RESUMO
The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice.
Assuntos
Perda Auditiva Neurossensorial , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores , Humanos , Masculino , Feminino , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/genética , Criança , Pré-Escolar , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/patologia , Adulto , Japão , Adolescente , Mutação , Lactente , Sequenciamento de Nucleotídeos em Larga Escala , Estudos de Coortes , Pessoa de Meia-Idade , População do Leste AsiáticoRESUMO
BACKGROUND AND AIMS: Superficial pharyngeal squamous cell carcinoma (PSCC) has received increasing attention as a therapeutic target in the GI field with recent innovations in endoscopic submucosal dissection (ESD). However, there are currently no defined criteria for the application of ESD to superficial PSCC. One of the problems encountered during follow-up after ESD is cervical lymph node metastasis (LNM). Identifying the clinicopathologic predictors of cervical LNM can help to provide a basis for the refinement of therapeutic strategies for superficial PSCC. METHODS: The risk of cervical LNM was evaluated in 331 patients with superficial PSCC who underwent initial ESD between 2008 and 2021. Since tumor size, rather than depth, is the dominant factor in the current TNM classification for PSCC, the correlation between tumor size and thickness was investigated. RESULTS: The median follow-up period was 4.8 years. The cumulative 5-year cervical LNM rate was 6.1%. Multivariate Cox proportional hazards regression analysis identified tumor thickness ≥1000 µm and lymphatic invasion as significant independent predictors. Among 204 cases with subepithelial invasion, both factors were also revealed to be significant independent predictors, suggesting that tumor thickness was superior to tumor size in predicting cervical LNM. Despite the positive correlation between tumor thickness and size, there was noticeable variability in the values (R = .20), and the current staging was inadequate to identify groups at high risk for cervical LNM. CONCLUSIONS: Tumor thickness and lymphatic invasion are validated as significant independent predictors for cervical LNM and can be useful indicators to optimize the therapeutic strategies for superficial PSCC.
Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias de Cabeça e Pescoço , Humanos , Metástase Linfática , Linfonodos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.
Assuntos
Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Estudos de Associação Genética , Perda Auditiva/genética , Perda Auditiva Central , Perda Auditiva Neurossensorial/genética , Humanos , Japão , Proteínas de Membrana/genética , MutaçãoRESUMO
BACKGROUND AND AIMS: Superficial pharyngeal cancers are being detected and treated using endoscopy in many medical facilities with increasing frequency. However, the reports focus on the hypopharynx. We identified reliable treatments by adapting the method for each region of the pharynx. Here, we introduce our methods for treating various pharyngeal regions and show their long-term results. METHODS: Of 308 consecutive patients who underwent pharyngeal endoscopic submucosal dissection between February 2007 and December 2018 at our institution, we selected 293 patients who were diagnosed histologically with squamous cell carcinoma. The patients were divided into 4 groups based on the specific location of superficial pharyngeal lesions and the short- and long-term outcomes, such as technical success, adverse events, overall survival, and case-specific survival, were evaluated. RESULTS: The procedure time was 51 minutes at location A where cancer develops most commonly. The rate of en bloc resection was 99.4%, and the R0 resection rate was 82.6%. With regard to adverse events, there were 2 cases of postoperative hemorrhage, both treated with endoscopic hemostasis. The average observation period was 61.2 months overall, with 14 cases of recurrent lymph node metastasis. The 5-year survival rate was 84.1%, and cause-specific survival was 100%. CONCLUSIONS: Adaptation of the treatment method according to the location of the lesion led to good results. Endoscopic treatment of superficial pharyngeal cancer is both feasible and beneficial.
Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Faríngeas , Endoscopia , Estudos de Viabilidade , Humanos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Faríngeas/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Metachronous cancer rate in the pharynx is high before and after the treatment of esophageal cancer. Endoscopic observation is difficult in the pharynx especially in the postcricoid area. Pharyngeal cancer in the postcricoid area has been often found in advanced stage. Valsalva maneuver has been reported to improve the visibility. METHODS: From May 2017 we introduced a dedicated mouthpiece to conduct Valsalva maneuver. One hundred consecutive patients who had been observed throughout the pharynx by one endoscopist were enrolled. A total of 200 image files before and after introduction were made and reviewed by three endoscopists. We retrospectively evaluated the utility and safety of Valsalva maneuver. RESULTS: The visibility before introduction was Good in three cases, Moderate in 12 cases and Poor in 85 cases. Meanwhile, the visibility after introduction was Good in 58 cases, Moderate in 23 cases, and Poor in 19 cases (P < 0.05). Nine lesions including hypopharyngeal cancer were found and adverse events were not observed in this study. CONCLUSION: The Valsalva maneuver was considered to be a safe and effective method in endoscopic observation of the pharynx.
Assuntos
Endoscopia/métodos , Segunda Neoplasia Primária/patologia , Faringe/patologia , Manobra de Valsalva/fisiologia , Idoso , Estudos de Casos e Controles , Detecção Precoce de Câncer/instrumentação , Detecção Precoce de Câncer/métodos , Endoscopia/estatística & dados numéricos , Desenho de Equipamento/métodos , Neoplasias Esofágicas/patologia , Feminino , Humanos , Neoplasias Hipofaríngeas/diagnóstico , Neoplasias Hipofaríngeas/patologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/epidemiologia , Neoplasias Faríngeas/diagnóstico , Neoplasias Faríngeas/patologia , Estudos Retrospectivos , SegurançaRESUMO
More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.
Assuntos
Suscetibilidade a Doenças , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Alelos , Família , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Genótipo , Perda Auditiva/diagnóstico , Humanos , Japão/epidemiologia , Mutação , Fenótipo , Prevalência , Vigilância em Saúde Pública , SíndromeRESUMO
OBJECTIVES: To present the cardiovascular risk factors in idiopathic sudden sensorineural hearing loss (SSNHL) patients enrolled in a nationwide epidemiological survey of hearing disorders in Japan. MATERIALS AND METHODS: We compiled the cardiovascular risk factors in 3073 idiopathic SSNHL subjects (1621 men and 1452 women) and compared their proportions with controls as part of the National Health and Nutrition Survey in Japan, 2014. The cardiovascular risk factors consisted of drinking and smoking habits, a history of five conditions related to cardiovascular disease and body mass index. RESULTS: The proportion of current smokers was significantly higher among men aged 50-59, 60-69 and 70+ and among women aged 30-39, 40-49 and 60-69. The proportion of patients with a history of diabetes mellitus was significantly higher among men aged 50-59, 60-69 and 70+, but not in women. In addition, male and female SSNHL subjects aged 60-69 showed lower proportions of current drinking; and female SSNHL subjects aged 60-69 showed higher proportions of overweight (BMI ≥25 kg/m2). CONCLUSIONS: The present cross-sectional study revealed showed significantly higher proportions of current smokers among both men and women as well as those with a history of diabetes mellitus among men across many age groups in patients with idiopathic SSNHL compared with the controls.
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Doenças Cardiovasculares/epidemiologia , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Súbita/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fumar/epidemiologia , Adulto JovemRESUMO
Previous studies reported that endoscopic resection is effective for the treatment of superficial pharyngeal cancers, as for digestive tract cancers. However, the optimal treatment for superficial cancer of the uvula has not been established because of the rarity of this condition. We present two male patients in their 70s with superficial cancer of the uvula, detected with upper gastrointestinal endoscopy. Both patients underwent surgical resection of the uvula under general anesthesia. The extent of the lesions was determined by means of gastrointestinal endoscopy by using magnifying observation with narrow-band imaging, enabling the performance of minimally invasive surgery. Endoscopic submucosal dissection was performed to achieve en bloc resection of the intramucosal carcinoma that had infiltrated the area adjacent to the uvula. Gastrointestinal endoscopists should carefully examine the laryngopharynx to avoid missing superficial cancers. Our minimally invasive treatment for superficial cancer of the uvula had favorable postoperative outcomes, and prevented postoperative loss of breathing, swallowing, and articulation functions.
RESUMO
BACKGROUND: Magnifying endoscopy with narrow band imaging (ME-NBI) is useful to diagnose invasion depth of superficial esophageal cancer. The purpose of this study was to evaluate the utility of ME-NBI of superficial pharyngeal cancer. METHODS: Between April 2008 and June 2012, 146 lesions in 104 patients who underwent ME-NBI and en bloc resection were retrospectively analyzed. Based on magnifying endoscopic classification, proposed by the Japan Esophageal Society, microvasculature type was classified into B1, B2, and B3. RESULTS: B1 alone, B2, and B3 were observed in 128, 14, and 4 lesions, respectively. The frequency of subepithelial cancer were 20.3% (26 of 128), 78.6% (11 of 14), and 100% (4 of 4), respectively (p < .05). Mean invasion distance were 650 µm, 720.0 µm, and 2256.5 µm. Positive and negative predictive value for diagnosing subepithelial cancer based on the presence of B2 or B3 was 83.3% (15 of 18) and 79.7% (102 of 128). CONCLUSION: ME-NBI is useful to determining invasion depth of superficial pharyngeal cancer.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Aumento da Imagem/métodos , Laringoscopia/métodos , Imagem de Banda Estreita , Neoplasias Faríngeas/patologia , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias Faríngeas/diagnóstico , Neoplasias Faríngeas/cirurgia , Estudos Retrospectivos , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estatísticas não ParamétricasRESUMO
BACKGROUND: Endoscopic submucosal dissection (ESD) can be used to perform resections en bloc for early-stage GI tumors. Pharyngeal ESD is less invasive, but technically difficult. Therefore, innovations to safely and easily perform this procedure are needed. OBJECTIVE: The aim of this study was to evaluate ESD under peroral countertraction, a new traction system for improving subepithelial cutting line visualization, compared with conventional ESD. DESIGN: Retrospective study. SETTING: Toranomon Hospital, Tokyo, Japan. PATIENTS: A total of 93 patients (140 lesions) with superficial pharyngeal cancers treated with ESD were enrolled. INTERVENTIONS: ESD under peroral countertraction or conventional ESD. MAIN OUTCOME MEASUREMENTS: En bloc resection rate, size of the tumor, and procedure time. RESULTS: All lesions were resected en bloc by using this technique. The mean longest lesion size was 23.4 mm in the peroral countertraction group and 18.1 mm in the conventional group (P = .038). The mean procedure time did not differ between the 2 groups. Subcutaneous emphysema as an adverse event was observed in the conventional ESD group. No treatment-related adverse events occurred in the peroral countertraction group. LIMITATIONS: Retrospective comparison. CONCLUSIONS: ESD under peroral countertraction is easier and appears to be safer for completely removing superficial mesopharyngeal and hypopharyngeal cancers.