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Objectives Preoperative fine needle aspiration (FNA) of parotid lesions often is used in the initial evaluation of parotid masses, but its role in guiding surgical decision making remains unclear, in part due to varying diagnostic accuracy reported. We sought to evaluate the role of preoperative FNA in detection of malignancy and impact on surgical management. Study design Retrospective study. Methods The medical records of patients who underwent parotidectomy at a single tertiary medical center were reviewed from 2000 to 2015. Patients who had a preoperative FNA comprised the study cohort. Results A total of 1,074 consecutive patients underwent parotidectomy during the study period; of those, 477 had a preoperative FNA. FNA was nondiagnostic in 26 cases. There were 29 false positives (6.4%), 26 false negatives (5.8%), 122 true positives (27.1%), and 274 true negatives (60.8%). The sensitivity and specificity of FNA were 82.4% and 90.4%, respectively, with a positive predictive value of 80.8% and a negative predictive value of 91.3%. The overall accuracy of preoperative FNA was 87.8%. The preoperative FNA resulted in a change in the surgical plan in 85 (18.9%) cases. In 66 of these cases (78%), surgery was extended to include neck dissection at time of resection. In 10 cases, FNA led to surgical management over surveillance. In 11 cases, FNA downgraded the extent of surgery planned to an excisional biopsy. Conclusion Preoperative FNA is a valuable adjunct in the surgical management of parotid lesions, with high specificity for the detection of malignant disease. Level of evidence 4. Laryngoscope, 128:398-402, 2018.

Objective To determine the relationship between frailty and comorbidity, in-hospital mortality, postoperative complications, length of hospital stay (LOS), and costs in head and neck cancer (HNCA) surgery. Study design Cross-sectional analysis. Methods Discharge data from the Nationwide Inpatient Sample for 159,301 patients who underwent ablative surgery for a malignant oral cavity, laryngeal, hypopharyngeal, or oropharyngeal neoplasm in 2001 to 2010 was analyzed using cross-tabulations and multivariate regression modeling. Frailty was defined based on frailty-defining diagnosis clusters from the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. Results Frailty was identified in 7.4% of patients and was significantly associated with advanced comorbidity (odds ratio [OR] = 1.5[1.3-1.8]), Medicaid (OR = 1.5[1.3-1.8]), major procedures (OR = 1.6[1.4-1.8]), flap reconstruction (OR = 1.7[1.3-2.1]), high-volume hospitals (OR = 0.7[0.5-1.0]), discharge to a short-term facility (OR = 4.4[2.9-6.7]), or other facility (OR = 5.4[4.5-6.6]). Frailty was a significant predictor of in-hospital death (OR = 1.6[1.1-2.4]), postoperative surgical complications (OR = 2.0[1.7-2.3]), acute medical complications (OR = 3.9[3.2-4.9]), increased LOS (mean, 4.9 days), and increased mean incremental costs ($11,839), and was associated with higher odds of surgical complications and increased costs than advanced comorbidity. There was a significant interaction between frailty and comorbidity for acute medical complications and length of hospitalization, with a synergistic effect on the odds of medical complications and LOS in patients with comorbidity who were also frail. Conclusion Frailty is an independent predictor of postoperative morbidity, mortality, LOS, and costs in HNCA surgery patients, and has a synergistic interaction with comorbidity that is associated with an increased likelihood of medical complications and greater LOS in patients with comorbidity who are also frail. Level of evidence 2c. Laryngoscope, 128:102-110, 2018.

Objective To examine associations between quality, complications, and costs in commercially insured patients treated for laryngeal cancer. Study Design Retrospective cross-sectional analysis of MarketScan Commercial Claim and Encounters data (Truven Health Analytics, Ann Arbor, Michigan, U.S.A.). Methods We evaluated 10,969 patients diagnosed with laryngeal cancer from 2010 to 2012 using cross-tabulations and multivariate regression. Using quality indicators derived from guidelines for recommended care, summary measures of quality were calculated for diagnosis, initial treatment, surveillance, treatment for recurrence, performance, and an overall summary measure of quality. Results Higher-quality care in the initial treatment period was associated with lower odds of 30-day mortality (odds ratio [OR] = 0.21, 95% confidence interval [CI] [0.04–0.98]), surgical complications (OR = 0.39 [0.17–0.88]), and medical complications (OR = 0.68 [0.49–0.96]). Mean incremental 1-year costs were higher for higher-quality diagnosis ($20,126 [$14,785–$25,466]), initial treatment ($17,918 [$10,481–$25,355]), and surveillance ($25,424 [$20,014–$30,834]) quality indicators, whereas costs were lower for higher-quality performance measures (−$45,723 [−$56,246–−$35,199]) after controlling for all other variables. Higher-quality care was associated with significant differences in mean incremental costs for initial treatment in surgical patients ($−37,303 [−$68,832–−$5,775]), and for the overall summary measure of quality in patients treated nonoperatively ($10,473 [$1,121–$19,825]). After controlling for the overall summary measure of quality, costs were significantly lower for patients receiving high-volume surgical care (mean −$18,953 [−$28,381–−$9,426]). Conclusion Higher-quality larynx cancer care in commercially insured patients was associated with lower 30-day mortality and morbidity. High-volume surgical care was associated with lower 1-year costs, even after controlling for quality. These data have implications for discussions of value and quality in an era of healthcare reform. Level of Evidence 2c. Laryngoscope, 127:2805–2812, 2017

Objectives/Hypothesis To examine associations between treatment, complications, and costs in patients with laryngeal cancer. Study Design Retrospective cross-sectional analysis of MarketScan Commercial Claim and Encounters data. Methods We evaluated 10,969 patients diagnosed with laryngeal cancer from 2010 to 2012 using cross-tabulations and multivariate regression. Results Chemoradiation was significantly associated with supraglottic tumors (relative risk ratio [RRR] = 5.9 [4.4–7.8]), pretreatment gastrostomy (RRR = 4.0 [2.7–6.1]), and alcohol abuse (RRR = 0.5 [0.3–0.9]). Treatment-related complications occurred in 23% of patients, with medical complications in 22% and surgical complications in 7%. Chemoradiation (odds ratio [OR] = 3.7 [2.6–5.2]), major surgical procedures (OR = 4.9 [3.5–6.8]), reconstruction (OR = 7.7 (4.1–14.7)], and advanced comorbidity (OR = 9.7 [5.7–16.5] were associated with acute complications. Recurrent/persistent disease occurred in 23% of patients and was associated with high-volume care (OR = 1.4 [1.1–1.8]). Salvage surgery was performed in 46% of patients with recurrent/persistent disease and was less likely for supraglottic disease (OR = 0.5 [0.4–0.8]) and after chemoradiation (OR = 0.4 [0.2–0.6]). Initial treatment and 1-year overall costs for chemoradiation were higher than all other treatment categories, after controlling for all other variables including complications and salvage. High-volume care was associated with significantly lower costs of care for surgical patients but was not associated with differences in costs of care for nonoperative treatment. Conclusions In commercially insured patients

Introduction The use of fine-needle aspiration (FNA) cytology for the preoperative evaluation of salivary gland lesions is an accepted but, currently, nonstandardized practice. More specifically, cystic major salivary gland lesions are relatively rare and can be very challenging to diagnose on FNA due to low cellularity and an incredibly broad differential diagnosis. The purpose of this study was to investigate the diagnostic utility of preoperative FNA cytology for cystic major salivary gland lesions. Methods and materials The electronic pathology archives of The Johns Hopkins Hospital were searched to identify FNA specimens of cystic major salivary gland lesions over a 15 year period (January 1, 2000 to December 21, 2015). The age, race, sex, biopsy site, use of ultrasound guidance, cytopathologic diagnosis, and presence or absence of clinical follow-up were recorded for each patient. Cases were divided into those with and without follow-up. Diagnostic performance between FNA and follow-up data were recorded. Results A total of 145 cases met the inclusion criteria, while 123 (84.8%) patients had follow-up data available. Of these patients, 67.5% underwent FNA as the only pathologic diagnostic modality. Sensitivity, specificity, positive predictive value, and negative predictive value for the detection of cystic neoplasms were 41.6%, 99.0%, 90.9%, and 87.6%, respectively. For cases containing mucin, 100.0% sensitivity and specificity were achieved. Conclusion FNA of cystic salivary gland lesions is a useful clinical decision-making tool that can reduce the number of patients ultimately requiring surgical excision. Although specificity is high, a relatively low overall sensitivity makes clinical and radiologic correlation imperative.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.

BACKGROUND Human papillomavirus (HPV) is a well-established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non-OP) head and neck squamous cell cancers (HNSCCs). METHODS This retrospective, multi-institution study included OPSCCs and non-OP HNSCCs of the oral cavity, larynx, and nasopharynx diagnosed from 1995 to 2012. Race/ethnicity was categorized as white non-Hispanic, black non-Hispanic, Asian non-Hispanic, and Hispanic of any race. Tumors were centrally tested for p16 overexpression and the presence of HPV by HPV16 DNA and high-risk HPV E6/E7 messenger RNA in situ hybridization. Kaplan-Meier and Cox proportional hazards models were used to evaluate overall survival (OS). RESULTS The study population included 239 patients with OPSCC and 621 patients with non-OP HNSCC with a median follow-up time of 3.5 years. After adjustments for the tumor HPV status, age, current tobacco use, and stage, the risk of death was lower for women versus men with OPSCC (adjusted hazard ratio, 0.55; P = .04). The results were similar with p16. In contrast, for non-OP HNSCCs, HPV positivity, p16 positivity, and sex were not associated with OS. CONCLUSIONS For OPSCC, there are differences in survival by sex, even after the tumor HPV status has been taken into account. For non-OP HNSCC, the HPV status and the p16 status are not of prognostic significance. Cancer 2017;123:1566–1575. © 2017 American Cancer Society.

Background The prevalence of survivors of oropharyngeal cancer (OPC) is increasing due to improved survival for individuals with human papillomavirus (HPV)-related disease. Although elderly survivors of OPC are known to have a high burden of comorbidities, to the authors' knowledge it is unknown how this compares with a similar cohort without a history of cancer. Methods The current retrospective, cross-sectional study included individuals with a first incident primary diagnosis of OPC from 2004 through 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked databases and matched controls. The baseline prevalence and subsequent incidence of comorbid conditions were identified. The association between comorbidity and overall survival was evaluated. Results A total of 2497 eligible patients with OPC were matched to 4994 noncancer controls. Baseline comorbidity was higher in cases (Charlson Comorbidity Index >0 for 48.5% of cases vs 35.8% of controls). At 5 years, cases were more likely than controls to develop comorbidities. Survivors of OPC were at high risk (≥20% cumulative prevalence by 5 years) of developing several comorbidities, including cardiovascular diseases, cerebrovascular disease, chronic obstructive pulmonary disease, and tobacco abuse, and were at moderately high risk (10%-19% cumulative prevalence) of developing other conditions including carotid artery occlusive stroke, alcohol abuse, depression, and anxiety. In both cases and controls, the presence of the majority of comorbidities either at the time of diagnosis or during the follow-up period was associated with worse survival. Conclusions Patients with OPC have a higher comorbidity burden compared with matched controls, both at baseline and during survivorship, the majority of which are associated with decreased survival. Oncologic surveillance of survivors of OPC should include screening for highly prevalent conditions.

Introduction Little is known regarding how human papillomavirus-positive oropharyngeal cancer (HPV-OPC) patient goals change with treatment. This study evaluates whether patient ranking of non-oncologic priorities relative to cure and survival shift after treatment as compared to priorities at diagnosis. Materials and Methods This is a prospective study of HPV-OPC patient survey responses at diagnosis and after treatment. The relative importance of 12 treatment-related priorities was ranked on an ordinal scale (1 as highest). Median rank (MR) was compared using Wilcoxon matched-pairs signed-rank tests. Prevalence of high concern for 11 treatment-related issues was compared using paired t-test. The effect of patient characteristics on change in priority rank and concern was evaluated using linear regression. Results Among 37 patients, patient priorities were generally unchanged after treatment compared with at diagnosis, with cure and survival persistently ranked top priority. Having a moist mouth uniquely rose in importance after treatment. Patient characteristics largely did not affect change in priority rank. Concerns decreased after treatment, except concern regarding recurrence. Discussion Treatment-related priorities are largely similar at diagnosis and after treatment regardless of patient characteristics. The treatment experience does not result in a shift of priorities from cure and survival to non-oncologic domains over cure and survival. The rise in importance of moist mouth implies that xerostomia may have been underappreciated as a sequelae of treatment. A decrease in most treatment-related concerns is encouraging, whereas the persistence of specific areas of concern may inform patient counseling.

OBJECTIVES To evaluate the performance characteristics of seven predetermined imaging features on pretreatment computed tomography (CT) in identifying extranodal extension (ENE) in cervical lymph node metastases from human papillomavirus-positive oropharyngeal carcinoma (HPV-OPC). STUDY DESIGN Retrospective study. METHODS Seventy-three patients with HPV-OPC who underwent primary surgery and cervical lymph node dissection were included. Preoperative contrast-enhanced CT (cCT) imaging was evaluated by two radiologists blinded to pathological results. Each cCT was scored for seven imaging features of interest: 1) indistinct capsular contours, 2) irregular nodal margins, 3) perinodal fat stranding, 4) perinodal fat planes, 5) nodal necrosis, 6) intranodal cysts, and 7) nodal matting. Logistic regression was employed to determine radiologist-specific odds ratios (OR) of predicting ENE for each imaging feature and radiologist-specific receiver operating characteristics (sensitivity [Sn], specificity [Sp], area under the curve [AUC], positive predictive value [PPV], negative predictive value [NPV]) for each imaging feature. RESULTS Thirty-two (44%) patients had ENE-positive lymph nodes. The presence of irregular margins (ORA = 12.3, 95% confidence interval [CI]A = 2.3-65.9; ORB = 7.0, 95% CIB = 1.4-36.3) and absence of perinodal fat plane (ORA = 6.8, 95% CIA = 2.0-23.3; ORB = 14.2, 95% CIB = 1.7-120.5) were significantly associated with ENE for each radiologist. Irregular nodal margin status was most specific for ENE (SnA = 45%, SpA = 94%, AUCA = 69%, PPVA = 82%, NPVA = 73%; SnB = 28%, SpB = 95%, AUCB = 61%, PPVB = 80%, NPVB = 64%). Absence of perinodal fat plane was most sensitive for ENE (SnA = 87%, SpA = 50%, AUCA = 69%, PPVA = 59%, NPVA = 62%; SnB = 96%, SpB = 34%, AUCB = 65%, PPVB = 53%, NPVB = 63%). CONCLUSIONS Of the seven imaging features hypothesized to be associated with ENE-status, the presence of irregular nodal margins and absence of perinodal fat plane were the most specific and sensitive features, respectively. LEVEL OF EVIDENCE 4 Laryngoscope, 130:1479-1486, 2020.

Objective To review recent literature on human papillomavirus-related (HPV-positive) oropharyngeal squamous cell carcinoma (OPC) and focus on implications of recurrent and metastatic disease. Methods Primary articles from 1990 to 2016 indexed in MEDLINE (1) pertaining to the epidemiology of HPV-positive OPC and (2) providing clinical insight into recurrent and metastatic OPC. Results The incidence of HPV-positive OPC is increasing globally. HPV-positive OPC is a subtype with distinct molecular and clinical features including enhanced treatment response and improved overall survival. While disease recurrence is less common in patients with HPV-positive OPC, up to 36% of patients experience treatment failure within eight years. Recurrent and metastatic OPC has historically signified poor prognosis, however recent data are challenging this dogma. Here, we discuss recurrent and metastatic OPC in the context of HPV tumor status. Conclusion HPV-positive OPC exhibits distinct genetic, cellular, epidemiological, and clinical features from HPV-negative OPC. HPV tumor status is emerging as a marker indicative of improved prognosis after disease progression in both locoregionally recurrent and distant metastatic OPC. Level of Evidence N/A.

BACKGROUND Patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC) have improved survival when compared with those with HPV-negative OPC. Unfortunately, the American Joint Committee on Cancer seventh edition (AJCC-7ed) staging system does not account for the prognostic advantage observed with HPV-positive OPC. The purpose of the current study was to validate and compare 2 recently proposed staging systems for HPV-positive OPC. METHODS Patients treated for HPV-positive OPC from 2005 to 2015 at Johns Hopkins Hospital (JHH) were included for analysis. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) and The University of Texas MD Anderson Cancer Center (MDACC) staging systems were applied and survival was calculated using Kaplan-Meier methods. Cox proportional hazard regression was used to determine the relationship between stage of disease and survival. Models were compared using the Akaike information criterion (AIC). RESULTS A total of 435 patients were eligible for analysis. There was a dramatic shift in lymph node category and overall stage of disease when ICON-S and MDACC stage were applied to the JHH cohort. There was superior stratification of overall survival and progression-free survival by ICON-S stage. Both proposed models had an improved fit based on AIC scores (P

Sialodochitis fibrinosa and allergic parotitis have described rare patients with recurrent salivary gland swelling and mucus plugs, often with atopy. We have evaluated three patients with atopic disease, recurrent salivary gland swelling and an eosinophilic sialodochitis. Two had eosinophil-rich mucus plugs. 56 additional cases were identified in a medical literature database search, each defined by recurrent salivary gland swelling associated with eosinophil-rich mucus plugs or sialodochitis with periductal eosinophilic infiltration. The majority (78%) were reported from Japan. Females were predominantly affected (F:M=2.3) with a median age of 47 years at evaluation. The parotid and submandibular glands were involved, respectively, in 71% and 46%. Allergic symptoms were present in 66%, atopic disease in 63% of those with reported allergy testing, and blood eosinophilia in 71%. Contrast sialography and other imaging modalities documented ductal dilatation in 82%. Treatments included anti-allergic medications (58%), systemic glucocorticoids (25%), duct cannulation with irrigation, steroid injection, and/or duct dilatation (36%), and glandular resection (19%). We recommend the diagnosis “eosinophilic sialodochitis” be applied to patients who meet this case definition. The disease is a unique cause of chronic recurrent salivary gland swelling. Its likely allergic etiology may be amenable to current or future biologic therapies. This article is protected by copyright. All rights reserved.

Objectives/Hypothesis To characterize clinical, imaging, and sialendoscopy findings in patients with chronic parotitis and multiple parotid calcifications. Study Design Retrospective review. Methods Clinical history, radiographic images and reports, lab tests, and operative reports were reviewed for adult patients with chronic parotitis and multiple parotid calcifications who underwent parotid sialendoscopy. Results Thirteen of 133 (10%) patients undergoing parotid sialendoscopy for chronic sialadenitis had more than one calcification in the region of the parotid gland. Seven patients (54%) were diagnosed with immune-mediated disease from autoimmune parotitis (positive Sjogren's antibodies or antinuclear antibodies) or human immunodeficiency virus (HIV) disease. The six patients (46%) who did not have an immune-mediated disorder had most calcifications located anterior or along the masseter muscle. Eight of 13 patients (61%) had at least one calculus found in the parotid duct on sialendoscopy. Four patients (38%) had multiple punctate calcifications within the parotid gland, all of whom had either autoimmune parotitis or HIV. None of the proximal or punctate parotid calcifications posterior to the masseter were visualized on sialendoscopy. Conclusions Chronic parotitis in conjunction with multiple parotid calcifications is uncommon and was identified in 10% of our cohort. We contrast two classifications of parotid calcifications: 1) intraductal stones that cause recurrent duct obstruction and are often located within the main parotid duct along or anterior to the masseter and 2) punctate intraparenchymal parotid gland calcifications that are not visualized on sialendoscopy and may represent underlying inflammatory disease. Level of Evidence 4 Laryngoscope, 127:1565–1570, 2017

Objective To examine 30-day readmission rates and associations with risk factors, survival, length of hospitalization, and costs in elderly patients with laryngeal and oropharyngeal squamous cell cancer (SCC). Study Design Retrospective cross-sectional analysis of Surveillance, Epidemiology, and End Results-Medicare data. Methods We evaluated 1,518 patients diagnosed with laryngeal or oropharyngeal SCC from 2004 to 2007 who underwent primary surgery using cross-tabulations, multivariate regression modeling, and survival analysis. Results Thirty-day readmission occurred in 14.1% of hospitalizations. Readmission was more likely in patients with postoperative complications during initial hospitalization (24.8% vs. 4.5%, P < 0.001), and was associated with an increased 30-day mortality incidence rate (5.1% vs. 0.9%; P < 0.001). On multivariate analysis, 30-day readmission was significantly associated with advanced stage (odds ratio [OR] = 1.81 [1.13–2.90]), comorbidity (OR = 2.69 [1.65–4.39]), divorced/separated marital status (OR = 2.00 [1.19–3.38]), preoperative tracheostomy (OR = 3.39 [1.55–7.44]), major surgical procedures (OR = 2.58 [1.68–3.97]), greater length of initial hospitalization (OR = 1.72 [1.09–2.71]), pneumonia (OR = 2.86 [1.28–6.40]), postoperative dysphagia (OR = 5.97 [2.48–15.83]), and cardiovascular events (OR = 5.84 [1.89–17.96]). Thirty-day readmission was significantly associated with 30-day mortality (OR = 5.89 [2.21–15.70) and higher 1-year mortality (68.0% vs. 89.2%, P < 0.001). The mean incremental costs of surgical care were significantly greater for patients with unplanned readmission ($15,123 [$10,514–$19,732]), after controlling for all other variables. Conclusion Unplanned readmissions are associated with increased short- and long-term mortality and costs. Elderly patients with advanced disease, advanced comorbidity, lack of spousal support, pretreatment organ dysfunction, more extensive surgery, postoperative pneumonia, postoperative dysphagia, and prolonged hospitalization are at increased risk of 30-day readmission. These findings suggest a need for targeted interventions before, during, and after hospitalization to reduce morbidity, mortality, and excess costs in this high-risk population. Level of Evidence 2c. Laryngoscope, 127:631–641, 2017

Changes in the US healthcare economic system are requiring academic health centers (AHCs) to restructure in pursuit of their traditional tripartite missions; engaging the individuals focused on clinical care is becoming more important. We conducted this study to guide our institution's transformation by identifying ways to formally recognize clinicians who are excelling in patient care and understand which forms of acknowledgment would be acceptable and motivating.A survey was developed by a large committee with representation spanning the AHC and was sent electronically in spring 2014 to stakeholders across the institution. Items assessed perceptions of the importance and present state of valuing clinical excellence, the utility of 14 potential metrics to assess clinical excellence, and the meaningfulness of seven potential rewards for clinical excellence. Bivariate and multivariate logistic regression models analyzed differences (P0.05) by respondent sex, ethnicity, academic rank, primary clinical affiliation, and time spent in patient care and research activities.A total of 1716 of 3168 (54%) stakeholders responded, including 1198 of 2151 (56%) individuals from academic hospitals, 114 of 276 (41%) from the outpatient affiliated practices, and 304 of 741 (54%) from satellite locations. Nearly everyone (96%) agreed that clinical accomplishments should be recognized, although a minority (47%) believed that clinicians were already valued. Most respondents selected 7 or more of 14 metrics as valid and reasonable for assessing clinical excellence. Popular metrics (eg, clinical productivity) were not believed to represent clinical excellence as much as others (eg, professionalism). Multivariate analysis found the least agreement among stakeholders on using published scholarship as evidence for clinical excellence, with the widest differences comparing senior faculty versus nonfaculty (88% vs 27%) and those with75% of their time spent in patient care versus others (37% vs 73%). Most (six of seven) types of reward were perceived as meaningful by the majority of respondents, with little variation among subgroups across bivariate and multivariate analyses.This system-wide assessment was successful at identifying new strategies for recognizing clinical excellence. Other AHCs seeking institutional transformation may wish to perform a similar assessment.

OBJECTIVES/HYPOTHESIS To assess clinical outcomes of patients with airway venous malformations treated with percutaneous sclerotherapy (VMPS). We highlight the role of foamed bleomycin as a less inflammatory sclerosant and the importance of collaboration between interventional radiology and otolaryngology-head and neck surgery (OHNS). STUDY DESIGN Retrospective, consecutive, single-center series. METHODS Sixteen airway VMPS treatment sessions were performed (5 patients). Endoscopic needle guidance was performed by OHNS. Sclerosants included ethanol and foamed bleomycin. The following data were tabulated for each patient: hospital length of stay (LOS), clinical response, and the presence/absence of airway swelling requiring prolonged intubation. Univariate analysis was performed. P < 0.05 was considered significant. RESULTS Thirty-one percent (5 of 16) of treatments required endoscopic guidance. Eighty-seven percent (7 of 8) of airway VMs treated with ethanol caused significant airway swelling compared to 0% (0 of 8) of airway VMs treated with bleomycin (P = 0.0004). The LOS was significantly greater for ethanol (5 ± 0.3 days) than for bleomycin (1 day, P = 0.001). Ninety-four percent (15 of 16) of airway VM treatments had at least a partial clinical response. There was no significant difference in clinical response between ethanol and bleomycin (P = 0.30). CONCLUSION Endoscopic and image-guided needle placement may be necessary to treat deep airway VMs. Bleomycin may cause less significant airway swelling than ethanol. This may reduce hospital LOS and prolonged intubation. Our results should be interpreted with caution because this is a very small retrospective study. Additional investigation is needed to establish safety and efficacy of foamed bleomycin. LEVEL OF EVIDENCE 4. Laryngoscope, 126:2726-2732, 2016.

BACKGROUND Understanding health-related quality of life (HRQOL) is crucial to providing high-quality survivorship care for patients with head and neck squamous cell carcinoma (HNSCC). Trends in and prognostic significance of HRQOL before and after HNSCC have not been well described. METHODS HRQOL for older individuals with HNSCC was examined using the linked Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey database. Surveys assessing HRQOL from 5 years prediagnosis to 10 years postdiagnosis were included. HRQOL over time was modeled using multilevel linear regression with restricted cubic splines and was reported as either total HRQOL or change in HRQOL (denoted Δ). The association of prediagnosis HRQOL with survival was examined. RESULTS In total, 1653 individuals were included; of these, 61% completed 1 survey, and 39% completed multiple surveys. Overall HRQOL decreased progressively until 13 months postdiagnosis, then recovered toward baseline between 2 and 5 years. However, after stratification by survival group, the postdiagnosis recovery was not observed. Individuals with shorter survival had lower HRQOL prediagnosis ( 5-year survivors, 96.4; P = .004) with a steeper decline in HRQOL during diagnosis and treatment ( 5-year survivors: Δ, −0.9; 95% CI, −1.8, 0.08). Radiotherapy and advanced stage were associated with greater declines in HRQOL during diagnosis and treatment (P

The incidence of oropharyngeal cancer (OPC) is significantly increasing in the United States. Given that these epidemiologic trends are driven by human papillomavirus (HPV), the potential impact of prophylactic HPV vaccines on the prevention of OPC is of interest. The primary evidence supporting the approval of current prophylactic HPV vaccines is from large phase 3 clinical trials focused on the prevention of genital disease (cervical and anal cancer, as well as genital warts). These trials reported vaccine efficacy rates of 89% to 98% for the prevention of both premalignant lesions and persistent genital infections. However, these trials were designed before the etiologic relationship between HPV and OPC was established. There are differences in the epidemiology of oral and genital HPV infection, such as differences in age and sex distributions, which suggest that the vaccine efficacy observed in genital cancers may not be directly translatable to the cancers of the oropharynx. Evaluation of vaccine efficacy is challenging in the oropharynx because no premalignant lesion analogous to cervical intraepithelial neoplasia in cervical cancer has yet been identified. To truly investigate the efficacy of these vaccines in the oropharynx, additional clinical trials with feasible endpoints are needed. Cancer 2016;122:2313-2323. © 2016 American Cancer Society.

Objectives/Hypothesis To describe the impact of a mentored clerkship initiative on underrepresented minority medical students interested in otolaryngology–head and neck surgery (OHNS). Study Design Prospective observational study. Methods An outreach effort to recruit underrepresented minority students was initiated in 2008, consisting of either a 3-month research clerkship or a 1-month clinical rotation. Financial assistance and faculty mentorship was provided for students. Upon conclusion of the clerkship, students completed a post-clerkship evaluation form. Students were followed regarding residency applications, match status, and publications. Evaluations were compiled and analyzed. The number of publications resulting from interaction with faculty mentors was calculated. Results Fifteen students participated in the clerkship from 11 medical schools. Of those, 10 students participated in the clinical clerkship, four in the research clerkship, and one in both clerkships. Evaluation (5-point Likert scale) average scores and comments revealed high student satisfaction with the rotations (4.85), provided individual mentorship (4.85), and provided exposure to academic medicine (4.92). Participants indicated the rotation favorably impacted their decision to apply for OHNS residency training and increased their interest in academic medicine. The participants had an average number of 1.7 publications, with 1.18 publications in OHNS journals. Six publications resulted from direct interaction between students and faculty during the clerkship. Seven students applied for OHNS residency programs, and six matched successfully. Conclusion Mentored clerkships for underrepresented minority medical students increases interest in applying to OHNS residency training programs and is a successful approach to increasing physician diversity. It provides a pathway to expand research opportunities and increase student interest in academic medicine. Level of Evidence NA Laryngoscope, 126:2684–2688, 2016

Objectives/Hypothesis Patients may perceive resident procedural participation as detrimental to their outcome. Our objective is to investigate whether otolaryngology–head and neck surgery (OHNS) housestaff participation is associated with surgical morbidity and mortality. Study Design Case-control study. Methods OHNS patients were analyzed from the American College of Surgeons National Surgical Quality Improvement Program 2006 to 2013 databases. We compared the incidence of 30-day postoperative morbidity, mortality, readmissions, and reoperations in patients operated on by resident surgeons with attending supervision (AR) with patients operated on by an attending surgeon alone (AO) using cross-tabulations and multivariable regression. Results There were 27,018 cases with primary surgeon data available, with 9,511 AR cases and 17,507 AO cases. Overall, 3.62% of patients experienced at least one postoperative complication. The AR cohort had a higher complication rate of 5.73% than the AO cohort at 2.48% (P < .001). After controlling for all other variables, there was no significant difference in morbidity (odds ratio [OR] = 1.05 [0.89 to 1.24]), mortality (OR = 0.91 [0.49 to 1.70]), readmission (OR = 1.29 [0.92 to 1.81]), or reoperation (OR = 1.28 [0.91 to 1.80]) for AR compared to AO cases. There was no difference between postgraduate year levels for adjusted 30-day morbidity or mortality. Conclusions There is an increased incidence of morbidity, mortality, readmission, and reoperation in OHNS surgical cases with resident participation, which appears related to increased comorbidity with AR patients. After controlling for other variables, resident participation was not associated with an increase in 30-day morbidity, mortality, readmission, or reoperation odds. These data suggest that OHNS resident participation in surgical cases is not associated with poorer short-term outcomes. Level of Evidence 3b Laryngoscope, 2016

BACKGROUND The incidence of oropharyngeal cancer (OPC) and a subset of oral cavity cancer (OCC) is increasing in the United States. To the authors' knowledge, the presumed growing prevalence of survivors of OPC and OCC has not been investigated to date. METHODS Retrospective analysis of Surveillance, Epidemiology, and End Results data (1975-2012) estimated changes in incidence, 5-year cause-specific survival, and prevalence for OPC and OCC. Changes in incidence, cause-specific survival and prevalence were estimated by linear regression and expressed as the percentage change (B). Differences in incidence trends over time were determined by joinpoint analysis. RESULTS The incidence of OPC increased by 62.6% from 1975 through 2012. Notable increases in OPC incidence were observed among men, white individuals, and those of younger ages. The 5-year survival for OPC increased significantly for all sexes, races, and individuals aged >30 years, with white individuals and males experiencing the largest increase in survival. By contrast, the incidence of OCC declined by 22.3% during the same time period. OCC incidence decreased across all groups but increased among individuals aged 30 to 39 years. Significant increases in survival were observed for OCC, except for those who were female, black, and aged

Human papillomavirus (HPV) is responsible for increasing incidence of oropharyngeal cancer. At present, there are no biomarkers in the surveillance algorithm for HPV-positive oropharyngeal cancer (HPV-OPC). HPV16 E6 antibody precedes oropharyngeal cancer diagnosis. If HPV16 E6 indeed precedes primary diagnosis, it is similarly expected to precede disease recurrence and may have a potential role as a biomarker for surveillance of HPV-OPC. To determine whether HPV antibody titers have a potential role as early markers of disease recurrence or prognosis, a retrospective pilot study was designed to determine whether HPV16 early antibody titers E6, E7, E1, and E2 decrease after treatment of HPV16-positive OPC. Trends in pretreatment, early (≤6 months after treatment), and late posttreatment (>6 months after treatment) HPV16 antibody titers were examined. There were 43, 34, and 52 subjects with serum samples available for pretreatment, early, and late posttreatment intervals. Mean pretreatment antibody levels were higher than posttreatment antibody levels. Average antibody levels decreased significantly over time for E6 (Ptrend = 0.001) and E7 (Ptrend < 0.001). Six disease recurrences were observed during the follow-up period (median, 4.4 years). In univariate analysis, a log-unit increase in pretreatment E6 titer was significantly associated with increased risk of disease recurrence (HR, 5.42; 95% CI, 1.1–25.7; P = 0.03). Therefore, levels of antibodies to HPV16 early oncoproteins decline after therapy. Higher E6 titers at diagnosis are associated with significant increases in the risk of recurrence. These data support the prospective evaluation of HPV16 antibodies as markers of surveillance and for risk stratification at diagnosis. Cancer Prev Res; 9(2); 135–41. ©2015 AACR.

The incidence of human papillomavirus (HPV)-associated head and neck cancers is rising, particularly among men. Whether observed epidemiological differences in sex are explained by differences in sexual exposure and/or by immune response is unclear. In this cross-sectional, multi-institutional study, seroprevalence of antibodies to HPV L1 capsid antigen was compared by patient characteristics among 374 adult patients without cancer. A significantly higher seroprevalence was observed among women compared with men for HPV16 (OR = 2.96, 95% CI = 1.21–7.21) and HPV18 (OR = 2.84, 95% CI = 1.06–7.60) L1 antibodies. This difference persisted for HPV16 after controlling for lifetime and recent sexual behavior. After controlling for sex, HPV16 and HPV18 L1 seroprevalence was also significantly associated with higher number of lifetime (HPV16 OR = 1.05, 95% CI = 1.01–1.08; HPV18 OR = 1.04, 95% CI = 1.01–1.08) and recent (HPV16 OR = 1.54, 95% CI = 1.15–2.07; HPV18 OR = 1.40, 95% CI = 1.07–1.82) oral but not vaginal sexual partners. These findings potentially suggest a more robust immune response to HPV16/18 among women compared with men that may not be explained by differences in number of sexual partners, and thereby presumably HPV exposure. The independent association of HPV16/18 L1 seroprevalence with higher number of oral sexual partners suggests a possible role for site of mucosal exposure in the HPV immune response.

To evaluate if a simple method for assessing tumor-infiltrating lymphocytes (TIL) in primary tumor specimens improves the prognostic value of the American Joint Committee on Cancer, 8th Edition (AJCC8) cancer staging system in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-OPC).Retrospective study.In this study, TIL density was quantified on hematoxylin and eosin (HE)-stained specimens from patients presenting to Johns Hopkins Hospital between 2009 and 2017 who underwent primary surgical therapy and had primary tumor specimens available for analysis. The prognostic effect of TIL density was evaluated by Kaplan-Meier method and Cox proportional hazards models considering recurrence-free survival (RFS) as the primary outcome.This study included 132 patients. Ninety-five percent were classified by clinical criteria with AJCC8 early-stage disease (stage I: 82%, stage II: 13%). After 84 months of follow-up, 15 recurrences were observed. Among clinically early-stage disease, TILIn patients with AJCC8 stage I disease, low TIL density was associated with diminished RFS. Our data suggest that assessing TIL density on HE-stained primary tumor specimens may enhance the prognostic resolution of the AJCC8 staging criteria for HPV-OPC.4 Laryngoscope, 130:930-938, 2020.

OBJECTIVES/HYPOTHESIS To examine associations between survival and adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines using an observed-to-expected (O/E) ratio for greater adherence as a risk-adjusted hospital measure of quality care in elderly patients treated for larynx cancer. STUDY DESIGN Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data. METHODS Patients diagnosed with larynx cancer from 2004 to 2007 were evaluated using multivariate regression and survival analysis. A fit logistic regression model was used to calculate an O/E ratio for guideline adherence for each hospital using quality indicators derived from NCCN guidelines for recommended treatment and stratified by hospital volume. RESULTS Of 1,721 patients treated at 395 hospitals, 43.0% of patients received NCCN guideline-adherent care. Low-volume hospitals (N = 295) treating six or fewer cases treated 765 patients (44.5%), with a mean O/E of 0.96 ± 0.45. Hospitals treating more then six cases with an O/E

Importance Hypocalcemia is a common complication of total thyroidectomy. Objectives To identify factors associated with hypocalcemia after total thyroidectomy and to explore the association between hypocalcemia, magnesium disorders, and costs of care. Design, Setting, and Participants A retrospective cross-sectional analysis was performed using data from the MarketScan Commercial Claim and Encounters database on 126 766 commercially insured patients younger than 65 years undergoing total thyroidectomy between January 1, 2010, and December 31, 2012. Statistical analysis was performed from January 1, 2016, to May 30, 2019. Main Outcomes and Measures Short- and long-term hypocalcemia and the costs of care were examined using multivariable regression modeling. Results Among the 126 766 patients in the study (81.6% women; mean age, 46.5 years [range, 18-64 years]), postoperative hypocalcemia was present in 19.1% of patients in the initial 30-day postoperative period and in 4.4% of patients at 1 year. Magnesium disorders were present in 2.1% of patients at the time of surgery. Short- and long-term hypocalcemia were significantly more likely in women (short-term: odds ratio [OR], 1.39 [95% CI, 1.29-1.50]; long-term: OR, 1.69 [95% CI, 1.52-1.89]), those younger than 40 years (short-term: OR for ages 40-64 years, 0.83 [95% CI, 0.78-0.87]; long-term: OR for ages 40-64 years, 0.73 [95% CI, 0.67-0.79]), those with a diagnosis of thyroiditis (short-term: OR, 1.48 [95% CI, 1.16-1.89]; long-term: OR, 1.60 [95% CI, 1.13-2.26]) or cancer (short-term: OR, 1.32 [95% CI, 1.05-1.67]; long-term: OR, 1.17 [95% CI, 0.83-1.63]), vitamin D deficiency (short-term: OR, 1.96 [95% CI, 1.74-2.21]; long-term: OR, 3.72 [95% CI, 3.30-4.18]), concurrent lateral neck dissection (short-term: OR, 1.51 [95% CI, 1.37-1.66]; long-term: OR, 1.95 [95% CI, 1.69-2.26]), concurrent central neck dissection (short-term: OR, 1.15 [95% CI, 1.07-1.24]; long-term: OR, 1.25 [95% CI, 1.12-1.40]), intraoperative parathyroid (short-term: OR, 1.58 [95% CI, 1.46-1.71]; and long-term: OR, 2.05 [95% CI, 1.82-2.31]) or recurrent laryngeal nerve injury (short-term: OR, 1.49 [95% CI, 1.27-1.74]; long-term: OR, 2.04 [95% CI, 1.64-2.54]), and magnesium disorders (short-term: OR, 8.40 [95% CI, 7.21-9.79]; long-term: OR, 25.23 [95% CI, 19.80-32.17]). Compared with the initial postoperative period, the odds of hypocalcemia decreased by 90.0% (OR, 0.10 [95% CI, 0.09-0.11]) at 6 months and 93.0% (OR, 0.07 [95% CI, 0.06-0.08]) at 1 year. After controlling for all other variables, magnesium disorders were associated with the highest odds of short- and long-term postoperative hypocalcemia. Hypocalcemia ($3392) and magnesium disorders ($14 314) were associated with increased mean incremental 1-year costs of care. Conclusions and Relevance Hypocalcemia is common after total thyroidectomy but resolves in most patients by 1 year. Magnesium disorders are significantly independently associated with short- and long-term hypocalcemia and are associated with greater costs of care. These data suggest a potentially modifiable target to reduce the incidence and cost of long-term hypocalcemia at patient and systemic levels.

Importance A volume-outcome association exists for larynx cancer surgery, but to date it has not been investigated for specific surgical procedures. Objectives To characterize the volume-outcome association specifically for laryngectomy surgery and to identify a minimum hospital volume threshold associated with improved outcomes. Design, Setting, and Participants In this cross-sectional study, the Nationwide Inpatient Sample was used to identify 45 156 patients who underwent laryngectomy procedures for a malignant laryngeal or hypopharyngeal neoplasm between January 2001 and December 2011. The analysis was performed in 2018. Hospital laryngectomy volume was modeled as a categorical variable. Main Outcomes and Measures Associations between hospital volume and in-hospital mortality, complications, length of hospitalization, and costs were examined using multivariate logistic regression analysis. Results Among 45 156 patients (mean age, 62.6 years; age range, 20-96 years; 80.2% male) at 5516 hospitals, higher-volume hospitals were more likely to be teaching hospitals in urban locations; were more likely to treat patients who had hypopharyngeal cancer, were of white race/ethnicity, were admitted electively, had no comorbidity, and had private insurance; and were more likely to perform flap reconstruction or concurrent neck dissection. After controlling for all other variables, hospitals treating more than 6 cases per year were associated with lower odds of surgical and medical complications, with a greater reduction in the odds of complications with increasing hospital volume. High-volume hospitals in the top-volume quintile (>28 cases per year) were associated with decreased odds of in-hospital mortality (odds ratio, 0.45; 95% CI, 0.23-0.88), postoperative surgical complications (odds ratio, 0.63; 95% CI, 0.50-0.79), and acute medical complications (odds ratio, 0.63; 95% CI, 0.48-0.81). A statistically meaningful negative association was observed between very high-volume hospital care and the mean incremental length of hospitalization (−3.7 days; 95% CI, −4.9 to −2.4 days) and hospital-related costs (−$4777; 95% CI, −$9463 to −$900). Conclusions and Relevance Laryngectomy outcomes appear to be associated with hospital volume, with reduced morbidity associated with a minimum hospital volume threshold and with reduced mortality, morbidity, length of hospitalization, and costs associated with higher hospital volume. These data support the concept of centralization of complex care at centers able to meet minimum volume thresholds to improve patient outcomes.

OBJECTIVES/HYPOTHESIS Scheduling otolaryngology interviews may be a challenge for residency applicants due to overlapping interview dates. Our objective was to identify otolaryngology interview date patterns and scheduling conflicts over the past six application cycles. STUDY DESIGN Retrospective review of otolaryngology online forums (Otomatch.com and Student Doctor Network). METHODS Online threads related to residency interview dates posted during the 2012 to 2013 through 2017 to 2018 interview seasons on Otomatch.com were reviewed. Program directors were contacted to complete any missing data. The χ- goodness-of-fit test and the χ2 test of independence was used to compare proportions. Analysis of variance was used to compare values across years. RESULTS Data from an average of 98 programs (99%) per year were obtained. The majority of invitations arrived late October (49%), followed by early November (37.1%). Interviews occurred primarily in December (48.4%) and January (37.5%). Programs on average scheduled 2.47 (range, 0-4) interview dates. Most interviews fell on Fridays (28.7%) and Saturdays (22.7%) (P

Over the past 30 years, hypoglossal nerve stimulation has moved through a development pathway to become a viable treatment modality for patients with OSA. Initial pilot studies in animals and humans laid the conceptual foundation for this approach, leading to the development of fully implantable stimulating systems for therapeutic purposes. These devices were then shown to be both safe and efficacious in feasibility studies. One such closed-loop stimulating device was found to be effective in treating a limited spectrum of apneic patients and is currently approved by the US Food and Drug Administration for this purpose. Another open-loop stimulating system is currently being rigorously tested in a pivotal trial. Collectively, clinical trials of hypoglossal nerve stimulating systems have yielded important insights that can help optimize therapeutic responses to hypoglossal nerve stimulation. These insights include specific patient selection criteria and methods for delivering stimulation to specific portions of the hypoglossal nerve and/or genioglossus muscle. New approaches for activating efferent and afferent motor pathways are currently in early-stage laboratory development and hold some long-term promise as a novel therapy.

To examine the cumulative effect of diagnostic steps for primary tumor identification in patients with head and neck squamous cell carcinoma of unknown primary (HNSCCUP), including lingual tonsillectomy, and the impact of primary tumor identification on subsequent treatment.Retrospective analysis.We reviewed the records of 110 patients diagnosed with HNSCCUP between 2003 and 2015. Results of diagnostic imaging (fluorodeoxyglucose-positron emission tomography/computed tomography [FDG-PET/CT]), tumor detection with direct laryngoscopy with biopsies, palatine tonsillectomy, and transoral robotic surgery (TORS) lingual tonsillectomy were recorded. Associations between demographic and treatment variables with overall survival (OS) and progression-free survival (PFS) were modeled with Cox proportional hazards models.FDG-PET/CT was suspicious for a primary site in 23/77 (30%) patients. Direct laryngoscopy identified a primary tumor in 34/110 patients (31%). Forty-seven patients underwent palatine tonsillectomy, which identified 17 primaries (36%), yielding a cumulative primary tumor identification of 51/110 (46%). Fourteen patients underwent TORS lingual tonsillectomy, which identified eight primaries (57%), resulting in a cumulative identification of 59/110 (53%). The detection rate increased from 28/63 (44%) to 31/47 (66%) after the addition of TORS lingual tonsillectomy to our institutional approach. Detection rates varied by HPV status. Primary tumor identification altered subsequent radiation planning, as patients with an identified primary tumor received radiation to a smaller volume of tissue than did those without an identified primary tumor. However, there was no significant association between primary tumor identification and OS or PFS.A stepwise approach to primary tumor identification identifies a primary tumor in a majority of patients.4 Laryngoscope, 129:1610-1616, 2019.

The increasing incidence of human papillomavirus (HPV)-related head and neck cancer (HNC) has led to the increasing prevalence of survivors, yet to the best of the authors' knowledge the prevalence of comorbidities during the survivorship period and their effects on survival are relatively unknown.In this retrospective cross-sectional study, individuals with a first incident primary diagnosis of HNC from 2004 through 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked databases were included in the analysis and classified as patients with HPV-related or HPV-unrelated HNC. The presence of 30 comorbid conditions of interest was identified. Associations between comorbidity and treatment group as well as overall survival were evaluated.The study population consisted of 8025 patients with HPV-unrelated HNC and 2499 patients with HPV-related HNC. Hypertension, congestive heart failure, cerebrovascular disease, and chronic obstructive pulmonary disease all were found to be highly prevalent at the time of the cancer diagnosis and increased over time for both groups. These comorbidities were found at significantly lower rates in the HPV-related HNC population, yet were associated with an increased risk of death in both groups. The probabilities of developing cancer-related comorbidities such as pneumonia, dysphagia, weight loss, malnutrition, and dental issues rose significantly in both groups after treatment but were more likely in patients with HPV-related HNC. In both groups of patients, the presence of each comorbidity either at the time of diagnosis or during survivorship was associated with a significantly increased risk of death.There is a large burden of comorbidities in both patients with HPV-related and HPV-unrelated HNC, both of which are associated with decreased survival. Oncologic surveillance should not be limited to the evaluation of disease status, but also should include screening for the highly prevalent conditions associated with the risk of death.

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.

Background: The discovery of mutations in epidermal growth factor receptor (EGFR) has dramatically changed the treatment of patients with non-small-cell lung cancer (NSCLC), the leading cause of cancer deaths worldwide. EGFR-targeted therapies show considerable promise, but drug resistance has become a substantial issue. Methods: We reviewed the literature to provide an overview of the drug resistance to EGFR tyrosine kinase inhibitors (TKIs) in NSCLC. Results: The mechanisms causing primary, acquired and persistent drug resistance to TKIs vary. Researchers and clinicians, who have used study findings to develop more effective therapeutic approaches, have found that the sequential use of single agents presents a formidable challenge, suggesting that multidrug combinations must be considered. Conclusions: In the era of precision medicine, oncologists should promptly obtain an accurate diagnosis of drug resistance in each patient to be able to design the most relevant combination therapy to overcome patient-specific drug resistance.

Oncocytic lipoadenoma is an extremely rare benign salivary gland tumor with few reported cases. We provide a comprehensive description of key radiographic features suggesting the diagnosis of oncocytic lipoadenoma and review its clinical and pathologic features. We present a case of a 70-year-old woman with a slowly enlarging submandibular mass. Magnetic resonance imaging showed a heterogeneous fat-containing lesion without aggressive features. The solid components enhanced with gadolinium. Fine needle aspiration biopsy showed oncocytic cells. After surgical resection, histology showed a well-encapsulated mass with a mixture of oncocytes and adipocytes consistent with oncocytic lipoadenoma. While the usual differential diagnosis of oncocytes in a salivary gland aspirate includes oncocytoma, Warthin’s tumor, oncocytic carcinoma, and oncocytic metaplasia/hyperplasia, specific radiographic features on MRI of a well-circumscribed soft tissue and fat-containing mass, can direct preoperative diagnosis a...

Objectives: Nodular fasciitis (NF) is a self-limited, mass-forming, fibrous proliferation that can occur in the head and neck and may mimic malignancy. Fine-needle aspiration biopsy (FNAB) is a minimally invasive, rapid, accurate method of obtaining diagnostic material from head and neck masses. In this study, we verify the usefulness of FNAB in obtaining a definitive diagnosis of NF. Methods: Cases were identified from our laboratory information system. Cytology slides were reviewed to note morphologic features and confirm diagnoses. Clinical history was obtained to document the case presentations and outcomes. Results: All 9 cases were found to have clinical presentations and common distinguishing morphologic features consistent with NF. Two cases were excised surgically, and the remainder regressed spontaneously. There were no recurrences. Conclusions: FNAB can produce a definitive diagnosis of NF, providing an opportunity to avoid surgical excision in patients with a typical clinical presentation.

Drug resistance is a major obstacle to the success of EGFR-targeted therapy. We recently studied the mechanism by which a small subset of EGFR mutant lung cancer cells remains viable after EGFR inhibition. We found that this drug-tolerant subpopulation develops because EGFR inhibition prevents AKT activity and thus inactivates Ets-1 function. In this article, we discuss how changes in intrinsic cell signaling after EGFR inhibition open a new avenue to drug resistance in NSCLCs, and comment on combined TKI and MEK inhibitor treatment to reduce the probability of emergent resistance to EGFR TKIs.

Background Factors associated with disease-free survival (DFS) after salvage therapy for recurrent oropharyngeal squamous cell carcinoma (SCC) in the context of human papillomavirus (HPV) are poorly understood. Methods A retrospective cohort analysis was conducted of patients with recurrent oropharyngeal SCC with known HPV tumor status who received salvage therapy. Results Eighty-six patients were eligible for analysis. Sixty-four patients (74%) were HPV-positive. In multivariable analysis, HPV-positive tumor status (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.13–0.71; p = .007), clinical response to any salvage therapy (HR = 0.29; 95% CI = 0.11–0.77; p = .01), and surgical salvage (HR = 0.38; 95% CI = 0.16–0.88; p = .02) were associated with improved overall survival (OS). Positive surgical margin was associated with worse DFS after salvage (HR = 8.43; 95% CI = 1.99–35.70; p = .004). Conclusion For recurrent oropharyngeal SCC, HPV-positive tumor status, surgical salvage, and clinical response to salvage therapy are independently associated with improved OS, but not DFS after salvage. Surgical margin is the only independent predictor of DFS. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Objectives/Hypothesis We hypothesized that personal characteristics of residents may affect how well competency is attained in a surgical residency. To this end, we examined two concepts of global trait emotional intelligence and learner autonomy profile and their factor relationship with competency outcomes in a residency program in otolaryngology–head and neck surgery. Study Design A cohort study prospectively gathered competency change scores for 1 year and retrospectively analyzed the factor associations. Methods We measured two personal characteristics using the Trait Emotional Intelligence Questionnaire-Short Form and Learner Autonomy Profile-Short Form between 2013 and 2014 in a tertiary otolaryngology–head and neck residency program. We prospectively examined faculty-rated resident competency scores monitored in the same time period and correlated the personal attributes with cumulative competency improvement scores. Statistical analyses included factor correlations and univariate regression. Results With a response rate of 64% (N = 16/25), we identified two statically significant predictors of competency improvement outcome attained by the end of the year. Regression analyses showed that emotionality factor of global trait emotional intelligence (P = .04) and learner autonomy profile (P < .01) were significant predictors for the higher improvement of aggregate competency outcome. Conclusions Personal factors of individual residents can affect their improvement of overall competency. Practicing competency-based education should, therefore, include assessing individual resident factors as well as teaching clinical knowledge and technical skills. Level of Evidence NA Laryngoscope, 2015

Objectives/Hypothesis Introduce the Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire to quantify chronic sialadenitis symptoms and assess the impact of sialendoscopic-assisted salivary duct surgery (SASDS). Study Design Retrospective outcome symptoms questionnaire study. Methods The COSS questionnaire assesses the severity of sialadenitis symptoms from 0 to 100. Patients who underwent SASDS from April 2006 to December 2013 completed the COSS questionnaire and the ShortForm8 Health Survey (SF-8) based on current symptoms, and reported whether they had complete, partial, or no symptomatic response to SASDS. Results Sixty-six of the 156 (43%) contacted patients completed the questionnaires who had had symptoms in 26 submandibular ducts and 53 parotid ducts. The mean COSS score was higher for parotid ducts (12.0; interquartile range [IQR] 1.0–20.0) than for submandibular ducts (7.6; IQR 0.5–15.0) but not significantly so (P = 0.20). Thirty-eight (60%) patients reported complete resolution of symptoms, with a mean COSS score of 4.5 (IQR 0–7). Twenty-one (33%) patients reported partial resolution, with a mean COSS score of 18.5 (IQR 11.3–22.8). Five (8%) patients reported no improvement, with a mean COSS score of 25.1 (IQR 15.2–35). Thirty-six (46%) ducts with sialoliths had a significantly lower mean COSS score (5.8; IQR 0−9.5) compared to those without sialoliths (14.2; IQR 4.5−21.5, P = 0.0004). There was no significant difference in SF-8 survey scores between these groups. Conclusion The COSS questionnaire is a novel survey instrument to measure obstructive sialadenitis symptom severity that could be helpful in defining outcomes of SASDS. COSS scores under 10 correlate with complete resolution of symptoms, whereas scores between 10 and 25 correlate with partial resolution. Level of Evidence 4. Laryngoscope, 2015

Objectives/Hypothesis To describe a 10-year diversity initiative to increase the number of women and underrepresented minorities in an academic department of otolaryngology–head and neck surgery. Study Design Retrospective review. Methods A multifaceted approach was undertaken to recruit and retain women and underrepresented minority (URM) faculty: creation of a climate of diversity, aggressive recruitment, achievement of parity of salary at rank regardless of gender or minority status, provision of mentorship to women and URM faculty, and increasing the pipeline of qualified candidates. Primary outcomes measures included number of women and URM faculty, academic rank, and salary. Results From 2004 to 2014, the percentage of women clinical faculty increased from 5.8% to 23.7%; women basic science faculty increased from 11.1% to 37.5%. The number of women at associate professor rank increased from 0 to eight. During this period, underrepresented minority faculty increased in number from two to four; URM full professors increased in number from 0 to 1. In 2004, women earned 4% to 12% less than their male counterparts; there were no salary differences for URM. In 2014, salary was equal by rank and subspecialty training independent of gender or minority status. Conclusion A comprehensive diversity and inclusion initiative has increased representation of women and URM faculty in an academic department of otolaryngology–head and neck surgery. However, there continue to be opportunities to further increase diversity. Level of Evidence N/A. Laryngoscope, 2015

Background Parathyroid scintigraphy using (99m) Tc-MIBI single photon emission computed tomography (SPECT)/CT has been proposed as one of the most accurate localization techniques in patients with primary hyperparathyroidism (PHPT). The purpose of this review was to meta-analyze published data on the detection rate of (99m) Tc-MIBI SPECT/CT in the preoperative planning of patients with PHPT. Methods A comprehensive literature search of studies published through June 2014 was performed. The pooled detection rate of this scintigraphic method including 95% confidence intervals (95% CIs) was calculated on a per patient-based and on a per lesion-based analysis by using a random effects model. Results Twenty-three articles including 1236 patients with PHPT were selected. The pooled detection rate of (99m) Tc-MIBI SPECT/CT in the preoperative planning of patients with PHPT was 88% (95% CI = 84% to 92%) and 88% (95% CI = 82% to 92%) on a per patient-based and per lesion-based analysis, respectively. Conclusion The (99m) Tc-MIBI SPECT/CT has high detection rate for hyperfunctioning parathyroid glands in patients with PHPT. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2159-E2172, 2016.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (HN the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.