Workforce analysis of practicing rhinologists in the united states.

OBJECTIVES: The objective of this study is to analyze the current rhinology workforce in the United States in terms of demographics, fellowship training, and regional distribution. METHODS: The American Rhinologic Society (ARS) member database was queried for workplace zip code, age, gender, and fellowship training of practicing U.S. rhinologists through 2017. The San Francisco Match data were examined for rhinology fellowships from 2006 through 2017. Each rhinologist was assigned to a specific hospital referral region (HRR) determined by the Dartmouth Healthcare Atlas to assess geographic distribution and market density. RESULTS: There were 296 ARS members self-identifying as rhinologists. Of those, 69.2% were fellowship-trained (FTR). The median age of FTRs and non-FTRs were 41 and 54 years, respectively (P < 0.001). Eighty percent of FTRs were male compared to 85.7% non-FTRs. Given the recent growth of rhinology fellowships, the number of FTRs is currently expanding at approximately 16% per year. HRRs with the most rhinologists were Los Angeles, Boston, and Manhattan, all with 14. Approximately 100 million people live in HRRs without a practicing rhinologist. A wide variation in rhinologist density was observed, ranging from 133,047 to 3,636,809 people per rhinologist, with a median of 747,864. CONCLUSION: There may be a need for rhinologists in select parts of the country. Whereas the ARS database is likely an underestimation of the growing workforce, under current training rates we could pass the ideal number of U.S. rhinologists within 5 years. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1116-1121, 2020.

Oral tongue squamous cell carcinoma survival as stratified by age and sex: A surveillance, epidemiology, and end results analysis.

OBJECTIVES/HYPOTHESIS: To utilize the Surveillance, Epidemiology, and End Results (SEER) database to elucidate differences in predictors of survival in oral tongue squamous cell carcinoma (OTSCC) as stratified by age and sex. STUDY DESIGN: Retrospective, population-based database analysis. METHODS: The SEER registry was utilized to calculate survival trends for patients with OTSCC between 1973 and 2012. Patient data were then stratified by age (≤40 years vs. >40 years) and sex, then analyzed with respect to race, stage, grade, and treatment modalities. Overall survival (OS) and disease-specific survival (DSS) were calculated and compared. RESULTS: There were 16,423 cases of OTSCC identified, with 526 and 706 young female and male patients, respectively. Young female patients had improved OS and DSS as compared to young male patients (75% vs. 67% at 5 years), which is better than older patients (P < .001). Younger patients were more likely to receive surgery (P < .001) and combination surgery and radiation (P < .001) as compared to older patients. On multivariate analysis, tumor stage was uniformly associated with worse OS and DSS (P < .05), with surgery predicting improved OS and DSS in all groups except young females (P < .05). Higher tumor grade predicted worse OS and DSS in older patients, but not younger patients (P < .05). CONCLUSIONS: OTSCC appears to present with relatively heterogeneous characteristics across different age groups and sexes. Despite the rising incidence of OTSCC in young individuals, our study demonstrates that young patients have improved survival rates compared to older patients. LEVEL OF EVIDENCE: NA Laryngoscope, 129:2076-2081, 2019.

The genetic landscape of programmed death ligand-1 (PD-L1) alterations in head and neck cancer.

OBJECTIVES: Nivolumab has recently been shown in the phase III clinical trial CheckMate-141 to have superior survival rates compared to the current standard of care chemotherapy for recurrent or metastatic platinum-resistant head and neck squamous cell carcinoma (HNSCC). Nivolumab targets the immune inhibitory receptor programmed cell death 1 (PD-1). Programmed cell death ligand 1 (PD-L1) genomics have been poorly characterized in the context of HNSCC, including expression levels of PD-L1 in individual tumors as well as related up or down-regulated genes that might function as co-targets. STUDY DESIGN: Data mining of The Cancer Genome Atlas (TCGA). METHODS: 530 patients with HNSCC were pulled from the TCGA using cBioPortal. Primary tumor site data was available in 279 of the samples (52.6%), of which oral cavity was the most common site (61.6%) followed by larynx (25.8%). Other PD-1-sensitive tumors were analyzed to compare PD-L1 expression in HNSCC relative to other tumors including bladder, renal cell carcinoma, melanoma, and lung carcinomas. RESULTS: A significant fraction of HNSCC tumors have genetic alterations in PD-L1 (6.2%). HNSCC has the highest PD-L1 expression of all of the tumor types examined, with a median 60-fold increase. Several important genes were identified in this study including Caspase 7, ZFYVE9, and Plg-R(KT) that have a strong relationship with alterations in PD-L1. CONCLUSION: In light of the role of PD-1 and PD-L1 as key immunotherapy targets in HNSCC, several potential co-targets identified in this study warrant further investigation. Further, while the number of genetic alterations were small in head and neck carcinomas, alterations in PD-L1 expression were highly significant. LEVEL OF EVIDENCE: NA.

Anatomic Variations in Pituitary Endocrinopathies: Implications for the Surgical Corridor.

Objectives/Hypotheses Functioning pituitary adenomas may produce endocrinopathies such as acromegaly and Cushing syndrome. Both conditions lead to characteristic anatomic variations as a result of hormonally induced abnormal soft tissue deposition. We evaluate the anatomic differences between acromegalics and Cushing disease patients and compare these dimensions to controls. Design Radiographic review of preoperative magnetic resonance images (MRI) of the pituitary gland. Setting Tertiary academic medical center. Participants Patients who underwent transnasal, transsphenoidal surgery for pituitary adenomas found to have acromegaly or pituitary Cushing between January 1, 2007 and September 1, 2015. A total of 15 patients with similar MRIs and no history of pituitary or sinonasal disease were selected as controls. Main Outcome Measures Dimensions assessed were intercarotid distance; carotid canal width; piriform aperture width; distance from the piriform aperture to the anterior face of the sphenoid; sphenoid sinus height, width, and length; angle from anterior nasal spine to anteroinferior face of sphenoid sinus; choanal height; and nasal cavity height at the level of the vertical segment of the middle turbinate. Sphenoid sinus pneumatization patterns were recorded. Results There were 30 acromegalics and 31 Cushing disease patients. When compared with controls, both acromegalics and Cushing disease patients had significantly wider piriform apertures and a longer distance from the piriform aperture to the anterior face of the sphenoid sinus (p < 0.05). Acromegalics had a significantly less acute angle (19 ± 3 degrees) from the anterior nasal spine to the sphenoid (p < 0.05). Cushing disease patients had significantly lower sphenoid sinus length and shorter nasal cavity height (p < 0.05). There were no differences in intercarotid distance or carotid canal width. Conclusions As acromegalics and Cushing disease patients have known anatomic variations, the skull base surgeon should be aware of these differences and adapt their techniques and approaches as needed.

Multiple endocrine neoplasia type 2 kindred with novel tandem RET mutations: Case report with an applied in silico mutational tolerance analysis.

BACKGROUND: The American Thyroid Association (ATA) has established guidelines for prophylactic thyroidectomy in multiple endocrine neoplasia type 2A (MEN2A) based on rearranged during transfection (RET) mutations. In silico analysis, which uses computer modeling to predict alterations in protein structure, is a new method for studying these mutations. METHODS: We describe a kindred with MEN2A, all sharing a well-documented RET mutation, p.C634Y, as well as a mutation of undetermined significance, p.I852M, which we analyzed via in silico analysis. RESULTS: The p.C634Y mutation resulted in severe predicted RET alterations, whereas the p.I852M resulted in only modest changes. Both mutations together resulted in only a small additional disruptive effect in protein structure beyond that which occurred with p.C634Y alone. CONCLUSION: Although in silico analysis may be helpful in quantitating changes in protein structure that occur in patients who have novel RET mutations (single or multiple), additional factors must account for the highly variable aggressiveness of the disease (C-cell hyperplasia/medullary thyroid carcinoma [MTC]) noted in our kindred. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1881-E1885, 2016.

Idiopathic Chronic Parotitis: Imaging Findings and Sialendoscopic Response.

BACKGROUND/AIMS: The purpose of this study was to correlate imaging and sialendoscopic findings to therapeutic response in patients with idiopathic chronic parotitis. METHODS: We retrospectively reviewed 122 consecutive sialendoscopies performed in an academic medical center by two surgeons between 2008 and 2013. Forty-one (34%) and 54 (44%) patients were excluded on the basis of having parotid or submandibular sialolith, respectively. Nineteen cases were included in the study with idiopathic chronic parotitis. There was a median follow-up of 5 months. RESULTS: Computed tomography (CT) imaging had a sensitivity and specificity of 80.0 and 71.4%, respectively, for predicting abnormal findings on sialendoscopy, while magnetic resonance imaging (MRI) had 100% accuracy in a small set of cases. In glands with noticeable pathology present on preoperative imaging or sialendoscopy, 11 out of 12 glands (92%) treated experienced symptomatic improvement, while 3 out of 7 glands (43%) without pathology on imaging or endoscopy experienced symptomatic improvement (p = 0.038). CONCLUSIONS: Sialendoscopy for the treatment of idiopathic chronic parotid disease can improve pain and swelling with a higher frequency of success in patients with abnormalities noted on endoscopy. CT and MRI have a moderate degree of accuracy in predicting which patients will benefit from therapeutic sialendoscopy.

Is Intraoperative Parathyroid Hormone Monitoring Warranted in Cases of 4D-CT/Ultrasound Localized Single Adenomas?

OBJECTIVE: To analyze the utility of intraoperative parathyroid hormone (IOPTH) monitoring for patients with primary hyperparathyroidism who had evidence of single-gland disease on preoperative imaging with modified 4-dimensional computed tomography that was done in conjunction with ultrasonography (Mod 4D-CT/US). STUDY DESIGN: Case series with chart review. SETTING: Tertiary care university medical center. SUBJECTS AND METHODS: Patients were drawn from consecutive directed parathyroidectomies performed between December 2001 and June 2013 by the senior authors. All patients had primary hyperparathyroidism and underwent a Mod 4D-CT/US study that showed findings on both studies that were consistent with a single adenoma. The modified Miami criteria were used for IOPTH monitoring (parathyroid hormone decrease by >50% and into the normal range). RESULTS: Of 356 patients who underwent parathyroid surgery, 206 had a single gland localized on the Mod 4D-CT and the US studies. IOPTH monitoring was used in 172 cases, of which 169 had adequate clinical follow-up to assess the surgical outcome. Twenty-one patients (12.4%) had IOPTH values that did not meet modified Miami criteria after removal of one gland, of which 7 were found to have multigland disease (4.1%). Three patients (1.8%) had persistent primary hyperparathyroidism despite an IOPTH that met modified Miami criteria. CONCLUSIONS: Although IOPTH monitoring correctly identifies a small percentage of patients with multigland disease, some patients will be subjected to unnecessary neck explorations that can result in difficult intraoperative decisions, such as whether to remove normal or equivocal-sized glands when they are encountered.

In Silico Analysis of NF2 Gene Missense Mutations in Neurofibromatosis Type 2: From Genotype to Phenotype.

HYPOTHESIS: Computer-based (in silico) protein modeling to examine genotype-phenotype relationships for a given mutation has been applied to many genes but never to NF2. BACKGROUND: Missense mutations in the merlin protein occur in approximately 9% of patients with neurofibromatosis type 2 (NF2). Within this subset of patients, no genotype-phenotype correlations have been established. The aim of this study was to determine if genotype correlates with phenotype in the cohort of NF2 patients with missense mutations as a first step to defining a method to predict clinical phenotype from genotype for these patients. METHODS: We analyzed 45 patients with NF2 as a result of missense mutations drawn from the United Kingdom NF2 registry. Our analysis included 17 different NF2 mutations from NF2 patients and six single-nucleotide polymorphisms (SNP)--presumed benign because they are observed in the dbSNP National Center for Biotechnology Information database and 1000 Genomes. We analyzed the mutations using three mutation tolerance prediction approaches: Align GVGD, SIFT, and PolyPhen-2. The mutation sites were also modeled on the three-dimensional crystal structure of merlin to investigate the spatial relationship of NF2-causing mutations. RESULTS: Two mutation tolerance predictors (SIFT and PolyPhen-2) were able to distinguish NF2-causing mutations from non-NF2-causing SNPs (p < 0.05). Mapping mutations on the molecular structure of merlin suggest that mutations resulting in greater structural conflicts within the protein are more likely to correlate with severe phenotypes. CONCLUSION: This work is a step toward a better understanding of genotype-phenotype relationships in NF2 caused by missense mutations using a computer-based methodology.

Parathyroid Localization and Preservation during Transcervical Resection of Substernal Thyroid Glands.

OBJECTIVE: The feasibility of parathyroid preservation during thyroidectomy has not been well documented for cases in which the thyroid gland extends into the mediastinum. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic referral center. SUBJECTS AND METHODS: In this retrospective cohort study, 70 consecutive patients who had substernal thyroid glands treated with a transcervical thyroidectomy between 1993 and 2013 were compared with 286 thyroidectomies that did not entail substernal extension within that same time period. All localized parathyroid glands were confirmed histologically. RESULTS: Of 160 possible parathyroid glands in the substernal cases, 119 (74%) were histologically confirmed intraoperatively (67 superior and 52 inferior). In nonsubsternal cases, 725 (89%) were histologically confirmed (372 superior and 353 inferior). There was a statistically significant difference between the substernal and nonsubsternal cases in the total number of glands found (P < .0001) and the number of superior and inferior glands that were identified (P = .009 and < 0.0001). CONCLUSIONS: Even when the thyroid gland extends into the mediastinum, it is often possible, although with reduced efficiency, to identify and preserve the parathyroid glands.

In silico analysis of RET variants in medullary thyroid cancer: from the computer to the bedside.

OBJECTIVE: The American Thyroid Association (ATA) medullary thyroid cancer (MTC) guidelines group RET variants, in the setting of familial medullary thyroid cancer and multiple endocrine neoplasia type 2, into 4 classes of severity based on epidemiological data. The aim of this study was to determine if genotype correlates with phenotype in RET missense mutations. STUDY DESIGN: In silico mutational tolerance prediction. SETTING: Academic research hospital. SUBJECTS AND METHODS: We analyzed all RET variants currently listed in the ATA guidelines for the management of MTC using 2 computer-based (in silico) mutation tolerance prediction approaches: PolyPhen-2 HumVar and PolyPhen-2 HumDiv. Our analysis also included 27 different RET single-nucleotide polymorphisms resulting in missense variants. RESULTS: There was a statistically significant difference in the overall HumDiv score between ATA groups A and B (P = .025) and a statistically significant different HumVar score between benign polymorphisms and ATA group A (P = .023). Overall, RET variants associated with a less aggressive clinical phenotype generally had a lower Hum Div/Var score. CONCLUSIONS: Polyphen-2 Hum Div/Var may provide additional clinical data to help distinguish benign from MEN2/familial medullary thyroid carcinoma-causing RET variants as well as less aggressive phenotypes (ATA A) from more aggressive ones (ATA B-C). In silico genetic analyses, with proper validation, may predict the phenotypic severity of RET variants, providing clinicians with a tool to aid clinical decision making in cases in which the RET variant is currently unknown or little epidemiological data are available.

Factors predictive of voice and swallowing outcomes after anterior approaches to the cervical spine.

OBJECTIVE: To quantify the incidence of postoperative voice, swallowing, and other problems, including time to resolution following anterior transcervical approaches to the cervical spine, and to assess surgical factors associated with outcomes. STUDY DESIGN: Historical cohort study. SETTING: Academic medical center. SUBJECTS AND METHODS: One hundred eighty-eight consecutive patients with cervical spine disease who underwent an anterior transcervical approach to the spine by a single head and neck surgeon over a 4-year time period. Rather than primary, single-level approaches, all patients in this study had multilevel, high-cervical (above C4), low-cervical (below C6), and/or revision approaches. Postoperative voice, swallowing, and other complaints were measured as well as time to resolution using Kaplan-Meier method. Surgical factors related to outcomes were analyzed using regression analysis. RESULTS: Follow-up was available for 129 patients, with average and median time of 35 months. Seventy-seven patients (60%) had a postoperative issue, including 35 patients (27%) with postoperative voice complaint, 62 patients (48%) with postoperative swallowing complaint, and 16 patients (12%) with other problems. Swallowing and voice complaints persisted beyond 1 year in 28% and 9% of patients, respectively. Approaching spinal levels above C4 and exposing more than 3 spinal levels were 2 factors significantly related to voice and swallowing problems. CONCLUSION: There is a high incidence of subjective voice and swallowing complaints following transcervical anterior approaches to the spine, and such complaints can persist beyond 1 year in many patients. Exposure of more than 3 spinal levels or above level C4 are 2 factors significantly associated with outcome.

Impact of a large breast separation on radiation dose delivery to the ipsilateral lung as result of respiratory motion quantified using free breathing and 4D CT-based planning in patients with locally advanced breast cancers: a potential for adverse clinical implications.

PURPOSE: We examined the effects of large breast separation (BS) on dosimetric and positional differences of radiation treatment plans of locally advanced breast cancers during a free-breathing respiratory cycle. MATERIALS AND METHODS: Computed tomography (CT) datasets of 18 patients were acquired using 3D, 4D-0% (end-inspiration), and 4D-50% (end-exhalation). BS was examined in relation to the positional and dosimetric changes to organs-at-risk (OAR). Based on dosimetric analysis of all three plans, we compared 4D-0% and 4D-50% for V5, V10, and V20 to 3D for heart and ipsilateral lung. Using 4D-0% and 4D-50% CTs, we recorded positional variations of the organs' centroid (centers of mass) and their effects on dosimetry. RESULTS: Median BS was 23.95 cm (range: 16.86-29.48 cm). There was a strong positive correlation between BS and dose to the ipsilateral lung for V5, V10, and V20, with the greatest linearity observed at V20 (R(2) = 0.23). At BS ≥ 27 cm, the dose increased during inspiration at V5, V10 , and V20 (P < 0.05). When comparing 4D and 3D for the heart, V5 and V10, decreased by average of 0.94% and 0.96% (P < 0.008), respectively. CONCLUSIONS: This study offers the first evidence of the impact of a large BS on radiation dose to the ipsilateral lung.