Disparities in access to translational research.

Translational research describes the process of applying observations and scientific discoveries made in the laboratory to clinical applications that can improve the health of individual patients, most often through clinical trials. To apply the findings of translational research studies to the broader population, the study population must accurately reflect the group of patients afflicted by a particular disease. Yet, it is well known that significant disparities exist for underrepresented groups and lower socioeconomic populations in clinical trials. In fact, only 20% of randomized controlled studies published in high-impact oncology journals include subgroup analyses to assess differences in outcomes based on race or ethnicity.1 If effective interventions to decrease health disparities in research are to be implemented, it is critical to understand the multifactorial influences that create such differences. These are complex and include individual patient factors, family and social support, provider and organizational factors, as well as policy and community factors. Patient access to tertiary or quaternary care academic centers or designated cancer centers with the funding and resources to carry out translational research and knowledge of ongoing available research endeavors is often critical. Active community engagement and outreach and deep understanding of a particular health system's catchment area are necessary to increase both awareness and participation in clinical trials. Without significant progress in biomedical research patient recruitment, existing racial and ethnic health disparities will be challenging to overcome.

Non-Squamous Cell Malignancies of the Larynx.

OBJECTIVES/HYPOTHESIS: Non-squamous cell carcinoma (SCC) malignancies are rare, but well described laryngeal pathologies. However, the epidemiology and clinical behavior of these tumors is not well studied. STUDY DESIGN: Retrospective cohort study. METHODS: Patients diagnosed with non-squamous cell larynx cancer from 2004 to 2017 in the National Cancer Database were selected. Demographic, clinicopathologic factors, treatments, and survival were analyzed. Univariable and multivariable cox regression were performed. Survival was compared with a propensity score-matched (PSM) population of laryngeal SCC patients. RESULTS: A total of 136,235 cases of larynx cancer were identified. After excluding SCC variants, 2,172 (1.6%) patients met inclusion criteria. The most common histology was chondrosarcoma (374, 17.2%), followed by small cell (345, 15.9%), and spindle cell carcinoma (268, 12.3%). The most common treatment was surgery (683, 31.4%) followed by chemoradiation (409, 18.8%) and surgery and adjuvant radiation (288, 13.3%). Overall, 3- and 5-year survival was 67.9% and 59.4%, respectively. In multivariate analysis controlling for age, stage, comorbidity, histology, and treatment modality; chondrosarcoma had the best survival (hazard ratio [HR] 0.11, confidence interval [CI] 0.07-0.19, P < .001). In a PSM population, matched for age, stage, comorbidity, and treatments; non-SCC patients had significantly lower survival (51.5% vs. 59.9%, P < .001). CONCLUSION: A diverse range of non-squamous cell malignancies occur in the larynx. In general, these tumors have poor survival, with few exceptions such as chondrosarcoma. While the majority of these histologies undergo surgical-based treatments in other sites, only 53% of patients underwent surgical-based treatment in the larynx. These data could guide clinicians in determining the outcome of treatment in these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1771-1777, 2022.

Nodal disease burden and outcome of medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare malignancy with high incidence of cervical lymph node (CLN) metastasis. We investigated the impact of nodal disease burden on survival. METHODS: We searched the National Cancer Database for MTC patients treated surgically. Impact of nodal metastasis on survival was analyzed using Cox univariable and multivariable regression. RESULTS: We identified 2627 patients from 2004 to 2015. Positive CLNs were identified in 1433 (54.5%), and 542 (20.6%) had >10 CLN+. Overall survival was 94.5% and 89.6% at 3 and 5 years. Patients with 11 to 20 CLN+ had significantly worse survival than patients with 1 to 10 CLN+ in univariable and multivariable analyses (HR = 3.56 (2.31-5.50) vs 2.26 (1.60-3.20); P < .0001). The ratio of positive to dissected CLN was associated with overall survival. CONCLUSIONS: Higher burden of nodal disease is associated with worse survival in MTC. The number of positive nodes could be a valuable prognosticator in addition to the current staging system.

Socioeconomic and Racial Disparities and Survival of Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To investigate differences in epidemiology of oropharyngeal squamous cell carcinoma (OPSCC) with regards to human papillomavirus (HPV), race, and socioeconomic status (SES) using the National Cancer Database (NCDB). STUDY DESIGN: Population-based cohort study. SETTING: Racial and socioeconomic disparities in survival of OPSCC have been previously acknowledged. However, the distribution of HPV-related cancers and its influence on survival in conjunction with race and SES remain unclear. SUBJECTS AND METHODS: All patients with OPSCC in the NCDB with known HPV status from 2010 to 2016 were included. Differences in presentation, HPV status, treatment, and outcomes were compared along racial and socioeconomic lines. Univariable and multivariable Cox regression survival analyses were performed. RESULTS: In total, 45,940 patients met criteria. Most were male (38,038, 82.8%), older than 60 years (23,456, 51.5%), and white (40,156, 87.4%), and lived in higher median income areas (>$48,000, 28,587, 62.2%). Two-thirds were HPV positive (31,007, 67.5%). HPV-negative disease was significantly more common in lower SES (<$38,000, 2937, 41.5%, P < .001) and among blacks (1784, 55.3%, P < .001). Median follow-up was 33 months. Five-year overall survival was 81.3% (95% CI, 80.5%-82.1%) and 59.6% (95% CI, 58.2%-61.0%) in HPV-positive and HPV-negative groups, respectively. In univariable and multivariable analyses controlling for HPV status, age, stage, and treatment, black race (hazard ratio [HR], 1.22; 95% CI, 1.11-1.34; P < .001) and low SES (HR, 1.58; 95% CI, 1.45-1.72; P < .001) were associated with worse survival. CONCLUSION: Significant differences in HPV status exist between socioeconomic and racial groups, with HPV-negative disease more common among blacks and lower SES. When controlling for HPV status, race and SES still influence outcomes in oropharyngeal cancers.

Proton pump inhibitor administration in neonates and infants. Lack of consensus - An ASPO survey.

OBJECTIVE: Laryngopharyngeal and Gastroesophageal reflux (LPR and GER) are distinct clinical entities that present with a range of non-specific symptoms. The exact prevalence in the pediatric population is unknown. While there has been an increase in the use of PPIs, lack of clear guidelines, conflicting evidence regarding efficacy and safety concerns with long-term use require physicians to use their own anecdotal experience and clinical judgement when treating patients. The goal of this study was to evaluate practice patterns among pediatric otolaryngologists regarding the use of proton-pump inhibitors for reflux-related conditions. METHODS: A survey was submitted to American Society of Pediatric Otolaryngology (ASPO) members to determine practice patterns regarding use of PPIs for reflux-related conditions in the newborn and infant population. Statistical analysis using Fisher's exact test was performed. RESULTS: 37% of respondents would not prescribe PO PPIs in neonates, with 50% not prescribing IV PPIs. 60% would prescribe a PPI as second or third-line treatment for infants (10 weeks to 1-year). Only 10% would prescribe as first-line in this age group. 48% would prescribe PPIs once daily and 19% as BID. No significant practice differences exist based on years of experience, number of relevant patients seen, and setting of practice. CONCLUSION: There was no agreement regarding dosage, frequency and duration of PPI treatment for reflux disease in neonates and infants. There was also no correlation with experience or practice setting. This emphasizes the need for a multidisciplinary approach and consensus statement to guide management of GER and LPR in this population.

Oral Squamous Cell Carcinoma as a Complication of Treatment for Recurrent High-Grade Serous Cancer.

OBJECTIVES/HYPOTHESIS: Advances in cancer treatment have increased survival for many patients, prompting a need for greater recognition of the long-term complications of treatment. Chemotherapy agents have the potential to induce carcinogenesis and can increase the risk of secondary malignancy. Pegylated liposomal doxorubicin (PLD) used for maintenance treatment of recurrent high-grade serous cancers has been associated with the development of oral cavity squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective review. METHODS: Cases of oral cavity SCC in patients with recurrent high-grade serous cancer treated with PLD between 1997 and 2017 at a single institution were reviewed. RESULTS: Eight of 16 patients treated with PLD developed oral cavity SCC. The duration of PLD use ranged from 1.3 to 15 years (mean = 5.8 years) and cumulative dose ranged from 405 to 3,000 mg/m2 (mean = 1,542 mg/m2 ). Seven patients tested positive for BRCA mutations (four BRCA 1+, three BRCA 2+). No patients had a history of alcohol or tobacco use. All had early-stage oral cavity disease; five were T1N0, two were T2N0, and one had carcinoma in situ. All patients underwent surgery, and two received adjuvant radiation. Four developed locoregional recurrence requiring additional treatment. Of these, one patient died from complications of oral SCC, one developed recurrent ovarian cancer, and two had no evidence of disease of the oral cavity or ovarian cancer at the last follow-up. CONCLUSIONS: Long-term PLD therapy may be associated with the development of oral cavity SCC. A high index of suspicion and routine head and neck examination should be included in follow-up for exposed patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2607-2610, 2020.

Nasolacrimal Duct Management During Endoscopic Sinus and Skull Base Surgery.

OBJECTIVE: To evaluate rates of epiphora after transection and marsupialization of the nasolacrimal duct (NLD) during endoscopic sinus and skull base surgery. INTRODUCTION: The nasolacrimal canal forms part of the medial wall of the maxillary sinus. Transecting the NLD is sometimes necessary for tumor resection or surgical access to maxillary sinus and infratemporal fossa pathology. There is no consensus for the endoscopic management of the NLD when only the duct is transected without involving the nasolacrimal sac. METHODS: Medical records of 29 patients from 2 academic institutions who underwent endoscopic sinus and skull base surgery with transection of the NLD were retrospectively reviewed. Whether the duct was marsupialized or simply transected was recorded, and the postoperative rate of epiphora was calculated. RESULTS: Mean age was 59 years (range, 14-86 years). Mean follow-up was 10.5 months (range, 1-33 months). The NLD was marsupialized in 16 (55%) and simply transected in 13 (45%) patients. Six patients underwent postoperative radiation. No patients in the marsupialization group had epiphora postoperatively, all with Munk score of 0. One patient in the transection group developed postoperative epiphora with Munk score of 1. Pathology included inverted papilloma (8), acute on chronic inflammation (6), B-cell lymphoma (3), juvenile nasopharyngeal angiofibroma (2), squamous cell carcinoma (2), Schneiderian papilloma (2), metastatic melanoma (1), HPV-related carcinoma (1), adenocarcinoma (1), benign epithelial cyst (1), adenoid cystic carcinoma (1), and erosive chronic sinusitis without nasal polyposis (1). CONCLUSION: Management after transection of the NLD varies widely. The duct may be simply transected or marsupialized, or a formal dacryocystorhinostomy can be performed. The surgeon must also choose whether to place a stent. Based on our small series and review of the literature, marsupialization or simple transection of the NLD results in a low rate of postoperative epiphora in the setting of endoscopic sinus and skull base surgery.

The patient's perioperative perspective during the treatment of obstructive sleep apnea: a pilot study.

PURPOSE: This study aims to determine patients' pre-operative and post-operative experiences relating to surgical treatment for obstructive sleep apnea (OSA), while understanding how patients' perceptions influence their outcome and satisfaction. METHODS: This is a phenomenological qualitative study using a semi-structured interview to evaluate patients who failed continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea and underwent airway surgery. Meaningful codes from the interviews were organized into overarching themes of patient experiences. The same surgeon in a tertiary care otolaryngology practice treated all patients. All patients underwent a modified or traditional uvulopalatopharyngoplasty (UPPP) between 2009 and 2013. Patients were diagnosed with OSA by polysomnogram and had failed CPAP use. Patients were interviewed regarding their experience with OSA, CPAP, and surgery. Thematic saturation was reached after 17 patients. RESULTS: Six themes exemplify patient's experience of OSA and treatment: (1) OSA impacted patients personally and professionally, (2) CPAP discomfort limited its therapeutic use, (3) patients had personal motivations for undergoing surgery, (4) patient knowledge influenced their perceptions, (5) post-operative challenges exceeded patient expectations, and (6) post-operative outcomes reflected positive effect on patients. CONCLUSIONS: Patients' experiences prior to surgery can largely influence their perceived outcome and satisfaction. Post-operative sleep studies may not capture the full outcome of the patients' response to surgery. This study suggests that the patient's subjective reported outcomes should be used in conjunction with objective post-operative sleep studies.

Is a Multidisciplinary Aerodigestive Clinic More Effective at Treating Recalcitrant Aerodigestive Complaints Than a Single Specialist?

OBJECTIVE: To determine the utility of a pediatric multidisciplinary aerodigestive clinic (ADC) in treating recalcitrant aerodigestive conditions. METHODS: Longitudinal observational study of presenting complaints, evaluation, management, and outcome of patients seen during 12 monthly ADCs beginning August 2013. RESULTS: Fifty-five patients were seen by the ADC team (otolaryngology/gastroenterology/pulmonology/speech pathology/nurse practitioner) and followed for a mean 17.6 months (range, 12-26 months). Mean age was 4.3 years (range, 0.5-19 years). All were seen by at least 1 specialist before ADC referral but without significant improvement. Chronic cough was the most common primary symptom (44%). Clinic evaluation included flexible nasopharyngolaryngoscopy (FFL, 53%) and pulmonary function testing (36%.) FFL influenced management in 79%. An operative procedure usually combined endoscopy was warranted in 58%. Endoscopy provided high diagnostic yield, detecting laryngeal cleft (8), adenoid hypertrophy (8), vocal cord dysfunction (4), pulmonary infection (4), reflux disease (3), laryngomalacia (3), tracheomalacia (2), cilia abnormality (2), celiac disease (1), Helicobacter pylori (1), duodenal web (1), and eosinophilic esophagitis (1). Outcome was available for 48 of 55 patients, with 73% reporting resolved to markedly improved symptoms and 27% minimal to no improvement. CONCLUSIONS: The ADC team approach resulted in resolved to markedly improved symptoms in 73% of patients whose symptoms persisted despite seeing a single specialist prior to referral.