Psychiatric Diagnoses and Psychotropic Drug Usage in Gender-Affirming Voice Surgery Patients.

OBJECTIVES: To describe the burden of psychiatric illness and psychotropic medication usage among the subset of transgender patients who undergo gender-affirming laryngeal surgery and describe some of the most commonly encountered conditions experienced by this population. METHODS: An Institutional Review Board-approved chart review was conducted for the 18 patients who have undergone gender-affirming laryngeal procedures from August 2019 to June 2022 performed at a single institution. Patient demographic data, treatment details, and psychiatric diagnoses and prescriptions for psychotropic medications were recorded. RESULTS: Of the 18 patients who underwent gender-affirming laryngeal surgery at this institution, 16 patients underwent these operations as part of a transition from male to female gender, while 2 patients were transitioning from female to male gender. In this cohort, 13 patients were diagnosed with a psychiatric comorbidity (72.2%). Of these patients, 11 were prescribed at least 1 psychotropic medication (61.1%). The most common psychiatric illnesses encountered in these patients were depression, anxiety, and post-traumatic stress disorder. Ten patients were diagnosed with more than 1 psychiatric comorbidity (55.6%). The most commonly prescribed psychotropic drugs were selective serotonin/norepinephrine reuptake inhibitors. Three patients in this cohort had a recorded history of at least one prior suicide attempt. CONCLUSIONS: Multiple studies have demonstrated increased rates of mental illness in transgender individuals, however, this is the first study to describe the burden of these conditions specifically in the subset of patients who undergo gender-affirming laryngeal surgery.

CIC-DUX4 Sarcoma Involving the Skull Base: A Rare Presentation and Review of the Literature.

Background CIC-DUX4 sarcoma is a rare, aggressive tumor that is difficult to diagnose. Although it is closely related to Ewing's sarcoma, each is a distinct pathologic entity and both have been previously reported in the skin, lymph nodes, and viscera. We report the first description of CIC-DUX4 involving the posterior cranial fossa and review the distinctive symptomatology, morphology, immunoprofile, and genetic signature that differentiate this rare tumor. Case Report A 32-year-old man presented with an enlarging right lateral neck mass, progressive hoarseness, and orofacial pain. Biopsy revealed a high-grade undifferentiated malignant neoplasm. Imaging demonstrated an 8-cm mass in the right neck extending to the skull base and abutting the carotid sheath, in addition to pulmonary nodules and pelvic lymphadenopathy. Despite initial response to chemotherapy, he experienced disease progression and underwent surgical resection, radical neck dissection, and brachytherapy. Definitive pathologic diagnosis was achieved with next-generation sequencing. Within weeks of treatment, he developed symptoms reflecting progression of disease involving the neck, posterior cranial fossa, and lung. Adjuvant chemotherapy was planned, but the patient succumbed to his disease prior to initiation of further therapy. Conclusion CIC-DUX4 sarcomas are uncommon and can progress rapidly. Diagnosis requires either fluorescence in situ hybridization or next-generation sequencing. Due to its rarity, there is no standard-of-care treatment for this tumor and further investigations are needed to understand disease behavior and develop targeted therapeutic modalities.

The Global Otolaryngology-Head and Neck Surgery Workforce.

Importance: A core component of delivering care of head and neck diseases is an adequate workforce. The World Health Organization report, Multi-Country Assessment of National Capacity to Provide Hearing Care, captured primary workforce estimates from 68 member states in 2012, noting that response rates were a limitation and that updated more comprehensive data are needed. Objective: To establish comprehensive workforce metrics for global otolaryngology-head and neck surgery (OHNS) with updated data from more countries/territories. Design, Setting, and Participants: A cross-sectional electronic survey characterizing the OHNS workforce was disseminated from February 10 to June 22, 2022, to professional society leaders, medical licensing boards, public health officials, and practicing OHNS clinicians. Main Outcome: The OHNS workforce per capita, stratified by income and region. Results: Responses were collected from 121 of 195 countries/territories (62%). Survey responses specifically reported on OHNS workforce from 114 countries/territories representing 84% of the world's population. The global OHNS clinician density was 2.19 (range, 0-61.7) OHNS clinicians per 100 000 population. The OHNS clinician density varied by World Bank income group with higher-income countries associated with a higher density of clinicians. Regionally, Europe had the highest clinician density (5.70 clinicians per 100 000 population) whereas Africa (0.18 clinicians per 100 000 population) and Southeast Asia (1.12 clinicians per 100 000 population) had the lowest. The OHNS clinicians deliver most of the surgical management of ear diseases and hearing care, rhinologic and sinus diseases, laryngeal disorders, and upper aerodigestive mucosal cancer globally. Conclusion and Relevance: This cross-sectional survey study provides a comprehensive assessment of the global OHNS workforce. These results can guide focused investment in training and policy development to address disparities in the availability of OHNS clinicians.

Gender Differences Among Head and Neck Microvascular Reconstructive Surgeons.

OBJECTIVE: To determine whether gender differences exist in the training history, practice patterns, and home lives of surgeons who perform microvascular reconstruction of the head and neck. STUDY DESIGN: Cross-sectional survey. SETTING: Medical facilities that employ surgeons who practice head and neck microvascular reconstruction in the United States. METHODS: A survey was created using the Research Electronic Data Capture Framework and was distributed via email to microvascular reconstructive surgeons. Descriptive statistics were performed using Stata software. RESULTS: No significant differences were found in training or current practice patterns between microvascular surgeons who identify as men versus those who identify as women. Women had fewer children (p = .020) and were more likely to be childless (p = .002). Whereas men were more likely to report a spouse/partner as primary caretaker, women were more likely to hire a professional caretaker or cite themselves as a primary caretaker (p < .001). Women were more likely to have finished residency (p = .015) and fellowship (p = .014) more recently and to practice in the Southeast (p = .006). Of the microvascular surgeons who reported practice setting switches, men more commonly changed positions for career advancement, whereas women were more likely to switch due to burnout (p = .002). CONCLUSION: This study found no gender-based differences in training or practice patterns. However, significant differences were identified in childbearing, family structure, geographic practice location, and motives for switching practice.

Carcinoma Ex Pleomorphic Adenomas: An Institutional Experience and Literature Review.

OBJECTIVES: To provide an institutional experience with cases diagnosed as carcinoma ex pleomorphic adenoma (CXPA), including the cytologic and histologic findings and clinical follow-up, followed by a comparison to the experience documented in the literature. METHODS: We identified cases of CXPA diagnosed at our institution from 2011 to 2021 and reviewed the cytologic and histologic diagnoses, as well as the treatment and clinical outcomes. Additionally, a literature review of the English literature was performed on CXPAs from 2011 to 2021. RESULTS: Forty-one cases of CXPA were identified, with the majority subclassified as adenocarcinoma, not otherwise specified. Five tumors underwent cytogenetic studies and five underwent molecular studies. To date, 36 patients are alive, 8 of whom experienced locoregional recurrence or distant metastasis. CONCLUSIONS: Our institutional experience was comparable to that reported in the literature. Further studies are required to inquire about the role of molecular profiles of CXPAs in clinical risk assessment.

LINE-1 ORF1p as a candidate biomarker in high grade serous ovarian carcinoma.

Long interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p) expression is a common feature of many cancer types, including high-grade serous ovarian carcinoma (HGSOC). Here, we report that ORF1p is not only expressed but also released by ovarian cancer and primary tumor cells. Immuno-multiple reaction monitoring-mass spectrometry assays showed that released ORF1p is confidently detectable in conditioned media, ascites, and patients' plasma, implicating ORF1p as a potential biomarker. Interestingly, ORF1p expression is detectable in fallopian tube (FT) epithelial precursors of HGSOC but not in benign FT, suggesting that ORF1p expression in an early event in HGSOC development. Finally, treatment of FT cells with DNA methyltransferase inhibitors led to robust expression and release of ORF1p, validating the regulatory role of DNA methylation in LINE-1 repression in non-tumorigenic tissue.

Primary sinonasal lymphoma: A multi-institutional experience of clinical presentation, treatment, and outcomes.

BACKGROUND: Sinonasal lymphoma (SL) is a heterogeneous, underrecognized neoplastic disorder with limited outcomes data. We sought to better define outcomes by subtype and treatment at 2 referral centers over the past 2 decades. METHODS: Demographics, clinicopathologic data, and treatment outcomes for patients treated for SL were queried from January 1, 2000 to December 31, 2021 at 2 tertiary academic medical centers. RESULTS: Eighty-four patients were included, with an average age at diagnosis of 63.4 ± 15 years. There were 34 females (40.5%). The majority of patients had an Eastern Cooperative Oncology Group (ECOG) score of <2 (76.2%) and the most common presenting symptom was facial swelling/pain (26.2%). The most common primary site was the nasal cavity (36.9%). Diffuse large B-cell lymphoma was the most common subtype (46.4%), followed by extranodal NK/T-cell lymphoma (17.9%). Chemotherapy was the most common treatment strategy (n = 59, 70.2%), followed by radiation therapy (n = 35, 41.7%) and immunotherapy (n = 24, 28.6%). Disease-specific survival rates at 1, 5, and 10 years were 85.7%, 73.6%, and 58.6%, respectively. Eighteen patients (21.4%) developed recurrence. On multivariate analysis, higher ECOG score (p < 0.0001) and history of head and neck radiation (p = 0.048) were associated with worse survival. Younger age was associated with greater risk of recurrence (p = 0.022) and male sex was associated with more treatment side effects (p = 0.012). CONCLUSION: This is the largest multi-institutional analysis of SL characteristics and outcomes. Our work suggests that, although disease control in the first 5 years is reasonable, 10-year outcomes remain challenging. Further studies are needed to investigate new treatment paradigms and risk stratification.

The Body Mass Index Paradox in Head and Neck Cancer: A Systematic Review and Meta-Analysis.

The body mass index (BMI) paradox describes that among patients with certain cancers, higher pretreatment BMI may be associated with improved survival. We examine the impact of BMI on overall survival (OS) in head and neck squamous cell carcinoma (HNSCC) patients. A literature search was performed, and articles using hazard ratios to describe the prognostic impact of BMI on OS in HNSCC were included. Random-effects DerSimonian and Laird methods were employed for meta-analysis. Meta-analysis of OS indicated a lower hazards of death in the overweight (BMI: 25 kg/m2-30 kg/m2) compared to the normal weight (BMI: 18.5 kg/m2-25 kg/m2). This protective relationship loses significance when BMI exceeds 30 kg/m2. Underweight patients (BMI < 18.5 kg/m2) demonstrate higher hazards of death compared to normal weight patients. Compared to HNSCC patients with normal weight, being overweight up to a BMI of 30 kg/m2 is a positive predictor of OS, while being underweight confers a prognostic disadvantage. Further studies are needed to determine the mechanisms by which increased body mass influences survival outcomes in HNSCC.

Outcomes Among Patients With Mucosal Head and Neck Squamous Cell Carcinoma Treated With Checkpoint Inhibitors.

Importance: Immune checkpoint inhibitors (CPIs) are now part of standard therapy for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) because of improved outcomes compared with chemotherapy in clinical trials. However, data on outcomes in patients with HNSCC in the general population who are treated with CPIs remain limited. Objective: To assess response rates, survival outcomes, and associations with key clinical covariates in a large, contemporary cohort of patients with recurrent or metastatic mucosal HNSCC who were treated with CPIs with or without chemotherapy. Design, Setting, and Participants: This retrospective cohort study included patients older than 18 years who received CPI-based therapy for recurrent or metastatic HNSCC at the University of Pennsylvania from January 1, 2015, through August 15, 2021. Clinical and survival data were abstracted through medical record review. Exposures: Treatment with CPIs with or without chemotherapy for a diagnosis of HNSCC. Main Outcomes and Measures: The main outcomes were overall survival, progression-free survival, and response rates. Overall survival and progression-free survival were estimated by Kaplan-Meier methods. Multivariable Cox proportional hazards regression was used to examine associations of key clinical variables with survival; a χ2 test and logistic regression were used to assess associations with response rate. Results: The study cohort consisted of 212 patients, of whom 165 (77.8%) were male, 148 (69.8%) were former or current smokers, and 66 (31.1%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater; median age was 63.2 years (IQR, 57.2-71.2 years). Primary tumor sites included the oropharynx (99 [46.7%]), oral cavity (61 [28.8%]), and larynx or hypopharynx (52 [24.5%]). Most (126 [59.4%]) received CPI as first-line systemic therapy, and 23 (10.8%) received combination CPI with chemotherapy. The overall response rate was 30.1%. Estimated 1-year overall survival was 51.8% (95% CI, 44.5%-58.8%), and estimated 1-year progression-free survival was 9.4% (95% CI, 5.0%-15.5%). Median overall survival was 12.9 months (IQR, 4.1-36.5 months), and median progression-free survival was 3.9 months (IQR, 1.9-17.8 months). Non-oral cavity primary site (vs oral cavity) was associated with improved overall survival (human papillomavirus-positive oropharynx: hazard ratio [HR], 0.567 [95% CI, 0.335-0.960]; all other sites: HR, 0.491 [95% CI, 0.298-0.810]), and T category of 4 at presentation (HR, 1.594; 95% CI, 1.062-2.394) and an ECOG performance status greater than 1 (HR, 2.720; 95% CI, 1.866-3.964) were associated with worse overall survival. Conclusions and Relevance: In this cohort study of patients with recurrent or metastatic HNSCC who received CPI therapy, the overall response rate was 30.1%. Patients with oral cavity cancer had worse overall survival compared with patients with HNSCC of other subsites. These findings support the use of CPI therapies for first- or second-line treatment of recurrent or metastatic HNSCC.

Enhanced recovery after surgery protocols for outpatient operations in otolaryngology: Review of literature.

Objective: Enhanced recovery after surgery (ERAS) protocols are patient-centered, evidence-based pathways designed to reduce complications, promote recovery, and improve outcomes following surgery. These protocols have been successfully applied for the management of head and neck cancer, but relatively few studies have investigated the applicability of these pathways for other outpatient procedures in otolaryngology. Our goal was to perform a systematic review of available evidence reporting the utility of ERAS protocols for the management of patients undergoing outpatient otolaryngology operations. Methods: A systematic literature review was conducted using MEDLINE, EMBASE, SCOPUS, and gray literature. We identified studies that evaluated ERAS protocols among patients undergoing otologic, laryngeal, nasal/sinus, pediatric, and general otolaryngology operations. We assessed the outcomes and ERAS components across protocols as well as the study design and limitations. Results: A total of eight studies fulfilled the inclusion criteria and were included in the analysis. Types of procedures evaluated with ERAS protocols included tonsillectomy and adenoidectomy, functional endoscopic sinus surgery, tympanoplasty and mastoidectomy, and septoplasty. A reduction in postoperative length of stay and hospital costs was reported in two and three studies, respectively. Comparative studies between ERAS and control groups showed persistent improvement in pre- and postoperative anxiety and pain levels, without an increase in postoperative complications and readmission rates. Conclusions: A limited number of studies discuss implementation of ERAS protocols for outpatient operations in otolaryngology. These clinical pathways appear promising for these procedures as they may reduce length of stay, decrease costs, and improve pain and anxiety postoperatively.