Chronic Rhinosinusitis Risk after Maxillectomy with Microvascular Reconstruction.

INTRODUCTION: Chronic rhinosinusitis (CRS) can be associated with tumors involving the maxillary sinus, but outcomes after undergoing maxillectomy with free flap reconstruction remain unclear. METHODS: A retrospective analysis of medical records was performed to evaluate evidence of CRS in patients who underwent maxillectomy with free flap reconstruction at a single tertiary care academic institution from 2013 through 2020. RESULTS: Eighty-four patients were assessed. Nineteen (22.6%) patients were diagnosed with CRS after surgery, 23 (27.4%) patients were treated for sinus symptoms, and 49 (58.3%) had radiographic evidence of sinus inflammation for more than 6 months. Risk factors for requiring sinus treatment included adjuvant or neoadjuvant chemotherapy (p = 0.002) and pre-operative use of sinus medication (p < 0.001). Radiographic evidence of sinusitis 6 months after surgery is also closely associated with sinusitis treatment (p = 0.051). CONCLUSIONS: CRS may be underdiagnosed in patients undergoing maxillectomy with microvascular reconstruction. Further evaluation into patient sinus disease and symptoms following neoplastic surgery may lead to a higher quality of life in some long-term survivors.

Matrix metalloproteinase-11 regulates inverted papilloma epithelial cell migration and invasion.

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.

Effects of Akt Activator SC79 on Human M0 Macrophage Phagocytosis and Cytokine Production.

Akt is an important kinase in metabolism. Akt also phosphorylates and activates endothelial and neuronal nitric oxide (NO) synthases (eNOS and nNOS, respectively) expressed in M0 (unpolarized) macrophages. We showed that e/nNOS NO production downstream of bitter taste receptors enhances macrophage phagocytosis. In airway epithelial cells, we also showed that the activation of Akt by a small molecule (SC79) enhances NO production and increases levels of nuclear Nrf2, which reduces IL-8 transcription during concomitant stimulation with Toll-like receptor (TLR) 5 agonist flagellin. We hypothesized that SC79's production of NO in macrophages might likewise enhance phagocytosis and reduce the transcription of some pro-inflammatory cytokines. Using live cell imaging of fluorescent biosensors and indicator dyes, we found that SC79 induces Akt activation, NO production, and downstream cGMP production in primary human M0 macrophages. This was accompanied by a reduction in IL-6, IL-8, and IL-12 production during concomitant stimulation with bacterial lipopolysaccharide, an agonist of pattern recognition receptors including TLR4. Pharmacological inhibitors suggested that this effect was dependent on Akt and Nrf2. Together, these data suggest that several macrophage immune pathways are regulated by SC79 via Akt. A small-molecule Akt activator may be useful in some infection settings, warranting future in vivo studies.

University of Washington Quality of Life subdomain outcomes after treatment of sinonasal malignancy: A prospective, multicenter study.

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.

Personalized Approach to Olfactory Neuroblastoma Care.

Olfactory neuroblastoma (ONB) is an uncommon neuroendocrine malignancy arising from the olfactory neuroepithelium. ONB frequently presents with nonspecific sinonasal complaints, including nasal obstruction and epistaxis, and diagnosis can be obtained through a combination of physical examination, nasal endoscopy, and computed tomography and magnetic resonance imaging. Endoscopic resection with negative margins, with or without craniotomy, as necessary, is the standard of care for definitive treatment of ONB. Regional metastasis to the neck is often detected at presentation or may occur in a delayed fashion and should be addressed through elective neck dissection or radiation. Adjuvant radiotherapy should be considered, particularly in the case of high grade or tumor stage, as well as positive surgical margins. Systemic therapy is an area of active investigation in both the neoadjuvant and adjuvant setting, with many advocating in favor of induction chemotherapy for significant orbital or intracranial involvement prior to surgical resection. Various targeted immunotherapies are currently being studied for the treatment of recurrent or metastatic ONB. Prolonged locoregional and distant surveillance are indicated following definitive treatment, given the tendency for delayed recurrence and metastasis.

Combined Transnasal, Transoral Excision of Odontogenic Cysts Offers Reduced Recurrence Rates and Favorable Sinonasal Outcomes.

Odontogenic cysts impact the adjacent dentition and maxillary sinus. A combined transnasal, transoral approach for removal offers reduced recurrence rates and favorable sinonasal outcomes compared with historic transoral-only approaches.

Endoscopic Repair of Anterior Skull Base Cerebrospinal Fluid Leaks is Successful in Frail Patients.

OBJECTIVE: Surgical frailty estimates a patient's ability to withstand the physiologic stress of an intervention. There is limited data regarding the impact of frailty on endoscopic cerebrospinal fluid (CSF) leak repair. METHODS: Patients undergoing CSF leak repair at two tertiary academic skull base programs were retrospectively reviewed. Demographic, treatment, and postoperative outcomes data were recorded. Frailty was calculated using validated indices, including the American Society of Anesthesiologists (ASA) classification, Charlson Comorbidity Index (CCI), and the Modified 5-Item Frailty Index (mFI-5). Outcomes included 30-day medical and surgical complications and readmission. RESULTS: A total of 185 patients were included with 128 (69.2%) female patients and average age of 54 ± 14 years. The average body mass index was 34.6 ± 8.5. The most common identified etiology was idiopathic intracranial hypertension (IIH) in 64 patients (34.6%). A total of 125 patients (68%) underwent perioperative lumbar drain placement (primarily to measure intracranial pressures and diagnose IIH). Most patients were ASA class 3 (48.6%) with mean CCI 2.14 ± 2.23 and mFI-5 0.97 ± 0.90. Three patients had postoperative CSF leaks, with an overall repair success rate of 98.4%. There was no association between increased frailty and 30-day medical outcomes, surgical outcomes, or readmission (all p > 0.05). CONCLUSIONS: Endoscopic CSF leak repair in a frail population, including lumbar drain placement and bed rest, was not associated with an increased rate of complications. Previous data suggests increased complications in open craniotomy procedures in patients with significant comorbidities. This study suggests that the endoscopic approach to CSF leak repair is well tolerated in the frail population. LEVEL OF EVIDENCE: IV Laryngoscope, 134:2713-2717, 2024.

SNOT-22 subdomain outcomes following treatment for sinonasal malignancy: A prospective, multicenter study.

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.

Akt activator SC79 stimulates antibacterial nitric oxide generation in human nasal epithelial cells in vitro.

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.

Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2).

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration-approved for the most common form, CRS without nasal polyps (also called "chronic sinusitis"). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays. OBJECTIVE: Assess EDS-FLU efficacy for CRS (irrespective of nasal polyps). METHODS: Two randomized, EDS-placebo-controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24. RESULTS: ReOpen1 (N = 332) composite symptom score least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -1.58 and -1.60 versus -0.62 (P < .001, P < .001); ReOpen2 (N = 223), -1.54 and -1.74 versus -0.81 (P = .011, P = .001). In ReOpen1, sinus opacification least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -5.58 and -6.20 versus -1.60 (P = .045, P = .018), and in ReOpen2, -7.00 and -5.14 versus +1.19 (P < .001, P = .009). Acute disease exacerbations were reduced by 56% to 66% with EDS-FLU versus EDS-placebo (P = .001). There were significant, and similar magnitude, symptom reductions in patients using standard-delivery nasal steroid products just before entering the study (P < .001). Adverse events were similar to standard-delivery intranasal steroids. CONCLUSIONS: EDS-FLU is the first nonsurgical treatment demonstrated to reduce symptoms, intrasinus opacification, and exacerbations in replicate randomized clinical trials in CRS, regardless of polyp status.

Utilizing Histopathology to Predict Success with Macrolide Therapy in CRS Patients.

There is currently interest regarding CRSsNP patients with refractory symptomatology following functional endoscopic sinus surgery, and which of these patients can derive benefit from low-dose macrolide therapy. In the present study, we analyze a cohort of over fifty CRSsNP patients on macrolide therapy; structured histopathological findings at the time of surgery were analyzed against the success of macrolide treatment. Independently, fibrosis, absence of squamous metaplasia, absence of eosinophilia, presence of neutrophilic infiltrate, and lymphoplasmocytic predominance were all associated with objective success of macrolide treatment; these findings may allow clinicians to more appropriately select patients for this therapy.

Multi-institutional Analysis of Endoscopic Sellar Surgical Volumes During the COVID-19 Pandemic.

OBJECTIVE: We sought to quantify trends in operative volumes and complications of endoscopic sellar surgery before and after the COVID-19 pandemic onset. STUDY DESIGN: We performed a retrospective analysis. SETTING: TriNetX database analysis. METHODS: All adults undergoing neuroendoscopy for resection of pituitary tumor (Current Procedural Terminology code 62165) with diagnosis of benign/malignant neoplasm of pituitary gland (D35.2/C75.1) or benign/malignant neoplasm of craniopharyngeal duct (D35.3/C75.2) were included using the TriNetX database for 2 years before (pre-COVID group) and 2 years after (post-COVID group) February 17, 2020. RESULTS: A total of 1238 patients in the pre-COVID group and 1186 patients in the post-COVID group were compared. Age, gender, and race were statistically similar between the groups (P > .05). Surgical volume decreased by 6% in the post-COVID group. In 2020 Q2, operative volume decreased by 19%, and in 2021 Q4 (peak COVID-19 caseload in the United States), operative volumes decreased by 29% compared to 2 years prior. Postoperative complications including meningitis (P = .49), cerebrospinal fluid leak (P = .36), visual field deficits (P = .07), postoperative pneumonia or respiratory failure (P = .42), and 30-day readmission rates (P = .89) were similar between the 2 groups. CONCLUSION: Overall, endoscopic sellar surgery may continue to fluctuate with increased COVID-19 outbreaks. Patient outcomes do not appear to be worsened by decreased operative volumes or delays in nonurgent surgeries.

Predictive factors for decreased baseline quality of life in patients with sinonasal malignancies.

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.

Impact of Frailty on Postoperative Outcomes in Extended Endonasal Skull Base Surgery for Suprasellar Pathologies.

OBJECTIVE: Frailty metrics estimate a patient's ability to tolerate physiologic stress and there are limited frailty data in patients undergoing expanded endonasal approaches (EEA) for suprasellar pathologies. Elevated frailty metrics have been associated with increased perioperative complications in patients undergoing craniotomies. We sought to examine this potential relationship in EEA. STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary academic skull base centers. METHODS: Cases of patients undergoing EEA for suprasellar pathologies were reviewed. Demographic, treatment, survival, and postoperative outcomes data were recorded. Frailty was calculated using validated indexes, including the American Society of Anesthesiologists (ASA) classification, the modified 5-item frailty index (mFI-5), and the Charlson comorbidity index (CCI). Primary outcomes included 30-day medical and surgical complications. RESULTS: A total of 88 patients were included, with 59 (67%) female patients and a mean age of 54 ± 15 years. The most common pathologies included 53 meningiomas (60.2%) and 21 craniopharyngiomas (23.9%). Most patients were ASA class 3 (54.5%) with mean mFI-5 0.82 ± 1.01 and CCI 4.18 ± 2.42. There was no association between increased frailty and 30-day medical or surgical outcomes (including postoperative cerebrospinal fluid leak), prolonged length of hospital stay, or mortality (all P > .05). Higher mFI-5 was associated with an increased risk for 30-day readmission (odds ratio: 2.35, 95% confidence Interval: 1.10-5.64, P = .04). CONCLUSION: Despite the patient population being notably frail, we only identified an increased risk for 30-day readmission and observed no links with deteriorating surgical, medical, or mortality outcomes. This implies that conventional frailty metrics may not effectively align with EEA outcomes.

Utility of a LangChain and OpenAI GPT-powered chatbot based on the international consensus statement on allergy and rhinology: Rhinosinusitis.

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.

Postoperative mometasone irrigations improve quality of life in skull base tumor patients.

Objectives: The use of topical corticosteroids to manage postoperative sinonasal symptoms after endoscopic skull base surgery (ESBS) has not been well studied. We quantified long-term impact of postoperative steroid irrigations (SIs) on quality of life of patients after ESBS. Methods: Retrospective review of patients at the University of Pennsylvania undergoing ESBS from 2010 to 2019. Data on patient demographics and postoperative treatment with nasal saline irrigation twice daily with and without dissolved steroids (mometasone or budesonide) was collected. Preoperative, and 1-, 3-, 6-, 12-, 18-, and 24-month postoperative Sino-Nasal Outcome Test (SNOT-22) scores were assessed. Results: A total of 727 patients were assessed (53.4% males), with 479 patients in the no SI group and 248 patients in the SI group. Preoperative SNOT-22 scores did not differ significantly (P = 0.19). 1-, 3-, 6-, 12-, 18-, and 24-month post-op SNOT-22 scores did not significantly differ between groups. However, mometasone irrigations resulted in significantly lower postoperative 2-year SNOT-22 scores compared to budesonide (P < 0.01) and saline (P = 0.03). Conclusions: Though corticosteroid irrigations are routine in managing inflammatory sinus disease, their role in postoperative management after ESBS for tumors is unclear. Our findings suggest that mometasone irrigation may be effective at improving postoperative quality of life in patients after ESBS.

Microdebrider complications in sinus surgery: Analysis of the openFDA database.

Objective: Functional endoscopic sinus surgery is a commonly performed otolaryngologic procedure that often uses the microdebrider device for tissue removal. Given the ubiquitous nature of the instrument, we sought to better define the patterns of device failure using the postmarket surveillance openFDA database. Methods: The openFDA database was queried for all microdebrider-related adverse events from January 1, 2000 to November 1, 2020. Descriptive information on the nature of device failure and any associated patient injury was compiled. Reports not directly related to device failure were excluded from the analysis. Results: A total of 641 events were included in the analysis. The most common device failure was overheating (n = 348, 54.3%), followed by material separation (n = 173, 27%), and inconsistent device activation (n = 52, 8.1%). Of the reported events, the vast majority did not result in patient harm (n = 579, 90.3%). On review of the remaining cases, only 24 events (3.7%) resulted in true harm to the patient, defined as a temporary or permanent injury or >30 min of additional anesthesia time. Of these cases, the need to reschedule surgical cases (n = 5, 0.8%), retained foreign body (n = 5, 0.8%), and thermal tissue injury (n = 3,0.5%) were the most common. Five patients suffered an injury due to surgeon error unrelated to device malfunction (n = 5, 0.8%). Conclusions: Microdebrider device failures are extremely rare. When they do occur, less than 10% result in patient harm. In cases of patient harm related to microdebrider failure, preoperative testing of the device before use could prevent many of the reported malfunctions.