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1.
Anticancer Res ; 40(1): 405-412, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892594

RESUMO

BACKGROUND/AIM: To evaluate the outcomes of curative resection for Borrmann type IV gastric cancer through an analysis of the clinical, surgical and pathological data and through identifying which of these prognostic factors are associated with survival. PATIENTS AND METHODS: We retrospectively analyzed 2798 patients who had undergone excision of the primary lesion and 122 patients with type IV gastric cancer undergoing curative resection (R0 or 1) at Yokohama City University Hospital and Kanagawa Cancer Center between November 1995 and May 2016. RESULTS: Borrmann type IV gastric cancer had more advanced and unfavorable clinicopathological factors compared to other types. The 5-year overall survival rate was 28%, and the median survival was 21.8 months. The overall survival rate was influenced by the depth of invasion, lymph node metastasis, peritoneal lavage cytology (CY), stage and intraoperative blood loss. Of these, independent prognostic factors were intraoperative blood loss (<400 vs. ≥400 ml, risk ratio 1.64; p=0.045) and CY (0 vs. 1, risk ratio 2.25; p=0.004). CONCLUSION: The control of intraoperative bleeding had a positive impact on the survival of patients receiving curative resection for Borrmann type IV gastric cancer.


Assuntos
Perda Sanguínea Cirúrgica , Cuidados Intraoperatórios , Neoplasias Gástricas/cirurgia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
2.
Anticancer Res ; 40(1): 421-426, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892596

RESUMO

BACKGROUND/AIM: Distant organ metastases do not occur at random in lung cancer. A retrospective study was conducted in order to evaluate 1) what kinds of metastatic patterns exist in three different types of lung cancer, and 2) whether metastatic patterns affected prognosis in the different types of lung cancer. PATIENTS AND METHODS: Data were collected from all consecutive patients with diagnosed lung cancer between April 2009 and October 2018 in our hospitals. Cluster analysis was performed to classify patients. Kaplan-Meier analysis, log-rank test, and Cox proportional hazards model were used. RESULTS: Epidermal growth factor-mutated adenocarcinoma, small cell lung cancer, and squamous cell lung cancer had different 'metastatic patterns', survival, and unfavorable prognostic factors, respectively. CONCLUSION: There might be different metastatic patterns, survival, and unfavorable prognostic factors in each pathological and genetic type of lung cancer. It is worthwhile carrying out diagnostic imaging and treatment considering information on metastatic patterns.


Assuntos
Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação/genética , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida
3.
Anticancer Res ; 40(1): 357-366, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892587

RESUMO

BACKGROUND/AIM: This study was carried out to compare the efficacy and toxicity of consolidation with cytarabine only to consolidation with anthracycline combination in patients with acute myeloid leukemia (AML) achieving complete remission (CR). PATIENTS AND METHODS: This was a multicenter, retrospective, longitudinal cohort study set between January 2010 and December 2016. RESULTS: Generally, high-dose cytarabine Ied to better survival compared to anthracycline-containing consolidation therapy, as expected. However, for patients not undergoing hematopoietic stem cell transplantation (HSCT), anthracycline use was not necessarily associated with worse survival, depending on the number of consolidation cycles. Post-remission, pre-HSCT consolidation with high-dose cytarabine did not negatively affect survival compared to previous reports. For those without FMS-like tyrosine kinase 3 (FLT3) mutation, anthracycline use was associated with a worse survival, but for those with mutation, anthracycline use did not negatively affect survival. CONCLUSION: For patients who are ineligible for HSCT, selective use of anthracycline consolidation can be a viable option, while for patients with the intention of HSCT, post-remission high-dose cytarabine is a reasonable option in the absence of available donors.


Assuntos
Antraciclinas/uso terapêutico , Quimioterapia de Consolidação , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Antraciclinas/efeitos adversos , Antraciclinas/farmacologia , Citarabina/uso terapêutico , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Idarubicina/farmacologia , Idarubicina/uso terapêutico , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Adulto Jovem
4.
Medicine (Baltimore) ; 99(1): e18530, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895788

RESUMO

The role of atopic dermatitis (AD) in the development of colorectal cancer (CRC) has been a matter of scientific debate with mixed results. We conducted a nationwide cohort study to assess the association between AD and risk of CRC. Drawing on Taiwan's National Health Insurance Research Database, 46,703 patients with AD (the AD cohort) and 186,812 sex, age, and index year-matched patients without AD (the non-AD cohort) were identified in the period between 2000 and 2008. Follow-up time was calculated from the date of entry in the cohort until the occurrence of a first CRC diagnosis, death, or the end of the observation period (December 31, 2013), whichever occurred first. Hazards ratios (HRs) and accompanying 95% confidence intervals (CIs) derived from the Fine-Gray competing risk model were used to estimate the association between AD and CRC risk. After multivariable adjustment, AD was associated with an increased risk of CRC (adjusted HR, 1.26; 95% CI, 1.14-1.40). Of note, a significant positive association between AD and CRC risk was evident in both men and women and in all age groups. In summary, this population-based cohort study revealed that AD was associated with an increased risk of CRC in an Asian population. It will be of interest for cohort studies with prediagnostic specimens to evaluate the potential relationship between AD and CRC using biomarkers for allergy status.


Assuntos
Neoplasias Colorretais/epidemiologia , Dermatite Atópica/complicações , Adulto , Neoplasias Colorretais/etiologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Adulto Jovem
5.
Anticancer Res ; 40(1): 35-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892551

RESUMO

BACKGROUND/AIM: Co-expression of c-Met and ALDH1A3 indicates a poor prognosis in stage III-IV breast cancers and contributes to cell proliferation and tumor formation by ALDH1-positive breast CSCs. PKCλ is overexpressed and contributes to a poor prognosis in several cancers. MATERIALS AND METHODS: A breast cancer genomics data set (METABRIC, n=2509) was downloaded and analyzed, as was the effect c-Met and PKCλ inhibitors on ALDH1high cell viability and tumor-sphere formation. RESULTS: c-Met expression correlates with expression of PKCλ in breast cancer. Stage III-IV breast cancer patients with c-Methigh PKCλhigh ALDH1A3high have a poorer prognosis than patients with c-Metlow PKCλlow ALDH1A3low Foretinib and auranofin suppressed cell viability and tumor-sphere formation by ALDH1high cells. These results suggest that c-Met and PKCλ are cooperatively involved in cancer progression and contribute to poor prognoses in breast cancer. CONCLUSION: c-Met and PKCλ are potentially useful prognostic markers and therapeutic targets in late-stage breast cancer.


Assuntos
Aldeído Oxirredutases/genética , Biomarcadores Tumorais , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Proteína Quinase C/genética , Proteínas Proto-Oncogênicas c-met/genética , Aldeído Oxirredutases/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo
6.
Anticancer Res ; 40(1): 81-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892555

RESUMO

BACKGROUND/AIM: Zinc finger protein ZKSCAN3 (ZNF306) is a promising oncogene candidate in colon, bladder, breast, uterine cervical, and prostate cancers. The present study aimed to investigate ZKSCAN3 protein expression in gastric carcinoma patient tissues and to evaluate oncological outcomes in these patients. MATERIALS AND METHODS: ZKSCAN3 was detected using the anti-ZKSCAN3 rabbit polyclonal antibody. For immunohistochemical examination, we used paraffin-embedded specimens from 87 consecutive patients with gastric cancer who underwent gastrectomy. We investigated ZKSCAN3 expression in relation with patient prognosis and clinicopathological factors. RESULTS: ZKSCAN3 was detected in 28 (32.2%) tumour specimens, with significant association with lymphatic system invasion and distant metastasis. Patients with ZKSCAN3-positive tumours had worse overall survival (OS) than those with ZKSCAN3-negative tumours based on log-rank testing. Furthermore, multivariate analysis revealed that ZKSCAN3 was an independent prognostic parameter for OS (hazard ratio: 2.6379, p=0.0164). CONCLUSION: ZKSCAN3 is a potential novel prognostic factor in gastric cancer patients.


Assuntos
Biomarcadores Tumorais , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Fatores de Transcrição/genética , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo
7.
Gut ; 69(1): 168-176, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878947

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) is a major cause of death worldwide and its incidence is expected to increase globally. Aim of this study was to assess whether the implementation of screening policies and the improvement of treatment options translated into a real-world survival benefit in HCC patients. DESIGN: 4078 patients diagnosed with HCC between 1998 and 2016 from the Munich Cancer Registry were analysed. Tumour characteristics and outcome were analysed by time period and according to age and presence of metastases at diagnosis. Overall survival (OS) was analysed using Kaplan-Meier method and relative survival (RS) was computed for cancer-specific survival. Cox proportional hazard models were conducted to control for prognostic variables. RESULTS: While incidence of HCC remained substantially stable, tumours were diagnosed at increasingly earlier stages, although the median age at diagnosis increased. The 3 years RS in HCC improved from 19.8% in 1998-2002, 22.4% in 2003-2007, 30.6% in 2008-2012 up to 31.0% in 2013-2016. Median OS increased from 6 months in 1998-2002 to 12 months in 2008-2016. However, analysis according to the metastatic status showed that survival improved only in patients without metastases at diagnosis whereas the prognosis of patients with metastatic disease remained unchanged. CONCLUSION: These real-world data show that, in contrast to the current assumptions, the incidence of HCC did not increase in a representative German region. Earlier diagnosis, likely related to the implementation of screening programmes, translated into an increasing employment of effective therapeutic options and a clear survival benefit in patients without metastases at diagnosis, irrespective of age.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/secundário , Detecção Precoce de Câncer/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida/tendências
8.
Medicine (Baltimore) ; 98(52): e18522, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876745

RESUMO

BACKGROUND: Breast cancer patients with sentinel lymph node (SLN) metastases may have a low risk of non-SLN metastases. Accurate estimates of the likelihood of additional disease in the non-SLN metastases can avoid many complications mentioned the axillary lymph node dissection (ALND). This study aims to develop a new model based on Chinese real-world patients to ascertain the likelihood of non-SLN metastases in a breast cancer patient with disease-positive SLN, enabling the surgeons to make a better choice of surgical procedures. METHODS: Out of the 470 patients from CSCO Breast Cancer Database collaborated Group, a proportion of 3 (347 cases): 1 (123 cases) was considered for assigning patients to training and validation groups, respectively. Two training models were created to predict the likelihood of having additional, non-SLN metastases in an individual patient. Training model 1 was created with pathological size of the tumor, pathological type, lymphovascular invasion, the number of positive SLNs/number of total SLNs ratio, and the Her-2 status based on multivariable logistic regression (P < .05). Training model 2 was based on the variables in model 1 and age, estrogen receptor status, progesterone receptor status, Ki-67 count, menopause status. RESULTS: The area under the receiver operating characteristic (ROC) curve of the training model 1 was 0.754, while the area of training model 2 was 0.766. There was no difference between model 1 and model 2 regarding the ROC curve, P = .243. Next, the validation cohort (n = 123) was developed to confirm the model 1's performance and the ROC curve was 0.703. The nomogram achieved good concordance indexes of 0.754 (95% CI, 0.702-0.807) and 0.703 (95% CI, 0.609-0.796) in predicting the non-SLN metastases in the training and validation cohorts, respectively, with well-fitted calibration curves. The positive and negative predictive values of the nomogram were calculated, resulting in positive values of 59.3% and 48.6% and negative predictive values of 79.7% and 83.0% for the training and validation cohorts, respectively. CONCLUSION: We developed 2 models that used information commonly available to the surgeon to calculate the likelihood of having non-SLN metastases in an individual patient. The numbers of variables in model 1 were less than in model 2, while model 1 had similar results as model 2 in calculating the likelihood of having non-SLN metastases in an individual patient. Model 1 was more user-friendly nomogram than model 2. Using model 1, the risk for an individual patient having ALND could be determined, which would lead to a rational therapeutic choice.


Assuntos
Neoplasias da Mama/patologia , Metástase Linfática/diagnóstico , Nomogramas , Biópsia de Linfonodo Sentinela , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Curva ROC , Medição de Risco
9.
Medicine (Baltimore) ; 98(52): e18537, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876751

RESUMO

Thyroid disorders are associated with blood glucose abnormalities. For rendering the patients euthyroid, routine screening and care are essential. Therefore, the aim of this study was to investigate the association between continuity of care (COC) and type 2 diabetes onset among patients with thyroid disorders.We used the national claim data. Our study population was 4099 patients with hyperthyroidism or hypothyroidism. For calculating COC, the Most Frequent Provider Continuity Index (MFPCI), Modified Modified Continuity Index (MMCI), and COC Index (COCI) were used. The dependent variable was type 2 diabetes onset. The Cox proportional hazard regression model was used.Among 4099 patients with thyroid disorders, 25.3% experienced onset of type 2 diabetes. Thyroid patients who had MFPCI and COCI below the median were more likely to experience onset of type 2 diabetes than who had these indices above the median (MFPCI: hazard ratio [HR] = 1.26, 95% confidence interval [CI] = 1.09-1.46; COCI: HR = 1.22, 95% CI = 1.06-1.41). Our subgroup analysis showed that female patients and those 20 to 34 years of age showed a significant association between COC and onset of type 2 diabetes.Patients with thyroid disorders with low COC showed an increased risk of developing type 2 diabetes. Therefore, efforts to enhance COC among patients with thyroid disorders needs to be encouraged.


Assuntos
Continuidade da Assistência ao Paciente , Diabetes Mellitus Tipo 2/etiologia , Doenças da Glândula Tireoide/complicações , Adulto , Fatores Etários , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/terapia , Hipotireoidismo/complicações , Hipotireoidismo/terapia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Fatores de Risco , Fatores Sexuais , Doenças da Glândula Tireoide/terapia , Adulto Jovem
10.
Medicine (Baltimore) ; 98(52): e18604, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876762

RESUMO

The various harmful impacts of distal radius fractures (DRFs) may cause adverse effects. Although previous studies have reported the adverse effects of DRFs on mortality, most studies were performed in adults of advanced age and paid little attention to confounding factors of mortality. Furthermore, most of these studies investigated the overall impact of DRFs on mortality without differentiating the specified causes of death.The purpose of the present study was to estimate the risk of mortality in DRF patients according to the cause of death.Data from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) from 2002 to 2013 were collected. A total of 27,295 DRF participants who were 50 years or older were 1:4 matched with control participants for age, sex, income, and region of residence. The causes of death were grouped into 12 classifications.DRFs were not associated with increased overall mortality. The adjusted hazard ratio (HR) of mortality was 1.04 (95% confidence interval [CI] = 0.98-1.11, P = .237). The adjusted HR for mortality was not significantly different according to age. The odds ratio of overall mortality was 1.03 (95% CI = 0.97-1.11, P = .329).DRFs were not associated with a significant increase in mortality.


Assuntos
Fraturas do Rádio/mortalidade , Fatores Etários , Idoso , Estudos de Casos e Controles , Causas de Morte , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais
11.
Medicine (Baltimore) ; 98(51): e18036, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860954

RESUMO

Cullin 4A (CUL4A) is a protein of E3 ubiquitin ligase with many cellular processes. CUL4A could regulate cell cycle, development, apoptosis, and genome instability. This study aimed to analyze the expression of CUL4A in nasopharyngeal carcinoma (NPC) tissues and the associations of CUL4A expression with prognostic significance. A total of 115 NPC patients were collected to assess the protein expression of CUL4A by immunohistochemistry, so as to analyze the relationships between CUL4A expression and clinicopathological and prognostic parameters. All patients were followed-up until death or 5 years. The results showed that high expression of CUL4A was significantly associated with larger primary tumor size (P = .026), higher nodal status (P = .013), more distant metastasis (P = .020), and higher TNM stage (P = .005). Kaplan-Meier curves showed that patients with higher CUL4A expression had significantly shorter overall survival (OS) and progression-free survival (PFS) (both P < .001). In multivariate Cox analysis, CUL4A is an independent prognostic factor for OS (P = .016; hazard ratio [HR] = 2.770, 95% CI: 1.208-6.351) and PFS (P = .022; HR = 2.311, 95% CI: 1.126-4.743). In conclusion, high expression of CUL4A was associated with advanced disease status of NPC, and might serve as an independent prognostic factor.


Assuntos
Proteínas Culina/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/mortalidade , Adulto , Idoso , China , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
12.
Medicine (Baltimore) ; 98(50): e18349, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852135

RESUMO

BACKGROUND: Particulate matter (PM) acts as an environment pollutant and thus plays a vital role in the development of human lung cancer. Whether PM is a risk factor for breast cancer (BC) morbidity and mortality, however, is not clear. Recently, several studies have reported inconsistent results for the association between PM and BC risk. This meta-analysis examines the indefinite relationship between exposure to PM and BC morbidity and mortality. METHODS: Based on a search of Pubmed, Embase, Web of Science and Cochrane Library, the hazard ratio (HR) and 95% confidence interval (CI) were extracted and analyzed by Review Manager 5.3 and Stata14.0 to estimate the association between PM and BC morbidity and mortality. The heterogeneity for the included studies was evaluated using a Chi-square test and the I statistic. Forest plot was used to illustrate the pooled HR and mean difference. A Funnel plot, Begg test, and Egger test were performed to explore the publication bias between the included studies.All analyses were based on previous published studies, thus, no ethical approval and patient consent are required. RESULTS: A total of 14 of 284 publications with 1,004,128 BC cases were gathered. The analysis showed each 10 µg/m of PM2.5 (diameter ≤2.5 µm) was associated with 1.17 (95% CI: 1.05-1.30, P = .004) fold risk BC mortality, and each 10 µg/m of PM10 (diameter ≤10 µm) was associated with 1.11 (95% CI: 1.02-1.21, P = .021) fold risk BC mortality. However, neither PM10 nor PM2.5 was found to be significantly associated with BC morbidity. Publication bias was detected in studies on PM2.5 and BC mortality. CONCLUSIONS: Our study suggests that PM exposure may raise the mortality but not the morbidity of BC. Still, further studies may be necessary to confirm this finding.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Neoplasias da Mama/mortalidade , Exposição Ambiental/efeitos adversos , Material Particulado/análise , Adulto , Idoso , Neoplasias da Mama/induzido quimicamente , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco
13.
Medicine (Baltimore) ; 98(50): e18355, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852138

RESUMO

BACKGROUND: The use of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis from various malignancies. However, the effectiveness of HIPEC for ovarian cancer is still controversial. Therefore, we performed this meta-analysis to identify patients with ovarian cancer who can obtain survival benefit from HIPEC. METHODS: Articles regarding HIPEC in the MEDLINE, EMBASE, and Cochrane Library were searched till December 2018. In total, 13 case-control studies and two randomized controlled trials were included in this meta-analysis. We investigated the effect of HIPEC on disease-free survival (DFS) and overall survival (OS), and performed subgroup analyses based on the study design, adjustment of confounding variables, and quality of the study. RESULTS: HIPEC improved both DFS (hazard ratio [HR], 0.603; 95% confidence interval [CI], 0.513-0.709) and OS (HR, 0.640; 95% CI, 0.519-0.789). In cases of primary disease, HIPEC improved DFS (HR, 0.580; 95% CI, 0.476-0.706) and OS (HR, 0.611; 95% CI, 0.376-0.992). Subgroup analyses revealed that HIPEC did not improve OS but improved DFS of patients with residual tumors ≤1 cm or no visible tumors. In cases of recurrent disease, HIPEC was associated with better OS (HR, 0.566; 95% CI, 0.379-0.844) but not with DFS. Subgroup analyses also revealed similar tendencies. However, HIPEC improved DFS of patients with residual tumors ≤1 cm or no visible tumors, while it improved OS of only those with residual tumors ≤1 cm. CONCLUSIONS: HIPEC may improve DFS of patients with ovarian cancer when residual tumors were ≤1 cm or not visible. It may also improve OS of only patients with recurrent disease whose residual tumors were ≤1 cm.


Assuntos
Hipertermia Induzida/mortalidade , Neoplasias Ovarianas/terapia , Seleção de Pacientes , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Resultado do Tratamento
14.
BMJ ; 367: l6377, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852659

RESUMO

OBJECTIVE: To explore associations between different frequencies of arts engagement and mortality over a 14 year follow-up period. DESIGN: Prospective cohort study. PARTICIPANTS: English Longitudinal Study of Ageing cohort of 6710 community dwelling adults aged 50 years and older (53.6% women, average age 65.9 years, standard deviation 9.4) who provided baseline data in 2004-05. INTERVENTION: Self reported receptive arts engagement (going to museums, art galleries, exhibitions, the theatre, concerts, or the opera). MEASUREMENT: Mortality measured through data linkage to the National Health Service central register. RESULTS: People who engaged with receptive arts activities on an infrequent basis (once or twice a year) had a 14% lower risk of dying at any point during the follow-up (809/3042 deaths, hazard ratio 0.86, 95% confidence interval 0.77 to 0.96) compared with those who never engaged (837/1762 deaths). People who engaged with receptive arts activities on a frequent basis (every few months or more) had a 31% lower risk of dying (355/1906 deaths, 0.69, 0.59 to 0.80), independent of demographic, socioeconomic, health related, behavioural, and social factors. Results were robust to a range of sensitivity analyses with no evidence of moderation by sex, socioeconomic status, or social factors. This study was observational and so causality cannot be assumed. CONCLUSIONS: Receptive arts engagement could have a protective association with longevity in older adults. This association might be partly explained by differences in cognition, mental health, and physical activity among those who do and do not engage in the arts, but remains even when the model is adjusted for these factors.


Assuntos
Arte , Participação da Comunidade/estatística & dados numéricos , Mortalidade/tendências , Idoso , Cognição , Inglaterra/epidemiologia , Exercício , Feminino , Seguimentos , Comportamentos Relacionados com a Saúde , Humanos , Longevidade , Estudos Longitudinais , Masculino , Saúde Mental , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medicina Estatal
15.
BMJ ; 367: l6058, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852664

RESUMO

OBJECTIVES: To evaluate the associations between birth month, birth season, and overall and cardiovascular disease mortality, and to examine the role of familial and socioeconomic factors in these associations. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study, established in 1976, an ongoing prospective cohort study in the United States. PARTICIPANTS: Female registered nurses who reported information on date of birth at study enrolment (n=116 911, 1976-2014, followed for 38 years). EXPOSURE: Birth month and astronomical birth season (based on solstices and equinoxes as boundaries of the season categories). MAIN OUTCOME MEASURES: Age and various multivariable adjusted hazard ratios and 95% confidence intervals for the association between birth months (using November as the reference), astronomical birth season (using autumn as the reference), and overall and cardiovascular disease specific mortality were assessed using Cox proportional hazards models. RESULTS: Among study participants, 43 248 overall deaths were documented during 4 136 364 person years of follow-up since enrolment, including 8360 cardiovascular disease related deaths. In fully adjusted multivariable analyses, no significant association was observed between birth month, birth season, and overall mortality. Compared with women born in November, increased cardiovascular disease mortality was observed among those born from March to July (hazard ratio for March, 1.09, 95% confidence interval 0.98 to 1.21; April, 1.12, 1.00 to 1.24; May, 1.08, 0.98 to 1.20; June, 1.07, 0.96 to 1.19; and July 1.08, 0.98 to 1.20). Those born in April had the highest cardiovascular disease mortality, and those born in December had the lowest (December, 0.95, 0.85 to 1.06). The relative difference between the lowest and highest risk month was 17.89%. Women born in spring (1.10, 1.04 to 1.17) and summer (1.09, 1.03 to 1.16) had a higher cardiovascular disease mortality than women born in the autumn. Adjustment for familial and socioeconomic factors did not change these results. The relative difference between the lowest and highest risk season was 10.00%. CONCLUSION: Participants born in the spring and summer (especially those born in March-July) had a slight but significant increase in cardiovascular disease specific mortality. However, no seasonal birth month effect was observed among women for overall mortality. Familial and socioeconomic factors did not appear to alter these associations. Further studies are required to confirm these findings and reveal mechanisms of these seasonal birth month effects in cardiovascular disease mortality.


Assuntos
Doenças Cardiovasculares/mortalidade , Estações do Ano , Fatores de Tempo , Adulto , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos
16.
Cell Physiol Biochem ; 53(5): 805-819, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31670920

RESUMO

BACKGROUND/AIMS: Despite effective therapeutic strategies for treating hormone receptor-positive (HR+) breast cancer, resistance to endocrine therapy that is either de novo or acquired still occurs. We investigated epidermal growth factor receptor (EGFR) as a therapeutic target for overcoming endocrine resistance in HR+ breast cancer models. METHODS: Using clinical data from 2,166 patients who had HR+ breast tumors and received tamoxifen, we analyzed survival rates. Levels of mRNA and protein expression were analyzed by real-time PCR and western blotting, respectively. Cell viability was analyzed by MTT assays and anchorage-independent growth by soft agar colony-formation assays. Efficacy of tamoxifen and/or gefitinib was analyzed using orthotopic xenograft mouse models. RESULTS: EGFR expression was significantly associated with more advanced stage and higher grade. EGFR expression was different in luminal A-like (Lum A, 1.3%) versus luminal B-like (Lum B, 11.4%) subtypes. On multivariate analyses for survival Lum B subtype EGFR+ tumors showed a hazard ratio (HR) of 5.22 (95% CI, 1.29-21.15, P = 0.020) for overall survival (OS) and HR of 2.91 (95% CI, 1.35-6.28, P = 0.006) for disease-free survival (DFS). Levels of EGFR inversely correlated with ER-α expression. Basal ER-α level was completely blocked by TGFA or EGF treatment. With TGFA pretreatment, ER+ breast cancer cells were resistant to 4-hydroxytamoxifen (4-OHT). Conversely, downregulation of ER-α by TGFA was reversed by gefitinib with recovered sensitivity to 4-OHT. Tumorigenicity of EGFR and ER+ breast cancer cells were significantly decreased by combined tamoxifen and gefitinib. CONCLUSION: Aberrant EGFR expression was associated with poor prognosis in ER+ breast cancers, especially the Lum B subtype. Loss of ER by EGFR activation induced tamoxifen resistance. Therefore, EGFR could be a therapeutic target for overcoming recurrence of ER+ breast cancer with high EGFR expression.


Assuntos
Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Adulto , Idoso , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Receptor ErbB-2/antagonistas & inibidores , Receptores Estrogênicos/metabolismo , Taxa de Sobrevida , Tamoxifeno/análogos & derivados , Tamoxifeno/química , Tamoxifeno/farmacologia
17.
Cell Physiol Biochem ; 53(5): 820-831, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31701729

RESUMO

BACKGROUND/AIMS: MLK4 (KIAA1804) is the second most frequently mutated kinase in microsatellite stable (MSS) colorectal carcinomas (CRC). This molecule is known to regulate different physiological cellular processes, including cell cycle, senescence and apoptosis, and mechanistic evidence has been provided that MLK4 plays a role in carcinogenesis. However, whether this kinase exerts a tumor suppressive role or an oncogenic function is still an object of debate. This study aims to elucidate the role of MLK4 in the pathogenesis of CRC by investigating human tumor specimens. METHODS: This study assessed MLK4 expression levels by immunohistochemistry in surgical tumor samples from 204 early-stage CRC patients and their correlation with various clinical-pathological features and patients' outcomes. In addition, MLK4 mRNA transcription was analysed in an independent cohort of 786 colon cancer samples. RESULTS: Loss of MLK4 staining was associated with poor overall (OS) and progression free survival (PFS) in CRC patients during a univariate analysis (OS:101 vs 164 months, p=0.0002; PFS:85 vs 125 months, p=0.0001), as well as in multivariate analysis (OS:HR=1.70; p=0.001; PFS:HR=1,61; p=0.001). This was confirmed by analysis of MLK4 mRNA in the second independent cohort. A subgroup analysis according to KRAS mutation status showed that MLK4 staining was associated with better OS and PFS in KRAS mutated cases (HR=2.77; p=0.0001 and HR=2.31; p=0.0003, respectively) and microsatellite stable tumors (HR=1.87; p=0.002 and HR=1.06; p=0.006) but not in KRAS wildtype and microsatellite unstable tumors. CONCLUSION: By providing the first report from clinical specimens on the prognostic significance of MLK4, we define an oncogenic loss-of-function of this kinase and suggest a possible role in the interaction with KRAS signaling in determining an aggressive phenotype of CRC. These findings warrant the further investigation of MLK4 in wider cohorts and various clinical settings.


Assuntos
Neoplasias Colorretais/patologia , MAP Quinase Quinase Quinases/metabolismo , Instabilidade de Microssatélites , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Idoso , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , MAP Quinase Quinase Quinases/genética , Masculino , Mutação , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas p21(ras)/genética
18.
Medicine (Baltimore) ; 98(45): e17862, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702650

RESUMO

Since the progression of cirrhosis is accelerated each time a complication recurs, the management and treatment of the complication is critical in enhancement of the quality of life and expectation of life in patients. The use of model for end-stage liver disease with incorporation of serum-sodium (MELD-Na) with physiological indicators can be used to assess severity and differentiate therapeutic interventions.This study is aimed to determine the mean survival period and cumulative survival rate by classifying patients into high-risk and low-risk groups based on MELD-Na, a predictor of mortality in liver disease, and to investigate the mortality prognostic factors.A retrospective cohort study, which follows the STROBE checklist, was performed. 263 patients who were diagnosed with liver cirrhosis complications for the first time and hospitalized were selected as the subjects of this study. The collected data were analyzed based on the survival package provided by the statistical program R version 3.4.2.Subjects were classified into high-risk and low-risk groups using MELD-Na 14 points where sensitivity and specificity crossed the cut-off point. Gender, age, and primary caregiver were significant variables in the mortality high-risk group, and AST, albumin, and primary caregiver were significant variables in the mortality low-risk group. Based on these mortality prognostic factors, it is possible to present the factors affecting mortality in patients who were diagnosed with liver cirrhosis complications for the first time. The classification of patients by risk level could be the foundation to provide accurate guidelines for management and it is necessary to modify prognostic factors and apply nursing interventions to manage complications.


Assuntos
Doença Hepática Terminal/mortalidade , Cirrose Hepática/mortalidade , Índice de Gravidade de Doença , Sódio/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Progressão da Doença , Doença Hepática Terminal/sangue , Doença Hepática Terminal/etiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
19.
Medicine (Baltimore) ; 98(45): e17914, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702670

RESUMO

There are very few reports of eczema and other prosthetic-related allergic skin complications following arthroplasty. We aimed to assess the risk of eczema after joint replacement.We performed a retrospective population-based cohort study in 2024 joint replacement patients using the Longitudinal Health Insurance Database. For comparison, 8096 controls were selected, with 4 control subjects for each joint replacement patient matched for age, sex, and index year, to assess eczema risk. We examined 14-year cumulative eczema incidence associated with age, sex, immunity, disease history, and joint replacement location.Eczema rates in the joint replacement patients were 38% higher than in the control group (57.90 vs 41.84 per 1000 person-years, respectively). Compared with the control group, joint replacement patients showed a 1.35-fold increased risk of eczema according to the multivariable Cox model (95% Confidence interval [CI] = 1.23-1.49). Knee replacement patients had higher eczema risk compared with the control group (Hazard ratio [HR] = 1.45, 95% CI = 1.33-1.70). Stratified by study period, the joint replacement cohort had a higher eczema risk after the 3-month follow-up.Our study revealed that joint arthroplasty increased risk of eczema in this 14-year follow-up study, and this was not related to personal atopic history or gender.


Assuntos
Artroplastia de Substituição/efeitos adversos , Eczema/epidemiologia , Prótese Articular/efeitos adversos , Idoso , Artroplastia de Substituição/estatística & dados numéricos , Estudos de Casos e Controles , Comorbidade , Dermatite Alérgica de Contato/epidemiologia , Eczema/etiologia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Metais/efeitos adversos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
20.
BMJ ; 367: l6055, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748235

RESUMO

OBJECTIVE: To determine the relation between age and troponin level and its prognostic implication. DESIGN: Retrospective cohort study. SETTING: Five cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC). PARTICIPANTS: 257 948 consecutive patients undergoing troponin testing for any clinical reason between 2010 and 2017. MAIN OUTCOME MEASURE: All cause mortality. RESULTS: 257 948 patients had troponin measured during the study period. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured during the patient's hospital stay. Troponin levels were standardised as a multiple of each laboratory's 99th centile of the upper limit of normal (ULN). During a median follow-up of 1198 days (interquartile range 514-1866 days), 55 850 (21.7%) deaths occurred. A positive troponin result (that is, higher than the upper limit of normal) signified a 3.2 higher mortality hazard (95% confidence interval 3.1 to 3.2) over three years. Mortality varied noticeably with age, with a hazard ratio of 10.6 (8.5 to 13.3) in 18-29 year olds and 1.5 (1.4 to 1.6) in those older than 90. A positive troponin result was associated with an approximately 15 percentage points higher absolute three year mortality across all age groups. The excess mortality with a positive troponin result was heavily concentrated in the first few weeks. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. A direct relation was seen between troponin level and mortality in patients without acute coronary syndrome (ACS, n=120 049), whereas an inverted U shaped relation was found in patients with ACS (n=14 468), with a paradoxical decline in mortality at peak troponin levels >70×ULN. In the group with ACS, the inverted U shaped relation persisted after multivariable adjustment in those who were managed invasively; however, a direct positive relation was found between troponin level and mortality in patients managed non-invasively. CONCLUSIONS: A positive troponin result was associated with a clinically important increased mortality, regardless of age, even if the level was only slightly above normal. The excess mortality with a raised troponin was heavily concentrated in the first few weeks. STUDY REGISTRATION: ClinicalTrials.gov NCT03507309.


Assuntos
Envelhecimento/sangue , Doenças Cardiovasculares , Troponina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/terapia , Estudos de Coortes , Tratamento Conservador/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Reino Unido/epidemiologia
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