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BACKGROUND: Numerous observational studies have highlighted associations of genetic predisposition of head and neck squamous cell carcinoma (HNSCC) with diverse risk factors, but these findings are constrained by design limitations of observational studies. In this study, we utilized a phenome-wide association study (PheWAS) approach, incorporating a polygenic risk score (PRS) derived from a wide array of genomic variants, to systematically investigate phenotypes associated with genetic predisposition to HNSCC. Furthermore, we validated our findings across heterogeneous cohorts, enhancing the robustness and generalizability of our results. METHODS: We derived PRSs for HNSCC and its subgroups, oropharyngeal cancer and oral cancer, using large-scale genome-wide association study summary statistics from the Genetic Associations and Mechanisms in Oncology Network. We conducted a comprehensive investigation, leveraging genotyping data and electronic health records from 308,492 individuals in the UK Biobank and 38,401 individuals in the Penn Medicine Biobank (PMBB), and subsequently performed PheWAS to elucidate the associations between PRS and a wide spectrum of phenotypes. RESULTS: We revealed the HNSCC PRS showed significant association with phenotypes related to tobacco use disorder (OR, 1.06; 95% CI, 1.05-1.08; P = 3.50 × 10-15), alcoholism (OR, 1.06; 95% CI, 1.04-1.09; P = 6.14 × 10-9), alcohol-related disorders (OR, 1.08; 95% CI, 1.05-1.11; P = 1.09 × 10-8), emphysema (OR, 1.11; 95% CI, 1.06-1.16; P = 5.48 × 10-6), chronic airway obstruction (OR, 1.05; 95% CI, 1.03-1.07; P = 2.64 × 10-5), and cancer of bronchus (OR, 1.08; 95% CI, 1.04-1.13; P = 4.68 × 10-5). These findings were replicated in the PMBB cohort, and sensitivity analyses, including the exclusion of HNSCC cases and the major histocompatibility complex locus, confirmed the robustness of these associations. Additionally, we identified significant associations between HNSCC PRS and lifestyle factors related to smoking and alcohol consumption. CONCLUSIONS: The study demonstrated the potential of PRS-based PheWAS in revealing associations between genetic risk factors for HNSCC and various phenotypic traits. The findings emphasized the importance of considering genetic susceptibility in understanding HNSCC and highlighted shared genetic bases between HNSCC and other health conditions and lifestyles.
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Estudo de Associação Genômica Ampla , Neoplasias de Cabeça e Pescoço , Humanos , Bancos de Espécimes Biológicos , Predisposição Genética para Doença , Estratificação de Risco Genético , Estudo de Associação Genômica Ampla/métodos , Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
BACKGROUND: Previous studies have shown that lifestyle/environmental factors could accelerate the development of age-related hearing loss (ARHL). However, there has not yet been a study investigating the joint association among genetics, lifestyle/environmental factors, and adherence to healthy lifestyle for risk of ARHL. We aimed to assess the association between ARHL genetic variants, lifestyle/environmental factors, and adherence to healthy lifestyle as pertains to risk of ARHL. METHODS: This case-control study included 376,464 European individuals aged 40 to 69 years, enrolled between 2006 and 2010 in the UK Biobank (UKBB). As a replication set, we also included a total of 26,523 individuals considered of European ancestry and 9834 individuals considered of African-American ancestry through the Penn Medicine Biobank (PMBB). The polygenic risk score (PRS) for ARHL was derived from a sensorineural hearing loss genome-wide association study from the FinnGen Consortium and categorized as low, intermediate, high, and very high. We selected lifestyle/environmental factors that have been previously studied in association with hearing loss. A composite healthy lifestyle score was determined using seven selected lifestyle behaviors and one environmental factor. RESULTS: Of the 376,464 participants, 87,066 (23.1%) cases belonged to the ARHL group, and 289,398 (76.9%) individuals comprised the control group in the UKBB. A very high PRS for ARHL had a 49% higher risk of ARHL than those with low PRS (adjusted OR, 1.49; 95% CI, 1.36-1.62; P < .001), which was replicated in the PMBB cohort. A very poor lifestyle was also associated with risk of ARHL (adjusted OR, 3.03; 95% CI, 2.75-3.35; P < .001). These risk factors showed joint effects with the risk of ARHL. Conversely, adherence to healthy lifestyle in relation to hearing mostly attenuated the risk of ARHL even in individuals with very high PRS (adjusted OR, 0.21; 95% CI, 0.09-0.52; P < .001). CONCLUSIONS: Our findings of this study demonstrated a significant joint association between genetic and lifestyle factors regarding ARHL. In addition, our analysis suggested that lifestyle adherence in individuals with high genetic risk could reduce the risk of ARHL.
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Estudo de Associação Genômica Ampla , Presbiacusia , Humanos , Estudos de Casos e Controles , Fatores de Risco , Presbiacusia/genética , Estilo de Vida Saudável , Predisposição Genética para DoençaRESUMO
PURPOSE: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. METHODS: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. RESULTS: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. CONCLUSION: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. TRIAL REGISTRATION: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 .
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BACKGROUND: Various cancer stem cell (CSC) biomarkers and the genes encoding them in head and neck squamous cell carcinoma (HNSCC) have been identified and evaluated. However, the validity of these factors in the prognosis of HNSCC has been questioned and remains unclear. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC, using five publicly available HNSCC cohorts. METHODS: To predict the prognosis of patients with HNSCC, we developed and validated the expression signatures of CSC biomarker genes whose mRNA expression levels correlated with at least one of the four CSC genes (CD44, MET, ALDH1A1, and BMI1). RESULTS: Patients in The Cancer Genome Atlas (TCGA) HNSCC cohort were classified into CSC gene expression-associated high-risk (CSC-HR; n = 285) and CSC gene expression-associated low-risk (CSC-LR; n = 281) subgroups. The 5-year overall survival and recurrence-free survival rates were significantly lower in the CSC-HR subgroup than in the CSC-LR subgroup (p = 0.04 and 0.02, respectively). The clinical significance of the CSC gene expression signature was validated using four independent cohorts. Analysis using Cox proportional hazards models showed that the CSC gene expression signature was an independent prognostic factor of non-oropharyngeal HNSCC which mostly indicates HPV (-) status. Furthermore, the CSC gene expression signature was associated with the prognosis of HNSCC patients who received radiotherapy. CONCLUSION: The CSC gene expression signature is associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC, especially in cases with HPV (-) status who were classified in more detail.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Transcriptoma , Neoplasias de Cabeça e Pescoço/patologia , Infecções por Papillomavirus/patologia , Carcinoma de Células Escamosas/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Células-Tronco Neoplásicas/metabolismo , RNA Mensageiro/metabolismoRESUMO
OBJECTIVES: To evaluate the prevalence of insomnia in patients with laryngopharyngeal reflux (LPR) and to analyze the relationship between the severity of insomnia and LPR-related symptoms. METHODS: We analyzed 69 patients with LPR and 61 healthy controls. The LPR was confirmed via the 24-h hypopharyngeal-esophageal multichannel intraluminal impedance pH monitoring. Reflux symptoms and sleep disturbances were assessed using the Reflux Symptom Index and Insomnia Severity Index. We compared the prevalence of insomnia between the two groups. We analyzed the relationship between reflux symptoms and severity of insomnia. RESULTS: The prevalence of insomnia was significantly higher in patients with LPR than in healthy controls (46.3% vs. 29.5%; p = 0.049). The severity of reflux-related symptoms was correlated with insomnia severity (rho = 0.44; p < 0.001). Patients with LPR with nighttime reflux were more likely to have sleep disturbances than patients with LPR without nighttime reflux. CONCLUSION: Patients with LPR are more likely to experience insomnia than healthy controls, and the severity of reflux symptoms was related to the severity of insomnia.
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Esofagite Péptica , Refluxo Laringofaríngeo , Distúrbios do Início e da Manutenção do Sono , Impedância Elétrica , Monitoramento do pH Esofágico , Humanos , Hipofaringe , Refluxo Laringofaríngeo/complicações , Refluxo Laringofaríngeo/diagnóstico , Refluxo Laringofaríngeo/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/etiologiaRESUMO
OBJECTIVE: To estimate the risk of developing autoimmune disease in patients diagnosed having recurrent aphthous stomatitis (RAS) through a nationwide population-based cohort study. METHODS: This study included two group of patients who had three or more episodes with aphthae diagnosed from their physician (RAS group) and a similar matched group of patients without aphthae (control group). Both groups were collected within the period of 2005-2007 from the Korean National Health Insurances claims database. Non-RAS cohort was matched after frequency matching. The final enrolled subjects were observed during a follow-up period from 2008 to 2015 and those who received autoimmune diseases diagnoses during follow-up were identified. The hazard ratio (HR) for developing autoimmune diseases was estimated. RESULTS: A total of 4,637 patients with RAS and 4,637 controls were included. The risk of overall autoimmune diseases was significantly increased in the RAS group (adjusted HR [aHR)], 1.19). With regard to each disease entity, patients with RAS showed an increased risk of Behcet's disease (31.16), systemic lupus erythematous (SLE) (1.74), ankylosing spondylitis (AS) (1.47), gout (1.47), Hashimoto thyroiditis (1.42), Graves' disease (1.37), and rheumatoid arthritis (RA) (1.19). CONCLUSION: RAS-like lesion may be an early sign of systemic autoimmune disease, as it was associated with an increased risk of Graves' disease, Hashimoto thyroiditis, SLE, AS, gout, RA, and Behcet's disease from real-world data.
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Doenças Autoimunes , Síndrome de Behçet , Estomatite Aftosa , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Estudos de Coortes , Humanos , Projetos de Pesquisa , Estomatite Aftosa/epidemiologia , Estomatite Aftosa/etiologiaRESUMO
PURPOSE: This study aimed to analyze pharyngeal reflux episodes in patients with suspected LPR versus healthy subjects using 24-h MII-pH monitoring. METHODS: One hundred twenty-one patients who visited our clinic with a chief complaint of LPR-related symptoms and underwent 24-h MII-pH monitoring were enrolled prospectively. Also, 27 healthy subjects were enrolled and underwent 24-h MII-pH monitoring during the same period. We analyzed sensitivity, specificity, and accuracy comprehensively to determine appropriate cut-off values of pharyngeal reflux episodes in 24-h MII-pH monitoring to diagnose patients with LPR. RESULTS: Twenty-nine of 121 patients with suspected LPR showed no pharyngeal reflux episodes, while 92 showed more than one pharyngeal reflux event. In contrast, the 22 healthy subjects showed no pharyngeal reflux episodes, three showed one reflux event, and two showed two reflux events. A cut-off value of ≥ 1 showed best accuracy reflected by combined sensitivity and specificity values, while ≥ 2 demonstrated better specificity with slight loss of sensitivity and slightly lower overall accuracy, suggesting cut-off value of ≥ 1 pharyngeal reflux episodes is a good clinical indicator. CONCLUSION: A cut-off value of ≥ 1 in pharyngeal reflux episodes on 24-h MII-pH monitoring in patients with suspected LPR might be an acceptable diagnostic tool for LPR.
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Refluxo Laringofaríngeo , Impedância Elétrica , Monitoramento do pH Esofágico , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Refluxo Laringofaríngeo/complicações , Refluxo Laringofaríngeo/diagnóstico , Estudos ProspectivosRESUMO
Several studies have highlighted the diagnostic potential of salivary microRNA (miRNA) in head and neck squamous cell cancer (HNSCC). The purpose of this meta-analysis was to summarize published studies and evaluate the diagnostic accuracy of salivary miRNA in HNSCC detection. In this meta-analysis, we systematically searched PubMed, EMBASE, and Cochrane Library databases for studies on miRNA and HNSCC diagnosis. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with a summary receiver-operating characteristic curve were calculated using a bivariate random-effect meta-analysis model. Furthermore, subgroup analyses were conducted to explore the main sources of heterogeneity. Seventeen studies from ten articles, including 23 miRNA and a total of 759 subjects, were included in this meta-analysis. The pooled sensitivity and specificity of salivary miRNA in the diagnosis of HNSCC were 0.697 (95% CI: 0.644-0.744) and 0.868 (95% CI: 0.811-0.910), respectively. The overall area under the curve was 0.803 with a DOR of 12.915 (95% CI: 9.512-17.534). Salivary miRNAs are a promising non-invasive diagnostic biomarker with moderate accuracy for HNSCC. These results must be verified by large-scale prospective studies.
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Neoplasias de Cabeça e Pescoço/diagnóstico , MicroRNAs/genética , Saliva/química , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Neoplasias de Cabeça e Pescoço/genética , Humanos , Razão de Chances , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
BACKGROUND: Conventionally, the Thiersch operation has typically involved blind positioning of the sling, and sling tension is subjectively based on a rule-of-thumb estimate. The aim of this study was to describe standardized methods for performing the Thiersch operation. METHODS: Seventeen patients with fecal incontinence underwent the calibrated method of the Thiersch procedure. As an encircling sling, a 6-mm-wide silastic tube was used. Through 4 minimal perianal skin incisions, the sling was placed proximal to the anal skin 3 cm from the anal verge and 4 cm in depth. The circumference of the sling was 10 cm in length. Results were assessed by clinical responses and by comparing pre- and postoperative Wexner scores. The data were collected retrospectively. RESULTS: The median follow-up period was 9 months (range 6-19). In 16 out of 17 fecal incontinence patients (94.1%), the median Wexner incontinence score was 0 (range 0-3) postoperatively. Localized sepsis developed in three cases (17.7%, 3/17), which were controlled with drainage and antibiotics. Fecal impaction occurred in one case (5.9%, 1/17). There was no removal or breakage of the inserted sling. CONCLUSIONS: The elasticity of the silastic tube reduced the incidence of sling breakage. According to the standardized method, the sling was placed external to the external anal sphincter muscle and at the junction of the external anal sphincter muscle and puborectalis muscle. Fecal incontinence was controlled effectively, and the incidence of fecal impaction was negligible. High reproducibility was observed with this method.
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Canal Anal/cirurgia , Defecação/fisiologia , Procedimentos Cirúrgicos do Sistema Digestório/normas , Incontinência Fecal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Canal Anal/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The purpose of this study was to evaluate alterations in gray matter volume (GMV) and cerebral blood flow (CBF) using structural MRI and arterial spin labeling (ASL) perfusion MRI, respectively, in burning mouth syndrome (BMS) patients METHODS: We prospectively enrolled 12 patients with BMS and 14 healthy controls. Volumetric T1-weighted magnetization-prepared rapid gradient-echo imaging and pseudo-continuous ASL were performed to obtain GMV and CBF, respectively. We analyzed differences in the GMV and CBF between the two groups, and their correlations with clinical parameters. RESULTS: The GMV was smaller in the left thalamus and left middle temporal gyrus in the BMS group when compared to controls. Regional CBF in the BMS group was significantly decreased in the left middle temporal gyrus, left insula, right middle temporal gyrus, and right insula compared with controls. In BMS patients, there was a significant correlation between GMV and pain severity in the left middle temporal gyrus. CONCLUSION: The reduced GMV seen in the thalami of BMS patients is consistent with the pattern observed in those with chronic pain disease, which implies that the pathogenesis of BMS may be associated with atrophy of the brain structures associated with thalamocortical processing. In addition, changes in CBF in the insula and middle temporal gyrus were also observed.
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Encéfalo/patologia , Síndrome da Ardência Bucal/patologia , Circulação Cerebrovascular , Substância Cinzenta/patologia , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: Preoperative detection of bone invasion is important in cases of gingival cancer. The aim of this study was to compare the diagnostic value of 3 imaging methods for the detection of bone invasion in upper and lower gingival cancer: computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) and CT. MATERIALS AND METHODS: This retrospective cohort study enrolled patients who underwent a maxillectomy or a mandibulectomy for gingival cancer. Each preoperative image (CT, MRI, or PET/CT) was reviewed for the presence of bone invasion, and the possibility for bone invasion was graded. These results were verified with pathology reports. Sensitivity, specificity, positive predictive value, and negative predictive value for the detection of mandibular involvement in alveolar bone were calculated, and a receiver operating characteristics (ROC) curve analysis was performed. RESULTS: Forty patients (27 men and 13 women) were enrolled. Pathologic examination disclosed bone invasion in 25 of the 40 patients. Of these patients, 13 had maxillary and 12 had mandibular alveolus involvement. The diagnostic accuracy of CT (90.0%) was highest among the 3 modalities for the detection of bone invasion. In the ROC curve analysis, values for the area under the curve for upper gingival cancer were lower than those for lower gingival cancer. CONCLUSIONS: The 3 imaging methods were less sensitive for the detection of bone invasion in upper gingival cancer than in lower gingival cancer. Cases of upper gingival cancer should be evaluated more carefully for bone invasion before surgery.
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Neoplasias Gengivais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gengiva/diagnóstico por imagem , Gengiva/patologia , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Maxila/diagnóstico por imagem , Maxila/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
PURPOSE: Intraoral removal of submandibular sialoliths is a surgical technique for the treatment of sialolithiasis and is reported to have excellent outcomes. The aim of this study was to determine the risk factors leading to complications of this procedure. PATIENTS AND METHODS: The medical records of 200 patients who had undergone intraoral removal of sialoliths from January 2006 through June 2015 were retrospectively reviewed. A telephone survey was used to check postoperative symptoms. Dry mouth, wound infection, lingual nerve dysfunction, and recurrence were considered complications. Computed tomograms of the neck were reviewed for location, shape, number, and size of the stone. RESULTS: Forty-four patients reported a complication. The incidence of complications was significantly higher in patients with stones in the proximal region of the salivary duct (proximal group) than in those with middle or distally located stones (middle/distal group; P < .05). The average stone size was larger in the proximal group; the operation time and length of admission also were longer in the proximal group, with a statistically significant difference (P < .05). Complaints of lingual nerve dysfunction were significantly higher in the proximal group than in the middle/distal group (P < .05). CONCLUSION: Patients with proximally located stones had more complications, especially lingual nerve dysfunction, than those with middle or distally located stones. The former group also required a longer operation time and hospital stay.
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Complicações Pós-Operatórias/etiologia , Cálculos das Glândulas Salivares/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Cálculos dos Ductos Salivares/epidemiologia , Cálculos dos Ductos Salivares/etiologia , Cálculos das Glândulas Salivares/diagnóstico por imagem , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
PURPOSE: To assess the ultrasonographic features affect accuracy of extrathyroid extension (ETE) evaluation on preoperative ultrasonography (US) in papillary thyroid microcarcinoma (PTMC). METHODS: Of the total patients who underwent thyroid surgery, 516 patients with a tumor measuring less than 1 cm on preoperative US were enrolled in this study. One blinded head and neck radiologist reviewed the preoperative US images to evaluate the US features of PTMC, and the pathologic reports were reviewed. The diagnostic accuracy rates, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, were calculated, and the factors associated with false-negative and false-positive results for ETE were analyzed. RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy for predicting ETE according to sonographic criteria were 32.8%, 87.5%, 51.0%, 76.6%, and 71.7%, respectively. Non-adjacent to the trachea and unilateral lesion on US were significant factors associated with false-negative results. CONCLUSION: Size, shape, and location of PTMC on US are important factors that affect the US results in ETE evaluation.
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Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Ultrassonografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto JovemRESUMO
Although the genetic alteration of CUB and Sushi multiple domains 1 (CSMD1) is known to be associated with poor prognosis in several cancers, there is a lack of clinical relevance in head and neck cancer. The aim of this study was to offer insight into the clinical significance of CSMD1, utilizing a multimodal approach that leverages publicly available independent genome-wide expression datasets. CSMD1-related genes were found and analyzed to examine the clinical significance of CSMD1 inactivation in the HNSCC cohort of publicly available databases. We analyzed the frequency of somatic mutations, clinicopathologic characteristics, association with immunotherapy-related gene signatures, and the pathways of gene signatures. We found 363 CSMD1-related genes. The prognosis of the CSMD1-inactivated subgroup was poor. FBXW7, HLA-A, MED1, NOTCH2, NOTCH3, and TP53 had higher mutation rates in the CSMD1-inactivated subgroups. The Interferon-gamma score and immune signature score were elevated in CSMD1-inactivated subgroups. We identified several CSMD1-related pathways, such as the phosphatidylinositol signaling system and inositol phosphate metabolism. Our study using three large and independent datasets suggests that CSMD1-related gene signatures are associated with the prognosis of HNSCC patients.
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Proteínas de Membrana/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Análise Multivariada , Mutação/genética , Modelos de Riscos Proporcionais , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Resultado do Tratamento , Proteínas Supressoras de TumorRESUMO
BACKGROUND: Although numerous recent studies have implicated a role for interleukin 17(IL17) in tumor development, the mechanisms of IL17 involvement are still uncharacterized. The aims of this study were to determine whether single nucleotide polymorphisms (SNPs) in IL17 and IL17R contribute to the development of papillary thyroid cancer (PTC) and to assess the relationship between IL17 and IL17R SNPs and the clinicopathologic characteristics of PTC. MATERIALS AND METHODS: Eight SNPs located within the IL17A, IL17RA, and IL17RB genes were genotyped using direct sequencing in 94 patients with PTC and 260 patients without PTC (controls). Genetic data were analyzed using commercially available software. Statistical analyses were then performed to examine the relationships between these SNPs and the clinicopathologic characteristics of PTC. RESULTS: Genotyping analysis demonstrated that the IL17RA SNP rs4819554 (codominant model 1, odds ratio (OR)=0.39, P=0.001) and the IL17RB SNP rs1025689 (dominant model, OR=0.59, P=0.043) were significantly associated with lack of PTC. Interestingly, the IL17A SNP rs2275913 (codominant model 2, OR=0.19, P=0.034) was significantly associated with lack of multifocality. Furthermore, the IL17RA SNP rs4819554 (dominant model, OR=0.25, P=0.010) was significantly associated with lack of cancer bilaterality. CONCLUSION: In this study of SNPs in the IL17 and IL17R genes in patients with PTC, we demonstrated that IL17RA polymorphisms can influence both the development and the bilaterality of PTC.
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Interleucina-17/genética , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-17/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Alelos , Sequência de Bases , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Razão de Chances , República da Coreia , Software , Neoplasias da Glândula Tireoide/etnologiaRESUMO
BACKGROUND: Endoscopic submucosal dissection (ESD) has been revealed as an effective treatment of early gastric neoplasm and should be performed under sedation with adequate pain control. Magnesium sulfate has analgesic, sedative, and sympatholytic properties. This study examined the effects of intravenous magnesium 50 mg/kg administered before ESD for gastric neoplasm on analgesic and sedative consumptions during ESD and pain after ESD. METHODS: In this randomized, double-blind, and prospective study, patients undergoing ESD randomly received either intravenous magnesium sulfate 50 mg/kg (magnesium group n = 30) or the same volume of normal saline (control group n = 30) over 10 min before the start of sedation. Fentanyl consumption during ESD was the primary end point. Hemodynamics was recorded during the procedure, and abdominal pain was evaluated at 30 min, 6 h, and 24 h after ESD. RESULTS: During ESD, fentanyl consumption was 24% less in the magnesium group than in the control group (96 ± 27 vs. 126 ± 41 µg, mean ± SD; p = 0.002), although there was no significant difference in propofol consumption (p = 0.317). In addition, magnesium attenuated the elevation of mean blood pressure at the time of epinephrine submucosal injection (p = 0.038) and 5 min after submucosal dissection (p = 0.004). Less patients of the magnesium group compared to the control group requested for additional analgesics in the recovery room (14 vs. 38 %, p = 0.043), and the intensity of abdominal pain was lower at 30 min after ESD in the magnesium group (p = 0.034). CONCLUSIONS: A single-dose intravenous administration of magnesium 50 mg/kg before sedation reduced analgesic requirements both during and after ESD for gastric neoplasm without adverse effects. In addition, magnesium contributed to stable hemodynamics throughout the procedure.
Assuntos
Dor Abdominal/prevenção & controle , Analgésicos/administração & dosagem , Gastroscopia , Hipnóticos e Sedativos/administração & dosagem , Sulfato de Magnésio/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Neoplasias Gástricas/cirurgia , Dor Abdominal/etiologia , Adenocarcinoma/cirurgia , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos/uso terapêutico , Dissecação/métodos , Método Duplo-Cego , Feminino , Mucosa Gástrica/cirurgia , Humanos , Hipnóticos e Sedativos/uso terapêutico , Infusões Intravenosas , Sulfato de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The surgical extent and indication for treatment in patients with papillary thyroid microcarcinoma (PTMC) remain a controversial issue. The aim of this study was to investigate the predictive factor for contralateral occult carcinoma in patients with unilateral PTMC by preoperative ultrasonographic and pathological features. METHODS: Of the total patients who underwent thyroidectomy, 455 patients with PTMC confined to one unilateral lobe as diagnosed using preoperative ultrasonography (US) were enrolled in the study. Occult contralateral carcinoma was defined as tumor foci in the contralateral lobe that was not detected preoperatively, but was detected pathologically. All patients underwent preoperative US review to investigate the US features of PTMC such as laterality, location, size, internal component, echogenicity, margin, calcification shape, multifocality, bilaterality, extrathyroidal extension, and location with respect to the trachea. Clinicopathological data were also analyzed. RESULTS: Of the total of 455 patients who underwent total thyroidectomy for preoperatively detected unilateral PTMC, 71 patients (15.6 %) had contralateral occult carcinoma. Clinicopathological characteristics did not significantly differ between patients with and without contralateral occult carcinoma. Multivariate analysis showed that the absence of a well-defined margin and the presence of a probably benign nodule in the contralateral lobe were independent predictive factors for contralateral occult carcinoma in patients with unilateral PTMC in preoperative US images. CONCLUSION: We demonstrated that an absence of a well-defined margin and the presence of a probably benign nodule in the contralateral lobe were independent predictive factors for contralateral occult carcinoma in patients with unilateral PTMC in preoperative US. The prediction of contralateral occult carcinoma in unilateral PTMC using preoperative US features could be useful for determining the optical extent of surgery.
Assuntos
Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Calcinose/diagnóstico por imagem , Calcinose/patologia , Carcinoma Papilar/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Período Pré-Operatório , Fatores de Risco , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Neoplasias da Traqueia/patologia , UltrassonografiaRESUMO
BACKGROUND: Endoscopic submucosal dissection (ESD) is the gold standard technique for en bloc resection of large superficial tumors in the upper and lower gastrointestinal tract. Little is known about the management of epigastric pain after ESD of gastric neoplasms. This study investigated the utility and safety of single-dose, perioperative, intravenous dexamethasone for epigastric pain relief following ESD. METHODS: The efficacy of intravenous dexamethasone 0.15 mg/kg (DEXA group) compared with saline-only placebo (placebo) for epigastric pain after ESD of early gastric neoplasms was assessed in a double-blinded, placebo-controlled trial. Patients completed a questionnaire about present pain intensity (PPI) and short-form McGill pain (SF-MP) categories for immediate and 6-, 12-, and 24-h postoperative periods. The primary outcome variable was PPI at 6 h following ESD. Secondary outcome variables included pain medication, SF-MP scores, complications, second-look endoscopic findings, and length of stay. RESULTS: A total of 36 patients participated in the study. The mean 6-h PPI value was lower (p < 0.001) in the DEXA group (1.61 ± 0.21) than in the placebo group (2.66 ± 0.19). The total 6-h SF-MP score, especially the sensory domain, was higher (p = 0.054) in the placebo group (11.56 ± 0.75) than in the DEXA group (8.89 ± 0.75). Tramadol for epigastric pain relief was more frequent (p = 0.026) in the placebo group (44.4%) than in the DEXA group (11.1%). No differences were noted between groups in length of stay or complications, including acute or delayed bleeding. The distribution of artificial ulcer patterns at 48-h post-ESD as determined by second-look endoscopy was similar in both groups. CONCLUSION: Single-dose perioperative intravenous dexamethasone after ESD effectively relieved epigastric pain 6 h postoperatively.