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Objectives Although adjuvant radiotherapy may be indicated in patients with sinonasal squamous cell carcinoma (SNSCC) following primary surgery, some patients choose to forgo recommended postoperative radiation therapy (PORT). This study aimed to elucidate factors associated with patient refusal of recommended PORT in SNSCC and examine overall survival. Methods Retrospective analysis of patients with SNSCC treated with primary surgery from the National Cancer Database diagnosed between 2004 and 2016. A multivariable logistic regression model was created to determine the association between clinical or demographic covariates and likelihood of PORT refusal. Unadjusted Kaplan–Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival. Results A total of 2,231 patients were included in the final analysis, of which 1,456 (65.3%) were males and 73 (3.3%) refused recommended PORT. Patients older than 74 years old were more likely to refuse PORT than those younger than 54 (odds ratio [OR] 3.43, 95% confidence interval [CI]: 1.84–6.62). Median survival among the entire cohort, those who received recommended PORT, and those who refused PORT was 83.0 months (95% CI: 74.6–97.1), 83.0 months (95% CI: 74.9–98.2), and 63.6 months (95% CI: 37.3–101.4), respectively. Refusal of PORT was not associated with overall survival (hazard ratio: 0.99, 95% CI: 0.69–1.42). Conclusions PORT refusal in patients with SNSCC is rare and was found to be associated with several patient factors. The decision to forgo PORT is not independently associated with overall survival in this cohort. Further study is required to determine the clinical implications of these findings as the treatment decisions are complex.

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.

ObjectiveFor recalcitrant chronic maxillary sinusitis, modified endoscopic medial maxillectomy has been shown to be clinically beneficial after failed maxillary antrostomy as endoscopic medial maxillectomy may offer improved topical therapy delivery. This study compared irrigation patterns after maxillary antrostomy versus endoscopic medial maxillectomy, using computational fluid dynamic modelling.Case reportA 54-year-old female with left chronic maxillary sinusitis underwent maxillary antrostomy, followed by endoscopic medial maxillectomy. Computational fluid dynamic models were created after each surgery and used to simulate irrigations.ResultsAfter maxillary antrostomy, irrigation penetrated the maxillary sinus at 0.5 seconds, initially contacting the posterior wall. The maxillary sinus was half-filled at 2 seconds, and completely filled at 4 seconds. After endoscopic medial maxillectomy, irrigation penetrated the maxillary sinus at 0.5 seconds and immediately contacted all maxillary sinus walls. The maxillary sinus was completely filled by 2 seconds.ConclusionComputational fluid dynamic modelling demonstrated that endoscopic medial maxillectomy allowed faster, more forceful irrigation to all maxillary sinus walls compared with maxillary antrostomy.

Background: Aspirin therapy and/or type 2 (T2) biologics are used in the management of aspirin-exacerbated respiratory disease (AERD). Objective: To identify the number of patients with AERD who tolerated aspirin therapy, yet due to persistent symptoms, incorporated T2 biologic management. Methods: A retrospective review was performed between July 2016 and June 2019. Patients with AERD and who underwent endoscopic sinus surgery (ESS), aspirin desensitization (AD), and at least 6 months of aspirin therapy (ATAD) after AD, and who remained biologic-naive up through this timepoint were included in the study. Introduction of a T2 biologic while on ATAD was the primary outcome. The secondary outcome was a change in a validated patient-reported outcome measure for chronic rhinosinusitis score between the postoperative predesensitization timepoint, and the 6-month postdesensitization timepoint, presented as means and compared by using the Student's t-test. Results: A total of 103 patients met inclusion criteria. Two patients (1.9%) ultimately supplemented ATAD with a T2 biologic. The mean outcomes measure test score after 6 months of ATAD for patients who received biologics was 40.5 versus 15 in those who did not receive biologics (p = 0.02). The mean differences between the postoperative predesensitization test score and the 6-month postdesensitization test score for patients who went on to receive biologics was an increase of 13 versus a decrease of 10 for those patients who did not receive biologics (p = 0.12). Conclusion: ESS, coupled with AD and ATAD, was successful in the long-term management of the majority of the patients with AERD, which rarely required the incorporation of T2 biologics. Patient questionnaires, such as outcomes measure test score, may identify aspirin therapy failures and help guide the practitioner in deciding when to introduce T2 biologics into the patient's treatment regimen.

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.

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.

Background Aspirin-exacerbated respiratory disease (AERD) is an aggressive inflammatory disorder of the upper and lower respiratory tract. Corticosteroids, leukotriene modifiers, endoscopic sinus surgery (ESS), aspirin (ASA) desensitization, and biological immunomodulators are currently used to treat the disorder. Objective The objective of this study was to determine the psychosocial impact of ESS and ASA desensitization on AERD patients. Methods All AERD patients who underwent complete ESS were divided into two cohorts based on ASA desensitization status. The psychosocial metrics of the SNOT-22 were collected and analyzed at the following time points: pre-operative, 1-month, 3-month, 6-month, and 12-month after ESS. Results One hundred and eighty-four AERD patients underwent ESS from November 2009 to November 2018. From this group, 130 patients underwent ASA desensitization (AD cohort) and 54 patients remained non-desensitized (ND cohort). AD patients showed a significantly greater reduction in total SNOT-22 scores over the study period compared to ND patients (p = 0.0446). Analysis of SNOT-22 psychosocial metrics showed a significantly greater improvement in patient productivity in the AD cohort when compared to the ND cohort (p = 0.0214). Further, a sub-group analysis accounting for subject attrition showed a significantly greater improvement in both productivity and concentration in AD patients when compared to the ND cohort (productivity: p = 0.0068; concentration: p = 0.0428). Conclusions ESS followed by ASA desensitization decreases the overall psychosocial burden in AERD patients with a significant improvement in perceived productivity and concentration. This has significant implications given the psychosocial impact of chronic diseases.

OBJECTIVE To characterize the patient and clinical factors that determine variability in hospital costs following endoscopic transphenoidal pituitary surgery. METHODS All endoscopic transphenoidal pituitary surgeries performed from January 1, 2015, to October 24, 2017, with complete data were evaluated in this retrospective single-institution study. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables during each hospital stay. Multivariate linear regression was performed using Stata software. RESULTS The analysis included 190 patients and average length of stay was 4.71 days. Average total in-hospital cost was $28,624 (95% confidence interval $25,094-$32,155) with average total direct cost of $19,444 ($17,136-$21,752) and total indirect cost of $9181 ($7592-$10,409). On multivariate regression, post-operative cerebrospinal fluid (CSF) leak was associated with a significant increase in all cost variables, including a total cost increase of $40,981 ($15,474-$66,489, P = .002). Current smoking status was associated with an increased total cost of $20,189 ($6,638-$33,740, P = .004). Self-reported Caucasian ethnicity was associated with a significant decrease in total cost of $6646 (-$12,760 to -$532, P = .033). Post-operative DI was associated with increased costs across all variables that were not statistically significant. CONCLUSIONS Post-operative CSF leak, current smoking status, and non-Caucasian ethnicity were associated with significantly increased costs. Understanding of cost drivers of endoscopic transphenoidal pituitary surgery is critical for future cost control and value creation initiatives. LEVEL OF EVIDENCE 3 Laryngoscope, 131:760-764, 2021.

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.

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.

Inverted papilloma (IP) is the most common benign neoplasm of the nasal cavity with known risk of recurrence. There is no standardized approach to definitive treatment for attachment sites. This systematic review aims to determine whether surgeon choice of technique differs by anatomic attachment site and whether different surgical techniques contribute to reduced rates of recurrence.PubMed and Ovid Medline.A systematic review was conducted for studies reporting on IP. Those that included IP recurrence rates and primary tumor attachment site were reviewed.Of 122 published studies, 14 met eligibility criteria, representing 585 patients and a recurrence rate of 5.8%. The maxillary sinus (50.9%) was the most common primary attachment site, and the sphenoid sinus was associated with the highest rate of recurrence (10.4%). The most utilized technique included debulking the tumor, removing mucosa over the attachment site, and drilling the underlying bone. The most common Krouse stage represented was T3 (53.3%). No single technique predicted a propensity for recurrence, but certain techniques are favored depending on IP attachment site. Finally, frozen sections to obtain evidence of clear margins intraoperatively significantly reduced rates of recurrence (3.4% vs 7.3%,Based on the current literature, the most common technique to address site of attachment involves resecting mucosa and drilling the tumor base. Choice of technique appears to differ for various sites of attachment. Use of intraoperative frozen section analysis appears to be associated with decreased recurrence overall.3.

A 27-year-old female referred to tertiary rhinology practice 2 weeks after surgery for presumed inflammatory disease. Pathology revealed poorly differentiated squamous cell carcinoma and patient presents for definitive treatment. Her nasal endoscopy revealed significant sinonasal edema and no clear tumor pedicle was identified. She had no other pertinent past medical or surgical history. Of note, she denied any visual disturbances or history of facial trauma. Coronal images of her preoperative CT and post-contrast MRI can be seen in Fig. 2.1. The patient was counseled on the significance of the pathology and decided to proceed with definitive surgery to appropriately map the tumor and for possible complete extirpation. She was properly informed of the risks of endoscopic sinus surgery, including the risks of CSF leak, orbital injury with temporary or permanent vision loss, nasal bleeding, epiphora, loss of smell, and the potential for additional future procedures.

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.

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.

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.

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.

OBJECTIVES Rathke cleft cysts (RCCs) are rare, benign lesions formed from remnants of Rathke pouch during embryologic development. However, following marsupialization, maintaining tract patency remains a challenge. Several techniques for decreasing stenosis have been described, including free mucosal grafting, silastic spacing, and using steroid-eluting stents. Nasoseptal flaps (NSFs) have a reliable vascular supply and are widely utilized in skull base reconstruction. We present a novel technique to maintain patency of the marsupialized RCC cavity by lining it with an NSF to promote long-term drainage and re-epithelialization of the RCC cavity. METHODS Retrospective chart review of all patients who underwent surgery for symptomatic RCCs. These patients underwent endoscopic endonasal surgery between February 3, 2016, and June 12, 2018, with marsupialization followed by circumferential NSF lining. Primary outcomes include symptomatic control, surgical complications, and RCC cavity patency. RESULTS Seven patients underwent RCC marsupialization with no intraoperative cerebrospinal fluid leak, followed by circumferential lining of the marsupialized cavity with an NSF. In each case, no cyst re-accumulation or recurrent symptoms were noted, and the NSF lining provided long-term patency of the tract in all cases to a mean of 6.7 ± 10.1 months of follow-up, including one patient with sustained patency at 29 months follow-up. CONCLUSION Utilization of the NSF to "stent open" the RCC cavity following marsupialization is a safe and effective means to prevent restenosis. Advantages include sustained patency of RCC cavity for complete drainage and a dependable vascular supply. LEVEL OF EVIDENCE 4 Laryngoscope, 129:2258-2261, 2019.

Objectives Pituitary carcinoma is a rare entity with fewer than 200 total cases reported in the English literature. Analysis of the population-level data from the National Cancer Database (NCDB) affords the opportunity to study this poorly understood tumor type. Methods The NCDB was queried for site, histology, and metastasis codes corresponding to pituitary carcinoma. Statistical analyses were performed to determine factors associated with overall survival (OS). Results A total of 92 patients with pituitary carcinoma met inclusion criteria. The 1 and 5 years of OS for all patients was 93.3% (95% confidence interval [CI]: 88.2–98.6%) and 80.0% (95% CI: 71.6–89.4%), respectively. Patients with invasive primary tumor behavior had 1 and 5 years of OS of 69.2% (95% CI: 48.2–99.5%) and 52.7% (95% CI: 31.2–89.2%), respectively. Multivariate analysis demonstrated that compared with benign primary behavior, invasive behavior had increased all-cause mortality (hazard ratio [HR], 1,296, 95% CI: 15.1– > 2,000). Surgery without adjuvant radiation or chemotherapy was the most common therapy (48.9%), followed by no treatment (40.2%). Compared with surgery alone, no treatment had worse OS (HR, 11.83, 95% CI: 1.41–99.56). Increasing age and female sex were both associated with increased mortality. Conclusions The most common treatment for pituitary carcinoma is surgery alone followed by no surgery. Surgery alone has significantly better OS compared with no treatment. The efficacy of radiation, chemotherapy, and neurohormonal treatments needs to be examined with prospective studies.

Objective Chronic rhinosinusitis (CRS) is a proposed risk factor for meningitis and other intracranial complications following the endoscopic endonasal transsphenoidal approach (TSA). Some have recommended staging TSA following surgery for CRS; however, delaying TSA has important ramifications. The objective of this study is to determine whether asymptomatic sinonasal inflammation (RSNI) on preoperative computed tomography scans, without clinical CRS, is associated with postoperative complications following TSA. Methods All consecutive TSA cases performed at a single tertiary care institution from January 1, 2009, to December 31, 2017, were reviewed for patient demographics, prior surgery, presence of RSNI on preoperative computed tomography scan based on Lund-Mackay (LM) score, intraoperative cerebrospinal fluid (CSF) leak, and postoperative complications (postoperative CSF leak, bleeding, infection). The association between preoperative RSNI and postoperative complications was analyzed via multivariate logistic regression. Results One hundred seventy-one cases of TSA were included with mean patient age of 52.6 years, 42.7% males, 18.1% revision cases, and mean LM score of 1.9 ± 2.7. Complications were identified in 9.9% of patients at the following rates: 5.3% postoperative CSF leak, 2.9% bleeding, and 1.8% infection (all sinusitis, no episodes of meningitis). Neither total LM score nor LM score > 5 (representative of clinically significant radiographic CRS) were predictors of any postoperative complication (both P > 0.05). Age, sex, revision status, intraoperative CSF leak, and total LM score were not independent predictors of any postoperative complication on multivariate analysis (all P > 0.05). Conclusion In asymptomatic patients, radiographic evidence of sinonasal inflammation is not associated with increased risk of complications following TSA. Level of evidence 4 Laryngoscope, 129:1545-1548, 2019.

With increasing adoption of endoscopic techniques and improved knowledge of skull base anatomy and approaches, transsphenoidal pituitary surgery is now being performed on patients of all ages. Surgical principles are similar between pediatric and adult patients, but there are special considerations for the pediatric population in terms of instrumentation, surgical anatomy, and postoperative care. Wide exposure to the sella, oftentimes to accommodate multiple instruments and the endoscope, is frequently necessary. Persistent collaboration among the otolaryngology, neurosurgery, and anesthesiology teams is of critical importance to ensure optimal outcomes.

Background Orbital cavernous hemangiomas (OCH) are the most common adult orbital tumor and represent an ideal index lesion for endonasal orbital tumor surgery. In order to standardize outcomes reporting, an anatomic-based staging system was developed. Methods An international, multidisciplinary panel of 23 experts in orbital tumor surgery was formed. A modified Delphi method was used to develop the cavernous hemangioma exclusively endonasal resection (CHEER) staging system with a total of 2 rounds being completed. Results Tumors medial to a plane along the long axis of the optic nerve may be considered amenable for an exclusively endonasal resection. In select cases, tumors may extend inferolaterally if the tumor remains below a plane from the contralateral naris through the long axis of the optic nerve (ie, plane of resectability [POR]). This definition reached consensus with 91.3% of panelists in agreement. Five stages were designed based on increasing technical resection difficulty and potential for morbidity. Stages were based on the relationship of the tumor to the extraocular muscles, the inferomedial muscular trunk of the ophthalmic artery (IMT), and orbital foramina. Staging by anatomic location also reached consensus with 87.0% of panelists in agreement. Size was not included in the staging system due to the lack of agreement on the contribution of size to resection difficulty. Conclusion Endoscopic orbital tumor surgery is a nascent field with a growing, yet heterogeneous, body of literature. The CHEER staging system is designed to facilitate international, high-quality, standardized studies establishing the safety, efficacy, and outcomes of endonasal resection of OCH.

Purpose of review To review the recent literature regarding the growing role of rhinologists and otolaryngologists with neurosurgeons in the joint multidisciplinary team approach for managing patients with Rathke's cleft cysts (RCC). Recent findings The transnasal endoscopic approach to the skull base has become relatively mainstream for surgical treatment of RCCs. Suprasellar lesions, especially those that are purely suprasellar, are associated with higher recurrence rates, though an extended approach may improve dissection and access and therefore aid in lesion removal. Endoscopic cyst drainage is a well tolerated and effective way to treat RCC, and often avoids the postoperative endocrinopathies associated with complete cyst wall removal. Novel techniques have been described for maintaining tract patency, including the use of stents and flaps, in order to prevent cyst stenosis and reaccumulation. A frontier in skull base surgery is in applications for pediatric patients, and managing RCCs in this population surgically appears to be associated with positive outcomes overall. Summary Team-based endoscopic skull base surgery has spurred advances in our understanding of skull base disease, including RCCs. Optimal outcomes are most apparent when the experience and technique of both the endoscopist and neurosurgeon have developed jointly over time.

Purpose of review Lesions of the petrous apex of the temporal bone can be challenging to access and approaches laterally through the mastoid as well as medially through an endonasal approach are utilized to access this region while preserving function of adjacent structures. Cholesterol granulomas of the petrous apex requiring surgery are marsupialized to prevent expansion of the inflamed cyst and relieve associated clinical symptoms. The endonasal approach to the petrous apex has in the past been limited to lesions medial to the internal carotid artery. Recent findings Endoscopic approaches have been developed to expand the range of petrous apex lesions that are accessible endonasally. These endonasal corridors include a nasopharyngeal/transclival corridor, lateralization of the internal carotid artery to create an expanded medial window, a pterygopalatine infrapetrosal approach, and a contralateral maxillary approach, which allow improved access to the inferior and lateral petrous apex. Nasoseptal flaps may reduce the risk of postoperative stenosis of the drainage tract. Summary Endoscopic endonasal approaches can be used safely to address both medial and lateral/inferior petrous apex lesions. Morbidity of these procedures is low and use of a nasoseptal flap may limit restenosis of the drainage pathway.

BACKGROUND: Broncho-Vaxom® (OM-85 BV) is an extract of infectious respiratory bacteria that is used as an immunostimulant outside of the United States for the prevention and treatment of bronchitis and rhinosinusitis. Prior studies have demonstrated that use of OM-85 BV is associated with reduction in frequency of respiratory infection and decreased duration of antibiotic usage. However, the effects of OM-85 BV on respiratory mucosal innate immunity are unknown. METHODS: Human sinonasal epithelial cells were grown at an air-liquid interface (ALI). Ciliary beat frequency (CBF) and nitric oxide (NO) production in response to stimulation with OM-85 BV was measured in vitro. Pharmacologic inhibitors of bitter taste receptor (T2R) signaling were used to determine if this pathway was taste-receptor mediated. RESULTS: Apical application of OM-85 BV resulted in an NO-mediated increase in CBF (p

OBJECTIVES/HYPOTHESIS Currently, due to the rarity of pathology, there are limited data surrounding outcomes of pediatric skull base surgery. Traditionally, surgeons have proceeded with caution when electing endonasal endoscopic transsellar/transplanum approaches to the skull base in pediatric patients due to poor sphenoid pneumatization. In this study, we review outcomes of endoscopic pediatric skull base surgery based on sphenoid pneumatization patterns. STUDY DESIGN Retrospective chart review. METHODS A review of all cases of pediatric (age

OBJECTIVES/HYPOTHESIS Inverted papillomas (IPs) are benign tumors of the sinonasal tract with a malignant transformation potential. Predicting the transformation propensity of IPs and corresponding risk factors has long been a challenge. In this study, we aimed to use radiographic findings on magnetic resonance imaging (MRI) and computed tomography (CT) to help differentiate IP from IP-transformed squamous cell carcinomas (IP-SCC). STUDY DESIGN Retrospective cohort study. METHODS A retrospective analysis was performed at two institutions comparing IP (n = 76) and IP-SCC (n = 66) tumors, evaluating preoperative radiographic imaging with corresponding surgical pathology reports. The presence of a convoluted cerebriform pattern (CCP) using postcontrast T1-weighted and T2-weighted MRI was evaluated. Using MRI diffusion-weighted imaging (DWI), we calculated the apparent diffusion coefficient (ADC) value of each tumor. We also determined the tumor origin, attachment sites, and presence of bony erosion using CT imaging. RESULTS Benign IPs had a higher prevalence of CCP on MRI compared to IP-transformed SCC (P = .0001. The mean value ADC of malignant IP-SCC (ADCb0,1000 = 1.12 × 10-3 mm2 /s) was significantly lower than that of benign IPs (ADCb0,1000 = 1.49 × 10-3 mm2 /s, P = .002). IP-SCC tumors were more likely to be have orbital wall attachment (P = .002) and bony erosion (P

To survey patients following sinonasal surgery regarding postoperative pain and opioid use.Patients were surveyed for 4 days following sinus and/or nasal surgery regarding their pain level and use of prescribed opioids.Four academic medical centers and 1 private practice institution.Consecutive adult patients undergoing sinonasal surgery.A total of 219 subjects met criteria and were included for analysis; 134 patients (61%) took 5 or fewer combination oxycodone (5-mg) and acetaminophen (325-mg) tablets in the first 3 postoperative days, and 196 patients (89.5%) took fewer than 15. Fifty-one patients (23%) consumed no opioid pain medication. Opioid consumption was positively correlated with postoperative pain ( RAn evidence-based approach to postoperative pain control following sinonasal surgery that reduces the number of unused and potentially diverted opioids is needed. The current study suggests that 15 combination oxycodone (5-mg) and acetaminophen (325-mg) tablets provide sufficient pain control for 90% of patients in the immediate postoperative period following sinonasal surgery, irrespective of the specific procedures performed, use of acetaminophen, or use of systemic steroids. Smoking status may help surgeons predict which patients will require larger opioid prescriptions.

Background Aspirin-exacerbated respiratory disease (AERD) is optimally managed by endoscopic sinus surgery (ESS) followed by aspirin therapy after desensitization (ATAD). Most AERD quality of life (QOL) studies use the 22-item Sinonasal Outcomes Test (SNOT-22), which focuses predominantly on sinonasal outcomes. Objective This study seeks to assess QOL outcomes in AERD patients after ESS and ATAD via the 12-item Short Form Survey (SF-12), a well-validated QOL measure for general health status of chronic conditions. Methods Retrospective review of 112 AERD patients who underwent ESS followed by ATAD at our institution between 2016 and 2019. SF-12 was collected preoperatively, postoperatively/pre-AD, and serially post-AD (1–3, 4–6, 7–12, and >12 months). Optum® PRO CoRE software was used to compare data to national norms. ANOVA was performed comparing physical component summary (PCS), mental component summary (MCS) and eight health domains (physical functioning, role physical, general health, bodily pain, vitality, social functioning, role emotional, and mental health). Results AERD patients showed improvement in PCS scores across all timepoints after ESS and ATAD (p = 0.004). When stratified by gender, women demonstrated an improvement in PCS scores (p = 0.004). Within the domains, there were significant improvements in social functioning (SF), role physical (RP), and bodily pain (BP) at all timepoints (SF: p = 0.006; RP: p = 0.005; BP: p Conclusions AERD patients undergoing ESS and ATAD show improvement in physical QOL and 3 of the 8 health domains as measured by the SF-12. Future studies can use the SF-12 to study the impact of AERD treatment versus other chronic diseases and health demographics.

Objective Chondrosarcomas of the skull base are rare tumors most commonly treated surgically with or without adjuvant radiation therapy. Using the National Cancer Database (NCDB), we analyzed overall survival (OS), treatment modalities, and prognosticators. Methods The NCDB was queried for all cases of histologically confirmed skull base chondrosarcoma treated between 2004 and 2015, excluding patients with more than one malignant tumor, on palliative care, receiving unrelated concurrent treatments, or having less than 1 month of follow-up. Chi-square test for categorical variables, Cox proportional hazards models, and Kaplan-Meier log-rank analysis were used to test associations with use of adjuvant radiation, OS, and survival time. Results A total of 498 patients with skull base chondrosarcoma were identified in the NCDB. 224 (45.0%) and 198 (39.8%) were treated with either surgery alone or surgery with adjuvant radiation therapy, respectively. Patients more likely to undergo surgery with adjuvant radiation had higher tumor grade (p = 0.008), later year of diagnosis (p = 0.002), positive surgical margins (p Conclusion The mainstay of treatment for skull base chondrosarcoma is surgery, with consideration of adjuvant radiation. This study demonstrated worse overall survival associated with more frail patients and aggressive histology types. It is important to consider these factors when planning the clinical management of these patients.

In recent years, improvements in endoscopic technology and techniques have pushed the frontiers of orbital surgery. Specifically, the transnasal corridor has now been established as an extremely reliable and direct route to the orbit, permitting the orbital surgeon to access this area without the need for external incisions. The first step to every surgical corridor, however, is gaining mastery of the surgical anatomy. In this chapter, the various anatomic structures of the nasal cavity, including the nasal septum and turbinates, and paranasal sinuses are reviewed. Additionally, surgical nuances, pearls, and pitfalls related to dissection of these structures

Purpose of review The purpose of this study was to give an overview of recently published articles investigating the cause of inverted papilloma and possible mechanisms mediating malignant transformation into squamous cell carcinoma (SCCa). Recent findings Inverted papilloma is a sinonasal tumour that is benign in nature, but has a tendency for local invasion, recurrence and malignant degeneration. Its pathogenesis has not been elucidated and the etiological role for human papillomavirus virus (HPV) has been controversial. Recent reports have varied in detection method (mRNA ISH, DNA ISH and PCR amplification of highly conserved regions of the viral genome), ranging from 0 to 100%. Advances in meta-genomics have permitted detection of HPV viral signatures that were previously cost-prohibitive, and there appears to be a potential role for both low-risk and high-risk in the cause of the disease. Activating EGFR mutations have also been identified to be correlated with malignant transformation, which may be exclusive of HPV infection. Furthermore, more comprehensive approaches in detecting genomic markers have been reported, with HOX-related genes and epithelial-mesenchymal-transition-related gene sets appear to be differentially upregulated. Summary Sinonasal inverted papilloma is a diverse disease that is predominantly benign, but it harbours the potential for malignant degeneration in the SCCa with cause yet to be elucidated. Current evidence supports a potential role for high-risk HPV in a subset of SCCa, with the role of low-risk HPV yet to be defined. Historic studies of individual and small groups of molecular markers have not consistently adequate characterize signalling pathways underpinning the oncogenesis, and comprehensive genomic studies are needed to better understand the disease.

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 one of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes one 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 (FDR0.05). 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.

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.

Introduction The COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) virus has altered the health care environment for the management of head and neck cancers. The purpose of these guidelines is to provide direction during the pandemic for rational Head and Neck Cancer management in order to achieve a medically and ethically appropriate balance of risks and benefits. Methods Creation of consensus document. Results The process yielded a consensus statement among a wide range of practitioners involved in the management of patients with head and neck cancer in a multihospital tertiary care health system. Conclusions These guidelines support an ethical approach for the management of head and neck cancers during the COVID‐19 epidemic consistent with both the local standard of care as well as the head and neck oncological literature.

BackgroundTrefoil factor family cytokines (TFF1-3) have documented reparative and immunoregulatory effects on mucosal epithelial cells that include: blocking apoptosis, directed cell migration, and regulation of pro-inflammatory cytokine production. TFF1 and TFF3 have been shown to undergo altered expression within sinonasal tissues of patients with various forms of chronic rhinosinusitis including those with or wthout polyp associated disease, but the cellular source(s) of TFF members in CRS remains unclear. To further explore the role of TFF3 in inflammatory sinonasal disease, we sought to determine its expression pattern in immune and non-immune cell types in CRS disease.MethodsPolyp and inferior turbinate tissues were isolated from patients undergoing surgical resection for treatment of CRS. Tissue homogenates and single cell suspensions were subjected to enzyme linked immunosorbent assay (ELISA) and single-cell RNA sequencing. Air liquid interface cultures of sinonasal epithelia were subjected to immunofluorescence (IF) microscopy. Interleukin 25, TFF2 and TFF3 protein levels were compared to sinonasal outcome test scores (SNOT-22) to determine whether levels associated with post-operative outcomes.ResultsTFF3 was broadly expressed in goblet cells, ciliated cells, Tuft cells and T lymphocytes. TFF3 protein levels positively associated with IL-25 in CRSwNP patients. Lastly, TFF3 protein levels positively associated with clinical improvement post-surgery.ConclusionsTFF3 is broadly expressed within multiple epithelial and immune cell lineages in patients with CRSwNP. Protein levels of TFF3 correlate with IL-25 and clinical signs of disease, however TFF3 levels associate with clinical improvement following surgical intervention indicating a potential beneficial role for this reparative cytokine in CRS patients.

BACKGROUND: Topical sinus irrigations (neti-pot, squeeze bottles) play a critical role in the management of sinonasal disease. However, due to the intricate nasal anatomy, the penetration of topical irrigations to targeted sinus regions may be highly variable, and difficult to objectively predict. Variables, including head positions, injection angles, flow rates, etc. may vary significantly depending on individual’s anatomy. OBJECTIVE: The purpose of this study was to propose a novel idea: using 3D printed model of sinonasal cavities to visualize and develop patient-specific personalized irrigation strategy. METHODS: As a proof of concept, 3D replicas of one patient’s sinonasal cavities pre- and post-surgery were printed with a Form2 SLA 3D printer based on their CT scans. The setup included rubber/silicon seals attached to the model’s nostrils to create a water-tight seal with the irrigation device and food color dye added for better visualization of irrigation results. RESULTS: Irrigations were performed on the 3D models with various head positions, injection angles, and flow rates, and were successful to determine the optimal strategy to targeted sinuses. Significant differences were observed between different targeted sinuses and between pre and post-surgery models. CONCLUSION: With more affordable 3D printing, this technology may potentially improve patient care and patient education, allowing clinicians and patients to develop personalized irrigation strategy and have visual confirmation.

Background Endoscopic sinus surgery is often performed to improve delivery of topical medication into sinus cavities. Intranasal steroids are guideline recommended in post-surgical patients, and experiments with cadavers suggest that surgery improves delivery of drug into sinuses. Exhalation delivery systems (EDS) use a new mechanism for intranasal delivery and have been shown to reach superior/posterior regions of the nasal cavity better than nasal sprays in unoperated patients. Methods Silicone casts of the nasal cavity and sinuses from a patient after Draf II, and then Draf III, were made from high-resolution computed tomography (CT) data using 3D printing. Internal surfaces were coated with liquid-sensitive, color-changing gel. Color changes were evaluated following conventional nasal spray delivery (0.1 mL x 2) (Nasonex), EDS delivery (0.1 mL x 2) (XHANCE), and high-volume, low-flow (HVLF) delivery (80 mL) with head tilted either 45° or 90°. Results Conventional nasal spray deposited liquid only in anterior nasal segments. EDS deposited liquid throughout the nasal cavity, in surgically opened ethmoid and maxillary spaces, at entrances of the frontal sinuses in Draf II geometry, and into frontal sinuses in Draf III. Tilted 45° HVLF delivery enters the maxillary sinuses but not the frontal sinuses or the ethmoid region. At full 90° inclination, HVLF delivery reaches most of the frontal and maxillary sinuses but not the roof and posterior wall of the ethmoid region. Conclusions HVLF and EDS produced a deep intranasal/intrasinal deposition in the silicone cast compared with conventional nasal spray delivery; both deposited liquid inside the surgically opened sinuses. HVLF offers the benefit of lavage, whereas EDS may be more efficient and convenient.

Modern endonasal surgery that is widely being performed in the world today has been developed and transformed for more than 100 years. Numerous physiologists, anatomists, and surgeons such as Grunwald, Hilding, Killian, van Alyea, Hayek, Ingal, Moscher, and Onodi have paved the way for this development. In the first period of endonasal approach, complication rates were high related to limited view and lack of comprehensive anatomical knowledge. Nasal polyposis (NP) constitutes the subgroup of one-fifth of patients with chronic rhinosinusitis accompanying a more intense mucosal inflammation and more frequent relapse. Surgical and medical treatments or almost both treatments have a part in the treatment of NP. Nevertheless, the content, timing, and duration of treatment are contradictive. NP may be considered as a consequence of common phenotype generated in the nasal mucosa of many diseases or pathological processes, and the medical approach is basically paramount for treatment. Surgical treatment is used for patients who have resistance to maximal medical treatment and who are not able to use systemic steroid and for those with massive nasal polyposis with advanced nasal congestion. This treatment indicates a spectrum extending from simple polypectomy to radical “nasalization.” The most widespread surgical approach is “functional endoscopic sinus surgery” (FESS). There is no completely curative surgical method and the relapse rate is high. The main goals of FESS are to clean polyps and the polypoid mucosa, to increase ventilation by opening the sinus ostia, heal mucociliary clearance, and provide paranasal physiologic restoration. Furthermore, FESS states an approach rather than operation that can be standardized and it is quite difficult to do a randomized controlled study that is able to evaluate the results for NP treatment due to several reasons. In the surgical treatment of NP, FESS has supplanted conventional methods or techniques at the present time.

Background Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic eosinophilic rhinosinusitis, nasal polyps, asthma, and respiratory sensitivity to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). In addition to sensitivity to aspirin and NSAIDs, the majority of patients with AERD have been reported to have respiratory intolerance associated with the consumption of alcohol. Methods A multicenter prospective cohort study was performed. Patients with AERD confirmed by aspirin challenge were eligible to participate. Those who described themselves as able to tolerate alcohol consumption were excluded. Patients underwent aspirin desensitization following endoscopic sinus surgery. A questionnaire was distributed to patients before and after desensitization to determine pre-desensitization and post-desensitization symptoms associated with alcohol ingestion. Results Forty-five patients were enrolled and 37 patients completed the study. The most common pre-desensitization symptoms were nasal congestion (95.6%), rhinorrhea (46.7%), and wheezing (40%). Improvement in the ability to tolerate alcohol was noted in 86.5% of participants (95% confidence interval [CI], 75.5% to 97.5%) and 70.3% of participants (95% CI, 55.5% to 85.0%) described desensitization to be "very helpful" or "extremely helpful" for their ability to tolerate alcohol. Conclusion The majority of patients with AERD who experience respiratory symptoms with alcohol consumption describe improvement in this domain following aspirin desensitization.

Sinonasal inverted papilloma (IP) is a typically benign sinonasal tumor with a tendency to recur and the potential for malignant transformation. Varying degrees of dysplasia may be present, of which carcinoma in situ (CIS) is most advanced. We hereby describe the biological and clinical behavior of IP with CIS (IPwCIS).Retrospective cohort.Tertiary academic referral center.Patients who underwent surgical resection for IP between 2002 and 2017. Pertinent clinical data were obtained, and all IPwCIS cases were histologically confirmed.In total, 37 of 215 cases (17.2%) were identified with IPwCIS. Mean age was 57 years and 86.5% of patients were male. Median follow-up was 82 months, and the recurrence rate was 27%. The maxillary sinus was the most common primary site (37.8%) and 14 tumors (37.8%) demonstrated multifocal attachment, which was associated with recurrence (odds ratio [OR], 9.7; 95% confidence interval [CI], 1.4-112.8;IPwCIS represents the most severe degree of dysplasia prior to malignant transformation and is associated with higher recurrence rate and multifocal involvement but low rate of conversion to invasive carcinoma. The need for adjuvant therapy remains controversial, and further research into the etiology of the disease is warranted.

BACKGROUND Inadequate efficacy of current intranasal steroids in chronic rhinosinusitis (CRS) is attributable to ineffective and/or inconsistent drug delivery to target anatomic sites. A new exhalation delivery system with fluticasone (EDS-FLU) may improve outcomes by significantly increasing superior/posterior corticosteroid delivery. A study was conducted to assess the long-term efficacy and safety outcomes of EDS-FLU in individuals with CRS. METHODS This was a 12-month, multicenter, single-arm study evaluating the safety and efficacy of EDS-FLU 372 μg twice daily in CRS patients (with [n = 34] or without [n = 189] nasal polyps [NP]). Efficacy assessments by serial nasal endoscopy and patient report included: 22-item Sino-Nasal Outcome Test (SNOT-22), NP grade, standardized surgical indicator assessment, Lund-Kennedy score, and Patient Global Impression of Change. Adverse event (AE) evaluations included nasal endoscopy. Additional safety and efficacy outcomes were assessed. RESULTS Of 223 patients who received EDS-FLU, 96% reported prior corticosteroid use and 29% prior sinus surgery. The EDS-FLU AE profile was similar to conventional intranasal steroids studied in similar populations. Most patients (87%) reported symptom improvement. Through 12 months, mean SNOT-22 scores improved by -21.5 and -21.1 for CRS with and without NP, respectively. Among patients with NP, 54.2% had polyp elimination in at least 1 nostril and 83.3% had ≥1-point improvement in polyp grade. CONCLUSION Over 1 year of treatment in CRS with and without NP, EDS-FLU 372 μg twice daily was well tolerated and produced improvements across a broad range of objective and subjective measures. EDS-FLU may be a desirable new option for patients with this condition.

BACKGROUND: Surgical resection is the primary treatment for nonfunctional (NF) pituitary adenomas, but gross-total resection is difficult to achieve in all cases. NF adenomas overexpress folate receptor alpha (FRα). OBJECTIVE: To test the hypothesis that we could target FRα for highly sensitive and specific intraoperative detection of NF adenomas using near-infrared (NIR) imaging. METHODS: Fourteen patients with NF pituitary adenoma were infused with the folate analog NIR dye OTL38 preoperatively. NIR fluorescence signal-to-background ratio (SBR) was recorded for each tumor during resection of the adenomas. Extent of surgery was not modified based on the presence or absence of fluorescence. Immunohistochemistry was performed to assess FRα expression in all specimens. Magnetic resonance imaging (MRI) was performed postoperatively to assess residual neoplasm. RESULTS: Nine adenomas overexpressed FRα and fluoresced with a NIR SBR of 3.2 ± 0.52, whereas the 5 non-FRα-overexpressing adenomas fluoresced with an SBR of 1.5 ± 0.21. Linear regression demonstrated a significant correlation between intraoperative SBR and the FRα expression (P-value

Background Disagreement exists about the relationship between Lund-Mackay CT scores (LMCTS) and quality-of-life outcome (QoL) measures. We investigated whether preoperative LMCTS are associated with preoperative QoL, and whether LMCTS is predictive of postoperative QoL outcomes in chronic rhinosinusitis (CRS) patients. Methods Adult patients with medically recalcitrant CRS (n = 665) were enrolled in a prospective, observational cohort study. Preoperative LMCTS and pre- and postoperative self-reported QoL outcomes (22-item Sino-Nasal Outcomes Test [SNOT-22]) were collected and evaluated over 12 months. Five hundred sixty-eight patients met the inclusion criteria. Longitudinal linear mixed-effects modeling was used to investigate the effect of LMCTS on QoL after functional endoscopic sinus surgery (FESS). Results Preoperative LMCTS were significantly associated with preoperative SNOT-22 scores (p Conclusion Our study demonstrates that preoperative LMCTS correlate with preoperative extranasal and rhinologic symptom severity and that the LMCTS is an indicator of postsurgical QoL outcomes for medically recalcitrant chronic rhinosinusitis patients in a large tertiary otolaryngology setting.