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1.
Int Forum Allergy Rhinol ; 13(8): 1525-1534, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36565436

RESUMO

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


Assuntos
Rinite , Sinusite , Humanos , Ácido Succínico/metabolismo , Cálcio/metabolismo , Epitélio/metabolismo , Doença Crônica , Inflamação , Peptídeos Antimicrobianos , Células Epiteliais/metabolismo
2.
Int Forum Allergy Rhinol ; 13(8): 1492-1502, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36433723

RESUMO

BACKGROUND: Sinonasal lymphoma (SL) is a heterogeneous, underrecognized neoplastic disorder with limited outcomes data. We sought to better define outcomes by subtype and treatment at 2 referral centers over the past 2 decades. METHODS: Demographics, clinicopathologic data, and treatment outcomes for patients treated for SL were queried from January 1, 2000 to December 31, 2021 at 2 tertiary academic medical centers. RESULTS: Eighty-four patients were included, with an average age at diagnosis of 63.4 ± 15 years. There were 34 females (40.5%). The majority of patients had an Eastern Cooperative Oncology Group (ECOG) score of <2 (76.2%) and the most common presenting symptom was facial swelling/pain (26.2%). The most common primary site was the nasal cavity (36.9%). Diffuse large B-cell lymphoma was the most common subtype (46.4%), followed by extranodal NK/T-cell lymphoma (17.9%). Chemotherapy was the most common treatment strategy (n = 59, 70.2%), followed by radiation therapy (n = 35, 41.7%) and immunotherapy (n = 24, 28.6%). Disease-specific survival rates at 1, 5, and 10 years were 85.7%, 73.6%, and 58.6%, respectively. Eighteen patients (21.4%) developed recurrence. On multivariate analysis, higher ECOG score (p < 0.0001) and history of head and neck radiation (p = 0.048) were associated with worse survival. Younger age was associated with greater risk of recurrence (p = 0.022) and male sex was associated with more treatment side effects (p = 0.012). CONCLUSION: This is the largest multi-institutional analysis of SL characteristics and outcomes. Our work suggests that, although disease control in the first 5 years is reasonable, 10-year outcomes remain challenging. Further studies are needed to investigate new treatment paradigms and risk stratification.


Assuntos
Linfoma Extranodal de Células T-NK , Linfoma Difuso de Grandes Células B , Neoplasias dos Seios Paranasais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/epidemiologia , Neoplasias dos Seios Paranasais/terapia , Resultado do Tratamento , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/patologia , Cavidade Nasal/patologia , Estudos Retrospectivos , Prognóstico
5.
Int Forum Allergy Rhinol ; 11(6): 967-975, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32885614

RESUMO

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.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Humanos , Compostos de Amônio Quaternário , Percepção Gustatória
6.
Int Forum Allergy Rhinol ; 11(2): 115-119, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32671928

RESUMO

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.


Assuntos
Asma Induzida por Aspirina , Pólipos Nasais , Sinusite , Aspirina/efeitos adversos , Dessensibilização Imunológica , Humanos , Pólipos Nasais/terapia , Estudos Retrospectivos , Sinusite/tratamento farmacológico
7.
Int Forum Allergy Rhinol ; 11(5): 857-865, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32846055

RESUMO

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


Assuntos
Pólipos Nasais , Sinusite , Humanos , Receptores Acoplados a Proteínas G , Paladar , Percepção Gustatória
10.
Int Forum Allergy Rhinol ; 10(9): 1043-1048, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32558306

RESUMO

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


Assuntos
Asma Induzida por Aspirina , Pólipos Nasais , Anti-Inflamatórios não Esteroides , Aspirina/efeitos adversos , Dessensibilização Imunológica , Humanos , Pólipos Nasais/cirurgia , Projetos Piloto , Estudos Retrospectivos , Resultado do Tratamento
11.
Int Forum Allergy Rhinol ; 10(3): 278-281, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32022422

RESUMO

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.


Assuntos
Papiloma Invertido/diagnóstico por imagem , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Sinusite/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Papiloma Invertido/complicações , Papiloma Invertido/patologia , Neoplasias dos Seios Paranasais/complicações , Neoplasias dos Seios Paranasais/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Sinusite/complicações , Sinusite/patologia , Centros de Atenção Terciária , Tomografia Computadorizada por Raios X
12.
Int Forum Allergy Rhinol ; 10(4): 521-525, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32104979

RESUMO

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


Assuntos
Seios Paranasais , Rinite , Doença Crônica , Endoscopia , Humanos , Incidência , Seios Paranasais/diagnóstico por imagem , Seios Paranasais/cirurgia , Estudos Retrospectivos , Rinite/epidemiologia , Rinite/cirurgia , Fatores de Risco , Base do Crânio/diagnóstico por imagem , Base do Crânio/cirurgia , Resultado do Tratamento
13.
Int Forum Allergy Rhinol ; 10(2): 265-270, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32086998

RESUMO

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


Assuntos
Antialérgicos/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Cetotifeno/farmacologia , Administração Tópica , Células Cultivadas , Cílios/efeitos dos fármacos , Cílios/fisiologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Humanos , L-Lactato Desidrogenase/metabolismo , Irrigação Terapêutica
14.
Int Forum Allergy Rhinol ; 10(1): 23-28, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794110

RESUMO

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


Assuntos
Imunossupressores/efeitos adversos , Rinite/induzido quimicamente , Sinusite/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Doença Crônica , Endoscopia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Seios Paranasais/patologia , Fenótipo , Rinite/patologia , Rinite/cirurgia , Sinusite/patologia , Sinusite/cirurgia
15.
Int Forum Allergy Rhinol ; 9(S3): S145-S365, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31329374

RESUMO

BACKGROUND: Endoscopic skull-base surgery (ESBS) is employed in the management of diverse skull-base pathologies. Paralleling the increased utilization of ESBS, the literature in this field has expanded rapidly. However, the rarity of these diseases, the inherent challenges of surgical studies, and the continued learning curve in ESBS have resulted in significant variability in the quality of the literature. To consolidate and critically appraise the available literature, experts in skull-base surgery have produced the International Consensus Statement on Endoscopic Skull-Base Surgery (ICAR:ESBS). METHODS: Using previously described methodology, topics spanning the breadth of ESBS were identified and assigned a literature review, evidence-based review or evidence-based review with recommendations format. Subsequently, each topic was written and then reviewed by skull-base surgeons in both neurosurgery and otolaryngology. Following this iterative review process, the ICAR:ESBS document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:ESBS document addresses the role of ESBS in primary cerebrospinal fluid (CSF) rhinorrhea, intradural tumors, benign skull-base and orbital pathology, sinonasal malignancies, and clival lesions. Additionally, specific challenges in ESBS including endoscopic reconstruction and complication management were evaluated. CONCLUSION: A critical review of the literature in ESBS demonstrates at least the equivalency of ESBS with alternative approaches in pathologies such as CSF rhinorrhea and pituitary adenoma as well as improved reconstructive techniques in reducing CSF leaks. Evidence-based recommendations are limited in other pathologies and these significant knowledge gaps call upon the skull-base community to embrace these opportunities and collaboratively address these shortcomings.


Assuntos
Endoscopia/métodos , Procedimentos Neurocirúrgicos/métodos , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Base do Crânio/cirurgia , Humanos , Avaliação de Resultados em Cuidados de Saúde
16.
Int Forum Allergy Rhinol ; 9(9): 1046-1053, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31314958

RESUMO

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


Assuntos
Carcinoma Mucoepidermoide/epidemiologia , Neoplasias dos Seios Paranasais/epidemiologia , Grupos Populacionais , Adulto , Idoso , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/mortalidade , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/mortalidade , Seios Paranasais , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
17.
Int Forum Allergy Rhinol ; 9(8): 865-869, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31125506

RESUMO

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.


Assuntos
Recidiva Local de Neoplasia , Papiloma Invertido/cirurgia , Neoplasias dos Seios Paranasais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seios Paranasais/cirurgia
18.
Int Forum Allergy Rhinol ; 9(7): 730-737, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30892837

RESUMO

BACKGROUND: Solitary 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. METHODS: Multicolor 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. RESULTS: SCCs 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. CONCLUSION: Although 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.


Assuntos
Alérgenos/imunologia , Antígenos de Fungos/imunologia , Células Quimiorreceptoras/imunologia , Micetoma/imunologia , Mucosa Nasal/citologia , Rinite/imunologia , Sinusite/imunologia , Alternaria/imunologia , Aspergillus fumigatus/imunologia , Fungos/imunologia , Humanos , Interleucina-17/imunologia , Mucosa Nasal/imunologia
19.
Int Forum Allergy Rhinol ; 9(6): 688-694, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30768764

RESUMO

BACKGROUND: Sinonasal malignancies are a rare subset of head and neck tumors, and surveillance strategies after definitive tumor treatment are often generalized from those for overall head and neck cancer outcomes data. However, recent literature suggests that the posttreatment period in sinonasal cancer is fundamentally different and a more tailored surveillance approach may be beneficial. Although rates of symptomatology are high in head and neck cancer recurrence and patient-driven follow-up is common, rates of symptomatology are unknown in sinonasal cancer specifically. METHODS: Patients with recurrence of sinonasal malignancy were identified at 3 academic rhinology and skull base surgery centers. Demographic, tumor, and treatment data were collected. Rates of symptomatology at presentation were tabulated and examined in the context of several other variables. RESULTS: Fifty-five patients had recurrence of sinonasal malignancy after definitive treatment. Fifty-one percent of patients had no suspicious symptoms at the time of tumor recurrence, with an average time to recurrence of 33 months. Male patients and patients with stage IVA or lower disease were significantly more likely to be asymptomatic at the time of recurrence (p < 0.05). CONCLUSION: Patients with sinonasal malignancy have a much lower rate of symptomatology during tumor recurrence than that observed in head and neck cancer overall. Furthermore, time to recurrence is substantially longer, as a majority of head and neck cancer recurrences occur in the first 12 months after treatment. These differences highlight the need for more tailored surveillance paradigms in asymptomatic patients with a history of a definitively treated sinonasal neoplasm.


Assuntos
Neoplasias dos Seios Paranasais/epidemiologia , Neoplasias dos Seios Paranasais/patologia , Adulto , Idoso , Doenças Assintomáticas , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias dos Seios Paranasais/terapia , Recidiva , Análise de Sobrevida , Fatores de Tempo
20.
Int Forum Allergy Rhinol ; 9(4): 427-434, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30645040

RESUMO

BACKGROUND: Sinonasal adenoid cystic carcinoma (SNACC) is a rare malignancy with a propensity for distant metastasis. In this study we describe the incidence and determinants of survival among patients with SNACC between the years 2004 and 2012 using the National Cancer Database (NCDB). METHODS: This was a retrospective, population-based cohort study performed at a tertiary academic medical center. All participants were diagnosed with SNACC between 2004 and 2012 within the NCDB. The main outcome was overall survival (OS). RESULTS: A total of 793 patients were identified. The cohort was composed of 46.9% males. Mean age at diagnosis was 59.6 years. The maxillary sinus was the most common primary site (49.7%). Nodal disease was seen in 3.6% of the patients, whereas 3.7% had distant metastases. Stage IV disease was seen in 49.1% of cases. In total, 77.4% of patients underwent surgery, 68.2% received radiation therapy, and 16.4% had chemotherapy. Median OS was 78.5 months; OS at 1, 2, and 5 years was 91%, 83%, and 61%, respectively. On multivariate analysis, advanced age (p = 0.001), frontal sinus primary site (p < 0.001), positive margins (p < 0.001), Charlson comorbidity index >0 (p = 0.01), residing in an urban setting (p = 0.04), poorly differentiated or undifferentiated tumor grade (p = 0.003), and advanced tumor stage (p = 0.01) were associated with worse OS, whereas surgery (p < 0.001), but not radiation therapy (p = 0.52) or chemotherapy (p = 0.57), predicted improved OS. CONCLUSION: Predictors of survival in SNACC include age, comorbidity status, grade, and stage. Surgery is associated with improved survival and remains the mainstay of therapy, whereas the roles of radiation therapy and chemotherapy require future investigation.


Assuntos
Carcinoma Adenoide Cístico/epidemiologia , Neoplasias dos Seios Paranasais/epidemiologia , Idoso , Carcinoma Adenoide Cístico/terapia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias dos Seios Paranasais/terapia , Estudos Retrospectivos
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