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BACKGROUND Management of sinonasal malignancy (SNM) often includes surgical resection as part of the multimodality treatment. Treatment-related surgical morbidity can occur, yet risk factors associated with complications in this population have not been sufficiently investigated. METHODS Adult patients with histologically confirmed SNM whose primary treatment included surgical resection were prospectively enrolled into an observational, multi-institutional cohort study from 2015 to 2020. Sociodemographic, disease, and treatment data were collected. Complications assessed included cerebrospinal fluid leak, orbital injury, intracranial injury, diplopia, meningitis, osteoradionecrosis, hospitalization for neutropenia, and subsequent chronic rhinosinusitis. The surgical approach was categorized as endoscopic resection (ER) or open/combined resection (O/CR). Associations between factors and complications were analyzed using Student's t test, Fisher's exact test, and logistic regression modeling. RESULTS Overall, 142 patients met the inclusion criteria. Twenty-three subjects had at least 1 complication (16.2%). On unadjusted analysis, adjuvant radiation therapy was associated with developing a complication (91.3% vs 65.5%, p = 0.013). Compared with the ER group (n = 98), the O/CR group (n = 44) had a greater percentage of higher T-stage lesions (p = 0.004) and more frequently received adjuvant radiation (84.1% vs 64.4%, p = 0.017) and chemotherapy (50.0% vs 30.6%, p = 0.038). Complication rates were similar between the ER and O/CR groups without controlling for other factors. Regression analysis that retained certain factors showed O/CR was associated with increased odds of experiencing a complication (odds ratio, 3.34; 95% confidence interval, 1.06-11.19). CONCLUSIONS Prospective, multicenter evaluation of SNM treatment outcomes is feasible. Undergoing O/CR was associated with increased odds of developing a complication after accounting for radiation therapy. Further studies are warranted to build upon these findings.

To assess knowledge regarding head and neck cancers (HNCs) in 2020, factors associated with knowledge of the role of human papillomavirus (HPV) in HNCs, and factors associated with exposure to Oral, Head and Neck Cancer Awareness Week (OHANCAW).Cross-sectional survey.Online.The survey was distributed to 517 participants via a paid panel and utilized US Census-built quotas to represent the US population.Participants surpassed 50% awareness rates in only 5 of 10 (50.0%), 2 of 6 (33.3%), and 5 of 9 (55.5%) preselected answer choices for subsites, risk factors, and signs/symptoms of HNCs, respectively. Knowledge of HPV's role in oropharyngeal cancer was also low, at 30.6%. However, of the controlled variables, exposure to OHANCAW was closely associated with knowledge of HPV's role in HNC (odds ratio, 10.25; 95% CI, 5.36-19.62). Women and elderly individuals were less likely to be exposed to OHANCAW, while those with higher education, those who drink heavily (4 drinks/d), and current but not former tobacco users were more likely to be exposed.Knowledge of HNCs and the causal role of HPV remains suboptimal, though our results suggest that OHANCAW remains a viable educational pathway. However, certain at-risk populations, such as former smokers and older individuals, whom we may not be effectively reaching and screening, represent a priority for future outreach efforts.

There has been a drastic increase in the incidence of nonmelanoma (NMSC), including squamous, basal cell, and melanoma skin cancers worldwide. Most cases of skin cancer can be treated effectively with surgery; fewer than 10% of cases are advanced and may require additional therapies. A better understanding of the biology of skin cancer will help contribute to better prognostic information and identification of possible new therapeutic targets. Herein, the authors review the biology and pathogenesis of both NMSC and melanoma, focusing on critical cell signaling pathways mediating the disease and current therapeutic strategies targeted to underlying genetic pathways.

Bacterial biofilms are often found in chronically infected wounds. Biofilms protect bacteria from antibiotics and impair wound healing. Surgical debridement is often needed to remove the biofilm from an infected wound. Laser-generated shockwave (LGS) treatment is a novel tissue-sparing treatment for biofilm disruption. Previous studies have demonstrated that LGS is effective in disrupting biofilms in vitro. In this study, we aim to determine the safety threshold of the LGS technology in an in vivo rodent model. To understand the in vivo effects of LGS on healthy cutaneous tissue, the de-haired dorsal skin of Sprague-Dawley rats were treated with LGS at three different peak pressures (118, 296, 227 MPa). These pressures were generated using a 1064 nm Nd/YAG laser (pulse duration 5 ns and laser fluence of 777.9 mJ) with laser spot size diameters of 2.2, 3.0, and 4.2 mm, respectively. Following treatment, the animals were observed for 72 h, and a small subset was euthanized at 1-h, 24-h, and 72-h post-treatment and assessed for tissue injury or inflammation under histology. Each treatment group consisted of 9 rats (n = 3/time point for 1-h, 24-h, 72-h post-treatment). An additional 4 control (untreated) rats were included in the analysis, for a total of 31 animals. Gross injuries occurred in 21 (77%) animals and consisted of minor erythema, with prevalence positively correlated with peak pressure (p < 0.05). Of injuries under gross observation, 94% resolved within 24 h. Under histological analysis, the injuries and tissue inflammation were found to be localized to the epidermis and superficial dermis. LGS appears to be well tolerated by cutaneous tissue for the laser energy settings shown to be effective against bacterial biofilm in vitro. All injuries incurred, at even the highest peak pressures, were clinically mild and resolved within 1 day. This lends further support to the overall safety of LGS and serves to translate LGS towards in vivo efficacy studies.

Cerebrospinal fluid (CSF) leaks can occur when there is a communication between the intracranial cavities and the external environment. They are a common and serious complication of numerous procedures in otolaryngology, and if not treated, persistent leaks can increase a patient’s risk of developing life-threatening complications such as meningitis. As it is not uncommon for patients to exhibit increased secretions post operatively, distinguishing normal secretions from those containing CSF can be difficult. Currently, there are no proven, available tests that allow a medical provider concerned about a CSF leak to inexpensively, rapidly, and non-invasively rule out the presence of a leak. The gold standard laboratory-based test requires that a sample is sent to a tertiary site for analysis where days to weeks may pass before results return. To address this, our group recently developed a semi-quantitative, barcode-style lateral-flow immunoassay (LFA) for the quantification of the beta-trace protein, which has been reported as an indicator of the presence of CSF leaks. In the work presented here, we created a rapid diagnostic test kit comprised of our LFA, a collection swab, dilution buffers, disposable pipettes, and instructions. Validation studies demonstrated excellent predictive capabilities of this kit in distinguishing between clinical specimens containing CSF and those that did not. Our diagnostic kit for CSF leak detection can be operated by an untrained user, does not require any external equipment, and can be performed in approximately 20 min, making it well-suited for use at the point-of-care. This kit has the potential to transform patient outcomes.

Purpose The role of chemoradiation (CRT) in treating patients with early-stage glottic squamous cell carcinoma (SCC), especially for T2N0M0 glottic SCC with impaired vocal cord mobility, remains unexplored. We sought to evaluate the impact of CRT on survival in early-stage glottic SCC by using the SEER database. Patients and Methods We included patients with localized (T1-4N0M0) glottic SCC (N = 4,743) diagnosed between 2004 and 2014 and treated with definitive radiotherapy (RT) alone, CRT, or laryngectomy alone in the SEER database. Disease-specific mortality (DSM) was evaluated via multivariable regression using a competing risk model that accounts for other-cause mortality as a competing risk event for DSM. One-to-one propensity score matching between CRT and RT cohorts was also performed to facilitate comparison of cumulative DSM and other-cause mortality incidences stratified by T stage. Results After stratification by T stage, CRT was associated with increased DSM in T1-2N0M0 glottic SCC (adjusted hazard ratios [AHRs], 4.222 and 2.260 for T1 and T2 disease, respectively; P < .001 for both). For T2N0M0 glottic SCC with and without impaired vocal cord mobility, CRT resulted in significantly increased DSM compared with RT alone in both cohorts (AHR, 2.084; P = .046 and AHR, 2.412; P < .001, respectively). After propensity score matching, cumulative incidence plots demonstrated a statistically significant increase in DSM associated with CRT compared with RT alone for both T1 and T2 glottic SCC ( P < .001 and P = .003, respectively). Conclusion CRT for T1-2N0M0 glottic SCC was associated with increased DSM compared with RT alone. This pattern persisted upon further stratification on the basis of vocal cord mobility status for T2N0M0 glottic SCC. This finding warrants careful consideration of chemotherapy in early-stage glottic SCC.

Objectives To evaluate the incidence, causes, risk factors, and costs associated with 30-day readmissions in parotidectomy patients utilizing the Nationwide Readmissions Database (NRD). Study design Retrospective cohort study. Methods We examined the NRD for patients who underwent parotidectomy between 2010 and 2014. Rates, causes, and costs of 30-day readmissions were determined. Multivariate logistic regression was used to identify risk factors for readmission. Results Among 15,102 included patients, 594 (3.9%) were readmitted within 30 days. The average cost per readmission was $12,502. Infectious (22.7%) and wound (11.2%) complications were the two most common causes of readmission. After controlling for other covariates, significant predictors of readmission included advanced comorbidity (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.09-2.37), a malignant parotid tumor (OR, 2.37; 95% CI, 1.63-3.43), length of stay ≥2 days (OR, 1.54; 95% CI, 1.09-2.18), and nonroutine discharge destinations (home with care [OR, 1.88; 95% CI, 1.27-2.78] and nursing facility [OR, 2.69; 95% CI, 1.55-4.67]). Conclusion In this nationwide database analysis, we found that nearly 4% of all patients undergoing parotidectomy are readmitted within 30 days. Readmissions are commonly due to infections and wound complications. Quality improvement proposals targeting avoidable readmissions should focus on early recognition and prevention of infection and wound complications. Risk factors contributing to readmission include advanced comorbidity, malignant parotid tumor, prolonged index hospitalization, and nonroutine discharge destinations. Level of evidence NA Laryngoscope, 130:1212-1217, 2020.

Background Survival outcomes for adjuvant chemoradiotherapy (aCRT) and adjuvant radiotherapy (aRT) were compared in patients with oropharyngeal squamous cell carcinoma (OPSCC) with intermediate-risk features. Methods We identified 2164 patients with OPSCC in the National Cancer Database without positive margins or extracapsular extension and with at least one intermediate-risk feature: pT3-T4 disease, ≥two positive lymph nodes, level IV/V nodal disease, and/or lymphovascular invasion. We assessed predictors of aCRT use and covariables impacting overall survival. Results aCRT was commonly used for both human papillomavirus (HPV)-positive (62.0%) and HPV-negative (64.3%) patients with OPSCC. Higher N stage, level IV/V neck disease, and younger age strongly predicted aCRT utilization. There was no significant survival benefit associated with aCRT vs aRT in HPV-positive (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.62-1.38; P = .71) or HPV-negative (HR, 0.75; 95% CI, 0.51-1.10; P = .15) disease. Conclusions Despite high rates of utilization, aCRT is not associated with better survival vs aRT for OPSCC with intermediate-risk features, including HPV-negative tumors.

IMPORTANCE: Thirty-day hospital readmissions have substantial direct costs and are increasingly used as a measure of quality care. However, data regarding the risk factors and reasons for readmissions in head and neck cancer surgery reconstruction are lacking. OBJECTIVE: To describe the rate, risk factors, and causes of 30-day readmission in patients with head and neck cancer following free or pedicled flap reconstruction. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study analyzed medical records from the Nationwide Readmissions Database of 9487 patients undergoing pedicled or free flap reconstruction of head and neck oncologic defects between January 1, 2010, and December 31, 2014. Data analysis was performed in October 2017. EXPOSURES: Pedicled or free flap reconstruction of an oncologic head and neck defect. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day all-cause readmissions. Secondary outcomes included risk factors, causes, and costs of readmission. Multivariate regression analyses were conducted to determine factors independently associated with 30-day readmissions. RESULTS: Among 9487 patients included in the study (6798 male; 71.7%), the median age was 63 years (interquartile range, 55-71 years), and the 30-day readmission rate was 19.4% (n = 1839), with a mean cost per readmission of $15 916 (standard error of the mean, $785). The most common indication for readmission was wound complication (26.5%, n = 487). On multivariate regression, significant risk factors for 30-day readmission were median household income in the lowest quartile (vs highest quartile: odds ratio [OR], 1.58; 95% CI, 1.18-2.11), congestive heart failure (OR, 1.68; 95% CI, 1.14-2.47), liver disease (OR, 2.02; 95% CI, 1.22- 3.33), total laryngectomy (OR, 1.40; 95% CI, 1.12-1.75), pharyngectomy (OR, 1.47; 95% CI, 1.08-2.01), blood transfusion (OR, 1.30; 95% CI, 1.04-1.64), discharge to home with home health care (vs routine: OR, 1.32; 95% CI, 1.04-1.67), and discharge to a nursing facility (vs routine: OR, 1.77; 95% CI, 1.30-2.40). CONCLUSIONS AND RELEVANCE: Using the Nationwide Readmissions Database, we demonstrate that approximately 1 in 5 patients undergoing head and neck cancer surgery reconstruction is readmitted within 30 days of surgery. Readmissions are most commonly associated with wound complications. Socioeconomic status, complex ablative procedures, and patient comorbidities are independent risk factors for readmission. These findings may be useful to clinicians in developing perioperative interventions aimed to reduce hospital readmissions and improve quality of patient care.

Purpose To investigate the prognostic value of pre-treatment immune parameters including white blood cell count (WBC) and circulating lymphocyte count (CLC) among patients with oropharyngeal carcinoma treated by radiation therapy. Methods and Materials A total of 136 consecutive patients were treated by radiation therapy for locally advanced (stage III/IV) squamous cell carcinoma of the oropharynx with known human papillomavirus (HPV) status. Medical records were reviewed to identify patients with documented pre-treatment laboratory bloodwork. The Kaplan-Meier method and linear regression models were used to evaluate the association between pre-treatment CBC and CLC values with survival endpoints. Results One hundred and eleven patients satisfied inclusion criteria. Median age was 62 years (range, 22–91). Eighty-four patients were HPV-positive (76%) and 27 (24%) were HPV-negative. There was no difference in WBC and CLC mean values at baseline between HPV-positive and HV-negative (p > 0.05, for both). Trends were detected in the HPV-positive cohort favoring patients with higher CLC, with respect to 2-year local-regional control (93% vs. 82%, p = 0.06) and distant control (88% vs. 82%, p = 0.10) using the median CLC as cut-off. HPV-positive patients with CLC values in the lowest quartile had inferior local-regional control compared to those in the upper 3 quartiles (69% vs. 89%, p = 0.01). Conclusion Low pre-treatment CLC was correlated with local-regional recurrence and distant failure among HPV-positive patients. These associations were not observed in the HPV-negative cohort.

Objectives/hypothesis To characterize the demographics, clinicopathologic characteristics, and treatment and reconstructive outcomes of patients who underwent total glossectomy STUDY DESIGN: Retrospective chart review at an academic tertiary-care medical center. Methods All patients who had undergone total glossectomy (as an individual procedure or as part of a more extensive resection) between January 1, 1995 and December 31, 2014 were included in the analysis. Patient characteristics and clinical outcomes were reviewed. Results Forty-eight patients underwent total glossectomy for oral tongue and base of tongue cancer. The mean age of the patients was 56 (range, 29-92 years). History of tobacco and heavy alcohol use was found in 76% and 11% of patients, respectively. The majority of patients had advanced cancer (91.7% at stage IV), and 60.4% had salvage therapy for recurrent disease. T4 disease comprised 81% of patients. Sixty percent had clinical or radiographic evidence of nodal metastasis. Reconstruction of the defect was performed with free flaps from the rectus abdominus (40%), fibula (25%), anterolateral thigh (23%), and other donor tissues. One- and 5-year survival rates were 42% and 26%, with locoregional and distant recurrence reported at 36% and 25%, respectively. Conclusions Total glossectomy for oncologic control is most commonly performed in patients who have stage IV cancers. Despite high reconstructive success rates, the likelihood of locoregional and distance recurrence was high. Most patients can communicate intelligibly and achieve decannulation, but swallowing outcomes remain guarded, especially considering previous irradiation and resection of the base of tongue. Level of evidence 4 Laryngoscope, 129:1087-1092, 2019.

Background The impact of treatment delays on survival in oropharyngeal cancer and whether the effect varies by human papillomavirus (HPV) status have yet to be defined. Methods Retrospective analysis of the survival impact of time from diagnosis to surgery (DTS), surgery to radiation (SRT), and duration of radiation (RTD) for patients in the National Cancer Database with resected oropharyngeal cancer who underwent adjuvant radiation from 2010 to 2014. Results We identified optimal thresholds of 30, 40, and 51 days for DTS, SRT, and RTD, respectively, with treatment times exceeding these thresholds associated with significantly worse overall survival. Prolonged SRT and RTD were associated with mortality regardless of HPV status, although rising DTS was only predictive among patients with HPV-negative tumors. Conclusions Treatment delays significantly impact survival in oropharyngeal cancer. The consequences of prolonged DTS may be stronger in HPV-negative than HPV-positive disease. These data serve as a foundation for future research and clinical management.

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.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has led to a global surge in critically ill patients requiring invasive mechanical ventilation, some of whom may benefit from tracheostomy. Decisions on if, when, and how to perform tracheostomy in patients with COVID-19 have major implications for patients, clinicians, and hospitals. We investigated the tracheostomy protocols and practices that institutions around the world have put into place in response to the COVID-19 pandemic. Data Sources: Protocols for tracheostomy in patients with severe acute respiratory syndrome coronavirus 2 infection from individual institutions (n = 59) were obtained from the United States and 25 other countries, including data from several low- and middle-income countries, 23 published or society-endorsed protocols, and 36 institutional protocols. Review Methods: The comparative document analysis involved cross-sectional review of institutional protocols and practices. Data sources were analyzed for timing of tracheostomy, contraindications, preoperative testing, personal protective equipment (PPE), surgical technique, and postoperative management. Conclusions: Timing of tracheostomy varied from 3 to >21 days, with over 90% of protocols recommending 14 days of intubation prior to tracheostomy. Most protocols advocate delaying tracheostomy until COVID-19 testing was negative. All protocols involved use of N95 or higher PPE. Both open and percutaneous techniques were reported. Timing of tracheostomy changes ranged from 5 to >30 days postoperatively, sometimes contingent on negative COVID-19 test results. Implications for Practice: Wide variation exists in tracheostomy protocols, reflecting geographical variation, different resource constraints, and limited data to drive evidence-based care standards. Findings presented herein may provide reference points and a framework for evolving care standards.

Background: Immune checkpoint blockade that downregulates T cell evasion for effective immunity has provided a renewed interest in therapeutic cancer vaccines. Methods: Utilizing murine lung cancer models, we determined: tumor burden, TIL cytolysis, immunohistochemistry, flow cytometry, RNA Sequencing, CD4 T cells, CD8 T cells, CXCL9 chemokine, and CXCL10 chemokine neutralization to evaluate the efficacy of Programmed cell death protein 1 (PD-1) blockade combined with chemokine (C-C motif) ligand 21-dendritic cell tumor antigen (CCL21-DC tumor Ag) vaccine. Results: Anti-PD1 combined with CCL21-DC tumor Ag vaccine eradicated 75% of 12-day established tumors (150 mm3) that was enhanced to 90% by administering CCL21-DC tumor Ag vaccine prior to combined therapy. The effect of combined therapy was blocked by CD4, CD8, CXCL9, and CXCL10 neutralizing antibodies. Conclusion: PD-1 blockade therapy plus CCL21-DC tumor Ag vaccine could be beneficial to lung cancer patients.

Importance The novel coronavirus disease 2019 (COVID-19) has proven to be highly infectious, putting health care professionals around the world at increased risk. Furthermore, there are widespread shortages of necessary personal protective equipment (PPE) for these individuals. Filtering facepiece respirators, such as the N95 respirator, intended for single use, can be reused in times of need. We explore the evidence for decontamination or sterilization of N95 respirators for health care systems seeking to conserve PPE while maintaining the health of their workforce. Observations The filtration properties and fit of N95 respirators must be preserved to function adequately over multiple uses. Studies have shown that chemical sterilization using soap and water, alcohols, and bleach render the respirator nonfunctional. Decontamination with microwave heat and high dry heat also result in degradation of respirator material. UV light, steam, low-dry heat, and commercial sterilization methods with ethylene oxide or vaporized hydrogen peroxide appear to be viable options for successful decontamination. Furthermore, since the surface viability of the novel coronavirus is presumed to be 72 hours, rotating N95 respirator use and allowing time decontamination of the respirators is also a reasonable option. We describe a protocol and best practice recommendations for redoffing decontaminated N95 and rotating N95 respirator use. Conclusions and Relevance COVID-19 presents a high risk for health care professionals, particularly otolaryngologists, owing to the nature of viral transmission, including possible airborne transmission and high viral load in the upper respiratory tract. Proper PPE is effective when used correctly, but in times of scarce resources, institutions may turn to alternative methods of preserving and reusing filtering facepiece respirators. Based on studies conducted on the decontamination of N95 respirators after prior outbreaks, there are several options for institutions to consider for both immediate and large-scale implementation.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has caused physicians and surgeons to consider restructuring traditional cancer management paradigms. We aim to review the current evidence regarding the diagnosis and management of head and neck cancer, with an emphasis on the role of the multidisciplinary team (MDT) during a pandemic. DATA SOURCES: PubMed, Google Scholar, the American Academy of Otolaryngology—Head and Neck Surgery and the American Head and Neck Society COVID-19 resources were examined. REVIEW METHODS: Studies on the treatment of head and neck cancer guidelines during COVID-19 setting were reviewed. A total of 54 studies were included. Given the continuously evolving body of literature, the sources cited includes the latest statement from medical/dental societies. RESULTS: The unpredictable fluctuation of hospital resources and the risk of the nosocomial spread of SARS-CoV-2 have direct effects on head and neck cancer management. Using an MDT-approach to help define “essential surgeries” for immediately life- or function-threatening disease processes in the context of available hospital resources will help to maximize outcomes. Early enrollment in an MDT is often critical for considering non-surgical options to protect patients and health care workers. The role of MDT continues after cancer treatment if delivered, and the MDT plays an essential role in surveillance and survivorship programs in these challenging times. CONCLUSION: Head and neck cancer management during the COVID-19 pandemic poses a unique challenge for all specialists involved. Early MDT involvement is important to maximize patient outcomes and satisfaction in the context of public and community safety.

To evaluate the management and recurrence outcomes of head and neck Merkel cell carcinoma (HN-MCC) at a single institution.A retrospective review of outcomes in patients with HN-MCC.A tertiary center from May 1990 to December 2018.Electronic medical records of patients with HN-MCC were reviewed.Sixty cases were included, with 67% (40 of 60) males and a mean age of 73.3 years. Imaging had a moderate sensitivity and specificity for detection of occult disease when compared with histopathologic analysis. Forty-two percent (25 of 60) of patients underwent neck dissection, and 12% (7 of 60) had a sentinel lymph node biopsy (SLNB). There was a high rate of negative SLNB findings. The majority of patients were treated with surgery alone (29 of 60), followed by a cohort (21 of 60) treated with surgery plus adjuvant treatment, and 10 of 60 patients were treated with radiation therapy with or without chemotherapy. Recurrence-free survival was 50%, 45%, and 42% at 1, 2, and 5 years.We report higher recurrence rates and higher negative SLNB result rates than other studies. Our results affirm that imaging may not be a substitute for SLNB and that it had an intermediate ability to identify the occult disease. Traditional predictors, including SLNB and cervical node pathology, may not identify patients at risk for recurrence in HN-MCC. We report similar recurrence rates in patients who had treatment of the cervical nodes by radiation therapy or neck dissection as compared with those who did not receive neck treatment.

OBJECTIVES Determine the ability of three staging systems to stratify the risk of nodal metastases in cases of cutaneous squamous cell carcinoma (cSCC). Examine differential staging of tumors across the three systems and the resulting implications for clinical decision making. STUDY DESIGN Retrospective chart review. METHODS This study included 118 patients who underwent excision of primary cSCC of the head and neck as well as elective neck dissection for the same tumor between 2006 and 2017. Tumors were staged using the 2010 7th edition American Joint Committee on Cancer (AJCC 7) staging system, the 2016 8th edition AJCC staging system (AJCC 8), and the Brigham and Women's Hospital (BWH) alternative tumor staging system published in 2013. RESULTS There were 28 patients (23.7%) with positive nodal metastases at the time of tumor excision. Almost all tumors staged as tumor (T)2 using AJCC 7 were upstaged to T3 or T4 using the new AJCC 8, and these two groups accounted for the majority of the nodal metastases. Similarly, the BWH-staged T3 group contained the highest number of tumors with nodal metastases. None of the three staging systems significantly stratified tumors in a manner that predicted the presence of nodal metastases. CONCLUSION Individuals with cSCC tumors staged T3 or higher in the AJCC 8 and BWH staging systems should undergo neck dissection, whereas those with lower staging should be discussed with the patient on a case-by-case basis. LEVEL OF EVIDENCE 4.

Objective To characterize the epidemiology and clinicopathologic determinants of survival following the diagnosis of clear cell adenocarcinoma in the head and neck region. Study design Retrospective cohort study. Setting The Surveillance, Epidemiology, and End Results registry (1994 to 2014). Subjects and methods A total of 173 cases were identified. Study variables included age, sex, race, tumor subsite, tumor stage, tumor grade, surgical excision, and regional and distant metastases. Survival measures included overall survival (OS) and disease-specific survival (DSS). Results Median age at diagnosis was 63 years, 48% were female, and 80.2% were white. Fourteen percent of patients presented with regional lymph node metastases, while 3.3% of patients presented with distant metastases. Most of the tumors presented in the oral cavity, salivary glands, and pharynx. Kaplan-Meier analysis demonstrated OS and DSS of 77.2% and 83.7% at 5 years, respectively. Median OS after diagnosis was 153 months. Bivariate analysis showed that surgical excision was associated with 5-fold increased OS and DSS, whereas advanced age, high tumor grade, advanced stage, larger tumor size, nodal disease, and distant metastases were all significant predictors of decreased OS and DSS. Conclusions Clear cell adenocarcinoma is a rare neoplasm that typically affects white individuals in their early 60s, with a generally favorable prognosis. It most commonly arises in the oral cavity, major salivary glands, and pharynx. Surgical excision is associated with 5-fold survival benefit, whereas advanced age, high tumor grade, advanced stage, nodal disease, and distant metastases are independently associated with worse OS and DSS.

OBJECTIVE To determine the current epidemiology and management trends for patients with vestibular schwannomas (VS). STUDY DESIGN Retrospective cohort study. SETTING The Surveillance, Epidemiology, and End Results (SEER) tumor registry. PATIENTS The SEER database was queried to identify patients diagnosed with VS from 1973 to 2015. Demographics, patient and tumor characteristics, and treatment methods were analyzed. RESULTS A total of 14,507 patients with VS were identified. The mean age at diagnosis was 55 ± 14.9 years. Age-adjusted incidence from 2006 to 2015 was 1.4 per 100,000 per year and remained relatively stable. Incidence across age varied with sex, as younger women and older men had increased incidences comparatively. A higher percentage of patients underwent surgery alone (43%), followed by observation (32%), radiation alone (23%), and combined radiation and surgery (2%). Age 65 and older was associated with observation (odds ratio [OR] 1.417; p = 0.029) whereas age 20 to 39 and 40 to 49 were associated with surgery (OR 2.013 and 1.935; p

Purpose Lymph node status is the single most important prognostic factor for patients with early-stage cutaneous melanoma. Sentinel lymph node biopsy (SLNB) has become the standard of care for intermediate depth melanomas. Modern SLNB implementation includes technetium-99 lymphoscintigraphy combined with local administration of a vital blue dye. However, sentinel lymph nodes may fail to localize in some cases and false-negative rates range from 0 to 34%. Here we demonstrate the feasibility of a new sentinel lymph node biopsy technique using indocyanine green (ICG) and the SPY Elite near-infrared imaging system. Materials and methods Cases of primary cutaneous melanoma of the head and neck without locoregional metastasis, underwent SLNB at a single quaternary care institution between May 2016 and June 2017. Intraoperatively, 0.25 mL of ICG was injected intradermal in 4 quadrants around the primary lesion. 10–15 minute circulation time was permitted. SPY Elite identified the sentinel lymph node within the nodal basin marked by lymphoscintigraphy. Target first echelon lymph nodes were confirmed with a gamma probe and ICG fluorescence. Results 14 patients were included with T1a to T4b cutaneous melanomas. Success rates for sentinel lymph node identification using lymphoscintigraphy and the SPY Elite system were both 86%. Zero false negatives occurred. Median length of follow-up was 323 days. Conclusions In this pilot study, Indocyanine green near-infrared fluorescence demonstrates a safe, and facile method of sentinel lymph node biopsy for cutaneous melanoma of the head and neck compared with lymphoscintigraphy and vital blue dyes.

Background and Objectives Laser generated shockwave (LGS) is a novel modality for minimally invasive disruption of bacterial biofilms. The objectives of this study are to determine the mechanisms behind LGS treatment and non-biofilm effects on bacterial disruption, including (1) comparing bacterial load with and without LGS in its planktonic form and (2) estimating bacterial cell permeability following LGS. Study Design/Materials and Methods For the first study, planktonic S. epidermidis were treated with gentamicin (0, 8, 16, 32, 64 μg/ml) with and without LGS (1064 nm Nd:YAG laser, 110.14 mJ/mm2 , pulse duration 9 ns, spot size 3 mm, n = 8/group), and absorbances at 600 nm compared. For the second study, four samples of planktonic S. epidermidis were treated with LGS (same settings). Propidium iodide (PI) uptake via flow cytometry as a measure of cell permeability was measured at 0, 10, and 20 minutes following LGS. RESULTS: In comparing corresponding gentamicin concentrations within both LGS-treated samples and controls at 0 hours, there were no differences in absorbance (P = 0.923 and P = 0.814, respectively). Flow cytometry found modest PI uptake (10.4 ± 2.5%) immediately following LGS treatment, with time-dependent increase and persistence of the signal at 20 minutes (R2 = 0.449, P = 0.048). CONCLUSION: Taken together, LGS does not appear to have direct bacteriocidal properties, but rather by allowing for biofilm disruption and bacterial cell membrane permeabilization, both of which likely increase topical antibiotic delivery to pathogenic organisms. Insight into the mechanisms of LGS will allow for improved clinical applications and facilitate safe and effective translation of this technology. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

OBJECTIVES/HYPOTHESIS Squamous cell carcinoma of the retromolar trigone (RMT SCC) is a relatively uncommon primary site for oral cavity malignancy. However, given its proximity to the mandible and buccal mucosa, RMT SCC typically exhibits early invasion and generally presents at an advanced stage. Large-sample studies are needed to assess the epidemiology and clinical outcomes of this tumor. Our aim was to describe the determinants of survival in patients with RMT SCC. STUDY DESIGN Retrospective cohort study. METHODS Retrospective, population-based cohort study of patients in the Surveillance, Epidemiology, and End Results tumor registry who were diagnosed with RMT SCC from 1973 to 2012. Primary endpoints were overall survival (OS) and disease-specific survival (DSS). RESULTS A total of 4,022 cases of RMT SCC were identified. The mean age at diagnosis was 65 years. Thirty-nine percent of cases presented with stage IV disease. The median OS by stages I to IV were 73.7, 52.4, 27.5, and 23.4 months, respectively (P

Background Hospital readmissions are an increasingly scrutinized marker of surgical care delivery and quality. There is a paucity of information in the literature regarding the rate, risk factors, and common causes of readmission after surgery for sinonasal cancer. Methods We analyzed the Nationwide Readmissions Database for patients who underwent surgery for a diagnosis of sinonasal cancer between 2010 and 2014. Rates, causes, and patient-, procedure-, and hospital-level risk factors for 30-day readmission were determined. Multivariate logistic regression was used to identify predictors of 30-day readmission. Results Among the 4173 cases, the 30-day readmission rate was 11.6%, with an average cost per readmission of $18,403. The most common readmission diagnoses were wound complications (15.3%) and infections (13.4%). On multivariate regression, significant risk factors for readmission were chronic renal failure (odds ratio [OR], 2.95; 95% confidence interval [CI], 1.41-6.17), involvement of the skull base or orbit (OR, 1.67; 95% CI, 1.11-2.51), nonelective initial surgical admission (OR, 2.35; 95% CI, 1.42-3.89), and length of stay ≥7 days (OR, 1.87; 95% CI, 1.14-3.05). Conclusion Through the use of a large national database, we found that approximately 1 in 9 patients undergoing surgery for sinonasal cancer was readmitted within 30 days. Readmissions were most commonly associated with wound complications and infections. Factors related to procedural complexity were more important predictors of readmission than patients' demographics or comorbidities.

Purpose To evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field. Methods and materials The medical records of 54 consecutive patients who underwent re-irradiation for squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of recurrent disease that had previously been treated with doses of radiation therapy of at least 60 Gy were included. Determination of HPV status at the time of recurrence was performed by p16 immunohistochemistry. The median age at re-irradiation was 58.5 years (range, 27.9 to 81.5 years). Thirty patients (55.5%) were lifelong never-smokers. The Kaplan Meier method was used to calculate overall survival, progression-free survival, and local-regional control, and distant metastasis-free survival with comparisons between groups performed using the log-rank test. Results HPV status among tumors that were re-irradiated was as follows: 16 positive (29.7%); 7 negative (12.9%); 31 unknown (57.4%). The median overall survival in the entire cohort was 11.7 months (range, 8 to 27 months), with the 1-year and 2-year estimates of overall survival being 47.2% and 38.4%, respectively. A statistical trend was identified favoring patients with HPV-positive cancers with respect to the endpoints of overall survival (p = 0.06) and progression-free survival (p = 0.08) after re-irradiation when compared to the HPV-negative/unknown population. There was no significant difference in distant control between the two cohorts (p = 0.40). Conclusions The favorable prognostic significance of HPV seemingly extends to patients treated by re-irradiation suggesting that this biomarker may be useful in risk stratification in this setting.

Current treatments for alopecia with autograft hair transplantation face limitations that may preclude complete hair restoration and leave patients with donor site scars. Scaffold assisted artificial hair implantation as demonstrated in a rat model may provide an adjunct for hair restoration without donor site morbidity.To design and create porous high-density polyethylene (PHDPE) and expanded polytetrafluoroethylene (ePTFE) hair-bearing scaffolds and evaluate their biocompatibility in a rat model.For this single-institution randomized prospective animal study, 34 Sprague Dawley rats were randomly selected into 2 groups: 24 rats for direct implantation and 10 rats for delayed implantation. The direct-implantation group was randomly divided into 3 subgroups of 8 rats, which were observed for 2, 12, and 24 week.Each rat dorsum was implanted with 4 scaffolds-PHDPE and ePTFE with and without hair-in a randomized 4-quadrant manner. The rats in the direct-implantation group were observed to their selected time points of 2, 12, and 24 weeks. The rats in the delayed-implantation group were observed for 4 weeks at which, all well-healed scaffolds without hair were then percutaneously implanted with 2 follicular units of hair. These rats were then observed for another 4 weeks.During the clinical observation period, scaffolds were observed for signs of infection, extrusion, and persistence of follicular units. Following sacrifice, sagittal sections of scaffold and surrounding skin were fixed in formalin, stained with hematoxylin-eosin, and evaluated for degree of fibrovascular invasion and acute and chronic inflammation.Overall 94.5% (86 of 91) of the scaffolds were well healed at time of evaluation (2 week, 100% [32 of 32]; 12 week, 96.3% [26 of 27]; 24 week, 87.5% [28 of 32]); while 85.6% of artificial hair follicular units were intact at time of evaluation (2 week, 93.8% [30 of 32]; 12 week, 86.7% [26 of 30]; 24 week, 75.0% [21 of 28]). Within the delayed implant group 100% (19 of 19) of the hair-implanted scaffolds were well healed at 8 weeks, with 94.7% (36 of 38) of the follicular units intact; 100% of the delayed-hair implant scaffolds were well healed with 86.1% (36 of 38) of the follicular units intact. Kaplan-Meier log-rank analysis showed no significant difference in survival between ePTFE and PHDPE scaffolds, as well as scaffolds with hair and scaffolds without hair. Upon histological analysis, overall scaffolds with hair were noted to have greater chronic inflammation (95% CI, -0.81 to -1.10; P = .01), and PHDPE was noted to have significantly great fibrovascular integration (95% CI, -11.42 to -1.96; P = .01) compared with ePTFE.Overall, PHDPE and ePTFE hair bearing scaffolds were well tolerated in a rat model. Progressive loss of artificial hair may be percutaneously implanted without significant increases in infection or extrusion.NA.

OBJECTIVE The utility of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to predict outcome has been well-established for patients undergoing definitive radiation in the initial management of head and neck cancer. However, the usefulness of this modality in the recurrent setting remains uncertain. We sought to evaluate the prognostic value of metabolic tumor parameters measured on FDG-PET in patients treated by reirradiation for recurrent head and neck cancer. METHODS Thirty-four tumors occurring in 29 patients were reirradiated and were evaluable. The most common disease sites were the oropharynx (n = 9), oral cavity (N = 8), and nasopharynx (n = 6). Potential correlations of FDG-PET maximum standardized uptake value (SUV) and metabolic tumor volume (MTV) with survival endpoints were explored. Multivariate analysis was performed using Cox proportional hazard. RESULTS The median MTV, SUV, and gross tumor volume, as delineated using the 50% SUVmax threshold, were 366 cc (range, 0-3,567 cc), 8.1 (range, 0-25), and 48.5 cc (range, 1-190 cc), respectively. On univariate analysis, both MTVs (as measured as a continuous variable and using the median value of 266 cc as cutoff) were predictive of decreased overall survival (P

Objective To describe the determinants of survival for patients with floor of mouth (FOM) squamous cell carcinoma (SCC) from 1973 to 2013 with the SEER database (Surveillance, Epidemiology, and End Results). Study Design and Setting Retrospective cohort study with a national database. Subjects and Methods The SEER registry was utilized to calculate survival trends for patients with FOM SCC between 1973 and 2013. Patient data were analyzed with respect to age, sex, race, primary site, stage at presentation, tumor size, grade, and treatment modalities (surgery and radiotherapy). Overall survival (OS) and disease-specific survival (DSS) were calculated. Results A total of 14,010 FOM SCC cases were identified. The cohort was 69.5% male, and the median age at diagnosis was 62 years. Forty-six percent of cases were treated with surgery, while 14% received radiotherapy. Kaplan-Meier analysis demonstrated OS and DSS of 39% and 59% at 5 years, respectively. Multivariate analysis showed that age, grade, stage, size, and surgery were determinants for OS and DSS (all P < .05). For early- and advanced-stage cancers, age, grade, size, and surgery predicted OS and DSS, while radiotherapy was a predictor of OS and DSS in advanced-stage tumors only (all P < .05). Conclusion To our knowledge, this study is the largest to date investigating prognostic factors for survival of patients diagnosed with FOM SCC. Determinants of survival include age, grade, stage, size, and surgery. Surgery appears to play a critical role in the management of these tumors.

OBJECTIVE To describe the incidence and determinants of survival of patients with squamous cell carcinoma of the hard palate (SCCHP) between the years of 1973 to 2014 using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS Retrospective, population-based cohort study of patients in the SEER tumor registry who were diagnosed with SCCHP from 1973 to 2014. Outcomes and measures included overall survival (OS) and disease-specific survival (DSS). RESULTS A total of 1,489 cases of primary SCCHP were identified. Of those, 53.2% were females and 47.8% presented with stage IV disease. The mean age at diagnosis was 69.8 years. Overall survival at 2, 5, and 10 years was 44%, 33%, and 21%, respectively. A total of 66.2% of patients underwent surgery (with or without radiation therapy [RT]); 20.1% received RT; and 22.4% had both surgical and RT. On multivariate analysis, RT, advanced age, stage, and grade were associated with worse OS and DSS (P

OBJECTIVES/HYPOTHESIS Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine neoplasm of the skin. Growing evidence supports the benefit of postoperative adjuvant radiation therapy (RT) for locoregional control, but whether it improves overall survival (OS) has been debated. Our objective was to compare the OS of MCC patients who received postoperative RT with those who received surgery alone. STUDY DESIGN Retrospective case series. METHODS Cases of MCC between 2001 and 2016 at the University of California, Los Angeles Health System were reviewed. We identified 87 unique cases of MCC. Among the patients, 74% were identified as male and 26% as female. The average age at diagnosis was 71.2 years. The median survival was 48.0 months. The OS of all the patients at 2 years, 5 years, and 10 years was 54%, 46%, and 26%, respectively. Univariate analysis showed that stage, T stage, N stage, and M stage were significant determinants of OS. The inclusion of RT was not found to be a determinant; however, when restricting the analysis to early-stage MCC (stages I and II), postoperative adjuvant RT was associated with significantly improved OS. A Cox regression model confirmed that inclusion of RT was an independent prognosticator of OS even when controlled for overall stage and negative margin status. The small sample size and retrospective nature of this study limit its statistical power. CONCLUSIONS MCC is an aggressive tumor with a poor prognosis for survival especially in elderly patients. In this study, we found that RT during early-stage MCC improves OS. Prospective randomized control trials are necessary to validate the observed benefit for MCC patients. LEVEL OF EVIDENCE 4 Laryngoscope, 1862-1866, 2018.

Background The purpose of this study was to present our findings on the use of limited-field, oropharynx-directed ipsilateral irradiation for p16-positive squamous cell carcinoma of unknown primary origin. Methods Between April 2011 and January 2016, 25 patients with a histological diagnosis of p16-positive squamous cell carcinoma were selectively irradiated to the ipsilateral oropharynx and cervical neck for tumors of unknown primary origin. The dose to the oropharynx ranged from 54-60 Gy (median 60 Gy) in 30-33 fractions. Concurrent cisplatin-based chemotherapy was administered to 8 patients (32%). Results The actuarial 2-year estimates of locoregional control, progression-free survival, and overall survival were 91%, 87%, and 92%, respectively. One patient failed in the contralateral neck. There was no grade 3 + toxicity in either the acute or late setting. Conclusion Oropharynx-directed, ipsilateral radiation results in disease control that compares favorably with historical controls treated by comprehensive mucosal and bilateral neck radiation.

Objectives To describe the incidence and determinants of survival of patients with verrucous carcinoma (VC) of the oral cavity between the years of 1973 and 2012 using the Surveillance, Epidemiology, and End Results (SEER) database. Study Design Retrospective cohort study using a national database. Methods The SEER registry was utilized to calculate survival trends for patients with VC of the oral cavity between 1973 and 2012. Patient data was then analyzed with respect to histopathology, age, sex, race, stage, grade, and treatment modalities (surgery and radiation therapy). Overall survival (OS) and disease-specific survival (DSS) were calculated. Results A total of 1,481 cases of VC of the oral cavity were identified. The cohort was composed of 50.5% males. The mean age at diagnosis was 69.5 years. The oral tongue was the most common primary site (28.9%), followed by the alveolar ridge (21.4%) and buccal mucosa (19.0%). The vast majority of cases (79.1%) presented with stage I and stage II disease. Nodal disease was present in only 1.6% of cases. The median OS was 94.6 months. Eighty-seven percent of cases underwent surgery, and 11.5% received both surgery and radiation therapy. Overall survival at 2, 5, and 10 years was 83%, 64%, and 42%, respectively. On multivariate analysis, advanced age (P

This article explores the evolving world of cancer care that requires increasing collaboration and is focused on value, quality, and efficiency, while placing the utmost importance on patient autonomy and individualized care plans. The expanding membership of the multidisciplinary team and the role of integrated patient care units are reviewed in the context of care for the patient with head and neck cancer.

Objectives To analyze the epidemiology and describe the prognostic indicators of patients with primary squamous cell carcinoma of the thyroid. Study Design and Setting Retrospective cohort study based on a national database. Methods The US National Cancer Institute's SEER registry (Surveillance, Epidemiology, and End Results) was reviewed for patients with primary squamous cell carcinoma of the thyroid from 1973 to 2012. Study variables included age, sex, race, tumor size, tumor grade, regional and distant metastases, and treatment modality. Survival measures included overall survival (OS) and disease-specific survival (DSS). Results A total of 199 cases of primary squamous cell carcinoma of the thyroid were identified. Mean age at diagnosis was 68.1 years; 58.3% were female; and 79.4% were white. Following diagnosis, 46.3% of patients underwent surgery; 55.7%, radiation therapy; and 45.8%, surgery with radiation therapy. Kaplan-Meier analysis demonstrated OS and DSS of 16% and 21% at 5 years, respectively. Median survival after diagnosis was 9.1 months. Multivariate Cox regression analysis showed that predictors of OS and DSS included age ( P < .001, P < .001, respectively), tumor grade ( P < .001, P = .001), and tumor size ( P < .001, P = .001). Surgical management was a predictor of OS but not DSS. Conclusion Squamous cell carcinoma of the thyroid is a rare malignancy with a very poor prognosis. Surgical resection confers an overall survival benefit. Age, tumor grade, and tumor size are predictors of OS and DSS.

Despite significant reductions in tobacco use in the US, oral tongue cancer incidence has reportedly increased in recent years, particularly in young white women. We conducted age-period-cohort analyses to identify birth cohorts that have experienced increased oral tongue cancer incidence, and compared these with trends for oropharyngeal cancer, a cancer caused by human papillomavirus (HPV) that has also recently increased.We utilized cancer incidence data (1973-2012) from 18 registries maintained by the NCI SEER Program. Incidence trends were evaluated using log-linear joinpoint regression and age-period-cohort modeling was utilized to simultaneously evaluate effects of age, calendar year, and birth year on incidence trends.Incidence of oral tongue cancer increased significantly among white women during 1973-2012 (0.6% annual increase, p0.001) and white men during 2008-2012 (5.1% annual increase, p=0.004). The increase was most apparent among younger white individuals (50years; annual increase of 0.7% for men [p=0.02] and 1.7% for women [p0.001] during 1973-2012). Furthermore, the magnitude of the increase during 1973-2012 was similar between young white men and women (2.3 vs. 1.8 cases per million, respectively). Incidence trends for oropharyngeal cancer were similar to trends for oral tongue cancer and similar birth cohorts (born after the 1940s) experienced rising incidence of these cancers (p-value: white men=0.12, white women=0.42), although the magnitude of increase was greater for oropharyngeal cancer.The incidence of oral tongue and oropharyngeal cancer has significantly increased among young white men and women within the same birth cohorts in the US.

Background and objectives Bacterial biofilm formation within chronic wound beds, which provides an effective barrier against antibiotics, is a known cause of recalcitrant infections and a significant healthcare burden, often requiring repeated surgical debridements. Laser-generated shockwaves (LGS) is a novel, minimally invasive, and nonthermal modality for biofilm mechanical debridement which utilizes compressive stress waves, generated by photonic absorption in thin titanium films to mechanically disrupt the biofilm. Prior studies have demonstrated LGS monotherapy to be selectively efficacious for biofilm disruption and safe for host tissues. In this study, we sought to determine if LGS can enhance the antimicrobial activity and biofilm disruption capability of topical antibiotic therapy. Study design/materials and methods Staphylococcus epidermidis biofilms grown in vitro on glass were treated with topical gentamicin (31, 62, and 124 μg/ml) with and without LGS (n = 3-11/treatment group). Mechanical shockwaves were generated with a 1,064 nm Nd:YAG laser (laser fluence 110.14 mJ/mm2 , pulse duration 5 ns, spot size 3 mm). Following a 24-hour incubation period, bacterial viability was assessed by determining the number of colony-forming units (CFU) via the Miles and Misra method. Residual biofilm bioburden was analyzed using the crystal violet biofilm assay. Results With gentamicin monotherapy, CFU density (CFU/mm2 ) at 31, 62, and 124 μg/ml were (282 ± 84) × 104 , (185 ± 34) × 104 , and (113 ± 9) × 104 , respectively. With LGS and gentamicin therapy, CFU density decreased to (170 ± 44) × 104 , (89 ± 24) × 104 , and (43 ± 3) × 104 , respectively (P = 0.1704, 0.0302, and 0.0004 when compared with gentamicin alone). Biofilm burden as measured by the assay in the gentamicin 31, 62, and 124 μg/ml groups was reduced by 80%, 95%, and 98% when LGS was added (P = 0.0102, >0.0001, and 0.0001 for all groups when compared with gentamicin alone). Furthermore, samples treated with LGS saw an increase in susceptibility to gentamicin, in terms of reduced biofilm bioburden and CFU densities. Conclusion LGS enhances the efficacy of topical antibiotics in an in vitro model. This has significant implications for clinical applications in the management of chronic soft tissue infections and recalcitrant chronic rhinosinusitis. Lasers Surg. Med. 49:539-547, 2017. © 2017 Wiley Periodicals, Inc.

Background The purpose of this study was to determine the effect of fraction size on laryngoesophageal dysfunction among patients treated by chemoradiotherapy for laryngeal and hypopharyngeal cancer. Methods Forty patients underwent chemoradiotherapy for stage III/IV squamous cell carcinomas of the larynx and hypopharynx. Median radiation dose was 70 Gy (range, 69.3–70.4 Gy) with daily fractionation ranging from 2 Gy to 2.2 Gy. Results When comparing 2 Gy versus >2 Gy daily fractionation, there was no difference in 2-year overall survival (71% vs 72%; p = .68), locoregional control (79% vs 77%; p = .43), or laryngectomy-free survival (60% vs 61%; p = .72). Use of 2 Gy versus >2 Gy fractionation improved laryngoesophageal dysfunction-free survival (2-year estimates, 49% vs 27%; p = .07). Patient-reported voice and swallowing were improved with the former. Conclusion As the importance of a functional larynx becomes recognized as an endpoint for patients treated by voice preservation, the results of our study help refine treatment guidelines. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1322–1326, 2017

Objectives/Hypothesis Small cell carcinoma (SmCC) of the head and neck is an extremely rare neuroendocrine malignancy. In this study, we describe the incidence and determinants of survival of patients with SmCC of the head and neck between the years of 1973 and 2012 using the Surveillance, Epidemiology, and End Results database as differed by primary site. Study Design Retrospective, population-based cohort study. Methods A total of 237 cases of SmCC of the head and neck were identified, which was divided into sinonasal primaries (n = 82) and all other head and neck primaries (n = 155). Clinicopathologic and epidemiologic variables were analyzed as predictors of overall survival (OS) and disease-specific survival (DSS) based on the Kaplan-Meier method. Results More than half of sinonasal primaries presented with Kadish stage C or D. On multivariate analysis, surgery was the only independent predictor of improved DSS (P = .008) for sinonasal primaries; in contrast, radiation therapy was a favorable prognosticator for OS (P = .007) and DSS (P = .043) in extrasinonasal sites. Comparison of survival between sinonasal primaries and all other sites demonstrated that sinonasal SmCC had uniformly better OS (P = .002) and DSS (P = .006). Conclusions SmCC in the head and neck remains rare, and sinonasal primaries appear to have improved survival compared to other sites. Based on these results, optimal treatment for sinonasal SmCC appears to be surgical therapy, whereas radiation therapy is the preferred treatment for SmCC of other primary sites, particularly the larynx. Level of Evidence 4. Laryngoscope, 127:1785–1790, 2017

BACKGROUND Head and neck squamous cell carcinomas (HNSCCs) are debilitating diseases for which a patient's prognosis depends heavily on complete tumor resection. Currently, the surgeon's fingers determine the location of tissue margins. This study evaluated the diagnostic utility of a novel imaging modality, dynamic optical contrast imaging (DOCI), in the detection of HNSCC. This system generates contrast by illuminating the tissue with pulsed light and detecting variations in endogenous fluorophore lifetimes. METHODS A total of 47 fresh ex vivo samples from 15 patients were imaged with the DOCI system immediately after surgical resection. DOCI maps were analyzed to determine the statistical significance of contrast between tumors and adjacent nonmalignant tissue. Pilot intraoperative clinical data were also acquired. RESULTS Statistical significance (P

Summary Background In the present study, we investigated the role of p38-p38IP signaling in the inflammation-induced promotion of epithelial-to-mesenchymal transition (EMT) in Head and Neck Squamous Cell Carcinoma (HNSCC). Methods Quantitative RT-PCR, western blot analysis, spheroid modeling and immunohistochemical staining of human HNSCC tissue sections were used. Results p38 inhibitor treated and p38 shRNA HNSCC cell lines demonstrate a significant upregulation in E-cadherin mRNA and a decrease in the mRNA expression of Snail. p38 binds to and stabilizes p38IP, a subunit of histone SPT3-TAF9-GCN5 acetyltransferase (STAGA), resulting in enhanced transcription of Snail. p38 shRNA HNSCC cell lines show a less invasive phenotype in a spheroid model. In clinical HNSCC samples, p38 interacting protein (p38IP) is significantly increased compared to adjacent normal tissue. An inverse relationship between p38, p38IP and E-cadherin is demonstrated. Conclusions Herein we provide the first report that p38-p38IP is required for the Snail-induced E-cadherin down-regulation and cell invasion in HNSCC.

Objectives/Hypothesis To report the clinical presentation, treatment, and management outcomes of patients with Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) of the head and neck, which is a newly characterized pathologic entity with aggressive morphology but follows an indolent, self-limiting clinical course. Study Design Case report and literature review. Methods A case of EBVMCU of the base of tongue is reported and a retrospective review of all cases of EBVMCU of the head and neck at a single academic institution was conducted between January 1, 1986 and April 1, 2015. The MEDLINE database was additionally queried from January 1, 1950 to April 1, 2015 for all reports of EBVMCU of the head and neck, and all pertinent clinical data were extracted. Results The clinical presentation, treatment, and response of a patient with EBVMCU of the base of tongue are presented. Interim follow-up of the patient has revealed a complete remission with discontinuation of immunosuppression and rituximab therapy. A review of the literature supports conservative management and reduction of immunosuppression. Overall, 96.6% of patients with follow-up greater than 2 months achieved complete remission with conservative management. The current study is the largest series to report on the clinical presentation and treatment outcomes of EBVMCU of the head and neck. Conclusions EBVMCU tends to follow an indolent and self-limiting clinical course, responding to reduction of immunosuppression and conservative treatment. It is imperative for clinicians to consider EBVMCU in the differential diagnosis of mucocutaneous ulcers of the head and neck to avoid excessive treatment. Level of Evidence NA Laryngoscope, 2016

OBJECTIVE: A cerebrospinal fluid leak is one of the most serious complications in Otolaryngology. It may occur as a result of injury to the skull base, typically traumatic or iatrogenic. While the presence of a leak is often discerned in the emergent setting, it can be difficult to distinguish normal secretions from those containing cerebrospinal fluid during postoperative visits in the clinic. As most current laboratory-based assays are labor-intensive and require several days to result, we aim to develop a more user-friendly and rapid point-of-care cerebrospinal fluid detection device. STUDY DESIGN: A barcode-style, lateral-flow immunoassay utilizing antibodies for beta-trace protein, a protein abundant in and specific for cerebrospinal fluid, has been developed by our laboratory using a concentration of 1.3 mg/L of beta-trace protein to delineate a positive result. SETTING: Tertiary medical center SUBJECTS AND METHODS: Tests using known concentrations of resuspended beta-trace protein and the contents of discarded lumbar drains (presumed to contain cerebrospinal fluid) were performed to validate our novel device. RESULTS: Our results demonstrate the ability of our device to semi-quantitatively identify concentrations of beta-trace protein from 0.3–90 mg/L, which is within the required range to diagnose a leak, thus making beta-trace an excellent target for rapid clinical detection. CONCLUSION: Herein we detail the creation and initial validation of the first point-of-care cerebrospinal fluid detection device. This device is a feasible method to more efficiently and cost-effectively identify cerebrospinal fluid leaks, minimize costs, and improve patient outcomes.

To describe rates of complications and mortality within 30 days of open anterior skull base surgery using a large, multi-institutional outcomes database.Retrospective cohort study.The study included patients who underwent open anterior skull base surgery as listed in the American College of Surgeons National Surgical Quality Improvement Project database from 2007 through 2014.A total of 336 open anterior skull base surgeries were identified. One hundred nine (32.4%) patients experienced a complication, reoperation, or mortality. The most common events were postoperative transfusion (15.8%), reoperation (10.1%), and readmission (8.0%). Significant independent predictors of any adverse event included higher American Society of Anesthesiologists (ASA) score and increased total operative time (both P.05). The only predictor of mortality was higher ASA score (P = .02). Predictors of increased hospital stay included impaired sensorium (P = .04), coma24 hours (P.001), lower preoperative hematocrit (P = .02), higher ASA score (P = .04), and increased total operative time (P.001).Open anterior skull base surgery is understandably complex, and is thus associated with a relatively high adverse event rate. Knowledge of factors associated with adverse events has the potential to improve preoperative optimization of controllable variables and translate into improved surgical outcomes for patients.NA Laryngoscope, 129:1407-1412, 2019.

Objectives Delays in the initiation of postoperative radiation have been associated with worse outcomes; however, the effect of the overall treatment package time (interval from surgery through the completion of radiation) remains undefined. The purpose of this study was to determine the impact of package time on survival and to evaluate this effect among different subgroups of head and neck cancer patients. Patients and methods In this observational cohort study, the National Cancer Database was used to identify 35,167 patients with resected nonmetastatic head and neck cancer who underwent adjuvant radiation from 2004 to 2014. Kaplan-Meier survival estimates and multivariate Cox regression analyses were performed to determine the effect of treatment package time on overall survival. Results Median package time was 96 days (interquartile range, 85–112 days). After adjusting for covariates, package times of 11 weeks or less were associated with improved survival (adjusted hazard ratio (aHR), 0.90; 95% confidence interval, 0.83–0.97) compared to an interval of 12–13 weeks, whereas package times of more than 14 weeks were associated with worse survival (aHR, 1.14, 1.14, and 1.22 for 14–15, 15–17, and >17 weeks, respectively). A significant interaction was identified between package time and disease site, nodal status, and stage. Specifically, patients with oropharyngeal tumors, advanced stage (III or IV) disease, or nodal involvement experienced more pronounced increases in mortality risk with delays in treatment time. Conclusions Treatment package time independently impacts survival. This effect may be strongest for patients with oropharyngeal tumors or advanced stage disease.

Objectives To describe the incidence and determinants of survival of patients with squamous cell carcinoma of the soft palate (SCCSP) using the Surveillance, Epidemiology, and End Results (SEER) database. Study Design Retrospective, population-based cohort study of patients. Setting SEER cancer registry. Subjects and Methods Patients from the SEER cancer registry from 1973 to 2015 were used to analyze demographics and survival of SCCSP. Results A total of 4366 cases were identified. The average overall survival (OS) and disease-specific survival (DSS) were 68.7 months and 161.3 months, respectively. Multivariate analysis revealed that male sex, stage, and treatment (hazard ratio [HR] = 0.690, P = .019; HR = 1.73, P < .001; HR = 0.64, P < .001, respectively) were independent determinants of better or worse DSS. Age, stage, and treatment (HR = 1.02, P < .001; HR = 1.49, P < .001; HR = 0.66, P < .001; HR = 0.48, P < .001, respectively) were independent determinants of better or worse OS. For stages I, II, and III, radiation alone and surgery alone have nearly equivalent OS. Patients with stage IV disease who underwent both surgery and radiation had a significantly higher median OS at 50.0 months. Conclusion Radiation alone and surgery alone both have nearly equivalent OS benefit for stages I to III, while surgery and radiation provide the most survival benefit for stage IV disease. The large discrepancy between OS and DSS can be due to significant comorbidities. Future studies should aim to address the determinants of quality-of-life variables that help direct treatment decisions and might indirectly affect survival.

Objective Esthesioneuroblastoma is an uncommon malignancy of the sinonasal tract arising from the olfactory epithelium. Surgical management of the primary site, often via an endoscopic approach, with or without adjuvant radiation, is often curative. There is growing but ultimately limited data regarding management of the neck and the risk of nodal metastases. In this study, we examine the incidence and patterns of esthesioneuroblastoma-related cervical nodal metastases using the Surveillance, Epidemiology, and End Results (SEER) database. Methods The SEER registry was queried for all patients with esthesioneuroblastomas diagnosed between 1973 and 2012. Patient data was then analyzed with respect to age, sex, race, modified Kadish stage, grade, survival functions, and nodal disease including specific nodal basins. Results Three hundred and eighty-one cases of esthesioneuroblastoma with information on nodal metastases were identified. The overall cervical nodal metastasis rate was 8.7%. Level II metastases were most common (6.6%). A total of 4.5% of cases presented with multiple positive nodal basins. Male sex (P = 0.009) and higher tumor grade (P = 0.009) correlated with the presence of level II metastases. There was no association of primary tumor site to the presence of nodal metastases (P > 0.05). The presence of nodal disease significantly predicted poorer overall (P = 0.001) and disease-specific survival (P = 0.017). Conclusion The incidence of nodal metastases in esthesioneuroblastoma at diagnosis is rare, and elective management of the neck remains controversial. Primary tumor site does not appear to predict metastases at specific nodal basins. Higher tumor grade may be a harbinger of eventual nodal metastases. Level of evidence NA Laryngoscope, 129:1025-1029, 2019.

Purpose of review The quantity of tissue removed during an oncologic surgical procedure is not standardized and there are numerous reports of local recurrence despite histologically adequate resection margins. The oral cavity is one of the sites in the head and neck with high chances of recurrence following negative margins. To address this need, this article reviews the recent applications of Dynamic Optical Contrast Imaging (DOCI) towards both oral screening and the intraoperative evaluation of tumor margins in head and neck surgery. Recent findings Human ex-vivo and in-vivo trials suggest DOCI is well tolerated, low-cost, and sensitive for differentiating cancerous from normal tissues throughout the head and neck, in addition to the oral cavity. Ex-vivo imaging of OSCC specimens generated histologically verified image contrast. Furthermore, in-vivo intraoperative results demonstrate significant potential for image-guided detection and resection of oral cavity squamous cell carcinoma (OSCC). Summary DOCI augments tissue contrast and may enable surgeons to clinically screen patients for oral cancer, make histologic evaluations in vivo with fewer unnecessary biopsies, delineate clinical margins for tumor resection, provide guidance in the choice of biopsy sites, and preserve healthy tissue to increase the postoperative functionality and quality of life of the patient.

Objective To characterize patterns of secondary complications after inpatient head and neck surgery. Study Design Retrospective cohort study. Setting National Surgical Quality Improvement Program (2005-2015). Subjects and Methods We identified 18,584 patients who underwent inpatient otolaryngologic surgery. Four index complications were studied: pneumonia, bleeding or transfusion event (BTE), deep/organ space surgical site infection (SSI), and myocardial infarction (MI). Each patient with an index complication was matched to a control patient based on propensity for the index event and event-free days. Rates of 30-day secondary complications and mortality were compared. Results Index pneumonia (n = 254) was associated with several complications, including reintubation (odds ratio [OR], 11.7; 95% confidence interval [CI], 5.2-26.4), sepsis (OR, 8.8; 95% CI, 4.5-17.2), and death (OR, 5.3; 95% CI, 1.9-14.9). Index MI (n = 50) was associated with increased odds of reintubation (OR, 17.2; 95% CI, 3.5-84.1), ventilatory failure (OR, 5.8; 95% CI, 1.8-19.1), and death (OR, 24.8; 95% CI, 2.9-211.4). Index deep/organ space SSI (n = 271) was associated with dehiscence (OR, 7.2; 95% CI, 3.6-14.2) and sepsis (OR, 38.3; 95% CI, 11.6-126.4). Index BTE (n = 1009) increased the odds of cardiac arrest (OR, 3.9; 95% CI, 1.8-8.5) and death (OR, 2.9; 95% CI, 1.6-5.1). Conclusions Our study is the first to quantify the effect of index complications on the risk of specific secondary complications following inpatient head and neck surgery. These associations may be used to identify patients most at risk postoperatively and target specific interventions aimed to prevent or interrupt further complications.