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Objective  Surgical resection is widely accepted as a critical component for definitive treatment of sinonasal mucosal melanoma. Systemic immunotherapy, including multiple newer agents, has been used to treat metastatic or unresectable disease. In this study, we examine its efficacy in locoregional control when used in conjunction with surgical resection for primary mucosal lesions. Design  Present study is a retrospective review of all patients at a tertiary academic medical center with primary sinonasal mucosal melanoma and distant metastatic disease. Results  A total of four patients were identified. In all cases, patients were treated with a combination of surgical resection of the primary tumor and systemic immunotherapy. Three patients were initially treated with surgery at the primary site followed by immunotherapy for distant metastases. Response to immunotherapy at the sites of primary and metastatic disease was seen in two patients. All four patients developed progression or recurrence at the primary site following initiation of immunotherapy for which they underwent surgical resection. One patient remains in follow-up without evidence of disease 20 months after initial treatment; three succumbed to the disease at 135, 37, and 16 months after initial treatment. Conclusion  Surgical resection for local control plays a critically important role in the treatment of sinonasal mucosal melanoma regardless of the presence of metastases and whether immunotherapy will be given. This case series suggests that, though immunotherapy may demonstrate efficacy in managing distant disease, surgery should remain the first-line treatment for the primary site.

Objective  Radiation therapy represents an uncommon but important component of treatment plans for some pituitary adenomas (PAs). Although radiation therapy has been used to treat pituitary adenomas for over a century, general trends in the usage of radiation therapy for this purpose have not been reviewed. Additionally, there are few large studies evaluating how radiation therapy is used for the treatment of these benign tumors. Investigating these trends and identifying any variations in radiation therapy utilization would help to better inform treatment decisions and improve patient outcomes. Design  Present study is a retrospective analysis of cases using the National Cancer Database. Setting  The research was organized at a tertiary academic medical center. Participants  Patients were diagnosed with pituitary adenoma between 2004 and 2014 within the National Cancer Database (NCDB). Methods  Temporal trends in the usage of radiation therapy to treat pituitary adenoma were analyzed through a retrospective analysis of 77,142 pituitary adenoma cases from the NCDB between 2004 and 2014. Univariate and multivariate analyses were to examine the relationship between patient, tumor, and treatment factors, and the incorporation of radiation therapy into the treatment of pituitary adenomas. We adjusted for potential confounders such as age, sex, race, comorbidity score, facility type, and year of diagnosis. Results  A total of 77,142 patients met inclusion criteria. Inclusion of radiation therapy in pituitary adenoma treatment was 8.0% in 2004 and steadily declined to a low of 3.1% in 2014. Overall, patients were less likely to receive radiation for their pituitary adenoma over time ( p

Background  Sinonasal adenocarcinoma (SNAC) is a rare malignancy arising from mucus-secreting glandular tissue. Limited large-scale studies are available due to its rarity. We evaluated SNAC in the National Cancer Database (NCDB), a source that affords multi-institutional, population studies of rare cancers and their outcomes. Methods  The NCDB was queried for adenocarcinoma in the sinonasal tract. Multivariate analyses were performed to evaluate for factors contributing to overall survival (OS). Results  A total of 553 patients were identified. The cohort was composed of 59.3% males. The nasal cavity was the most common primary site, representing 44.1% of cases. About 5.7% of patients presented with nodal disease, while 3.3% had distant metastases. About 40.6% of cases presented with stage IV disease. About 73.5% of patients underwent surgery, 54.2% received radiation therapy, and 27.7% had chemotherapy. Median OS was 71.7 months, while OS at 1, 2, and 5 years was 82, 73.0, and 52%, respectively. On multivariate analysis, advanced age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02-1.05), Charlson-Deyo score of 1 (HR: 1.99; 95% CI: 1.20-3.30), advanced tumor grade (HR: 2.73; 95% CI: 1.39-5.34), and advanced tumor stage (HR: 2.71; 95% CI: 1.33-5.50) were associated with worse OS, whereas surgery (HR: 0.34; 95% CI: 0.20-0.60) and radiation therapy (HR: 0.55; 95% CI: 0.33-0.91), but not chemotherapy (HR: 1.16; 95% CI: 0.66-2.05), predicted improved OS. Conclusions  SNAC is a rare malignancy with 5-year survival approximating 50%. Surgery and radiation therapy, but not chemotherapy, are associated with improved survival, and likely play a critical role in the interdisciplinary management of SNAC.

Objectives  A persistent craniopharyngeal canal (CPC) is a rare embryologic remnant that presents as a well-corticated defect of the midline sphenoid body extending from the sellar floor to the nasopharynx. Our case series aims to describe three unique presentations of this congenital anomaly and their subsequent management. Design  Retrospective review. Setting  Tertiary academic medical center. Participants  Patients who underwent endoscopic transnasal surgical repair of a CPC lesion. Main Outcome Measures  Resolution of symptoms and surgical outcomes. Results  A total of three patients were identified. The clinical presentation varied, however, all cases prompted further imaging which demonstrated a persistent CPC and associated pathologic lesion. The presentation of a persistent CPC with nasal obstruction and subsequent iatrogenic cerebrospinal fluid leak as in Case 1 demonstrates the importance of imaging in this work-up. Cases 2 and 3 in the series were representative of the larger subset of patients in the literature who present with the defect incidentally but still warrant surgical management. Nonetheless, a standard approach to diagnosis with preoperative imaging and subsequent transnasal endoscopic repair of the skull base defect was undertaken. Conclusion  The persistent CPC is a rare congenital anomaly associated with diverse pathology and careful review of preoperative radiology is critical to the management. When warranted, subsequent surgical repair and reconstruction is associated with excellent postoperative outcomes.

Introduction  Olfactory groove meningiomas (OGMs) are often associated with loss of smell following resection. Loss of smell has a measurable impact on quality of life. Smell preservation has been previously described in open approaches for early stage or unilateral OGMs. Evidence of smell preservation in endoscopic approaches is lacking. Design  A multi-institutional retrospective review was performed on consecutive patients who underwent unilateral endoscopic endonasal resection of OGM. A gross total resection was achieved with preservation of the contralateral olfactory cleft and bulb. Olfactory function was assessed with a six-point olfactory symptom score and the Sniffin' Sticks 12-item smell identification test (SS-12). Contralateral olfactory bulb volume was measured on postoperative magnetic resonance imaging. Results  Four patients (age 42.0 ± 7.5, 75% female) were assessed. Olfactory function was assessed at 21.8 ± 5.6 months following surgery. All patients reported some degree of smell preservation (75% described a slight/mild impairment in smell or better). Olfactory identification was preserved with an SS-12 score of 9 ± 1.4 (anosmia defined as ≤6). The olfactory bulb volume was calculated to be 47.4 ± 15.9 mm 3 (normal >40 mm 3 ). Conclusion  Smell preservation is possible following unilateral endoscopic endonasal resection of carefully selected OGM.

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.

BackgroundSolitary chemosensory cells (SCCs) are rare epithelial cells enriched in nasal polyps and are the primary source of interleukin-25 (IL-25), an innate cytokine eliciting T-helper 2 (Th2) immune response. Although it is proposed that SCCs are stimulated by antigens released by upper airway pathogens, the exogenous triggers of human SCCs remain elusive. We studied patients with noninvasive fungal rhinosinusitis to determine whether extracts of Aspergillus fumigatus and Alternaria alternata stimulate SCC proliferation as an early event in type 2 inflammation.MethodsMulticolor flow cytometry, immunofluorescence, and enzyme-linked immunoassay were used to interrogate mucosa from patients with mycetomas and allergic fungal rhinosinusitis (AFRS) for SCCs and IL-25. Primary sinonasal epithelial cells from AFRS patients and noninflamed inferior turbinates were stimulated with fungal extracts for 72 hours, and SCC population frequency as well as mitotic activity were quantified using flow cytometry.ResultsSCCs producing IL-25 are enriched in inflamed mucosa compared with intrapatient noninflamed control tissue (38.6% vs 6.5%, p = 0.029). In cultured sinonasal epithelial cells from AFRS nasal polyps, Aspergillus fumigatus and Alternaria alternata stimulated higher SCC frequency compared with controls (27.4% vs 10.6%, p = 0.002; 18.1% vs 10.6%, p = 0.046), which led to increased IL-25 secretion in culture media (75.5 vs 3.3 pg/mL, p < 0.001; 32.3 vs 3.3 pg/mL, p = 0.007). Ki-67 expression was higher in SCCs grown in fungal stimulation conditions compared with controls.ConclusionAlthough fungal antigens are known to potentiate immune response through innate cytokines, including IL-25, the early expansion of SCCs in the presence of fungus has not been described. This early event in the pathogenesis of noninvasive fungal rhinosinusitis may represent a target for intervention.

BackgroundBroncho-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 shown 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.MethodsHuman 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.ResultsApical application of OM-85 BV resulted in an NO-mediated increase in CBF (p

Objective  Sinonasal undifferentiated carcinoma (SNUC) is an aggressive neoplasm, with conflicting existing literature regarding prognosis and treatment due to the rarity of disease. Characterization of optimal SNUC management is necessary for improved outcomes. Study Design  Case series with planned data collection and analysis. Setting  Hospital of the University of Pennsylvania and Pennsylvania Hospital. Participants  Patients with pathologically confirmed SNUC treated within a 15-year period were identified, and records were obtained and evaluated for several demographic characteristics. Main Outcomes Measures  Disease-specific survival from diagnosis was the primary endpoint, while disease recurrence was a secondary endpoint of the study. Results  Twenty-seven patients with established SNUC were included in this cohort, with a median age of 55 years. Eighty-five percent of patients were surgically treated, and 85% of patients presented with stage IV disease. Two-year disease-specific survival was 66% and 5-year disease-specific survival was 46%. Ninety-six percent of patients received both chemotherapy and radiation as adjuvant treatment. Nodal disease at presentation and disease recurrence both significantly decreased patient survival ( p

The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence for technical factors that optimize outcomes in skull base reconstruction following endoscopic skull base surgery for intradural pathologies. These topics include the use of free mucosal grafts versus vascularized pedicled nasoseptal flaps; the use of autologous versus synthetic grafts; and the roles of lumbar drains, dural sealants, and nasal packing. This EPS was developed following the recommended methodology and approval process as previously outlined. As there are a myriad of techniques and limited agreement on the accepted principles of skull base reconstruction, this EPS aims to summarize the existing evidence and provide clinically meaningful guidance on these divergent practices. Following a modified Delphi approach, five statements were developed, four of which reached consensus and one of which reached near consensus. These statements and the accompanying evidence are summarized along with an assessment of future needs. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion 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.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.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.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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) is commonly characterized by type-2 inflammation. It is established that group-2 innate lymphoid cells (ILC2s) are a subset of immune cells important in orchestrating mucosal type-2 response. IL-25 is an epithelial-derived cytokine that is a critical activator of ILC2s. Recent evidence demonstrates that specialized taster epithelial cells, such as solitary chemosensory cells (SCCs), may be producers of IL-25. To elucidate the relationship between SCCs and ILC2s in CRSwNP, we sought to quantify ILC2s and SCCs to determine if these cell types are enriched in nasal polyps compared to healthy sinonasal mucosa. We quantified SCCs and ILC2s using multicolor flow cytometry in nasal polyps and non-inflamed turbinate mucosa from seven patients and investigated the role of IL-13 and dexamethasone on SCC frequency using tissue explants of nasal polyps and turbinate mucosa. SCCs were found to be the primary source of IL-25. Nasal polyps demonstrated higher populations of SCCs (33.0% vs 5.6%, p < 0.001) and ILC2s (2.40% vs 0.19%, p = 0.008) compared to patient-matched nonpolypoid turbinates. In cultured polyp explants, exogenous IL-13 increased the proportion of epithelial SCCs (40.2% IL-13 condition vs 28.9% untreated, p = 0.012), and this effect was reversed by addition of dexamethasone (40.2% vs 8.9%, p < 0.0005). These data support SCC and ILC2 expansion as well as increased IL-25 production in nasal polyps and may represent early events in the pathogenesis of CRSwNP. IL-13 stimulates proliferation of SCC in a feed-forward loop, a process that is steroid-sensitive.

Background An ectopic pituitary adenoma presenting as a clival or sphenoid mass is a rare clinical occurrence that may mislead the clinician and result in unnecessary interventions or potential medicolegal consequences. Here, we present one of the largest multi-institutional case series and review the literature with an emphasis on radiological findings and critical preoperative workup. Methods Retrospective chart review. Results Nine patients were identified with ectopic pituitary adenomas of the sphenoid or clivus. There were four females and five males. Median age was 60 years old (range, 36-73 years). The most common presenting symptom was headache (56%). Five (56%) patients presented with a mass arising from the clivus while four (44%) presented with a mass in the sphenoid. Six (67%) patients demonstrated biochemical evidence of hypersecretion on full endocrinology panel. All masses showed evidence of enhancement with gadolinium with a propensity for adjacent bone involvement. Lesions also had a predilection for growth toward the cavernous sinus, carotid artery, or sellar floor. Surgical intervention was performed in eight patients (89%). In eight patients (89%), tumors demonstrated immunoreactivity to prolactin. Conclusions Pituitary adenomas can rarely present as an isolated sphenoid or clival mass. Lesions displayed similar magnetic resonance imaging findings with an erosive growth pattern toward the sellar floor, cavernous sinus, or adjacent carotid artery. Patients with clival or parasellar lesions with comparable features should have a preoperative workup which includes prolactin level and alert the physician to consider an ectopic pituitary adenoma in the differential to prevent unnecessary surgery and potential complications.

BackgroundThere is preliminary evidence that patients with chronic rhinosinusitis (CRS) and comorbid obstructive sleep apnea (OSA) have reduced quality-of-life (QOL) improvements after functional endoscopic sinus surgery (FESS) compared with patients without OSA. The effect of OSA severity on QOL improvement after FESS is unknown.ObjectivesTo better characterize the QOL improvement after FESS for patients with comorbid OSA and to assess whether QOL improvement is dependent on OSA severity.MethodsThis multi-institution, retrospective cohort study evaluated adult patients with CRS who underwent FESS between 2007 and 2015. Preoperative, 1-month, 3-month, 6-month, and 1-year postoperative 22-Item Sino-Nasal Outcome Test scores were used to evaluate QOL. We compared patients without OSA with patients with stratified OSA based on the preoperative apnea-hypopnea index. A multilevel, mixed-effects linear regression model was used for the analysis.ResultsOf 480 participants, 83 (17%) had OSA, and 47 of these patients had polysomnography results available for review. Both patients with OSA and patients without OSA reported significant QOL improvement after surgery (p < 0.0001) relative to baseline. In the unadjusted model, the subjects with OSA demonstrated a statistically worse outcome in 22-Item Sino-Nasal Outcome Test scores at each time point (2.4 points higher per time point, p = 0.006). When controlling for covariates, the adjusted model showed no difference in QOL outcome based on OSA status (p = 0.114). When stratified by OSA disease severity, the adjusted model showed no difference in the QOL outcome.ConclusionsPatients with CRS and comorbid OSA had worse QOL outcomes after FESS; however, when controlling for patient factors, there was no difference in QOL outcome. OSA disease severity did not seem to predict QOL improvement after FESS.

Background Sinonasal debridement is typically performed in the weeks following endonasal skull base surgery (ESBS). In the pediatric population, this second-look procedure may require general anesthesia; however, there is currently little evidence assessing the benefit of this practice. Methods This was a multicenter retrospective study of pediatric patients (age <18 years) undergoing a planned second-look debridement under general anesthesia following ESBS. Intraoperative findings, interventions performed, and perioperative complications were reviewed. Multivariate regression analysis was performed to identify associations between intraoperative findings and clinical factors. Results We reviewed 69 cases of second-look debridements (age mean 8.6 ± 4.2 years, range: 2–18 years), occurring a mean of 18.3 ± 10.3 days following ESBS. All abnormal findings were noted in patients age ≤12 years. Synechiae were noted in 8.7% of cases, bacterial rhinosinusitis in 2.9%, and failed reconstruction with cerebrospinal fluid leak in 4.5% (two cases of flap malposition and one case of flap necrosis). All failed reconstructions were noted following expanded endonasal cases for craniopharyngioma, and in each case, a revision reconstruction was performed during the second-look surgery. Synechiae were not significantly associated with younger age, revision cases, or cases with reconstructive flaps. There were no perioperative complications. Conclusion Second-look debridement under general anesthesia may be useful in the identification and intervention of sinonasal pathology following endoscopic skull base surgery, particularly in children ≤12 years old or those with pedicled flap reconstructions. Larger controlled studies are warranted to validate this practice and refine indications and timing of this second procedure. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]