Topical Application of 5-Fluorouracil for the Treatment of Sinonasal Adenocarcinoma and Inverted Papilloma.

BACKGROUND: Sinonasal tumors represent a rare and heterogeneous group of rhinologic neoplasms. Even with advancements in surgical approaches, mortality rates of patients with sinonasal adenocarcinoma (SNAC) have not significantly improved and persistently high rates of recurrence in certain patients with inverted papilloma (IP) are seen. The use of 5-fluorouracil (5-FU) has been successfully described as an adjuvant treatment of SNAC and in the prevention of IP recurrence. OBJECTIVE: This review aims to present the current evidence on the management of SNAC and IP with topical 5-FU. METHODS: A three-author independent literature review was conducted to identify research involving the use of topical 5-FU for the treatment of SNAC and IP. A total of nine papers on the treatment of SNAC and IP were collected. RESULTS: The earliest study looking at the combination of adjuvant low-dose radiation and topical 5-FU for adenocarcinoma of the ethmoid sinus showed a 5-year survival rate of 100%. A follow-up study evaluating a similar protocol reported adjusted disease-free survival at 2, 5, and 10 years of 96%, 87%, and 74%, respectively. Similar results have been demonstrated for adjuvant 5-FU use following endoscopic resection and have even been described in the novel setting of transcutaneous 5-FU delivery following frontal trephination. Topical 5-FU has also been described in the treatment of aggressive IP. The largest case series described the use of 5-FU for eighteen cases and demonstrated only a single recurrence. CONCLUSION: The use of topical 5-FU currently represents an underutilized therapeutic modality within the treatment of rhinologic neoplasms. Available literature suggests that neoadjuvant use of topical 5-FU can improve survival and decrease recurrence for SNAC and IP. However, the small sample sizes prevent advocation for routine use in the general population and further research on 5-FU is necessary.

Evaluation of Rhinology Fellowship Program Websites.

Objectives: Applicants for rhinology fellowship often utilize program websites to make informed application decisions. Although the American Rhinologic Society (ARS), the professional organization of rhinologists in the United States, maintains a directory of rhinology fellowships that includes basic information for each program, the ARS discloses that the information is provided directly by program directors and may therefore be inconsistent, inaccurate, or outdated. Methods: Our study evaluates the content and comprehensiveness of rhinology fellowship program websites in 31 areas related to either clinical training, research, application process, incentives, or administrative communications. Results: Of 32 unique rhinology fellowship programs, 29 of 32 (90.6%) had websites. On average program websites included 12.1 of the 31 items analyzed (39.0%). Information related to clinical training (mean 54.2%) and research (mean 60.9%) was included more often than information related to application process (mean 50.6%), and incentives (mean 14.9%). Programs with [Formula: see text] 5 dedicated physician faculty included more items than smaller programs (15.3 vs. 11.7 items, P = 0.015). Conclusion: Websites included information on clinical training and research more often than on incentives, even though these factors are important to many applicants. Few programs detailed past or ongoing research opportunities, which if included could help applicants identify mentors with similar research interests. Most websites had less than half of factors analyzed, emphasizing need for continued improvement.

Deletion of adipocyte Sine Oculis Homeobox Homolog 1 prevents lipolysis and attenuates skin fibrosis.

Background: The cardinal feature of systemic sclerosis (SSc) is skin thickening and tightening. Targetable mechanisms for skin features remain elusive. Drugs successful in treating internal organ manifestations have failed efficacy in skin. Dermal white adipose tissue (DWAT) is amongst the understudied contributors to skin manifestations. This study proposes the role of sine oculis homeobox homolog 1 (SIX1), a gene previously unrecognized as a contributor to dermal lipoatrophy characteristic of early skin fibrosis in SSc. Methods: Skin gene expression of SIX1 was analyzed in the GENISOS and PRESS SSc cohorts. Correlation analysis was performed with Spearman rank analysis. Novel mouse models were developed using the Cre-loxp system to knock out Six1 in all cells and mature adipocytes. Subcutaneous bleomycin was used to model early DWAT atrophy and dermal fibrosis characteristic of SSc. Findings: SIX1 was upregulated in SSc skin, the expression of which correlates with adipose-associated genes and molecular pathways. Genetic deletion of Six1 in all cells in mice challenged with bleomycin abrogated end-stage fibrotic gene expression and dermal adipocyte shrinkage. Adipocyte specific Six1 deletion was able to attenuate the early increase in skin thickness, a hallmark of experimental skin fibrosis. Further studies revealed a link between elevated SIX1 and increased expression of SERPINE1 and its protein PAI-1 which are known pro-fibrotic mediators. Interpretation: This work identifies SIX1 as an early marker of skin fibrosis in SSc. We also demonstrate a causative role of Six1 in skin fibrosis by promoting adipocyte loss and show that deletion of Six1 in adipocytes has the potential of impacting early disease progression.

Facility Volume and Changing Facilities for Postoperative Radiotherapy in Salivary Gland Cancer.

OBJECTIVES: Changing location of postoperative radiotherapy (PORT) after treatment at a high-volume facility (HVF) is associated with worse survival in various head and neck cancers. Our study investigates this relationship in salivary gland cancer (SGC). METHODS: The 2004-2016 National Cancer Database was queried for all cases of adult SGC treated with surgery and PORT with or without adjuvant chemotherapy. Patients with multiple cancer diagnoses, metastatic disease, or unknown PORT facility were excluded. Reporting facilities with >95th percentile annual case volume were classified as HVFs, the remainder were classified low-volume facilities (LVFs). RESULTS: A total of 7885 patients met inclusion criteria, of which 418 (5.3%) were treated at an HVF. Patients treated at an HVF had higher rates clinical nodal positivity (18.2% vs. 14.0%, p < 0.001) and clinical T3/T4 (27.3% vs. 20.7%, p = 0.001) disease. Patients at HVFs changed facility for PORT at lower rates (18.9% vs. 24.5%, p = 0.009). Patients treated at an HVF had higher 5-year overall survival (5-OS) than those treated at an LVF (79.0% vs. 72.0%, p = 0.042). Patients treated at an HVF that changed PORT facility had worse 5-OS (60.8% vs. 83.2%, p < 0.001). Radiation facility change was an independent predictor of worse survival in patients treated at an HVF (HR: 8.99 [3.15-25.67], p < 0.001) but not for patients treated at a LVF (HR: 1.11 [0.98-1.25], p = 0.109). CONCLUSIONS: Patients treated at an HVF changing facility for PORT for SGC experience worse survival. Our data suggest patients treated surgically at an HVF should be counseled to continue their PORT at the same institution. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Factors Associated with Research Productivity and National Institutes of Health Funding in Academic Otology.

OBJECTIVES: Bibliometrics, such as the Hirsch index (h-index) and the more recently developed relative citation ratio (RCR), are utilized to evaluate research productivity. Our study evaluates demographics, research productivity, and National Institutes of Health (NIH) funding in academic otology. METHODS: Academic otologists were identified, and their demographics were collected using institutional faculty profiles (N = 265). Funding data were obtained using the NIH Research Portfolio Online Reporting Tools Expenditures and Reports Database. The h-index was calculated using Scopus and mean (m-RCR) and weighted RCR (w-RCR) were calculated using the NIH iCite tool. RESULTS: H-index (aOR 1.18, 95% CI 1.10-1.27, p < 0.001), but not m-RCR (aOR 1.50, 95% CI 0.97-2.31, p = 0.069) or w-RCR (aOR 1.00, 95% CI 0.99-1.00, p = 0.231), was associated with receiving NIH funding. Men had greater h-index (16 vs. 9, p < 0.001) and w-RCR (51.8 vs. 23.0, p < 0.001), but not m-RCR (1.3 vs. 1.3, p = 0.269) than women. Higher academic rank was associated with greater h-index and w-RCR (p < 0.001). Among assistant professors, men had greater h-index than women (9.0 vs. 8.0, p = 0.025). At career duration 11-20 years, men had greater h-index (14.0 vs. 8.0, p = 0.009) and w-RCR (52.7 vs. 25.8, p = 0.022) than women. CONCLUSION: The h-index has a strong relationship with NIH funding in academic otology. Similar h-index, m-RCR, and w-RCR between men and women across most academic ranks and career durations suggests production of similarly impactful research. The m-RCR may correct some deficiencies of time-dependent bibliometrics and its consideration in academic promotion and research funding allocation may promote representation of women in otology. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Mechanisms of Pulmonary Hypertension in Acute Respiratory Distress Syndrome (ARDS).

Background: Acute respiratory distress syndrome (ARDS) is a severe and often fatal disease. The causes that lead to ARDS are multiple and include inhalation of salt water, smoke particles, or as a result of damage caused by respiratory viruses. ARDS can also arise due to systemic complications such as blood transfusions, sepsis, or pancreatitis. Unfortunately, despite a high mortality rate of 40%, there are limited treatment options available for ARDS outside of last resort options such as mechanical ventilation and extracorporeal support strategies. Aim of review: A complication of ARDS is the development of pulmonary hypertension (PH); however, the mechanisms that lead to PH in ARDS are not fully understood. In this review, we summarize the known mechanisms that promote PH in ARDS. Key scientific concepts of review: (1) Provide an overview of acute respiratory distress syndrome; (2) delineate the mechanisms that contribute to the development of PH in ARDS; (3) address the implications of PH in the setting of coronavirus disease 2019 (COVID-19).