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Key Points: Inverted papilloma conversion to squamous cell carcinoma is not always easy to predict. AutoML requires much less technical knowledge and skill to use than traditional ML. AutoML surpassed the traditional ML algorithm in differentiating IP from IP-SCC., (© 2024 ARS‐AAOA, LLC.)

Background: The inability of topical medications to reach sinus cavities is a potential reason for lack of efficacy in chronic rhinosinusitis (CRS). One purpose of endoscopic sinus surgery (ESS) is to enable delivery of medications into the sinus cavities. The exhalation delivery system with fluticasone (EDS-FLU; XHANCE) creates unique biomechanics that enable deposition of intranasal corticosteroid into sinuses and sinus drainage pathways but may have differing efficacy in operated versus unoperated sinuses. Two 24-week randomized trials (ReOpen1/2) evaluated EDS-FLU versus EDS-placebo in patients with CRS, stratified by surgical status., Methods: Surgery-naive (n = 332) and prior-surgery (n = 215) patient groups were analyzed as pooled data from ReOpen1/2. Outcome measures (least-squares mean change from baseline) included combined symptom score (CSS) and congestion score at weeks 4, 8, and 12 and average of percentages of opacified volume (APOV) of ethmoid/maxillary sinuses on CT and Sinonasal Outcome Test 22 (SNOT-22) total score at week 24., Results: Baseline scores suggested moderate-severe disease: mean CSS = 5.8; APOV = 67.2%. EDS-FLU produced significant improvement versus placebo (p < 0.05): CSS (surgery-naive, -0.68 vs. -1.42; prior ESS, -0.70 vs. -1.87); congestion (surgery-naive, -0.24 vs. -0.59; prior ESS, -0.24 vs. -0.69); and SNOT-22 (surgery-naive, -7.56 vs. -18.30; prior ESS, -10.72 vs. -18.74). Similar results were observed for APOV (p < 0.05). No statistically significant difference was observed between surgery subgroups with either EDS-FLU dose., Conclusion: EDS-FLU improved symptoms, sinus opacification, and quality of life in patients with CRS with or without prior ESS, suggesting a role for EDS-FLU in both populations., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Patients with sinonasal malignancy (SNM) present with significant sinonasal quality of life (QOL) impairment. Global sinonasal QOL as measured by the 22-item Sinonasal Outcomes Test (SNOT-22) has been shown to improve with treatment. This study aims to characterize SNOT-22 subdomain outcomes in SNM., Methods: Patients diagnosed with SNM were prospectively enrolled in a multi-center patient registry. SNOT-22 scores were collected at the time of diagnosis and through the post-treatment period for up to 5 years. Multivariable regression analysis was used to identify drivers of variation in SNOT-22 subdomains., Results: Note that 234 patients were reviewed, with a mean follow-up of 22 months (3 months-64 months). Rhinologic, psychological, and sleep subdomains significantly improved versus baseline (all p < 0.05). Subanalysis of 40 patients with follow-up at all timepoints showed statistically significant improvement in rhinologic, extra-nasal, psychological, and sleep subdomains, with minimal clinically important difference met between 2 and 5 years in sleep and psychological subdomains. Adjuvant chemoradiation was associated with worse outcomes in rhinologic (adjusted odds ratio (5.22 [1.69-8.66])), extra-nasal (2.21 [0.22-4.17]) and ear/facial (5.53 [2.10-8.91]) subdomains. Pterygopalatine fossa involvement was associated with worse outcomes in rhinologic (3.22 [0.54-5.93]) and ear/facial (2.97 [0.32-5.65]) subdomains. Positive margins (5.74 [2.17-9.29]) and surgical approach-combined versus endoscopic (3.41 [0.78-6.05])-were associated with worse psychological outcomes. Adjuvant radiation (2.28 [0.18-4.40]) was associated with worse sleep outcomes., Conclusions: Sinonasal QOL improvements associated with treatment of SNM are driven by rhinologic, extra-nasal, psychological, and sleep subdomains., (© 2024 ARS‐AAOA, LLC.)

Background: Sinonasal malignancy surveillance paradigms are often based on Head and Neck National Comprehensive Cancer Network guidelines, which do not recommend standard surveillance imaging beyond 6 months without concerning symptomatology or physical examination findings., Methods: This was a retrospective analysis of all patients who underwent resection of sinonasal malignancy at a tertiary care center over a 20-year period from 2000 to 2020, with an ensuing surveillance period demonstrating recurrence., Results: Fifty-two patients with sinonasal malignancy recurrence were included, with an average time to recurrence of 30.9 months and a follow-up period of over 60 months. Recurrence was diagnosed by routine imaging or endoscopy in asymptomatic patients in a majority (60%) of cases, while the remaining minority of diagnoses followed new symptomatology. Asymptomatic recurrence was associated with perineural spread of tumor at initial resection (p = 0.025), but not with age (p = 0.85) or stage at diagnosis (p = 0.68). Expectedly, positron emission tomography/computed tomography (CT) more often detected regional or distant recurrence, while structural imaging (CT/magnetic resonance imaging) demonstrated more frequent detection of recurrence in those with perineural spread of tumor (p = 0.01)., Conclusions: Our findings support high rates of asymptomatic recurrence in sinonasal malignancy, with the majority of recurrences diagnosed by routine endoscopy or imaging. Tailored and extended surveillance guidelines are necessary relative to those utilized for other head and neck mucosal cancers, and are especially appropriate when features such as perineural spread are present., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Inverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase-11 (MMP-11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP-11 in IP epithelial migration and invasion., Methods: Human IP and contralateral normal sinus mucosa (control) samples were obtained. IP-derived epithelial cultures and normal mucosa-derived epithelial cultures were grown in air‒liquid interface, followed by immunostaining to assess MMP-11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti-MMP-11 antibody on IP and control epithelial cultures., Results: IP-derived cultures demonstrated strong MMP-11 expression compared to controls. Treatment with anti-MMP-11 blocking antibody significantly reduced epithelial migration only in IP-derived cells compared to non-treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP-11 reduced IP epithelia's ability to invade through collagen-coated transwells, suggesting that MMP-11 plays a role in invasion., Conclusion: We established an in vitro model to study IP-derived epithelial cells. MMP-11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP-11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP-11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP-11 has a role in malignant transformation of IP., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: The role of Akt in nasal immunity is unstudied. Akt phosphorylates and activates endothelial nitric oxide synthase (eNOS) expressed in epithelial ciliated cells. Nitric oxide (NO) production by ciliated cells can have antibacterial and antiviral effects. Increasing nasal NO may be a useful antipathogen strategy in chronic rhinosinusitis (CRS). We previously showed that small-molecule Akt activator SC79 induces nasal cell NO production and suppresses IL-8 via the transcription factor Nrf-2. We hypothesized that SC79 NO production may additionally have antibacterial effects., Methods: NO production was measured using fluorescent dye DAF-FM. We tested effects of SC79 during co-culture of Pseudomonas aeruginosa with primary nasal epithelial cells, using CFU counting and live-dead staining to quantify bacterial killing. Pharmacology determined the mechanism of SC79-induced NO production and tested dependence on Akt., Results: SC79 induced dose-dependent, Akt-dependent NO production in nasal epithelial cells. The NO production required eNOS and Akt. The NO released into the airway surface liquid killed P. aeruginosa. No toxicity (LDH release) or inflammatory effects (IL8 transcription) were observed over 24 h., Conclusions: Together, these data suggest multiple immune pathways are stimulated by SC79, with antipathogen effects. This in vitro pilot study suggests that a small-molecule Akt activator may have clinical utility in CRS or respiratory other infection settings, warranting future in vivo studies., (© 2024 ARS‐AAOA, LLC.)

Purpose: Sinonasal malignancies (SNMs) adversely impact patients' quality of life (QOL) and are frequently identified at an advanced stage. Because these tumors are rare, there are few studies that examine the specific QOL areas that are impacted. This knowledge would help improve the care of these patients., Methods: In this prospective, multi-institutional study, 273 patients with SNMs who underwent definitive treatment with curative intent were evaluated. We used the University of Washington Quality of Life (UWQOL) instrument over 5 years from diagnosis to identify demographic, treatment, and disease-related factors that influence each of the 12 UWQOL subdomains from baseline to 5 -years post-treatment., Results: Multivariate models found endoscopic resection predicted improved pain (vs. nonsurgical treatment CI 2.4, 19.4, p = 0.01) and appearance versus open (CI 27.0, 35.0, p < 0.001) or combined (CI 10.4, 17.1, p < 0.001). Pterygopalatine fossa involvement predicted worse swallow (CI -10.8, -2.4, p = 0.01) and pain (CI -17.0, -4.0, p < 0.001). Neck dissection predicted worse swallow (CI -14.8, -2.8, p < 0.001), taste (CI -31.7, -1.5, p = 0.02), and salivary symptoms (CI -28.4, -8.6, p < 0.001). Maxillary involvement predicted worse chewing (CI 9.8, 33.2; p < 0.001) and speech (CI -21.8, -5.4, p < 0.001) relative to other sites. Advanced T stage predicted worse anxiety (CI -13.0, -2.0, p = 0.03)., Conclusions: Surgical approach, management of cervical disease, tumor extent, and site of involvement impacted variable UWQOL symptom areas. Endoscopic resection predicted better pain, appearance, and chewing compared with open. These results may aid in counseling patients regarding potential QOL expectations in their SNM treatment and recovery course., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Key Points: We created a LangChain/OpenAI API-powered chatbot based solely on International Consensus Statement of Allergy and Rhinology: Rhinosinusitis (ICAR-RS). The ICAR-RS chatbot is able to provide direct and actionable recommendations. Utilization of consensus statements provides an opportunity for AI applications in healthcare., (© 2023 ARS‐AAOA, LLC.)

Background: The impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT-22) and University of Washington Quality of Life (UWQOL) are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling., Methods: Patients with previously untreated SNMs were prospectively enrolled (2015-2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT-22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL., Results: Among 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT-22 QOL in patients with skull base erosion (p = 0.02). SNOT-rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005)., Conclusions: Our findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex-specific and symptom-related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T-staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL., (© 2023 ARS‐AAOA, LLC.)

Background: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field., Methods: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication., Results: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention., Conclusion: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Objective: To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM)., Methods: This was a multi-institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan-Meier tests were used to evaluate disease-free survival (DFS), overall survival (OS), and post-recurrence survival (PRS) reported with standard errors (SE) and log-rank testing used for comparison. Cox-regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported., Results: Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60-month DFS (SE) was 15.5% (2.9%), 60-month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60-month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60-month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12-month PRS (HR = 0.32, 95% CI = 0.11-0.92, p = 0.034), and no treatment group was associated with improved 24- or 60-month PRS (p > 0.05)., Conclusion: SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12-month PRS., (© 2023 ARS-AAOA, LLC.)

Background: Postoperative nausea and vomiting (PONV) are adverse effects after surgery, which may increase the risk of complications. Aprepitant is a neurokinin-1 receptor blocker and has been shown to reduce chemotherapy-related nausea and vomiting and PONV. However, its role in endoscopic skull base surgery remains unclear. The purpose of this study was to evaluate the effect of aprepitant in reducing PONV in endoscopic transsphenoidal (TSA) pituitary surgery., Methods: A retrospective chart review between July 2021 and January 2023 of 127 consecutive patients who underwent TSA was performed at a tertiary academic institution. Patients were divided into 2 groups based on preoperative aprepitant use. Two groups were matched based on known risk factors of PONV (age, sex, nonsmoking, and history of PONV). The primary outcome was the incidence of PONV. Secondary outcome measures included the number of anti-emetic use, length of stay, and postoperative cererebrospinal fluid (CSF) leak., Results: After matching, 48 patients were included in each group. The aprepitant group demonstrated a significantly lower incidence of vomiting than the non-aprepitant group (2.1% vs 22.9%, p = 0.002). The number of nausea episodes and anti-emetic use decreased with aprepitant use (p < 0.05). There was no difference in the incidence of nausea, length of stay, or postoperative CSF leak. Multivariate analysis demonstrated that aprepitant decreased the incidence of postoperative vomiting with odds ratio of 0.107., Conclusion: Aprepitant may serve as a useful preoperative treatment to reduce PONV in patients undergoing TSA. Further studies are needed to evaluate its impact in other arenas of endoscopic skull base surgery., (© 2023 ARS-AAOA, LLC.)

Key Points: Patients are increasingly turning to online education materials to aid with disease management. Patient education materials on aspirin-exacerbated respiratory disease are of poor readability with significant room for improvement., (© 2023 ARS-AAOA, LLC.)

Background: Quality of life (QOL) for individuals with sinonasal malignancy (SNM) is significantly under-studied, yet it is critical for counseling and may impact treatment. In this study we evaluated how patient, treatment, and disease factors impact sinonasal-specific and generalized QOL using validated metrics in a large cohort over a 5-year posttreatment time frame., Methods: Patients with SNM who underwent definitive treatment with curative intent were enrolled in a prospective, multisite, longitudinal observational study. QOL was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22) and University of Washington Quality of Life Questionnaire (UWQOL) instruments at pretreatment baseline and multiple follow-ups through 5 years posttreatment. Multivariable modeling was used to determine demographic, disease, and treatment factors associated with disease-specific and generalized physical and social/emotional function QOL., Results: One hundred ninety-four patients with SNM were analyzed. All QOL indices were impaired at pretreatment baseline and improved after treatment. SNOT-22 scores improved 3 months and UWQOL scores improved 6 to 9 months posttreatment. Patients who underwent open compared with endoscopic tumor resection had worse generalized QOL (p < 0.001), adjusted for factors including T stage. Pterygopalatine fossa (PPF) involvement was associated with worse QOL (SNOT-22, p < 0.001; UWQOL Physical dimension, p = 0.02). Adjuvant radiation was associated with worse disease-specific QOL (p = 0.03). Neck dissection was associated with worse generalized physical function QOL (p = 0.01). Positive margins were associated with worse generalized social/emotional function QOL (p = 0.01)., Conclusion: Disease-specific and generalized QOL is impaired at baseline in patients with SNM and improves after treatment. Endoscopic resection is associated with better QOL. PPF involvement, adjuvant radiation, neck dissection, and positive margins were associated with worse QOL posttreatment., (© 2023 ARS-AAOA, LLC.)

Introduction: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The role of human papillomavirus (HPV) in its pathogenesis has been controversial. The purpose of this study was to determine the virome associated with IP, with progression to carcinoma in situ (CIS), and invasive carcinoma., Methods: To determine the HPV-specific types, a metagenomics assay that contains 62,886 probes targeting viral genomes in a microarray format was used. The platform screens DNA and RNA from fixed tissues from eight controls, 16 IP without dysplasia, five IP with CIS, and 13 IP-associated squamous cell carcinoma (IPSCC). Paired with next-generation sequencing, 48 types of HPV with 857 region-specific probes were interrogated against the tumors., Results: The prevalence of HPV-16 was 14%, 42%, 70%, and 73% in control tissue, IP without dysplasia, IP with CIS, and IPSCC, respectively. The prevalence of HPV-18 had a similar progressive increase in prevalence, with 14%, 27%, 67%, and 74%, respectively. The assay allowed region-specific analysis, which identified the only oncogenic HPV-18 E6 to be statistically significant when compared with control tissue. The prevalence of HPV-18 E6 was 0% in control tissue, 25% in IP without dysplasia, 60% in IP with CIS, and 77% in IPSCC., Conclusions: There are over 200 HPV types that infect human epithelial cells, of which only a few are known to be high-risk. Our study demonstrated a trend of increasing prevalence of HPV-18 E6 that correlated with histologic severity, which is novel and supports a potential role for HPV in the pathogenesis of IP., (© 2023 ARS-AAOA, LLC.)

Background: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs., Methods: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class., Results: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05)., Conclusion: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs., (© 2023 ARS-AAOA, LLC.)

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have emerged as an alternative to opioids for optimal postoperative pain management. However, the adoption of NSAIDs in sinonasal surgery has been impeded by a theoretical concern for postoperative bleeding. Our objective is to systematically review the efficacy and safety of NSAIDs for patients undergoing sinonasal surgery., Methods: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO International Clinical Trials Registry Platform were searched from inception to January 27, 2022. Randomized controlled trials (RCTs) and comparative observational studies in any language were considered. Screening, data extraction, and risk of bias assessment were performed in duplicate. Our outcomes were postoperative pain scores, requirement for rescue analgesia, and postoperative adverse events (epistaxis, nausea/vomiting)., Results: Out of 4661 records, 15 RCTs (enrolling 1210 patients) and two observational studies were included. Following endoscopic sinus surgery, there was no difference in pain scores between NSAIDs and non-NSAIDs groups (standardized mean differences [SMD] 0.44 units better, 95% CI -0.18 to 1.05). Following septorhinoplasty, NSAIDs decreased pain scores compared to non-NSAID regimens (SMD 1.14 units better, 95% CI 0.61 to 1.67 units better). Overall, NSAIDs reduced the need for rescue medication with a relative risk (RR) of 0.45 (95% CI 0.24 to 0.84). In addition, NSAIDs decreased the risk of nausea with an RR of 0.62 (95% CI 0.42 to 0.91) and did not increase the risk of epistaxis (RR 0.72, 95% CI 0.23-2.22)., Conclusion: Among patients undergoing sinonasal surgery, NSAIDs are beneficial in postoperative pain management and avoidance of postoperative nausea without increasing the risk of postoperative epistaxis., (© 2023 ARS-AAOA, LLC.)

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., (© 2022 ARS-AAOA, LLC.)

Background: Succinate, although most famous for its role in the Krebs cycle, can be released extracellularly as a signal of cellular distress, particularly in situations of metabolic stress and inflammation. Solitary chemosensory cells (SCCs) express SUCNR1, the succinate receptor, and modulate type 2 inflammatory responses in helminth and protozoal infections in the small intestine. SCCs are the dominant epithelial source of interleukin-25, as well as an important source of cysteinyl leukotrienes in the airway, and have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis (CRS) and asthma., Methods: In this study, we used scRNAseq analysis, live cell imaging of intracellular calcium from primary sinonasal air-liquid interface (ALI) cultures from 1 donor, and measure antimicrobial peptide release from 5 donors to demonstrate preliminary evidence suggesting that succinate can act as a stimulant of SCCs in the human sinonasal epithelium., Results: Results from scRNAseq analysis show that approximately 10% of the SCC/ionocyte cluster of cells expressed SUCNR1 as well as a small population of immune cells. Using live cell imaging of intracellular calcium, we also demonstrate that clusters of cells on primary sinonasal ALI cultures initiated calcium-mediated signaling in response to succinate stimulation. Furthermore, we present evidence that primary sinonasal ALI cultures treated with succinate had increased levels of apical beta-defensin 2, an antimicrobial peptide, compared to treatment with a control solution., Conclusion: Overall, these findings demonstrate the need for further investigation into the activation of the sinonasal epithelium by succinate in the pathogenesis of CRS., (© 2022 ARS-AAOA, LLC.)

Background: Postoperative management strategies for endoscopic skull base surgery (ESBS) vary widely because of limited evidence-based guidance., Methods: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from January 1990 through February 2022 to examine 18 postoperative considerations for ESBS. Nonhuman studies, articles written in a language other than English, and case reports were excluded. Studies were assessed for levels of evidence, and each topic's aggregate grade of evidence was evaluated., Results: A total of 74 studies reporting on 18 postoperative practices were reviewed. Postoperative pain management, prophylactic antibiotics, and lumbar drain use had the highest grades of evidence (B). The literature currently lacks high quality evidence for a majority of the reviewed ESBS precautions. There were no relevant studies to address postoperative urinary catheter use and medical intracranial pressure reduction., Conclusion: The evidence for postoperative ESBS precautions is heterogeneous, scarce, and generally of low quality. Although this review identified the best evidence available in the literature, it suggests the urgent need for more robust evidence. Therefore, additional high-quality studies are needed in order to devise optimal postoperative ESBS protocols., (© 2022 ARS-AAOA, LLC.)

Background: Craniopharyngiomas have traditionally been treated via open transcranial approaches. More recent, endoscopic endonasal approaches have been increasingly used; however, there has been limited evaluation of long-term outcomes for this approach., Methods: A retrospective review was performed to analyze patients with pediatric craniopharyngioma undergoing endonasal endoscopic resection from 2012 to 2020. Demographic information, clinicopathologic factors, and outcomes including follow-up and recurrences were analyzed., Results: All 42 patients, with a mean age of 8.0 years, were included. The median follow-up time was 49 months. Mean tumor diameter was 3.6 cm. All of the tumors had sellar and suprasellar components. The most common presenting symptoms were headaches (64.3%), visual changes (59.5%), and nausea/vomiting (38.1%). Most patients (73.3%) had resolution of their presenting symptoms by their first postoperative visit. Vision improved or remained normal in 69.0% of patients. Postoperatively, incidence of panhypopituitarism or diabetes insipidus developed in 89.7% and 77.8% of patients, respectively. The postoperative cerebrospinal fluid leak rate was 7.1%. The recurrence rate was 9.5%., Conclusion: Endoscopic endonasal resection for pediatric craniopharyngiomas can achieve high rates of resection with low rates of disease recurrence when compared with the outcomes of open transcranial resection reported in the literature. However, hypothalamic-pituitary dysfunction remains a significant postoperative morbidity in both approaches., (© 2022 ARS-AAOA, LLC.)

Background: Patients with aspirin-exacerbated respiratory disease (AERD) are among the most challenging rhinologic patients to treat. AERD has a complex inflammatory milieu of lipid mediators and cytokines. In this study we evaluated cytokine differences in the complex AERD environment at the mucus, epithelial, and tissue levels., Methods: Samples were acquired at the time of sinus surgery from 21 patients (seven steroid-treated, 14 untreated) with aspirin challenge-confirmed AERD. Three methods (sponge adsorption, epithelial brushing, tissue biopsy) were used to acquire samples from the respective sinus sampling sites (mucus, polyp epithelium, and full-thickness polyp) of each patient. We measured and compared 16 cytokine concentrations in AERD patients with or without prednisone treatment using the Luminex platform., Results: In most sampling sites, IL-5, IL-6, IL-10, IL-13, IL-33, CCL20, and TNF-α were detected at higher concentrations than IFN-γ, IL-1β, IL-17A, IL-4, IL-22, IL-17E/IL25, and GM-CSF. Each sampling site had a different pattern of cytokine levels, and except for IL-5 and IL-25 there was no correlation among sampling methods for each cytokine tested. The most notable and significant decreases in cytokines from those treated with prednisone were observed in the epithelium for IL-5, IL-10, IL-33, and IFN-γ., Conclusions: In the epithelial samples, type 2-associated cytokines IL-5 and IL-33, the anti-inflammatory cytokine IL-10, and IFN-γ were lower in AERD patients treated with prednisone. This work serves as a basis to assess therapeutic-induced mucosal cytokine responses in AERD and indicates that the site of cytokine measurement is an important consideration when assessing results., (© 2022 ARS-AAOA, LLC.)

Background: Distinguishing benign inverted papilloma (IP) tumors from those that have undergone malignant transformation to squamous cell carcinoma (IP-SCC) is important but challenging to do preoperatively. Magnetic resonance imaging (MRI) can help differentiate these 2 entities, but no established method exists that can automatically synthesize all potentially relevant MRI image features to distinguish IP and IP-SCC. We explored a deep learning approach, using 3-dimensional convolutional neural networks (CNNs), to address this challenge., Methods: Retrospective chart reviews were performed at 2 institutions to create a data set of preoperative MRIs with corresponding surgical pathology reports. The MRI data set included all available MRI sequences in the axial plane, which were used to train, validate, and test 3 CNN models. Saliency maps were generated to visualize areas of MRIs with greatest influence on predictions., Results: A total of 90 patients with IP (n = 64) or IP-SCC (n = 26) tumors were identified, with a total of 446 images of distinct MRI sequences for IP (n = 329) or IP-SCC (n = 117). The best CNN model, All-Net, demonstrated a sensitivity of 66.7%, specificity of 81.5%, overall accuracy of 77.9%, and receiver-operating characteristic area under the curve of 0.80 (95% confidence interval, 0.682-0.898) for test classification performance. The other 2 models, Small-All-Net and Elastic-All-Net, showed similar performance levels., Conclusion: A deep learning approach with 3-dimensional CNNs can distinguish IP and IP-SCC with moderate test classification performance. Although CNNs demonstrate promise to enhance the prediction of IP-SCC using MRIs, more data are needed before they can reach the predictive value already established by human MRI evaluation., (© 2022 ARS-AAOA, LLC.)

Background: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma., Methods: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors., Results: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation)., Conclusions: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification., (© 2021 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is a multifactorial disease with a high co-occurrence with asthma. In this multicohort study, we tested whether single nucleotide polymorphisms (SNPs) associated with childhood asthma and rhinovirus (RV)-associated disease are related to an increased susceptibility to adult CRS in a multicohort retrospective case-control study., Methods: Participants at two tertiary academic rhinology centers, University of Arizona (UofA) and University of Pennsylvania (UPenn) were recruited. Cases were defined as those with physician diagnosed CRS (UofA, n = 149; UPenn, n = 250), and healthy controls were those without CRS (UofA, n = 66; UPenn, n = 275). Genomic DNA was screened for the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP. Gene dosage, or the number of combined risk alleles in a single subject was calculated. Meta-analysis of the association between GSDMB or CDHR3 genotypes and CRS was performed and additive gene dosage effect for each population calculated using p for trend., Results: A meta-analysis revealed a combined increased risk for CRS in subjects with the GSDMB rs7216389 SNP (odds ratio [OR] 1.40; 95% confidence interval [CI], 1.16-1.76; p = 0.004). Both the UofA (OR 1.73; 95% CI, 1.23-2.43; p = 0.002) and UPenn (OR 1.27; 95% CI, 1.02-1.58; p = 0.035) populations showed a significant positive association between the number of combined risk alleles of GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP and risk for CRS., Conclusion: Carriers of the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP are at increased susceptibility for CRS. These data suggest that therapeutic approaches to target aberrant responses to RV infection may play a role in the treatment of unified airway disease., (© 2021 ARS-AAOA, LLC.)

Background: Management of sinonasal malignancy (SNM) often includes surgical resection as part of the multimodality treatment. Treatment-related surgical morbidity can occur, yet risk factors associated with complications in this population have not been sufficiently investigated., Methods: Adult patients with histologically confirmed SNM whose primary treatment included surgical resection were prospectively enrolled into an observational, multi-institutional cohort study from 2015 to 2020. Sociodemographic, disease, and treatment data were collected. Complications assessed included cerebrospinal fluid leak, orbital injury, intracranial injury, diplopia, meningitis, osteoradionecrosis, hospitalization for neutropenia, and subsequent chronic rhinosinusitis. The surgical approach was categorized as endoscopic resection (ER) or open/combined resection (O/CR). Associations between factors and complications were analyzed using Student's t test, Fisher's exact test, and logistic regression modeling., Results: Overall, 142 patients met the inclusion criteria. Twenty-three subjects had at least 1 complication (16.2%). On unadjusted analysis, adjuvant radiation therapy was associated with developing a complication (91.3% vs 65.5%, p = 0.013). Compared with the ER group (n = 98), the O/CR group (n = 44) had a greater percentage of higher T-stage lesions (p = 0.004) and more frequently received adjuvant radiation (84.1% vs 64.4%, p = 0.017) and chemotherapy (50.0% vs 30.6%, p = 0.038). Complication rates were similar between the ER and O/CR groups without controlling for other factors. Regression analysis that retained certain factors showed O/CR was associated with increased odds of experiencing a complication (odds ratio, 3.34; 95% confidence interval, 1.06-11.19)., Conclusions: Prospective, multicenter evaluation of SNM treatment outcomes is feasible. Undergoing O/CR was associated with increased odds of developing a complication after accounting for radiation therapy. Further studies are warranted to build upon these findings., (© 2021 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin-exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL-25) in upper airways, leading to type 2 inflammation, and are activated by bitter-tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls., Methods: CRSsNP (n = 25), CRSwNP (n = 26), and AERD (n = 27) patients as well as controls (n = 25) tasted 6 DB concentrations in a fixed, random order, rating on a category scale of 0 (no intensity) to 12 (extremely intense). Sinonasal epithelial cultures were treated with and without denatonium and analyzed for IL-25 via flow cytometry., Results: CRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 × 10 -9 M, 1.00 × 10 -8 M, 1.78 × 10 -8 M, 3.16 × 10 -8 M, 5.62 × 10 -8 M, and 1.00 × 10 -7 M (all p < 0.0083). CRSwNP patients did not show significant differences from controls. AERD patients rated DB as significantly more intense than did controls at concentrations of 1.00 × 10 -8 M and 3.16 × 10 -8 M (p < 0.0083). In vitro data demonstrated significant increase in IL-25-positive cells after denatonium stimulation (n = 5), compared to control (n = 5) (p = 0.012)., Conclusion: Our findings link in vitro DB stimulation of sinonasal tissue with increased IL-25 and show differential DB taste perception in CRS subgroups relative to the control group, with CRSsNP being hyposensitive and AERD being hypersensitive. We propose a concentration of 3.16 × 10 -8 M for future study of clinical utility., (© 2020 ARS-AAOA, LLC.)

Background: Solitary chemosensory cells (SCCs) in the murine nasal epithelium are discrete specialized cells that respond to irritants and activate trigeminal nerve fibers through the release of acetylcholine (ACh), resulting in local neurogenic inflammation. In addition to releasing ACh, SCCs are the exclusive epithelial source of interleukin (IL)-25. In humans, SCCs are significantly expanded in sinonasal polyps (NPs). However, the SCC-trigeminal synapse has yet to be demonstrated in human sinonasal epithelium., Methods: Immunofluorescence for trigeminal nerve fiber markers, nicotinic ACh receptors (nChR), and SCC markers was performed in vibratome sections from polyp and healthy turbinate tissue. Quantitative polymerase chain reaction and immunofluorescence of cultured epithelial cells were used to evaluate the expansion of SCCs. Last, intracellular calcium imaging was used to demonstrate cholinergic signaling in sinonasal epithelial cells., Results: Calcitonin gene-related peptide (CGRP) immunostaining was used to identify cholinergic nerve endings, which were only evident in sections from the inferior turbinate and intertwined with SCCs (α-gustducin-positive cells). CGRP-positive nerve endings were not identified in sections from NPs. Human SCCs expressed nChR as well as the ACh synthetic enzyme choline acetyltransferase. Live cell calcium imaging demonstrated functionally active cholinergic signaling in discrete sinonasal epithelial cells, consistent with SCCs. Finally, SCC-specific genes were dramatically upregulated with pretreatment with IL-13 and nicotinic agonists., Conclusion: SCCs are innervated by trigeminal nerve endings in healthy turbinate tissue but not in NPs. SCCs express ACh receptors as well as choline acetyltransferase and, in the setting of a type 2 inflammatory environment, denervated SCCs dramatically expand with nicotinic stimulation., (© 2020 ARS-AAOA, LLC.)

Background: Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses., Methods: We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (n = 426) and without (n = 226) nasal polyps and controls (n = 356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand for TAS2R38), sucrose, and salt., Results: CRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (false discovery rate [FDR] <0.05) and CRS patients and controls did not differ in their ratings of salt (FDR >0.05). PTC bitter taste intensity differed between patient and control groups but were less marked than those previously reported. Though differences were statistically significant, overall effect sizes were small., Conclusion: CRS patients report bitter stimuli as less intense but sweet stimuli as more intense than do control subjects. We speculate that taste responses may reflect the competence of sinonasal innate immunity mediated by taste receptor function, and thus a taste test may have potential for clinical utility in CRS patients., (© 2020 ARS-AAOA, LLC.)

I., Executive Summary: BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document., Methods: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary., Results: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided., Conclusion: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS., (© 2021 ARS-AAOA, LLC.)

Background: Treatment of aspirin-exacerbated respiratory disease (AERD) includes endoscopic sinus surgery (ESS) and aspirin desensitization (AD) with aspirin therapy after desensitization (ATAD). The objective of this study was to determine the rate of major complications associated with aspirin use that resulted in the discontinuation of aspirin therapy., Methods: This study was a retrospective chart review of patients with AERD who underwent ESS, AD, and ATAD at a single AERD tertiary center between July 2016 and February 2019. Complications associated with aspirin that resulted in the discontinuation of aspirin therapy were analyzed via analysis of variance and logistic regression., Results: In total, 109 AERD patients underwent ESS with subsequent AD. Ten patients (9.2%) discontinued therapy after AD, before starting ATAD. Eight patients (7.3%) discontinued therapy after starting ATAD. There were 91 patients (83.5%) with no complications throughout ATAD. Reasons for discontinuation included gastritis, upper gastrointestinal (GI) bleed, anaphylaxis, persistent sinonasal symptoms, recurrent epistaxis, asthma exacerbation, and a nummular rash. There was no significant correlation between complication rate and (1) aspirin doses (analysis of variance [ANOVA] F: 0.69; p = 0.51), (2) gender (odds ratio [OR] 0.56; 95% confidence interval [CI], 0.19 to 1.65; p = 0.30), (3) age (OR 1.04; 95% CI, 0.96 to 1.09; p = 0.06), or (4) race/ethnicity (OR 1.12; 95% CI, 0.88 to 1.44; p = 0.36)., Conclusion: AD with ATAD was associated with only a 0.92% incidence of a clinically significant GI bleed, and only a 0.92% incidence of anaphylaxis. A remaining 16 patients (14.7%) discontinued aspirin therapy due to minor clinical sequelae. These findings demonstrate that the majority of AERD patients tolerate AD with ATAD without any major complications., (© 2020 ARS-AAOA, LLC.)

Background: Aspirin-exacerbated respiratory disease (AERD) is an aggressive respiratory tract inflammatory disorder manifesting as asthma, chronic rhinosinusitis with nasal polyposis, and a respiratory sensitivity to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Corticosteroids, both systemic and topical/inhaled, are used to treat inflammation of the upper and lower airways. Our objective was to examine the potential impact of complete endoscopic sinus surgery (ESS) and aspirin desensitization (AD) on short-term and long-term corticosteroid use., Methods: For this pilot study, a retrospective chart review of all patients with AERD who underwent ESS followed by AD was performed. Daily prednisone use, average daily prednisone dose, and inhaled corticosteroid use were analyzed at the following time points: preoperative, postoperative/pre-AD, and 2 to 3 months, 4 to 6 months, 7 to 12 months, and 13 to 24 months following AD., Results: A total of 125 patients underwent ESS followed by AD. Compared to preoperatively, patients who underwent ESS and AD were less likely to be on daily prednisone at all time points and upon long-term follow-up (32% preoperatively vs 10% at 13 to 24 months, McNemar's test = 9.00, p = 0.009). Average daily prednisone dose decreased from 10.6 ± 7.9 mg preoperatively to 3.8 ± 2.6 mg at 13 to 24 months following AD (Mann-Whitney U; W = 122, p = 0.01). Similarly, high-dose and medium-dose inhaled corticosteroid use decreased from 18% to 7% and from 36% to 22% respectively (Pearson's chi-square = 8.06, p = 0.05)., Conclusion: In our AERD cohort who underwent ESS followed by AD, there was an observed decrease in overall systemic and topical/inhaled corticosteroid use. These findings can have implications for treatment given the potentially hazardous side effects of corticosteroid use., (© 2020 ARS-AAOA, LLC.)

Background: Patients undergoing endoscopic resection of neoplasms with both sinonasal and skull base involvement can develop chronic rhinosinusitis (CRS) after treatment and may occasionally benefit from additional endoscopic sinus surgery (ESS). We investigate risk factors and outcomes associated with revision ESS (rESS) after endoscopic skull-base surgery (SBS) for neoplasms with combined sinonasal and skull base involvement., Methods: A retrospective review of patients with neoplasms with both sinonasal and skull base involvement who underwent endoscopic resection at a single tertiary care academic institution from 2004 through 2017 was performed. Eighty-three patients were included. Main outcome measures included incidence and timing of revision surgery, Lund-Mackay (LM) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores., Results: rESS was performed in 21 (25%) cases, 15 (18%) of which were due to CRS. Time between initial resection and rESS was an average of 42 months (range, 6 to 142 months). Pre-SBS and post-SBS LM scores were not significantly different (5.0 vs 4.7, p = 0.640), although pre-SBS and post-SBS SNOT-22 scores showed significant improvement (32.6 vs 24.5, p = 0.030). Malignant pathology correlated with need for rESS (odds ratio [OR] 5.07, p = 0.04), as well as treatment including chemotherapy (OR 5.10, p = 0.003) and radiation (OR 4.15, p = 0.013)., Conclusion: A significant proportion of patients develop clinically significant sinusitis after endoscopic SBS for neoplasms with combined sinonasal and skull base involvement and may benefit from rESS. Intervention occurred, on average, 3.5 years after initial tumor resection. Malignant pathology, radiation therapy, and chemotherapy correlate with need for rESS., (© 2020 ARS-AAOA, LLC.)

Background: The pathogenesis of inverted papilloma (IP) has not been fully elucidated. However, chronic paranasal sinus inflammation has been anecdotally observed in sites distant from tumor obstruction in IP patients, suggesting an association between inflammation and IP tumorigenesis. This study assesses the association between sinonasal inflammation found in IP and compares this to the level of inflammation observed in other sinonasal tumors., Methods: A retrospective chart review was performed identifying patients with unilateral IP. Pertinent clinical data was obtained and comparative analysis of preoperative computed tomography (CT) imaging and histopathology was performed. A sample of unilateral, sinonasal, non-IP and non-squamous cell tumors was used as the control. The Lund-Mackay scoring system was used to assess radiologic sinonasal inflammation both ipsilateral and contralateral to the tumor., Results: Seventy-one patients were included; 58.9% of patients with IP had evidence of contralateral sinusitis at the time of presentation. In the control group, 26.7% had evidence of contralateral inflammation. When comparing contralateral sinus inflammation between the 2 study groups, the IP patients had significantly higher Lund-Mackay scores than the control group (1.9 vs 0.26, p < 0.001). When comparing ipsilateral sinus inflammation, no significant difference was found in Lund-Mackay scores (5.44 vs 4.00, p < 0.184)., Conclusion: In this study, unilateral IPs were associated with a higher level of contralateral sinonasal inflammation when compared to control. This suggests that IP may be associated with inflammation that is independent of obstruction by the tumor. Further studies are needed to better understand the temporal relationship between chronic inflammation and tumorigenesis., (© 2020 ARS-AAOA, LLC.)

Background: Ketotifen is a second-generation noncompetitive H1-antihistamine and mast-cell stabilizer. It is commonly used to treat or prevent allergic conjunctivitis, asthma, chronic urticaria, anaphylaxis, mast-cell, and other allergic-type disorders. However, it has never been studied in aspirin-exacerbated respiratory disease (AERD), an aggressive phenotype of chronic rhinosinusitis with nasal polyps, where the mast cell plays a prominent role its pathogenesis., Methods: Human sinonasal epithelial cells were grown at an air-liquid interface (ALI). Ketotifen powder was dissolved in saline to make 4 test solutions at 1.04, 2.08, 10.4, and 20.8 µg/mL. Control (saline) or ketotifen solution was added apically to ALI cultures from tissue of 5 unique patients, and ciliary beat frequency (CBF) changes were recorded. Lactate dehydrogenase was measured at 24 and 48 hours to estimate long-term cellular toxicity., Results: Apical application of ketotifen at all concentrations was neither ciliotoxic nor ciliostimulatory, with no change in CBF over a period of 15 minutes after application. Cellular toxicity for all concentrations at 24 and 48 hours after application was <3% and <7%, respectively, that of lysed cultures., Conclusion: Topical application of ketotifen to an in vitro model of sinonasal epithelium is safe, as evaluated by CBF and lactate dehydrogenase. Ketotifen is neither ciliotoxic nor ciliostimulatory, and no long-term cellular toxicity was observed. Ketotifen may have promise as a topical nasal rinse in the treatment of AERD., (© 2019 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to tumor necrosis factor alpha inhibitors (TNFαis). The histologic features of CRS caused by TNFαis have yet to be determined and may have important implications in understanding the pathophysiology of the disease process., Methods: A structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). These structured histopathology variables were compared among patients with CRS on TNFαi (CRSαi), CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients., Results: Eighteen CRSαi, 91 CRSwNP, and 113 CRSsNP patients undergoing FESS were analyzed. Compared to CRSsNP, CRSαi patients exhibited increased mucosal ulceration (16.7% vs 0.9%, p < 0.008), increased fibrosis (100% vs 34.5%, p < 0.001), and increased presence of Charcot-Leiden crystals (16.7% vs 0%, p < 0.002). Compared to CRSwNP, CRSαi patients demonstrated increased fibrosis (100% vs 54.9%, p < 0.001), decreased presence of subepithelial edema (44.4% vs 69.2% p < 0.043), decreased eosinophil aggregates (22.2% vs 47.3% p < 0.042), and fewer eosinophils per high-power field (44.4% vs 73.6%, p < 0.017)., Conclusion: CRSαi exhibits structured histopathology more similar to CRSsNP. In the appropriate clinical context, it may be reasonable that the medical regimen for these patients be focused on a more antineutrophilic, macrolide-based approach. This study provides insight into the inflammatory environment of patients with CRSαi and may have implications for disease management., (© 2019 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is a common condition that affects people of all ages and negatively impacts quality of life. The goal of this study was to identify differences in outcomes by age following endoscopic sinus surgery (ESS) for CRS utilizing 22-item Sino-Nasal Outcome Test (SNOT-22) scores., Methods: Data from 1252 adult CRS patients electing to undergo ESS (2007-2018) were collected retrospectively. The median age of 50 years was used to divide the data into 2 groups for comparison of the impact of age on SNOT-22 scores at 0, 3, and 6 months after surgery. Changes in SNOT-22 scores were analyzed using a mixed models analysis., Results: After adjusting for gender, race, polyp status, and number of prior ESSs, patients younger than 50 years had a higher mean pre-ESS SNOT-22 score (44.0) compared to those of at least 50 years of age (38.9). Among patients younger than 50 years, SNOT-22 scores declined by 20.7 points at 3 months post-ESS and 16.1 points at 6 months post-ESS. The rate of change between the dichotomized age groups was not significantly different at 3 and 6 months post-ESS (p = 0.7952 and p = 0.1057, respectively)., Conclusion: Both age groups showed significant and durable improvement in SNOT-22 scores after ESS. Patients younger than 50 years of age have higher pre-ESS SNOT-22 scores, but converge to the same SNOT-22 scores by 3 months post-ESS. The rate of change of SNOT-22 scores is not different between those younger than 50 years and those of at least 50 years., (© 2019 ARS-AAOA, LLC.)

Background: Primary sinonasal mucoepidermoid carcinoma (SN-MEC) is a malignancy arising from seromucinous glands of the nasal cavity and paranasal sinuses. Given its rarity, few large-scale studies have been performed. In this study we describe the incidence and determinants of survival of patients with SN-MEC leveraging the National Cancer Database (NCDB)., Methods: This was a retrospective, population-based cohort study of patients diagnosed with SN-MEC between 2004 and 2012 within the NCDB. The main outcome measure was overall survival (OS)., Results: A total of 164 patients were identified. The cohort was composed of 47.6% males. Mean age at diagnosis was 59.7 years. The maxillary sinus was the most common primary site, accounting for 45.7% of cases. Eleven percent of patients presented with nodal disease, whereas 2.1% had distant metastases. Stage IV disease was seen in 30.4% of cases. A total of 79.8% of the patients underwent surgery, 61.0% received radiation therapy, and 15.1% had chemotherapy. OS at 1, 2, and 5 years was 83%, 77.0%, and 57%, respectively. On multivariate analysis, Medicaid insurance status (hazard ratio [HR], 7.29; 95% confidence interval [CI], 1.74-30.57), advanced tumor size (HR, 4.94; 95% CI, 1.19-20.5), and advanced nodal disease (N1: HR, 9.48; 95% CI, 1.66-54.23; N2B: HR, 19.3; 95% CI, 1.07-350.64) were associated with worse OS., Conclusion: Mucoepidermoid carcinoma is the most common salivary gland malignancy but a rare sinonasal malignancy, with 5-year survival for SN-MEC approximating 50%. A significant proportion of patients present with advanced disease. Both socioeconomic factors and tumor characteristics are associated with survival., (© 2019 ARS-AAOA, LLC.)

Background: Inverted papilloma (IP) is a benign sinonasal tumor with a well-known propensity to recur, especially at its bony attachment site. Anecdotal evidence suggests lower rate of recurrence in primary resection. We also aimed to evaluate the effect of multifocal vs single focus of attachment in disease control., Methods: This work is a retrospective review of 535 IP resections performed during the period from 2006 to 2016 at a tertiary-care center. Demographic data, tumor location and attachment sites, and follow-up duration data were obtained., Results: Two hundred ten patients were eligible for analysis. The mean age was 57 years, with an average postoperative surveillance of 36.4 months. Patients who had a previous procedure at an outside institution have a recurrence rate of 22.3%, compared with 12.4% for patients who had primary surgery at our institution. The most common site of attachment was maxillary sinus (47.6%), followed by ethmoid sinus (39%). Individual tumor review showed 50% of the patients to have multifocal attachment disease, of which there is a higher prevalence in secondary cases when compared with primary cases (53.7% vs 44.9%). Multiple tumor attachment sites had a significant effect on recurrence (odds ratio, 3.5; 95% confidence interval, 1.6-7.6; p = 0.002)., Conclusion: Primary resection and single-focus attachment of inverted papilloma are associated with lower recurrence rates at 3-year follow-up., (© 2019 ARS-AAOA, LLC.)