RESUMEN
PURPOSE: Since the 1980s, health-related quality of life (HRQOL) has been recognized in the assessment of medical treatment. To determine the health-related quality of life (HRQOL) of vestibular schwannoma (VS) patients, a specific questionnaire that has been validated in different languages is essential. METHODS: The Short Form-36 Health Survey (SF-36) and PANQOL questionnaires in German were evaluated in patients after removal of a VS via the translabyrinthine approach. Descriptive statistics of a comparison of the SF-36 results to those of a normal sample are illustrated. Criterion validity was investigated using Spearman's rank test to correlate the PANQOL domains with the SF-36 domains. A confirmatory factor analysis of the PANQOL was performed to determine the stability of the factor structure of the PANQOL questionnaire for our cohort. RESULTS: The criterion validity of the German PANQOL questionnaire is comparable to that of the original English version. The SF-36 domains values ranged from 49.31/100 (role physical) to 66.46/100 (physical functioning). Compared to the normal population, patients who underwent surgical removal of a VS showed a significantly reduced quality of life, mainly in domains such as physical and social functioning, as well as psychological wellbeing. CONCLUSION: The German PANQOL has been validated and is now available. Post-surgical treatment should be focused not only on physiological rehabilitation but also on improving the quality of life, especially aspects of psychological and social wellbeing.
Asunto(s)
Neuroma Acústico/cirugía , Calidad de Vida , Encuestas y Cuestionarios , Adulto , Estudios de Cohortes , Análisis Factorial , Femenino , Alemania , Encuestas Epidemiológicas , Humanos , Lenguaje , Masculino , Periodo PosoperatorioRESUMEN
Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2-6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2-6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2-6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene.
Asunto(s)
Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Células Germinativas/metabolismo , Mutación de Línea Germinal , Células Madre/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Adolescente , Adulto , Alelos , Neoplasias de la Mama/genética , Niño , Preescolar , Rotura Cromosómica , Daño del ADN , Exones , Anemia de Fanconi/diagnóstico , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/genética , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/metabolismo , Femenino , Fibroblastos/metabolismo , Eliminación de Gen , Duplicación de Gen , Técnicas de Inactivación de Genes , Prueba de Complementación Genética , Humanos , Masculino , Persona de Mediana Edad , Degradación de ARNm Mediada por Codón sin Sentido , Fenotipo , ARN Mensajero/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo , UbiquitinaciónRESUMEN
BACKGROUND: Monitoring the health-related quality of life (HRQOL) for patients with vestibular schwannoma (VS) has garnered increasing interest. In German-speaking countries, there is no disease-specific questionnaire available similar to the "Penn Acoustic Neuroma Quality-of-life Scale" (PANQOL). METHOD: We translated the PANQOL for German-speaking patients based on a multistep protocol that included not only a forward-backward translation but also linguistic and sociocultural adaptations. The process consists of translation, synthesis, back translation, review by an expert committee, administration of the prefinal version to our patients, submission and appraisal of all written documents by our research team. The required multidisciplinary team for translation comprised head and neck surgeons, language professionals (German and English), a professional translator, and bilingual participants. A total of 123 patients with VS underwent microsurgical procedures via different approaches at our clinic between January 2007 and January 2017. Among these, 72 patients who underwent the translabyrinthine approach participated in the testing of the German-translated PANQOL. RESULT: The first German version of the PANQOL questionnaire was created by a multistep translation process. The responses indicate that the questionnaire is simple to administer and applicable to our patients. CONCLUSION: The use of a multistep process to translate quality-of-life questionnaires is complex and time-consuming. However, this process was performed properly and resulted in a version of the PANQOL for assessing the quality of life of German-speaking patients with VS.
Asunto(s)
Microcirugia , Neuroma Acústico/cirugía , Calidad de Vida , Competencia Cultural , Humanos , Medición de Resultados Informados por el Paciente , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , TraduccionesRESUMEN
OBJECTIVE: To evaluate effectiveness of the cochlear implant (CI) to facilitate single-sided deafness (SSD) rehabilitation following translabyrinthine resection of the vestibular schwannoma. STUDY DESIGN: Retrospective patient review. SETTING: Single center, University hospital. PATIENTS: Patients with SSD who underwent translabyrinthine resection of a vestibular schwannoma with anatomical preservation of the cochlear nerve and subsequent CI on the same ear. INTERVENTIONS: CI at post-translabyrinthine resection of the acoustic neuroma to treat SSD, and evaluation by retrospective individual case review in a period from 2009 to 2016. MAIN OUTCOME MEASURES: Individual patients' clinical outcome and speech understanding. RESULTS: Thirteen patients were provided CI. In all cases, complete removal of the tumor was achieved and the cochlear nerve was preserved; in one case, the CI was implanted simultaneously. In most cases, the follow-up interval was 2 years. In 9 of 13 cases, the implanted ear achieved capability to understand and discriminate monosyllabic words at 65âdB. Level of speech understanding of over 50% at 65âdB was possible in 7 patients at 12 months after the first fitting of CI. CONCLUSIONS: Under certain conditions, CI was an effective solution to restore hearing in patients with SSD following translabyrinthine access to the skull base. Study with prospective design is required to provide more significant results.
Asunto(s)
Implantación Coclear/métodos , Pérdida Auditiva Unilateral/etiología , Pérdida Auditiva Unilateral/cirugía , Neuroma Acústico/cirugía , Procedimientos Neuroquirúrgicos/métodos , Adulto , Berlin , Implantes Cocleares , Nervio Coclear/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroma Acústico/complicaciones , Adulto JovenRESUMEN
OBJECTIVE: To quantify the postoperative quality of life (QOL) of patients after translabyrinthine surgery for vestibular schwannoma (VS) using the German version of the Penn acoustic neuroma quality-of-life questionnaire (PANQOL) in a university hospital. METHODS: The PANQOL questionnaire was administered to 72 patients who were treated in our department with translabyrinthine surgery for VS between January 2007 and January 2017. Descriptive evaluations of results were performed in addition to analyses of the reliability and convergent validity of the results and a subgroup analysis. RESULTS: For the first time, QOL was measured in German-speaking VS patients after translabyrinthine surgery. Cronbach's alpha for internal consistency and Guttman's split half, used as measures of reliability, showed values between 0.39 and 0.92 (raw alpha) and 0.58 and 0.98 (Lambda 4), respectively. DESCRIPTIVE STATISTICS: The mean total PANQOL score of patients after translabyrinthine VS resection was 61.96. The domain "hearing" had the lowest score (50.87), while "facial dysfunction" had the highest score (74.88). Subgroup analysis showed that neither preoperative tumor size nor elapsed time postoperatively significantly influenced QOL outcomes. CONCLUSIONS: Depending on the different domains the German PANQOL questionnaire showed poor to good internal consistency, reliability, and convergent validity. Moreover, some VS patients suffer from reduced QOL for a long time after the translabyrinthine procedure, thus psycho-oncological care should be recommended in these cases.
Asunto(s)
Neuroma Acústico/cirugía , Calidad de Vida , Encuestas y Cuestionarios , Resultado del Tratamiento , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Otológicos , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND/AIM: Head and neck squamous cell carcinomas (HNSCCs) form a heterogeneous tumor entity located throughout the oral cavity, pharynx and larynx that is caused predominantly by chemically or virally induced carcinogenesis. Heterozygous germline mutations in cancer susceptibility genes might also lead to increased incidence of HNSCCs. As DNA stability is typically impaired in HNSCC cells and genes of the Fanconi anemia/BRCA DNA repair pathway can be mutated or down-regulated in HNSCCs, we investigated here whether germline mutations occur in the X-chromosomal FANCB as candidate gene. MATERIALS AND METHODS: Germline DNA of 85 consecutive HNSCC patients was sequenced. Missense alterations in FANCB were functionally tested in reference cells. RESULTS AND CONCLUSION: Four single nucleotide polymorphisms were identified, three of which were located in untranslated regions of FANCB (rs2188383, rs2375729, rs2905223) and predicted to be associated with normal function. One missense alteration, c.1004G>A resulting in p.G335E (rs41309679), in exon 4 was detected in five men in homozygous and in five women in heterozygous state. Four in silico prediction programs uniformally predicted p.G335E to be associated with loss-of-function of the protein. To clarify these predictions, we expressed the FANCB p.G335E protein in primary human FANCB deficient fibroblasts. Cell cycle analysis of these fibroblasts established that the FANCB p.G335E was functionally indistinguishable from the wildtype FANCB protein. Thus, functional studies in genetically defined cells showed that the p.G335E germline alteration in FANCB is not associated with impaired function.
Asunto(s)
Carcinoma de Células Escamosas/genética , Proteínas del Grupo de Complementación de la Anemia de Fanconi/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias de Cabeza y Cuello/genética , Mutación Missense , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Ciclo Celular/genética , Femenino , Fibroblastos/metabolismo , Frecuencia de los Genes , Genotipo , Mutación de Línea Germinal , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
Dermoid cysts (DCs) are rare benign, epithelial-lined lesions. Up to 7% of them are found in the head and neck region and 80% of those predominantly occur in the orbit, in the nose, and in the floor of the mouth. The average age of presentation is around the age of six. Dermoid cysts located in the parotid gland have only been published in 19 cases so far. Interestingly, the mean age of occurrence in the parotid gland was much higher (31 years). We report on a four-year-old girl being the youngest patient who had ever been diagnosed with this disease.