pressure and peak force on the cochlear wall appears was found (r=0.91, p<0.001). Furthermore, a slow insertion speed showed a higher hydraulic pressure and a higher force on the cochlear wall compared to a fast insertion speed (p<0.001). No statistically signifcant effect of insertion method or the width of the opening of the RW was found on hydraulic pressure and on force on the cochlear wall. Conclusions Peak hydraulic pressure and peak force on the cochlear wall during electrode insertion seems to appear at approximately the same time. Furthermore, a slow insertion speed seems to result in a higher intracochlear hydraulic pressure and a higher force on the cochlear wall