RESUMEN
BACKGROUND: The Seventh Edition of the Tumor, Node, Metastasis Classification of Malignant Tumors in non-small cell lung cancer (NSCLC) proposes a more detailed classification of primary tumor diameter. Stage IA T1 disease is subdivided into two groups: T1a disease (tumor diameter, < or = 2 cm) and T1b disease (tumor diameter, >2 to < or = 3 cm). Tegafur-uracil (UFT) improves survival in patients with stage I NSCLC. However, whether it is effective in patients with T1 disease (stage IA) remains controversial. METHODS: Data from a 2005 meta-analysis of UFT were reanalyzed to evaluate the effectiveness of UFT according to T1a and T1b tumors as proposed by the new tumor, node, metastasis classification in patients who had T1 tumors with no lymph-node metastasis. RESULTS: Data from 1269 patients were analyzed: 670 (52.8%) had T1a tumors and 599 (47.2%) had T1b tumors. In the surgery-alone group, survival rates at 5 years were 85% in patients with T1a tumors and 82% in those with T1b tumors after surgery alone and 87% in patients with T1a tumors and 88% in those with T1b tumors after surgery followed by adjuvant treatment with UFT. In patients with T1b tumors, the survival rate was significantly higher in the UFT group than in the surgery-alone group (hazard ratio = 0.62; 95% confidence interval, 0.42-0.90; log-rank p = 0.011). The hazard ratio for death in the UFT group when compared with the surgery-alone group was 0.84 for those with T1a disease (95% confidence interval, 0.58-1.23). The results of a test for interaction between treatment response and T1 subgroup were not significant (p = 0.30). CONCLUSIONS: UFT significantly improves survival in patients with stage IA T1b NSCLC compared with surgery alone.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de Supervivencia , Tegafur/uso terapéutico , Resultado del Tratamiento , Uracilo/uso terapéuticoRESUMEN
The MMSE is a simple and commonly used instrument to evaluate cognitive impairment. With the aim of enabling the examiner to skip a large portion of the MMSE when screening subjects with lower possibility of cognitive impairment, we examined the internal distribution of the MMSE scores among 792 older adults visiting a teaching hospital, a long-term care hospital, nursing homes, and a geriatric clinic. The correlation coefficients between the summed scores of any two items of MMSE and the total score were compared. A receiver operating characteristic (ROC) curve was drawn to show the sensitivity and the specificity of predicting cognitive impairment, which was defined by the total MMSE score being less than 24. The mean MMSE score was 20.5 +/- 6.9 (+/-S.D.). A good predictor for cognitive impairment was the summed scores of the time orientation and serial sevens with a sensitivity of 98.2% and a specificity of 69.2% if cut-off was set at 7/7+. This finding appears to help streamline the screening process for cognitive impairment in general elderly population.
Asunto(s)
Trastornos del Conocimiento/diagnóstico , Evaluación Geriátrica/métodos , Pruebas Psicológicas , Anciano , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los Resultados , Distribuciones EstadísticasRESUMEN
BACKGROUND: Despite the recent dissemination of group homes in Japan for older adults with dementia, the behavioral and psychological features of the residents remain unknown. To clarify the association of such features with the levels of difficulty encountered by caregivers in coping with these symptoms, we have conducted a survey to compare the frequencies of the symptoms among group homes, nursing homes and a long-term care hospital. METHODS: Five hundred and eighty-six older adults aged 65 years or more were sampled. Data were consecutively collected from questionnaires given to the caregivers. The questionnaire included basic activities of daily living, the Mini-mental State Examination, frequencies of behavioral, psychological and physical symptoms, and the levels of difficulty in coping with the symptoms. RESULTS: In group homes, requests to go home, urinary incontinence and frequent complaining were the most commonly observed symptoms. The symptoms associated with disorientation, anxiety and depression were frequently observed in all three care settings. Most of the symptoms were more frequently observed in group homes than in the other two care settings. However, the levels of difficulty in coping with most of the symptoms were the highest in the long-term care hospital, followed in order by the group homes and nursing homes. In group homes, inappropriate sexual behavior was the symptom creating the most stress for the caregivers, followed by verbal and nonverbal abuse and changeable mood. CONCLUSIONS: The symptomatic traits of residents in group homes were clarified in the present study. These findings could be helpful in considering desirable placement or the improvement of eligible service provision for older adults with dementia in care facilities.
Asunto(s)
Enfermedad de Alzheimer/psicología , Conducta , Hogares para Grupos , Hogares para Ancianos , Trastornos Mentales/epidemiología , Anciano , Análisis de Varianza , Deluciones , Estado de Salud , Humanos , Encuestas y CuestionariosRESUMEN
PURPOSE: Recent clinical trials have shown the efficacy of platinum-based adjuvant chemotherapy for completely resected non-small-cell lung cancer (NSCLC). In Japan, many clinical trials of adjuvant chemotherapy with tegafur-uracil (UFT) have been conducted, and some trials showed positive results while others showed negative results. Thus, we performed a meta-analysis to assess the efficacy of postoperative adjuvant chemotherapy with UFT in NSCLC. METHODS: Among nine trials of postoperative adjuvant UFT-containing chemotherapy, six trials comparing surgery alone with surgery plus UFT were identified. Of six trials, two were three-arm trials including cisplatin-based chemotherapy followed by UFT, and data from that arm were not included in the meta-analysis. RESULTS: Of 2,003 eligible patients, most (98.8%) had squamous cell carcinoma or adenocarcinoma, and most had stage I disease; the tumor classification was T1 in 1,308 (65.3%), T2 in 674 (33.6%), and the nodal status was N0 in 1,923 (96.0%). The two treatment groups did not differ significantly in major prognostic factors. The median duration of follow-up was 6.44 years. The survival rates at 5 and 7 years were significantly higher in the surgery plus UFT group (81.5% and 76.5%, respectively) than in the surgery alone group (77.2% and 69.5%, respectively; P = .011 and .001, respectively). The overall pooled hazard ratio was 0.74, and its 95% CI was 0.61 to 0.88 (P = .001). CONCLUSION: This meta-analysis showed that postoperative adjuvant chemotherapy with UFT was associated with improved 5- and 7-year survival in a Japanese patient population composed primarily of stage I adenocarcinoma patients.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Tegafur/uso terapéutico , Quimioterapia Adyuvante , Terapia Combinada , Humanos , Análisis de SupervivenciaRESUMEN
PURPOSE: To evaluate the efficacy of postoperative adjuvant chemotherapy for completely resected p-stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients who underwent complete resection with lymph node dissection for p-stage I NSCLC (T1N0, T2N0, adenocarcinoma or squamous cell carcinoma, were eligible. After surgery, 150 patients were stratified according to tumor size and histologic type, and then randomly assigned to 1 of 3 groups (50 patients each group): surgery alone (control group), surgery with chemotherapy; PVU group (2 courses of cisplatin 80 mg/m2, i.v. x 1 (day 1), vindesine 3 mg/m2, i.v. x 1 (days 1 and 8) and UFT 400 mg/day, p.o. for a period of 2 years), and UFT group (UFT 400 mg/day, p.o. for 2 years). RESULTS: The 5-year survival rates of the PVU group, the UFT group, and the control group were 87.9, 67.7, and 66.3%, respectively. The difference in 5-year survival between the PVU group and the control group was statistically significant (p = 0.045, log rank). The 5-year disease-free survival rate of the PVU group (81.1%) was also significantly better than that of the control group (66.5%) (p = 0.042, log rank). According to multivariate analysis using Cox's proportional hazard model, the only significantly positive factor on outcome was PVU chemotherapy after surgery. CONCLUSION: Postoperative PVU chemotherapy is effective for Japanese patients with completely resected p-stage I NSCLC.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Adenocarcinoma/patología , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Análisis de Supervivencia , Tegafur/administración & dosificación , Vindesina/administración & dosificaciónRESUMEN
A 46-year-old man was referred to our hospital for the treatment of lung cancer. Computed tomography showed a well-defined tumor mass that was 50x45 mm in size and contained a trabecular pattern of calcification. Since he was diagnosed as having a primary lung adenocarcinoma (clinical stage IB), a left upper lobectomy with mediastinal lymph node dissection was performed. Histologically, the tumor was a poorly differentiated adenocarcinoma with rich fibrous stroma, in which there were island-shaped bone formation lesions. An immunohistochemical examination showed the expression of bone morphogenic protein-2 within tumor cells, which induce and stimulate bone formation. This finding may elucidate a possible mechanism of heterotopic bone formation.
Asunto(s)
Adenocarcinoma/patología , Neoplasias Pulmonares/patología , Osificación Heterotópica/patología , Proteínas Morfogenéticas Óseas/análisis , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
To search for the signaling events in lung carcinoma relevant to its tumorigenesis, we investigated the phosphorylation of MAPK and STAT3 in human lung carcinoma tissues and their paired normal tissues. Although relative amounts of MAPK levels differed among the cases examined, no clear difference in MAPK levels was observed between tumor tissues and their paired normal tissues. Of 79 cases examined, only 7 cases (8.9%) showed tumor-specific phosphorylation of MAPK, whereas 41 cases (52%) showed more than 2-fold lower levels of MAPK phosphorylation in tumor tissues. In contrast to MAPK, 42 cases (53%) showed tumor-specific increase in STAT3 expression. In addition, 15 cases (19%) showed tumor-specific increase of STAT3 phosphorylation and 51 cases (65%) had STAT3 phosphorylation proportional to its expression. Moreover, exogenous expression of either JAB or dominant negative STAT3 in lung carcinoma cell lines led to the suppression of STAT3 phosphorylation and the drastic reduction of anchorage- independent growth of the cells. Taken together, our results suggest that JAK-STAT3 signaling has a pivotal role for oncogenic growth of lung carcinoma cells.
Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas de Unión al ADN/metabolismo , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Represoras/metabolismo , Transactivadores/metabolismo , Adhesión Celular/efectos de los fármacos , Adhesión Celular/fisiología , División Celular , Ensayo de Unidades Formadoras de Colonias , Genes Dominantes , Humanos , Fosforilación , Factor de Transcripción STAT3 , Transducción de Señal , Proteína 1 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas , Células Tumorales Cultivadas , Tirosina/metabolismoRESUMEN
Activating mutations of RAS gene families have been found in a variety of human malignancies, including lung cancer, suggesting their dominant role in tumorigenesis. However, several studies have shown a frequent loss of the wild-type KRAS allele in the tumors of murine models and an inhibition of oncogenic phenotype in tumor cell lines by transfection of wild-type RAS, indicating that wild-type RAS may have oncosuppressive properties. To determine whether loss of wild-type KRAS is involved in the development of human lung cancer, we investigated the mutations of KRAS, NRAS and BRAF in 154 primary non-small cell lung cancers (NSCLCs) as well as 10 NSCLC cell lines that have been shown to have KRAS mutations. We also determined the loss of heterozygosity status of KRAS alleles in these tumors. We detected point mutations of KRAS in 11 (7%) of 154 NSCLCs, with 10 cases at codon 12 and 1 at codon 61, but no mutations of NRAS or BRAF were found. Using the laser capture microdissection technique, we confirmed that 9 of the 11 tumors and 7 of the 10 NSCLC cell lines retained the wild-type KRAS allele. Among the cell lines with heterozygosity of mutant and wild-type KRAS, all of the cell lines tested for expression were shown to express more mutated KRAS than wild-type mRNA, with higher amounts of KRAS protein also being expressed compared to the cell lines with a loss of wild-type KRAS allele. In addition, among 148 specimens available for immunohistochemical analysis, 113 (76%) showed positive staining of KRAS, indicating that the vast majority of NSCLCs continue to express wild-type KRAS. Our findings indicate that the wild-type KRAS allele is occasionally lost in human lung cancer, and that the oncogenic activation of mutant KRAS is more frequently associated with an overexpression of the mutant allele than with a loss of the wild-type allele in human NSCLC development.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Cromosomas Humanos Par 12/genética , Genes ras/genética , Pérdida de Heterocigocidad/genética , Neoplasias Pulmonares/genética , Secuencia de Bases , Carcinoma de Pulmón de Células no Pequeñas/clasificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Mapeo Cromosómico , Cartilla de ADN , Exones , Femenino , Marcadores Genéticos , Heterocigoto , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Células Tumorales CultivadasRESUMEN
We have found that a malignant mesothelioma cell line, NCI-H28, had a chromosome 3p21.3 homozygous deletion containing the beta-catenin gene (CTNNB1), which suggested that the deletion of beta-catenin might have a growth advantage in the development of this tumor. To determine whether beta-catenin has a growth-inhibitory activity, we transfected wild-type beta-catenin, Ser37Cys mutant beta-catenin as an activated type, and C-terminus deletion mutant beta-catenin that lacks the transcription activity, into the NCI-H28 cells. A non-small cell lung cancer cell line, NCI-H1299, which expressed endogenous beta-catenin, was also studied. We tested the localization of exogenous beta-catenin in the NCI-H28 cells with immunofluorescence, and found that the wild-type beta-catenin and the C-terminus deletion mutant were more strongly expressed in the plasma membrane and cytoplasm than in the nucleus, while the Ser37Cys mutant was more in the nucleus than in the cytoplasm. By using luciferase-reporter assay, the beta-catenin/T-cell factor 4-mediated transactivity of the Ser37Cys mutant was shown to be higher than that of the wild-type beta-catenin in both cell lines. However, the transactivity of the C-terminus deletion mutant was strongly reduced in both. Colony formation of the NCI-H28 cells was reduced by 50% after transfection with the wild-type beta-catenin, and 60% with the Ser37Cys mutant, but only 20% with the C-terminus deletion mutant compared to the vector control. Inhibition of colony formation in NCI-H28 cells was because of apoptosis, manifested by positive staining of Annexin V and TUNEL assays in transfected cells. In contrast, when transfected with the wild-type beta-catenin, no significant reduction in colony formation was seen in beta-catenin wild-type NCI-H1299 cells. In conclusion, our data indicate that inactivation of beta-catenin by a 3p21.3 homozygous deletion might be a crucial event in the development of the mesothelioma NCI-H28 cells. Thus, while beta-catenin is well known to be a positive growth-stimulating factor for many human cancers, it can also act as a potential growth suppressor in some types of human cancer cells.
Asunto(s)
Cromosomas Humanos Par 3 , Proteínas del Citoesqueleto/genética , Genes Supresores de Tumor , Mesotelioma/genética , Mesotelioma/patología , Transactivadores/genética , Anexina A5/metabolismo , Apoptosis/fisiología , División Celular/efectos de los fármacos , División Celular/genética , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Cisteína/genética , Citoplasma/metabolismo , Proteínas del Citoesqueleto/metabolismo , Proteínas del Citoesqueleto/farmacología , Regulación Neoplásica de la Expresión Génica , Homocigoto , Humanos , Etiquetado Corte-Fin in Situ , Mesotelioma/terapia , Mutación , Células Madre Neoplásicas , Eliminación de Secuencia , Serina/genética , Transactivadores/metabolismo , Transactivadores/farmacología , Transcripción Genética , Células Tumorales Cultivadas , beta CateninaRESUMEN
We report a case of a 40-year-old man with chylopericardium who developed purulent pericarditis caused by Salmonella enteritidis. Thoracoscopic pericardiotomy with debridement effectively controlled the pericardial infection.