Characterizing Immune Infiltration in Esthesioneuroblastoma Subtypes Through Gene Expression Deconvolution.

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare cancer deriving from the olfactory mucosa. Among the basal or neural genomic subtypes, the basal subtype is associated with poorer survival, poor differentiation, and higher levels of tumor-infiltrating immune cells (TIICs). The immune microenvironment of these ENB subtypes remains unclear. We used an established machine learning algorithm on ENB transcriptomic profiles. METHODS: The authors characterized 22 immune cell populations using the CIBERSORTx deconvolutional machine learning pipeline on RNA sequencing data from 18 ENB cases. The characterization aimed to elucidate differences in relative proportions and populations of TIICs between basal and neural ENB. RESULTS: No differences in age, Hyams, Dulguerov, IDH2 mutation, or PD-L1 expression were seen between basal and neural subtypes of ENB (P > 0.05). Also, no difference in median overall survival was appreciated (52.0 ± 13.1 months vs. 50.0 ± 43.2 months, P = 0.5). As a cohort, M2 macrophages were the most abundant subpopulation (14%) followed by naïve B cells (13%) and CD4 memory resting T cells (12%). No gross differences in CD20, CD4, or CD8 cells/mm2 were apparent on gross histology (P > 0.05). However, further analysis showed that activated CD4 memory T cells were significantly increased in the basal ENBs, whereas resting dendritic cells were increased in the neural ENB subtype. The TIIC profiles alone could not differentiate between basal and neural ENB, but did suggest immunoprofile differences. CONCLUSIONS: Basal and neural subtypes display distinct TIIC involvement, which may impact their difference in outcome. These findings provide the framework for further investigation in novel immunomodulation strategies for ENB.

Quantification of Budesonide Retained in the Sinonasal Cavity After High-Volume Saline Irrigation in Post-Operative Chronic Rhinosinusitis.

BACKGROUND: Budesonide high-volume saline irrigations (HVSIs) are routinely used to treat chronic rhinosinusitis (CRS) due to improved sinonasal delivery and efficacy compared to intranasal corticosteroid sprays. The off-label use of budesonide is assumed to be safe, with several studies suggesting the systemically absorbed dose of budesonide HVSI is low. However, the actual budesonide dose retained in the sinonasal cavity following HVSI is unknown. The objective of this study was to quantify the retained dose of budesonide after HVSI. METHODS: Adult patients diagnosed with CRS who had undergone endoscopic sinus surgery (ESS) and were prescribed budesonide HVSI were enrolled into a prospective, observational cohort study. Patients performed budesonide HVSI (0.5 mg dose) under supervision in an outpatient clinic, and irrigation effluent was collected. High-performance liquid chromatography was employed to determine the dose of budesonide retained after HVSI. RESULTS: Twenty-four patients met inclusion criteria. The average corrected retained dose of budesonide across the cohort was 0.171 ± 0.087 mg (37.9% of administered budesonide). Increased time from ESS significantly impacted the measured retained dose, with those 3 months post-ESS retaining 27.4% of administered budesonide (P = .0004). CONCLUSION: The retained dose of budesonide in patients with CRS after HVSI was found to be significantly higher than previously estimated and decreased with time post-ESS. Given that budesonide HVSI is a cornerstone of care in CRS, defining the retained dose and the potential systemic implications is critical to understanding the safety of budesonide HVSI.

Site-Specific Quality of Life Outcomes Following Anterior Skull Base Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: There is a limited understanding of site-specific, quality of life (QOL) outcomes in anterior skull base surgery (ASBS). The objective of the present investigation was to characterize postoperative change in QOL outcomes for anterior skull base lesions following open and endoscopic surgery. METHODS: A comprehensive review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using the PubMed, Scopus, Embase, and Cochrane databases for studies reporting pre- and postoperative, site-specific, QOL outcome measures in ASBS using validated questionnaires. Studies utilizing the anterior skull base quality of life (ASBQ) questionnaire or the skull base inventory were included. Investigations focusing on skull base surgery for pituitary lesions, as well as survey validation and non-English studies, were excluded. RESULTS: A total of 112 studies were screened; 4 studies, comprising a total of 195 patients and focusing exclusively on the ASBQ, were included in the systematic review. Using a fixed effect model for the meta-analysis, the mean ASBQ score was similar at six (3.45, P = 0.312; -0.19, 95% confidence interval: -0.57, 0.18) and 12 months postoperatively (3.6, P = 0.147; 0.3, 95% confidence interval: -0.11, 0.72) compared to baseline (3.53). CONCLUSIONS: Across a variety of anterior skull base pathologies, skull base-specific QOL demonstrated no improvement at 6 months and 12 months postsurgery. Few studies to date have published pre- and postoperative QOL data for patients undergoing ASBS, highlighting a current shortcoming in the available literature. Long-term follow-up in patients undergoing open and endoscopic approaches will be necessary to better understand and optimize outcomes for patients having ASBS.

The Impact of Acute Peri-operative Particulate Matter Exposure on Endoscopic Sinus Surgery Outcomes: A Preliminary Multi-site Investigation.

BACKGROUND: Environmental exposures have been postulated to play an important role in the pathophysiology of chronic rhinosinusitis (CRS). Particulate matter (PM) is one of the most widely studied ambient air pollutants, but its peri-operative impact on CRS is unknown. OBJECTIVE: To determine the effect of acute, peri-operative PM exposure on outcomes after endoscopic sinus surgery (ESS). METHODS: Participants with CRS who self-selected ESS were prospectively enrolled. The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility values scores were recorded. Using residence zip codes, a secondary analysis of patient exposure to PM <2.5 µm and <10 µm (PM2.5 and PM10, respectively) was performed for the month of surgery utilizing data from Environmental Protection Agency air quality monitors. Spearman's correlation coefficients (ρ), 95% confidence intervals (CIs), and effect estimates (ß) were used to determine the magnitudes of association. Simple, multivariate regression analysis was also completed. RESULTS: One hundred and seven patients from four geographically unique institutions across the US were enrolled with a follow-up of 6 months. Patients with higher peri-operative PM2.5 exposure had less improvement in their SNOT-22 scores after ESS compared to those with less exposure using both univariate analysis (ρ = 0.26, 95% CI: 0.08, 0.43; P = .01) and after covariate adjustment with multivariate analysis (B = 1.06, 95% CI: 0.001, 2.14, P = .05). Similar associations were not found with SF-6D outcomes or with PM10 as an exposure of interest. No significant correlations were found between peri-operative PM levels and Lund-Kennedy endoscopy scores post-operatively. CONCLUSION: Preliminary data from this pilot study reveal that PM exposure at the time of ESS may negatively associate with post-operative improvement in sinonasal quality-of-life. Larger, population-based studies with more standardized PM exposure windows are needed to confirm the clinical significance of the present findings.

Health care disparities and chronic rhinosinusitis: Does neighborhood disadvantage impact outcomes in sinonasal disease?

OBJECTIVE: Socioeconomic status (SES) is linked to health outcomes but has not been well studied in patients with chronic rhinosinusitis (CRS). The area deprivation index (ADI) is a comprehensive measure of geographic SES that ranks neighborhood disadvantage. This investigation used ADI to understand the impact of neighborhood disadvantage on CRS treatment outcomes. METHODS: A total of 642 study participants with CRS were prospectively enrolled and self-selected endoscopic sinus surgery (ESS) or continued appropriate medical therapy as treatment. The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility value scores were recorded pre- and post-treatment. Using residence zip codes, national ADI scores were retrospectively assigned to patients. Spearman's correlation coefficients (Rs) and Cramer's V effect size (φc) with 95% confidence interval (CI) were calculated. RESULTS: A history of ESS was associated with significantly worse ADI scores compared to no history of ESS (φc = 0.18; 95% CI: 0.10, 0.25; p < 0.001). Baseline total SNOT-22 (Rs = 0.14; 95% CI: 0.06, 0.22; p < 0.001) and SF-6D values (Rs = -0.20; 95% CI: -0.27, -0.12; p < 0.001) were significantly negatively correlated with national ADI rank. No significant correlations between ADI and within-subject improvement, or achievement of >1 minimal clinically important difference, in SNOT-22 or SF-6D scores after treatment were found. CONCLUSIONS: Geographic socioeconomic deprivation was associated with worse baseline disease severity and history of prior surgical intervention. However, ADI did not correlate with improvement in disease-specific outcomes. The impact of socioeconomic deprivation on outcomes in CRS requires further investigation.