Beta-defensin index: A functional biomarker for oral cancer detection.

There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry. The proportion of hBD-3/hBD-2 levels in non-invasively collected lesional cells compared to contralateral normal cells, obtained by ELISA, generates the beta-defensin index (BDI). Proof-of-principle and blinded discovery studies demonstrate that BDI discriminates OSCC from benign lesions. A multi-center validation study shows sensitivity and specificity values of 98.2% (95% confidence interval [CI] 90.3-99.9) and 82.6% (95% CI 68.6-92.2), respectively. A proof-of-principle study shows that BDI is adaptable to a point-of-care assay using microfluidics. We propose that BDI may fulfill a major unmet need in low-socioeconomic countries where pathology services are lacking.

Development of hypothyroidism following hemithyroidectomy: A population-based study.

PURPOSE: Hypothyroidism is a known possibility after hemithyroidectomy, with a highly variable incidence in the literature ranging from 8 to 60 %. Incidence of hypothyroidism after hemithyroidectomy was evaluated with a secondary aim to assess incidence in patients with Hashimoto's disease. MATERIALS & METHODS: A retrospective study using the TriNetX global federated research network was performed. We included patients within the last 15 years that were ≥18 years of age and had Current Procedural Terminology codes for hemithyroidectomy. Patients were excluded if they had a total or completion thyroidectomy at any time, a history of thyroid cancer, were preoperatively either on levothyroxine, diagnosed with hypothyroidism, or had a Thyroid Stimulating Hormone ≥ 4 m[IU]/L. We assessed the 3 month incidence of hypothyroidism postoperatively based on the International Classification of Diseases code, TSH ≥ 4 m[IU]/L, or taking levothyroxine after surgery. RESULTS: 6845 patients met the inclusion criteria. Most of the cohort was female (67 %) and white (63 %). The mean age at surgery for this population was 54 ± 14.8 years. During the 15 years of data, we found the 3-month incidence of hypothyroidism following hemithyroidectomy to be 23.58 %. The median time to develop the disease was 41.8 months. A subgroup analysis of those with Hashimoto's revealed a 3-month incidence of 31.1 % of patients developing hypothyroidism after surgery. CONCLUSIONS: This population-based study gives additional insight into the incidence of hypothyroidism after hemithyroidectomy. This will help improve perioperative patient counseling and management.

Is sentinel lymph node biopsy needed for lentigo maligna melanoma?

BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) is an area of debate in the management of lentigo maligna melanoma (LMM). The utility of SLNB and its prognostic value in LMM have not yet been studied with large databases. METHODS: We performed a retrospective review of the National Cancer Database (2012-2020) and the Surveillance, Epidemiology, and End Results (2010-2019) database for patients with cutaneous nonmetastatic LMM with Breslow thickness >1.0 mm. Multivariable logistic regression identified factors associated with SLNB performance and sentinel lymph node (SLN) positivity. Univariable and multivariable analyses assessed overall survival (OS) and melanoma-specific survival (MSS) based on SLNB performance and SLN status. RESULTS: Compared to other melanoma subtypes, LMM had lower rates of SLNB (66.6% vs. 80.0%-84.0%) and SLN positivity (11.3% vs. 18.6%-34.2%). Compared to patients who did not undergo SLNB, SLN status was significantly associated with improved OS in patients with SLN positive (HR = 0.64 [0.55-0.76]) and SLN negative (HR = 0.68 [0.49-0.94]), and worse MSS only in patients with positive SLN (HR = 3.93, p < 0.05). CONCLUSION: The improved OS associated with SLNB likely implies surgical selection bias. Analysis of MSS confirms appropriate patient selection and suggests important prognostic value associated with SLN status. These results support continued SLNB for LMM patients according to standard guidelines.

Prognostic significance of time trends in treatment of head and neck squamous cell carcinoma.

PURPOSE: To analyze the impact of demographic, clinical, and management variables on time to treatment initiation (TTI) and overall survival (OS). STUDY DESIGN: Retrospective chart review. MATERIALS AND METHODS: Medical records of patients diagnosed with head and neck cancer from 2018 to 2020 were reviewed. Univariate linear and Cox-regressions identified predictors of TTI and OS. Kaplan Meier (KM) curves assessed the difference in survival by diagnostic year and TTI. RESULTS: 381 patients met eligibility criteria. Median TTI was 35.0 days (IQR: 25.0-49.0). Only 10.8 % of all patients reported any treatment delay, with TTI exceeding 90 days found in 3.7 % of patients. TTI increased with African American race (p = 0.02), ED referrals (p = 0.02), and direct admission status (p = 0.01). When compared to treatment with surgery alone, TTI was shorter in patients undergoing surgery with adjuvant radiation (p = 0.02), adjuvant chemoradiation (p = 0.04), and salvage surgery (p = 0.04). Univariate Cox-regressions found smoking (p = 0.01), direct admission status (p = 0.02), increased duration of symptoms (p = 0.02), placement of PEG tubes (p < 0.01) and tracheostomies (p < 0.01), combination treatment (p < 0.01), and surgery with adjuvant chemoradiation treatment (p = 0.01) to increase mortality risk. Disease characteristics, including tumor size (p < 0.01), presence of nodal disease (p = 0.02), and late-stage disease (p < 0.01), increased mortality risk. TTI and diagnostic year did not impact survival. CONCLUSIONS: Our analysis determined several demographic, referral, and treatment factors impacted TTI. However, increased TTI did not impact survival. Characteristics consistent with advanced disease worsened OS. Despite the pandemic burden, patients diagnosed in 2020 showed no difference in short-term survival compared to prior years.

Loss to Follow-up in Head and Neck Cancer: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: To evaluate the reporting and rates of loss to follow-up (LTFU) in head and neck cancer (HNC) randomized controlled trials based in the United States. DATA SOURCES: Pubmed/MEDLINE, Cochrane, Scopus databases. REVIEW METHODS: A systematic review of titles in Pubmed/MEDLINE, Scopus, and Cochrane Library was performed. Inclusion criteria were US-based randomized controlled trials focused on the diagnosis, treatment, or prevention of HNC. Retrospective analyses and pilot studies were excluded. The mean age, patients randomized, publication details, trial sites, funding, and LTFU data were recorded. Reporting of participants through each stage of the trial was documented. Binary logistic regression was performed to evaluate associations between study characteristics and reporting LTFU. RESULTS: A total of 3255 titles were reviewed. Of these, 128 studies met the inclusion criteria for analysis. A total of 22,016 patients were randomized. The mean age of participants was 58.6 years. Overall, 35 studies (27.3%) reported LTFU, and the mean LTFU rate was 4.37%. With the exception of 2 statistical outliers, study characteristics including publication year, number of trial sites, journal discipline, funding source, and intervention type did not predict the odds of reporting LTFU. Compared to 95% of trials reporting participants at eligibility and 100% reporting randomization, only 47% and 57% reported on withdrawal and details of the analysis, respectively. CONCLUSION: The majority of clinical trials in HNC in the United States do not report LTFU, which inhibits the evaluation of attrition bias that may impact the interpretation of significant findings. Standardized reporting is needed to evaluate the generalizability of trial results to clinical practice.

Incidence and medical complications of COVID-19 in the total laryngectomy population: A population-based study.

OBJECTIVES: Laryngeal and hypopharyngeal cancers treated with total laryngectomy (TL) may provide a unique avenue for COVID-19 to infect cancer patients. The objective of this investigation was to identify incidence of COVID-19 infection and potential complications in TL patients. MATERIALS AND METHODS: Data was extracted from TriNetX COVID-19 research network from from 2019 to 2021 and ICD-10 codes were utilized to query for laryngeal or hypopharyngeal cancer, and outcomes of interest. Cohorts were propensity score-matched based on demographics and co-morbidities. RESULTS: A query of active patients in TriNetX from January 1, 2019 to December 31, 2021 identified 36,414 patients with laryngeal or hypopharyngeal cancer out of the 50,474,648 active patients in the database. The overall COVID-19 incidence in the non-laryngeal or hypopharyngeal cancer population was 10.8% compared to 18.8% (p < 0.001) in the laryngeal and hypopharyngeal cancer group. Those who underwent TL had a statistically significant increased incidence of acquiring COVID-19 (24.0%) when compared to those without TL (17.7%) (p < 0.001). TL patients with COVID-19 had a higher risk of developing pneumonia RR (risk ratio) 1.80 (1.43, 2.26), death 1.74 (1.41, 2.14), ARDS 2.42 (1.16, 5.05), sepsis 1.77 (1.37, 2.29), shock 2.81 (1.88, 4.18), respiratory failure 2.34 (1.90, 2.88), and malnutrition 2.46 (2.01, 3.01) when matched with those COVID-19 positive cancer patients without TL. CONCLUSIONS: Laryngeal and hypopharyngeal cancer patients had a higher rate of acquiring COVID-19 than patients without these cancers. TL patients have a higher rate of COVID-19 compared to those without TL and may be at a higher risk for sequalae of COVID-19.

Job market in head and neck surgery: A survey and analysis of recent fellowship graduates.

OBJECTIVE: Recent years have seen increase in individuals pursuing postgraduate fellowships in head and neck (HN) surgery. This has presented concerns about insufficient jobs where graduates can apply their scope of specialized training. METHODS: Data was collected in two manners- a survey and a manual online search of American Head and Neck Society (AHNS) fellowship graduates. A 25-question survey was sent in 2021 to approximately 400 HN fellows who graduated between 2010 and 2020. The AHNS list of graduates from the same years were searched online to collect information including gender, graduation year, fellowship training, and current job practice. RESULTS: Of the 78 survey responses, 64.1 % were male and 34.6 % female. 96.2 % reported ablative, 84.6 % microvascular, and 82.1 % TORS training. Mean number of interviews was 4 with most interviewing during the 3rd quarter (January to March). Majority reported being in academic and university-based practices (79.6 %). Online search was done on 393 graduates. Since 2010 the number of graduates almost doubled. There was a statistically significant increase in females by year (p = 0.022). There was a significant decrease (p = 0.022) in graduates with additional fellowship training from that of their AHNS fellowship. There was also a statistically significant increase in graduates being in academic practices (p = 0.022). CONCLUSION: Despite growing numbers, there appears to be more graduates entering an academic practice, although the definition of an academic HN practice may be evolving. These results provide guidance on how to approach the job search in a select market. LEVEL OF EVIDENCE: II.

Impact of intraoperative ischemia time on acute complications of head and neck microvascular free tissue transfer: A systematic review and meta-analysis.

BACKGROUND: To evaluate the relationship between intraoperative ischemia time with acute microvascular free tissue transfer (MFTT) complications in head and neck reconstruction. METHODS: A systematic review using PRISMA guidelines was performed. Inclusion encompassed all available studies published and indexed using PubMed, Medline, and Embase. Meta-analyses were performed using the Cochrane Review Manager tool. Methodological Index for Non-Randomized Studies (MINORS), the Revised Cochrane risk-of-bias tool for randomized trials, and the NIH Study Quality Assessment Tool for non-randomized prospective studies. RESULTS: A total of 430 citations were reviewed. 25 were included in our overall qualitative analysis, and 14 for meta-analysis. When comparing ischemia times for flaps with and without complications, no significant difference was observed (p = 0.98). Additionally, in a separate cohort, no significant effect was realized when correlating ischemia time to overall rates and total complications. CONCLUSION: Ischemia time was not significantly different between those with and without acute flap complications.

Occult nodal metastasis in major salivary gland malignancy: An update from the National Cancer Database.

OBJECTIVES: Malignant salivary gland tumors are rare neoplasms that are vastly heterogenous in their histological patterns and clinical behaviors. As a consequence, studies have lacked the robust sample sizes needed to define treatment strategies. In this study, we used the National Cancer Database to identify the incidence of occult nodal metastasis and effect on overall survival for the most common malignant salivary gland subtypes. A retrospective review of patients in the National Cancer Database with primary site malignancies of major salivary glands between 2004 and 2016 was performed. Subjects included in the study underwent surgical treatment with and without adjuvant radiation and had complete information on TNM pathological stage. MATERIALS AND METHODS: 8,689 patients with primary malignant salivary gland cancer were analyzed. The sample was stratified by histologic subtype. Univariate analysis of lymph node metastasis of the whole cohort showed a higher risk of death (p < 0.001), when compared to those without. Also when comparing occult vs evident metastasis, the risk of death was higher for the latter (p < 0.001). RESULTS AND CONCLUSION: Occult cervical lymph node metastasis ranged from 14.9% to 35.8% in malignant salivary gland cancers, depending on histological subtype. Occult nodal metastasis was a poor prognostic factor with significantly worse overall survival.

Validated Outcome Measures and Postsurgical Scar Assessment Instruments in Auricular Surgery: A Systematic Review.

BACKGROUND: The utilization of an assessment instrument that successfully analyzes validated outcome measures for auricular surgery is important for advancing evidence-based medicine. OBJECTIVE: To systematically review postsurgical scar assessment instruments and outcome measures after auricular surgery to assess if any individual or combination of 2 assessment instruments encompass all relevant, validated auricular outcome measures. METHODS: Two systematic reviews were conducted using the PubMed/MEDLINE and Ovid databases: one for postauricular surgical outcome measures and another for postsurgical scar assessment instruments. Auricular outcome measure articles were selected for inclusion if they included at least one auricular-specific validated outcome measure, and assessment tool articles were included if they referenced one or more specific tool(s) specifically designed to assess postsurgical scars. Assessment tools were evaluated based on which outcome measures each covered. RESULTS: There was no single postsurgical scar assessment instrument or combination of 2 instruments that covered all outcome measures within the 5 different categories (psychosocial well-being, functional, objective appearance, subjective appearance, and clinical-related outcomes) after auricular surgery. None of the instruments measured functional outcomes, such as the ability to wear glasses and hearing outcomes. CONCLUSION: There is currently no existing postsurgical scar assessment instrument that covers all outcome measures after auricular surgery.

Impact of perioperative pain management protocol on opioid prescribing patterns.

OBJECTIVES/HYPOTHESIS: The objective of this study was to demonstrate the impact of preoperative education, patient risk stratification, and a postoperative pain management protocol for common head and neck procedures on opioid prescribing patterns and postoperative pain reporting. STUDY DESIGN: Retrospective cohort study. METHODS: A postoperative pain management protocol was developed and implemented for patients undergoing head and neck surgical procedures. Medical charts were queried and postoperative patient satisfaction surveys were administered. Opioid prescribing patterns were evaluated in cohorts of patients undergoing procedures with anticipated mild pain (e.g., thyroidectomy, parotidectomy, lymph node biopsy) before and after the implementation of the protocol. Postoperative patient surveys were analyzed in the postimplementation group. RESULTS: A total of 302 patients were included for analysis. One hundred fifty-four patients and 148 patients underwent surgery before and after the implementation of the protocol, respectively. There was a decreased incidence of oxycodone-containing prescriptions (83% to 26%), and tramadol became the most common discharge medication (70%). There was a significant decrease in the total number of pills prescribed after the implementation of the protocol (34.71 to 25.36, P < .001). Ninety percent of patients reported high satisfaction (≥8) with pain management. CONCLUSIONS: This study shows that a comprehensive pain management protocol can significantly reduce the amount and potency of opioid pain medication prescribed after head and neck procedures while maintaining high patient satisfaction. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1180-1185, 2020.

Surgical outreach and microvascular surgery in developing countries.

Due to the discrepancy between surgical demand and resources in Low-Middle Income Countries (LMIC), surgical outreach programs (SOP) have increased in popularity. In these resource-constrained healthcare environments, the resources necessary to perform basic head and neck procedures are often lacking, and offering microvascular reconstruction adds yet another level of complexity. Here we discuss the difficulties and challenges in establishing a SOP abroad and more specifically some of the challenges specific to microvascular reconstruction - including patient selection, burden of cost, lack of infrastructure and equipment, and patient follow up and outcomes. Although challenges certainly exist, we present the feasibility and the benefit for patient care as well as the role it can play in the foundation development of a low-resource region. The goals of the SOP must be well-defined, and incorporating microvascular surgery can be used as an adjunct to enhance the development of many aspects of the LMIC healthcare system. We present a model of care in which the initial focus is centered on providing safe care to these patients undergoing complex procedures, but after the development of a strong foundation, the focus can begin to include program sustainability and education.

Submental artery island flap versus free flap reconstruction of lateral facial soft tissue and parotidectomy defects: Comparison of outcomes and patient factors.

OBJECTIVES: The submental artery island flap (SIF) has recently been described in temporal bone defects. At our institution we have broadened the application of the SIF and modified the harvest technique for complex lateral facial and skull base defects. Our primary aim is to evaluate the outcomes of patients undergoing complex lateral facial soft tissue, parotidectomy, and temporal bone defects who are reconstructed with the SIF to a similar cohort undergoing free tissue transfer reconstruction. MATERIALS AND METHODS: Nineteen patients undergoing SIF and 54 patients undergoing free tissue flaps for oncologic lateral facial, parotidectomy and temporal bone defects were retrospectively identified. Comparative statistics were used to analyze variables between the two cohorts, specifically operative time, flap size, length of stay, regional recurrence, disease free survival, and overall survival. RESULTS: No significant difference in demographic and disease related variables was observed. Operative time was significantly lower in SIF group with mean of 412.9 (SD 93.4) minutes compared to 544.1 (SD 139.9) minutes in free flap group. Flap size was significantly larger in free tissue transfer, 32.4 (SD 17.5) cm2 (SIF) compared to mean area of 105.2 (SD 53.2) cm2 (Free tissue transfer). A significant difference in length of stay was also noted between groups. There was no regional recurrence of disease in level I-III in SIF group. There was no significant difference in DFS or OS between the two groups. CONCLUSION: SIF is an oncologically sound option for reconstruction of lateral facial soft tissue, parotidectomy, and temporal bone defects.

Synthesis of triazole-oxazolidinones via a one-pot reaction and evaluation of their antimicrobial activity.

C-5-substituted triazole-oxazolidinones were synthesized using a bromide catalyzed cycloaddition between aryl isocyanates and epibromohydrin followed by a three-component Huisgen cycloaddition. The library of compounds was screened for antibacterial activity against Mycobacterium smegmatis ATCC 14468, Bacillus subtilis ATCC 6633, and Enterococcus faecalis ATCC 29212. Notably, the 3-(4-acetyl-phenyl)-5-(1H-1,2,3-triazol-1-yl)methyl)-oxazolidin-2-one (18) showed an MIC of 1 microg/mL against M. smegmatis ATCC 14468, fourfold lower than the MIC measured for isoniazid.