Faculty Bibliography

The relation between pharyngeal tonsil and the bony nasopharynx determines the nasopharyngeal airway patency. Despite its importance, an anatomical study utilizing advanced imaging has not been conducted. The aim of the study was to evaluate the pharyngeal tonsil and bony nasopharynx depth and their ratio (adenoid-nasopharyngeal ratio [ANR]) with relation to sex and age in the general pediatric population. After excluding reported history of adenoidectomy, acute upper airway illness, allergy, and poor quality, 200 randomly selected head computed tomographies (CTs) of children were evaluated. CTs were divided into five age groups (0-5, 5.1-8, 8.1-11, 11.1-14, and 14.1-17 years). For each CT scan, the pharyngeal tonsil, bony nasopharynx and ANR values were calculated. A significant difference was found in the bony nasopharynx and pharyngeal tonsil depth between the five age subgroups (P < 0.001). Both bony nasopharynx and pharyngeal tonsil depth significantly increased between the age groups of 0-5 years to 5.1-8 years (4.17 mm increase, P < 0.001 and 3.47 mm increase, P < 0.009, respectively). The pharyngeal tonsil depth gradually decreases following the age of 8 years. No difference was found between age groups beyond age of eight for both the pharyngeal tonsil tissue and the bony nasopharynx. The ANR has an upward trend in the age group of 5.1-8 years. No sexual predilection was found. The bony nasopharynx and the pharyngeal tonsil tissue both grow during childhood. Different growth rates result in the narrowest airway in the age group of 5.1-8 years (ANR peak). These growth curves should be taken under consideration when treating pediatric pharyngeal tonsil hypertrophy. Clin. Anat., 2019. © 2019 Wiley Periodicals, Inc.

OBJECTIVES/OBJECTIVE:To determine independent risk factors for 30-day readmission, prolonged length of stay (PLOS), and discharge to a rehabilitation facility for those with malignant otitis externa. METHODS:Retrospective cohort study of patients hospitalized with malignant otitis externa (International Classification of Diseases, 9th edition, code 380.14) in the Nationwide Readmissions Database (2013-2014). Overall and disease-specific complication and mortality data were analyzed using chi-squared and multivariate analysis. RESULTS:There were 1267 cases of malignant otitis externa extracted. A PLOS of ≥8 days (90th percentile) was found in 14.2% (n = 180) of patients, and 13.7% (n = 174) were discharged to a facility. Patients were readmitted within 30 days at a rate of 12.5% (n = 159). The overall rates of uncomplicated and complicated diabetes were found to be 42.1% and 17.8%, respectively. Factors independently associated with PLOS included undergoing a surgical procedure (odds ratio [OR] 2.08, P < .001), and having central nervous system complications (OR 3.21, P < .001). Independent risk factors for disposition to a facility included nutritional deficiency (OR 1.91, P = .029), PLOS (OR 4.61, P < .001), and age 65-79 years (OR 6.57, P = .001). Readmission was independently linked to PLOS (OR 3.14, P < .001). Diabetes was not an independent risk factor for any outcome. CONCLUSIONS:Thirty-day readmission, PLOS, and ultimate discharge to a rehabilitation facility were common and closely intertwined. Despite the classic association between diabetes and malignant otitis externa, diabetes was not an independent risk factor for any of our outcomes. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2019.

BACKGROUND AND OBJECTIVES/OBJECTIVE:laser cordectomy with KTP laser ablation for early GSCC, in terms of cure rates and vocal function. STUDY DESIGN/MATERIALS AND METHODS/METHODS:cordectomies and most KTP-ablation procedures were performed under general anesthesia. Some KTP cases with residual disease were treated also under local anesthesia. Videostroboscopy measures, voice handicap index (VHI), GRBAS (a hoarseness scale for Grade, Roughness, Breathiness, Asthenia and Strain) score, and acoustic analyses were performed pre-operatively, 6 months and 3 years after surgery. RESULTS:(50%), P = 0.043. Nevertheless, GRBAS and VHI scores improved comparably in both groups. CONCLUSIONS:cordectomy but may allow for better preservation of vocal fold's architecture and function. Yet, the clinical significance of these findings is unclear, since the subjective measures improved comparably for these two treatment modalities. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Advances in cancer treatment have increased survival for many patients, prompting a need for greater recognition of the long-term complications of treatment. Chemotherapy agents have the potential to induce carcinogenesis and can increase the risk of secondary malignancy. Pegylated liposomal doxorubicin (PLD) used for maintenance treatment of recurrent high-grade serous cancers has been associated with the development of oral cavity squamous cell carcinoma (SCC). STUDY DESIGN/METHODS:Retrospective review. METHODS:Cases of oral cavity SCC in patients with recurrent high-grade serous cancer treated with PLD between 1997 and 2017 at a single institution were reviewed. RESULTS:). Seven patients tested positive for BRCA mutations (four BRCA 1+, three BRCA 2+). No patients had a history of alcohol or tobacco use. All had early-stage oral cavity disease; five were T1N0, two were T2N0, and one had carcinoma in situ. All patients underwent surgery, and two received adjuvant radiation. Four developed locoregional recurrence requiring additional treatment. Of these, one patient died from complications of oral SCC, one developed recurrent ovarian cancer, and two had no evidence of disease of the oral cavity or ovarian cancer at the last follow-up. CONCLUSIONS:Long-term PLD therapy may be associated with the development of oral cavity SCC. A high index of suspicion and routine head and neck examination should be included in follow-up for exposed patients. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2019.

OBJECTIVE:To examine trends in female author representation within original otolaryngology research between 2000 and 2015. METHODS:Original research articles published in 11 otolaryngology journals were analyzed for 2000, 2003, 2006, 2009, 2012, and 2015. The genders of the first and last authors for each article were recorded. Overall female authorship was calculated by summing the numbers of the first, last, and both first and last female-authored articles. Student t test and Cochran-Armitage trend test were utilized to determine significance between years and groups. RESULTS:Of the 9,623 research articles published during 5 representative years, 223 were excluded due to one or more gender-indeterminate authors. Female first authorship exhibited a significant upward trend from 2000 to 2015 (P < 0.0001), as did the proportion of literature with female first and last authors (P < 0.0001). Although female senior authorship in literature with an impact factor (IF) greater than 2 did not increase significantly (10.0% in 2000 to 10.1% in 2015; P = 0.738), this metric did increase significantly just within journals with an IF between 1 and 2 (9.7%-12.3%, P = 0.036). The proportion of articles with a female author in the first, last, or both positions increased from 28% to 39% (P < 0.0001). CONCLUSION/CONCLUSIONS:Increasing female representation in otolaryngology literature may reflect the rising proportion of women within otolaryngology as well as greater mentorship availability. Despite these auspicious strides, female-authored articles nonetheless represent a smaller proportion of the literature, and female senior authors remain a stark minority. Future studies should identify the barriers to female access and advancement within the field. LEVEL OF EVIDENCE/METHODS:III Laryngoscope, 2019.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To assess the safety and efficacy of autologous cultured fibroblasts (ACFs) to treat dysphonia related to vocal fold scar and age-related vocal atrophy (ARVA). STUDY DESIGN/METHODS:Randomized, double-blinded, placebo-controlled, multi-institutional, phase II trial. METHODS:cells or placebo saline was performed at 4-week intervals for each vocal fold. Follow-up was performed at 4, 8, and 12 months. The primary outcome was improved mucosal waves. Secondary outcomes included Voice Handicap Index (VHI)-30, patient reported voice quality outcomes, and perceptual analysis of voice. RESULTS:Fifteen subjects received ACF and six received saline injections. At 4, 8, and 12 months after ACF treatments, a significant improvement in mucosal wave grade relative to baseline was observed in both vocal scar and ARVA groups. Relative to control group, mucosal waves were significantly improved in the ARVA group at 4 and 8 months. Perceptual analysis significantly improved in the vocal scar group 12 months after ACF treatments compared to controls. Vocal scar group reported significantly improved vocal quality from baseline. VHI and expert rater voice grade improved in both groups, but did not achieve significance. No adverse events related to fibroblast injections were observed. CONCLUSIONS:In this cohort, injection of ACFs into the vocal fold lamina propria (LP) was safe and significantly improved mucosal waves in patients with vocal scar and ARVA. ACF may hold promise to reconstruct the LP. LEVEL OF EVIDENCE/METHODS:1 Laryngoscope, 2019.

INTRODUCTION/BACKGROUND:It is estimated over 466 million people worldwide have disabling hearing loss, and untreated hearing loss is associated with poorer health outcomes. The influence of sex as a biological variable on hearing loss is not well understood, especially for differences in underlying mechanisms which are typically elucidated through non-clinical research. Although the inclusion of sex as a biological variable in clinical studies has been required since 1993, sex reporting has only been recently mandated in National Institutes of Health funded non-clinical studies. OBJECTIVE:This article reviews the literature on recent non-clinical and clinical research concerning sex-based differences in hearing loss primarily since 1993, and discusses implications for knowledge gaps in the translation from non-clinical to clinical realms. CONCLUSIONS:The disparity between sex-based requirements for non-clinical versus clinical research may inhibit a comprehensive understanding of sex-based mechanistic differences. Such disparities may play a role in understanding and explaining clinically significant sex differences and are likely necessary for developing robust clinical treatment options.

OBJECTIVE:To investigate and improve compliance of thyroid function monitoring in head and neck cancer patients who received radiotherapy to the cervical region before and after instituting quality improvement interventions. METHODS:Using the Plan, Do, Study, Act (PDSA) methodology, patients with head and neck malignancies who received radiotherapy to the cervical region from 2013-2015 were identified at a tertiary medical center. The status of the patients' thyroid monitoring and related characteristics were recorded. A quality improvement project was subsequently implemented by data sharing and providing feedback to practitioners involved in head and neck cancer care and creating a tracking database for all patients who received radiotherapy to the neck. After implementation of these interventions, data was collected on patients meeting the inclusion criteria from 2015-2017. RESULTS:One hundred fifty-six patients met criteria pre-intervention and ninety-eight patients met criteria post-intervention. Compliance of thyroid monitoring went up from 34% to 80% after interventions (P < .0001). There was a significant increase in thyroid testing performed by radiation oncologists after interventions from 2% to 21%, while medical oncologists and otolaryngologists remained consistent in their compliance rates. CONCLUSION/CONCLUSIONS:It is possible to improve compliance with evidence-based recommendations and improve the quality-of-care for head and neck cancer survivors through simple, cost effective interventions. LEVEL OF EVIDENCE/METHODS:2 Laryngoscope, 2019.

Tumors of the pineal region comprise several different entities with distinct clinical and histopathological features. Whereas some entities predominantly affect adults, pineoblastoma (PB) constitutes a highly aggressive malignancy of childhood with a poor outcome. PBs mainly arise sporadically, but may also occur in the context of cancer predisposition syndromes including DICER1 and RB1 germline mutation. With this study, we investigate clinico-pathological subgroups of pineal tumors and further characterize their biological features. We performed genome-wide DNA methylation analysis in 195 tumors of the pineal region and 20 normal pineal gland controls. Copy-number profiles were obtained from DNA methylation data; gene panel sequencing was added for 93 tumors and analysis was further complemented by miRNA sequencing for 22 tumor samples. Unsupervised clustering based on DNA methylation profiling separated known subgroups, like pineocytoma, pineal parenchymal tumor of intermediate differentiation, papillary tumor of the pineal region and PB, and further distinct subtypes within these groups, including three subtypes within the core PB subgroup. The novel molecular subgroup Pin-RB includes cases of trilateral retinoblastoma as well as sporadic pineal tumors with RB1 alterations, and displays similarities with retinoblastoma. Distinct clinical associations discriminate the second novel molecular subgroup PB-MYC from other PB cases. Alterations within the miRNA processing pathway (affecting DROSHA, DGCR8 or DICER1) are found in about two thirds of cases in the three core PB subtypes. Methylation profiling revealed biologically distinct groups of pineal tumors with specific clinical and molecular features. Our findings provide a foundation for further clinical as well as molecular and functional characterization of PB and other pineal tumors, including the role of miRNA processing defects in oncogenesis.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Upper airway stimulation for obstructive sleep apnea (OSA) via implantable hypoglossal nerve stimulation (HGNS) reduces airway obstruction by selectively stimulating nerve fibers that innervate muscles that produce tongue protrusion, while avoiding fibers that produce tongue retraction. This selective stimulation likely depends upon the location, intensity, and type of electrical stimulation delivered. This study investigates the impact of changing stimulation parameters on tongue muscle activation during HGNS using intraoperative nerve integrity monitoring in conjunction with electromyography (EMG). STUDY DESIGN/METHODS:Prospective case series. METHODS:Ten patients undergoing unilateral HGNS implantation for OSA in a university hospital setting were studied. Data included EMG responses in tongue muscles that produce protrusion (genioglossus), retraction (styloglossus/hyoglossus), and stiffening (transverse/vertical) in response to intraoperative bipolar probe electrical stimulation of lateral and medial branches of the hypoglossal nerve (HGN) and to implantable pulse generator (IPG) unipolar and bipolar settings after placement of the stimulation cuff. RESULTS:Stimulation of medial division HGN branches resulted in EMG responses in genioglossus muscles, but not in styloglossus/hyoglossus muscles, whereas stimulation of the lateral division HGN branches drove responses in styloglossus/hyoglossus muscles. Variable responses in transverse/vertical muscles were observed with stimulation of lateral and medial division branches. After electrode cuff placement, unipolar and bipolar HGN stimulation configurations of IPG resulted in unique patterns of muscle activation. CONCLUSIONS:The relative activation of extrinsic and intrinsic tongue musculature by HGNS is determined by stimulus location, intensity, and type. Intraoperative neurophysiological monitoring of tongue muscle activation enables proper electrode cuff placement and may provide essential data for stimulus optimization. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2019.