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Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC.
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Objective:To investigate the differences in the therapeutic effects of endoscopic surgery combined with chemotherapy and endoscopic surgery combined with radiotherapy in the treatment of early nasopharyngeal carcinoma, and to select individualized treatment strategy for early nasopharyngeal carcinoma. Methods:The clinical data of 68 patients with early nasopharyngeal carcinomaï¼Tî1-2N0M0ï¼ who received surgical treatment in a high-incidence area were retrospectively analyzed. According to different treatment methods, they were divided into the surgery + chemotherapy groupï¼n=34, treated with endoscopic surgery combined with chemotherapyï¼ and the surgery + radiotherapy groupï¼n=34, treated with endoscopic surgery combined with radiotherapyï¼. Propensity score matching was used to match the patient data between the two groups at a 1â¶1 ratio. Patients were followed up, and the survival rates and hematological toxicities were compared between the two groups. Results:Twenty-four cases in the surgery + chemotherapy group and 24 cases in the surgery + radiotherapy group were successfully matched. After matching, there was no statistically significant difference in T stage, and clinical stage between the two groupsï¼all P>0.05ï¼. The 3-year OS and DFS in the surgery + chemotherapy group were 100.0% and 95.8%, respectively, while the 3-year OS and DFS in the surgery + radiotherapy group were 100.0% and 100.0%, respectively, with no significant difference in survival rates between the two groupsï¼both P>0.05ï¼. After treatment, there was no statistically significant difference in bone marrow suppression between the surgery + chemotherapy group and the surgery + radiotherapy group ï¼all P> 0.05ï¼ Conclusion:Endoscopic surgery combined with chemotherapy and surgery combined with radiotherapy have comparable clinical efficacy in the treatment of early nasopharyngeal carcinoma, but without radiotherapy-related complications, which is worth further investigation.
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Carcinoma , Endoscopia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/radioterapia , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/radioterapia , Estudos Retrospectivos , Masculino , Prognóstico , Feminino , Terapia Combinada , Carcinoma/terapia , Taxa de Sobrevida , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Incidência , Resultado do Tratamento , AdultoRESUMO
Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease ï¼N-ERDï¼ is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis ï¼CRSï¼, asthma, and intolerance to cyclooxygenase 1 ï¼COX-1ï¼ inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.
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Anti-Inflamatórios não Esteroides , Humanos , Anti-Inflamatórios não Esteroides/efeitos adversos , China , Rinite/diagnóstico , Rinite/terapia , Rinite/induzido quimicamente , Sinusite/diagnóstico , Sinusite/terapia , Sinusite/tratamento farmacológico , Consenso , Asma/diagnóstico , Asma/tratamento farmacológico , Doença CrônicaRESUMO
OBJECTIVE: This study aimed to evaluate the sinonasal-related Quality of Life (QoL) in patients undergoing endoscopic skull base surgery. METHODS: A retrospective study was performed, including patients with benign and malignant tumors at a single institution. Each patient completed the 22-Item Sino-Nasal Outcome Test (SNOT-22) and the Empty Nose Syndrome 6 Item Questionnaires (ENS6Q) to assess their perceived QoL at least 2-months after treatment. RESULTS: Forty-nine patients were enrolled in this study. The average score was 25.1 (Stander Deviation [SD] 14.99) for SNOT-22 and 6.51 (SD=5.58) for ENS6Q. Analysis of the overall results for the SNOT-22 showed that olfactory damage was the most serious syndrome. The most frequently reported high-severity sub-domains in SNOT-22 were nasal symptoms and sleep symptoms. Nasal crusting was the most severe item in ENS6Q according to the report. Nine patients (18.4%) had a score higher than 10.5 which indicates the high risk of Empty Nose Syndrome (ENS). SNOT-22 score was related to the history of radiotherapy (p< 0.05), while the ENS6Q score was not. CONCLUSIONS: The possibility of patients suffering from ENS after nasal endoscopic skull base surgery is at a low level, although the nasal cavity structure is damaged to varying degrees. Meanwhile, patients undergoing endoscopic skull base surgery were likely to suffer nasal problems and sleep disorders. Patients who had received radiotherapy have a worse QoL than those without a history of radiotherapy. LEVEL OF EVIDENCE: Level 3.
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Endoscopia , Qualidade de Vida , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Endoscopia/métodos , Base do Crânio/cirurgiaRESUMO
Abstract Objective This study aimed to evaluate the sinonasal-related Quality of Life (QoL) in patients undergoing endoscopic skull base surgery. Methods A retrospective study was performed, including patients with benign and malignant tumors at a single institution. Each patient completed the 22-Item Sino-Nasal Outcome Test (SNOT-22) and the Empty Nose Syndrome 6 Item Questionnaires (ENS6Q) to assess their perceived QoL at least 2-months after treatment. Results Forty-nine patients were enrolled in this study. The average score was 25.1 (Stander Deviation [SD] 14.99) for SNOT-22 and 6.51 (SD = 5.58) for ENS6Q. Analysis of the overall results for the SNOT-22 showed that olfactory damage was the most serious syndrome. The most frequently reported high-severity sub-domains in SNOT-22 were nasal symptoms and sleep symptoms. Nasal crusting was the most severe item in ENS6Q according to the report. Nine patients (18.4%) had a score higher than 10.5 which indicates the high risk of Empty Nose Syndrome (ENS). SNOT-22 score was related to the history of radiotherapy (p < 0.05), while the ENS6Q score was not. Conclusions The possibility of patients suffering from ENS after nasal endoscopic skull base surgery is at a low level, although the nasal cavity structure is damaged to varying degrees. Meanwhile, patients undergoing endoscopic skull base surgery were likely to suffer nasal problems and sleep disorders. Patients who had received radiotherapy have a worse QoL than those without a history of radiotherapy. Level of evidence Level 3.
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BACKGROUND: The management of locally advanced recurrent nasopharyngeal carcinoma (rNPC) is challenging. The objective of our study was to compare salvage endoscopic nasopharyngectomy (ENPG) with intensity-modulated radiotherapy (IMRT) in clinical outcomes and complications of locally advanced rNPC. METHODS: Patients with histologically confirmed rNPC in rT3-4N0-3M0 stages were retrospectively enrolled between January 2013 and December 2019 in this multicenter, case-matched study. The baseline clinicopathological characteristics of patients were balanced by propensity score matching between the ENPG and IMRT groups. ENPG was performed in patients with easily or potentially resectable tumors. The oncological outcomes as well as treatment-related complications were compared between two groups. RESULTS: A total of 176 patients were enrolled and 106 patients were matched. The ENPG group (n = 53) and the IMRT group (n = 53) showed comparable outcomes in the 3-year overall survival rate (68.4% vs. 65.4%, P = 0.401), cancer-specific survival rate (80.9% vs. 74.4%, P = 0.076), locoregional failure-free survival rate (36.6% vs. 45.3%, P = 0.076), and progression-free survival rate (27.5% vs. 32.3%, P = 0.216). The incidence of severe treatment-related complications of patients in the ENPG group was lower than that in the IMRT group (37.7% vs. 67.9%, P = 0.002). The most common complications were post perioperative hemorrhage (13.2%) in ENPG group and temporal lobe necrosis (47.2%) in IMRT group, respectively. CONCLUSION: Salvage ENPG exhibits comparable efficacy but less toxicities than IMRT in carefully screened patients with locally advanced rNPC, which may be a new choice of local treatment.
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Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Nasofaríngeo , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologiaRESUMO
OBJECTIVE: To retrospectively analyze the comprehensive treatment strategy for internal carotid artery blowout syndrome (CBS) by nasopharyngeal carcinoma (NPC). METHODS: Of the 311 patients of NPC with carotid artery blowout syndrome admitted at our center from April 2018 to August 2022, 288 were enrolled. RESULTS: The patients were divided into two groups: treatment group (266 cases) and control group (22 cases). After comprehensive treatment, the survival rate of the treatment group was significantly higher than that of the control group, especially within 6 months to the 1 year. Preventive intervention for CBS I type may have considerable benefits. And in the long run, this treatment strategy did not significantly increase the incidence of stroke in the treatment group. CONCLUSION: The comprehensive treatment strategy for ICA-CBS of patients with NPC significantly reduced the mortality of asphyxia due to epistaxis, reduced the incidence of CBS during nasal endoscopy, and finally improved survival rate.
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Doenças das Artérias Carótidas , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/complicações , Artéria Carótida Interna , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/complicações , Estudos Retrospectivos , Doenças das Artérias Carótidas/etiologia , Análise de SobrevidaRESUMO
BACKGROUND: The use of neoadjuvant immunotherapy plus chemotherapy has revolutionized the management of esophageal squamous cell carcinoma (ESCC) patients. Nevertheless, patients who would maximally benefit from these therapies have not been identified. METHODS: We collected postoperative specimens from 103 ESCC patients, of which 66 patients comprised a retrospective cohort and 37 comprised a prospective cohort. Patient specimens were subjected to applied multi-omics analysis to uncover the mechanistic basis for patient responsiveness to cancer immunotherapy. The tumor microenvironment characteristics of these patient specimens was explored and identified by multiplex immunofluorescence and immunohistochemistry. RESULTS: Results demonstrated high COL19A1 expression to be a novel biomarker for successful immunotherapy (COL19A1high , odds ratio [95% confidence interval]: 0.31 [0.10-0.97], p = 0.044). Compared with COL19A1low patients, COL19A1high patients benefited more from neoadjuvant immunotherapy (p < 0.01), obtained better major pathological remissions (63.3%, p < 0.01), with a trend toward better recurrence-free survival (p = 0.013), and overall survival (p = 0.056). Moreover, analysis of an immune-activation subtype of patients demonstrated increased B cell infiltration to be associated with favorable patient survival and a better response to neoadjuvant immunotherapy plus chemotherapy. CONCLUSIONS: The findings of this study provide insight into the optimal design of individual treatments for ESCC patients.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Estudos Retrospectivos , Estudos Prospectivos , Esofagectomia , Biomarcadores , Microambiente TumoralRESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
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Asma , Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Doença Crônica , Consenso , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Omalizumab/uso terapêutico , Qualidade de Vida , Rinite/complicações , Rinite/tratamento farmacológico , Sinusite/complicações , Sinusite/tratamento farmacológico , Esteroides/uso terapêuticoRESUMO
Purpose: Radiotherapy (RT) is the mainstay treatment for head and neck cancers. However, chronic and recurrent upper respiratory tract infections and inflammation have been commonly reported in patients post-RT. The underlying mechanisms remain poorly understood. Method and Materials: We used a well-established model of human nasal epithelial cells (hNECs) that forms a pseudostratified layer in the air-liquid interface (ALI) and exposed it to single or repeated moderate dose γ-irradiation (1Gy). We assessed the DNA damage and evaluated the biological properties of hNECs at different time points post-RT. Further, we explored the host immunity alterations in irradiated hNECs with polyinosinic-polycytidylic acid sodium salt (poly [I:C]) and lipopolysaccharides (LPS). Results: IR induced DNA double strand breaks (DSBs) and triggered DNA damage response in hNECs. Repeated IR significantly reduced basal cell proliferation with low expression of p63/KRT5 and Ki67, induced cilia loss and inhibited mucus secretion. In addition, IR decreased ZO-1 expression and caused a significant decline in the transepithelial electrical resistance (TEER). Moreover, hyperreactive response against pathogen invasion and disrupted epithelial host defense can be observed in hNECs exposed to repeated IR. Conclusion: Our study suggests that IR induced prolonged structural and functional impairments of hNECs may contribute to patients post-RT with increased risk of developing chronic and recurrent upper respiratory tract infection and inflammation.
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One of the main clinical treatments for advanced nasopharyngeal carcinoma is chemotherapy, but systemic administration can cause serious adverse reactions. New type of nanomaterial which can actively targeting, imaging, and treating nasopharyngeal carcinoma at the same time to enhance the effect of chemotherapy, meanwhile monitoring the intracellular drug release process at the level of single cancer cell was urgently needed. GE11, an EGFR antagonist peptide, was used to target nasopharyngeal carcinoma which has positive expression of EGFR on its nucleus. GE11-modified graphene quantum dots (GQDs@GE11) were used as drug carriers for clinical chemotherapeutics cisplatin (CDDP) and doxorubicin (DOX). The emission spectrum of GQDs (460 nm) and the excitation spectrum of DOX (470 nm) have a good overlap, thus the transfer and release process of DOX can be sensitively detected by the fluorescence resonance energy transfer (FRET). CDDP was used to enhance the chemotherapy effect of nanoprobe, and the loading amount of DOX and CDDP on GQDs@GE11 nanoprobe were up to 67 and 50 mg/g, respectively. In vivo experiments have confirmed that GQDs@GE11/CDDP/DOX nanoprobe can be enriched to tumor site through specific targeting effect, and significantly inhibit tumor cell proliferation. This new type of targeted therapy fluorescent probe provides new ideas for the study of drug release process and the treatment of nasopharyngeal carcinoma.
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BACKGROUND: Squamous metaplasia (SM) is an irreversible form of airway epithelial remodeling. Hyperproliferation of basal cells was observed in squamous metaplastic epithelium of chronically inflamed airway. However, the association of such aberrant proliferation of basal cells with SM in the nasal epithelium after radiation damage remains unclear. The aim of this study was to investigate SM and accompanying levels of p63+Krt5+ (basal cell markers) cells in the nasal epithelium of patients with radiation-induced chronic rhinosinusitis (CRSr) and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared to healthy controls. METHODS: We assessed the prevalence of SM and the expression of p63+, Krt5+, p63+Krt5+, and Ki67+ cells through immunofluorescence(IF) staining of the inferior turbinate (IT) tissues from patients with CRSr (n = 36), CRSsNP (n = 33) and controls (n = 28). RESULTS: The prevalence of SM and the number of p63+Krt5+ cells were both significantly increased in patients with CRSr compared to patients with CRSsNP and controls. The number of Ki67+ cells were both significantly increased in patients with CRSr and CRSsNP compared to controls, but the ratio of Ki67+ cells to p63+Krt5+ cells was significantly lower in patients with CRSr compared to patients with CRSsNP. In patients with CRSr, an increased number of p63+Krt5+ basal cells was observed in SM epithelium compared to non-SM epithelium. CONCLUSION: SM is increased in the nasal epithelium of patients with CRSr, in which aberrant levels of p63+Krt5+ basal cells serves as an important pathologic feature in the squamous metaplastic epithelium.
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Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Queratina-5/metabolismo , Metaplasia/patologia , Radioterapia/efeitos adversos , Rinite/patologia , Sinusite/patologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto , Idoso , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Masculino , Metaplasia/etiologia , Metaplasia/metabolismo , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Prognóstico , Rinite/etiologia , Sinusite/etiologiaRESUMO
Objective:To observe the safety of omalizumab and glucocorticoid in the dose-increasing phase of rush allergen immunotherapyï¼RITï¼. Method:The clinical data of 88 patients with allergic rhinitis treated with RIT were retrospectively studied, including gender, age, pre-treatment total VAS score, blood EOS%, serum total IgE, local and systemic adverse reactions. Of all patients, fifty-seven were treated with omalizumab combined with RITï¼experimental groupï¼ and thirty-one were treated with hormone/antiallergic drugs combined with RITï¼control groupï¼. The safety of the two groups was compared in the dose-increasing phase. Result:There was no grade â systemic adverse reactions during the whole process in the experimental group, while Grade â ¡ systemic adverse reactions were 4 casesï¼7.1%ï¼ during the period of hospitalization, 2 casesï¼3.6%ï¼ after the first injection after discharge, zeroï¼0ï¼ after the second injection after discharge. No local pruritus and induration were observed. During the period of hospitalization, the first and second injection after discharge, control group had grade â level systemic adverse reactions were 1 caseï¼3.4%ï¼, 2 casesï¼6.9%ï¼, 1 caseï¼3.4%ï¼ at different time point, respectively. Grade â ¡ systemic adverse reactions were 5 casesï¼17.2%ï¼, 1 caseï¼3.4%ï¼, zeroï¼0ï¼ at different time point, respectively. Local injection site itching was observed in 8 patientsï¼5 cases were mild and 3 cases were moderateï¼ and 4 casesï¼13.8%ï¼ had induration during hospitalization. Conclusion:Omalizumab combined with RIT not only shortens the duration of dose-increasing phase of specific immunotherapy, but also increases the safety of the dose-increasing phase during hospitalization, the first and second injection after discharge and improves patient compliance.
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Glucocorticoides , Rinite Alérgica , Alérgenos , Dessensibilização Imunológica , Humanos , Imunoterapia , Omalizumab , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: Chronic and recurrent upper respiratory tract infection and inflammation is common in patients with nasopharyngeal carcinoma (NPC) post chemo-radiotherapy (CRT). Whether it is due to intrinsic (e.g., host-defense mechanisms of the epithelium), epigenetic or extrinsic factors is not fully understood. MATERIALS AND METHODS: Tissue biopsies of the middle turbinate (MT) and inferior turbinate (IT) from NPC patients after CRT (mean of 3 years, n = 39) were compared with the IT biopsies from healthy subjects (n = 44). The epithelial ultrastructure was examined by transmission electron microscope (TEM). mRNA and protein expressions of epithelial stem/progenitor cells markers, as well markers of cell proliferation and differentiation markers was analyzed. RESULTS: Abnormal epithelial architecture was observed in all tissue samples of NPC patients. Significantly decreased expression levels of mRNA and protein levels for p63 (basal cells), Ki67 (cell proliferation), p63+/KRT5+ (epithelial stem/progenitor cells), MUC5AC and MUC5B (secretary proteins from goblet cells), alpha-tubulin, beta-tubulin and TAp73 (ciliated cells), DNAH5 and DNAI1 and RSPH4A (microtubule assemblies of motile cilia), FOXJ1 and CP110 (ciliogenesis-associated markers) were evident in MT and IT biopsies from NPC patients when compared to healthy controls. CONCLUSION: CRT causes long-term defects of epithelial barrier functions and increases the susceptibility of these patients to upper respiratory tract infection and inflammation.
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Células Epiteliais , Neoplasias Nasofaríngeas , Quimiorradioterapia , Humanos , Mucosa Nasal , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genéticaAssuntos
Cílios/patologia , Transtornos da Motilidade Ciliar/genética , Mucosa Nasal/metabolismo , RNA/genética , Rinite Alérgica/genética , Análise Serial de Tecidos/métodos , Adulto , Biópsia , Cílios/metabolismo , Transtornos da Motilidade Ciliar/etiologia , Transtornos da Motilidade Ciliar/metabolismo , Feminino , Humanos , Masculino , Mucosa Nasal/patologia , Mucosa Olfatória/metabolismo , Mucosa Olfatória/patologia , Rinite Alérgica/complicações , Rinite Alérgica/metabolismoRESUMO
The Epstein-Barr virus (EBV) is tightly associated with a variety of human tumors, including Burkitt lymphoma and acquired immune deficiency syndrome-related lymphoma of B-cell origin, as well as nasopharyngeal carcinoma and gastric cancer of epithelial origin. The virus latently infects the host cells and expresses proteins and non-coding RNAs to achieve malignancy. MicroRNAs (miRNAs or miRs) are small RNAs consisting of 19-25 nucleotides, which directly bind to the 3'-untranslated region of mRNAs to promote degradation and inhibit translation of mRNAs. EBV-encoded miRs are generated from two regions of the viral genome, within the apoptosis regulator BHRF1 gene locus and near the BamHI A region in a latency type-dependent manner. In addition, EBV-encoded miRs epigenetically regulate the expression of molecules that are effectors of the cell cycle progression, migration, apoptosis and innate immunity, serving a vital role in supporting viral replication and occurrence of EBV-associated tumors. The feasibility of using such miRs as biomarkers for the diagnosis and prognosis of EBV-associated tumors is currently under investigation.
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INTRODUCTION: The pathways underlying chronic rhinosinusitis with nasal polyps (CRSwNP) are unclear. We conducted genome-wide gene expression analysis to determine pathways and candidate gene sets associated with CRSwNP. METHODS: We performed whole-transcriptome RNA sequencing on 42 polyp (CRSwNP-NP) and 33 paired nonpolyp inferior turbinate (CRSwNP-IT) tissues from patients with CRSwNP and 28 inferior turbinate samples from non-CRS controls (CS-IT). We analysed the differentially expressed genes (DEGs) and the gene sets that were enriched in functional pathways. RESULTS: Principal component-informed analysis revealed cilium function and immune regulation as the two main Gene Ontology (GO) categories differentiating CRSwNP patients from controls. We detected 6182 and 1592 DEGs between CRSwNP-NP versus CS-IT and between CRSwNP-NP versus CRSwNP-IT tissues, respectively. Atopy status did not have a major impact on gene expression in various tissues. GO analysis on these DEGs implicated extracellular matrix (ECM) disassembly, O-glycan processing, angiogenesis and host viral response in CRSwNP pathogenesis. Ingenuity Pathway Analysis identified significant enrichment of type 1 interferon signalling and axonal guidance canonical pathways, angiogenesis, and collagen and fibrotic changes in CRSwNP (CRSwNP-NP and CRSwNP-IT) tissues compared with CS-IT. Finally, gene set enrichment analysis implicated sets of genes co-regulated in processes associated with inflammatory response and aberrant cell differentiation in polyp formation. CONCLUSIONS: Gene signatures involved in defective host defences (including cilia dysfunction and immune dysregulation), inflammation and abnormal metabolism of ECM are implicated in CRSwNP. Functional validation of these gene expression patterns will open opportunities for CRSwNP therapeutic interventions such as biologics and immunomodulators.
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Pólipos Nasais/genética , Rinite/genética , Sinusite/genética , Transcriptoma , Doença Crônica , Estudos Transversais , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/imunologia , Rinite/complicações , Rinite/imunologia , Sinusite/complicações , Sinusite/imunologiaRESUMO
BACKGROUND: Upper airway inflammatory diseases are associated with abnormal expression of nasal epithelial forkhead-box J1 (FOXJ1) which regulates motile cilia formation. We sought to investigate whether aberrant FOXJ1 localizations correlate with the disease severity and the co-existence of allergic rhinitis (AR) or asthma in patients with nasal polyps (NPs). METHODS: We elucidated localization patterns of FOXJ1 by performing immunofluorescence assays in nasal specimens and cytospin samples from controls and patients with NPs. We also assayed mRNA expression levels of FOXJ1 by using quantitative real-time polymerase chain reaction. Four localization patterns [normal (N), intermediate (I), mislocalization (M), and absence (A)] were defined. A semi-quantitative scoring system was applied for demonstrating FOXJ1 localization in five areas per paraffin section, with individual sections being scored between 0 and 2. RESULTS: FOXJ1 localization score was significantly higher in samples from NPs than in controls (P < 0.001). Elevated FOXJ1 localization scores and down-regulation of FOXJ1 mRNA levels were observed in NPs with co-existing AR or asthma (all P < 0.05). Moreover, FOXJ1 localization scores positively correlated with Lund-Mackay score (r = 0.362, P = 0.007). Of primary cytospin samples, the mean percentage of patients with FOXJ1 localization patterns N, I, M and A was 15.0%, 3.3%, 53.3% and 28.3% in NPs, and 82.5%, 5.0%, 5.0% and 7.5% in controls, respectively (P < 0.001). CONCLUSIONS: Aberrant localization of FOXJ1 correlates with the severity and co-existence of AR or asthma in patients with NPs, and might be a novel target for assessment and intervention in NPs.
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We retrospectively reviewed the cases of 85 patients with primary sinonasal malignancies who had undergone endoscopic surgery with curative intent achieved by "regional resection." Our goal was to assess the efficacy of endoscopic surgical treatment vis-à-vis traditional open surgery. Kaplan-Meier data analysis revealed that the 1-, 3-, and 5-year disease-specific survival rates were 82, 60, and 49%, respectively. Multivariate Cox model survival analysis revealed that male sex, certain pathologic types of cancer (i.e., undifferentiated carcinoma, olfactory neuroblastoma, and rhabdomyosarcoma), and T3/T4 category negatively impacted survival (adjusted hazard ratios: 3.601, 0.012, 0.287, 0.068, and 0.339, respectively; p < 0.05 for all). We also performed a separate analysis of 47 patients who had category T3 or T4 cancer to determine if the type of surgical approach is a prognostic factor. For this, we identified 20 new patients who had undergone open resection, and we compared them to 27 of our endoscopically treated patients who had similar clinical characteristics. We found that the type of surgical approach did not appear to be a prognostic factor (p > 0.10), although those patients who had undergone endoscopic resection had significantly shorter hospital stays (p < 0.001). We conclude that patients with primary sinonasal malignancies who are treated with endoscopic surgery have acceptable survival rates and therefore endoscopic surgery is justified in the hands of highly experienced surgeons in selected cases.