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1.
Bone Joint J ; 101-B(10): 1186-1191, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31564149

RESUMO

AIMS: In previous studies, we identified multiple factors influencing the survivorship of hip resurfacing arthroplasties (HRAs), such as initial anatomical conditions and surgical technique. In addition, the University of California, Los Angeles (UCLA) activity score presents a ceiling effect, so a better quantification of activity is important to determine which activities may be advisable or detrimental to the recovered patient. We aimed to determine the effect of specific groups of sporting activities on the survivorship free of aseptic failure of a large series of HRA. PATIENTS AND METHODS: A total of 661 patients (806 hips) representing 77% of a consecutive series of patients treated with metal-on-metal hybrid HRA answered a survey to determine the types and amounts of sporting activities they regularly participated in. There were 462 male patients (70%) and 199 female patients (30%). Their mean age at the time of surgery was 51.9 years (14 to 78). Their mean body mass index (BMI) was 26.5 kg/m2 (16.7 to 46.5). Activities were regrouped into 17 categories based on general analogies between these activities. Scores for typical frequency and duration of the sessions were used to quantify the patients' overall time spent engaging in sporting activities. Impact and cycle scores were computed. Multivariable models were used. RESULTS: We found no association between any category of activity and a decrease in survivorship. Impact and hip cycle scores also failed to show any association with revision for aseptic failure or wear. CONCLUSION: Return to sporting activities after surgery is safe for patients treated with well-designed and well-implanted HRA. Cite this article: Bone Joint J 2019;101-B:1186-1191.


Assuntos
Artroplastia de Quadril/métodos , Exercício/fisiologia , Próteses Articulares Metal-Metal , Segurança do Paciente/estatística & dados numéricos , Volta ao Esporte/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Artroplastia de Quadril/reabilitação , California , Estudos Transversais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Falha de Prótese , Qualidade de Vida , Medição de Risco , Fatores Sexuais , Inquéritos e Questionários , Sobrevivência , Fatores de Tempo
2.
Bone Joint J ; 101-B(10): 1313-1320, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31564158

RESUMO

AIMS: The aim of this study was to report the outcomes of patients who underwent definitive surgery for secondary chondrosarcomas arising from osteochondromas. PATIENTS AND METHODS: A total of 51 patients with secondary chondrosarcomas occurring from osteochondromas were reviewed. Median age was 36 years (interquartile range (IQR) 15 to 82). Median follow-up was 6.9 years (IQR 2.8 to 10.6). The pelvis was the most commonly affected site (59%). Histological grades were grade I in 35 (69%), grade II in 13 (25%), and grade III in three patients (6%). RESULTS: Preoperative biopsy histology correctly predicted the final histological grade in 27% of patients. The ten-year disease-specific survival (DSS) for all patients was 89.4%. Local recurrence occurred in 15 patients (29%), more commonly in pelvic tumours (37%) compared with limb tumours (19%). Four patients with pelvic tumours died from progression of local recurrence. No patient with limb tumours died of disease. Wide/radical margin was associated with improved local recurrence-free survival (p = 0.032) and local recurrence was associated with worse DSS (p = 0.005). CONCLUSION: We recommend that a secondary chondrosarcoma arising from osteochondroma of the pelvis is resected with wide/radical resection margins. The balance between the morbidity of surgery and risk of local recurrence needs to be considered in patients with limb secondary chondrosarcomas. Cite this article: Bone Joint J 2019;101-B:1313-1320.


Assuntos
Neoplasias Ósseas/patologia , Condrossarcoma/secundário , Recidiva Local de Neoplasia/mortalidade , Osteocondroma/patologia , Adulto , Biópsia por Agulha , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/mortalidade , Condrossarcoma/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Extremidades/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Osteocondroma/diagnóstico por imagem , Osteocondroma/mortalidade , Osteocondroma/cirurgia , Ossos Pélvicos/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
3.
Anticancer Res ; 39(10): 5573-5579, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570452

RESUMO

BACKGROUND/AIM: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer, frequently infected with Merkel cell polyomavirus (MCPyV). H3K27me3 acts as a repressive histone modification that epigenetically controls gene transcription. The aim of this study was to examine H3K27me3 expression in MCC. MATERIALS AND METHODS: H3K27me3 expression levels were immunohistochemically analyzed in 20 MCPyV-positive MCCs, 15 MCPyV-negative MCCs with squamous cell carcinoma (SCC) (combined MCCs), and six MCPyV-negative pure MCCs. RESULTS: Reduced H3K27me3 expression was variously observed in MCCs. H3K27me3 H-score was significantly lower in MCPyV-negative MCCs than in MCPyV-positive MCCs (p=0.002). H3K27me3 expression was significantly lower in MCPyV-negative combined MCC component than in MCPyV-positive MCCs (p<0.001), MCPyV-negative pure MCCs (p=0.036), or pure MCC histology (p<0.001). Kaplan-Meier analysis showed no association of H3K27me3 with outcome. CONCLUSION: Differential reduction in H3K27me3 expression was observed based on MCPyV status and morphological type. These results implicate H3K27me3-mediated epigenetic changes in tumorigenesis of MCC, especially in MCPyV-negative MCC combined with SCC.


Assuntos
Carcinoma de Célula de Merkel/genética , Carcinoma de Células Escamosas/genética , Histonas/genética , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/genética , Carcinoma de Célula de Merkel/virologia , Carcinoma de Células Escamosas/virologia , Epigênese Genética/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Poliomavírus das Células de Merkel/patogenicidade , Pessoa de Meia-Idade , Infecções por Polyomavirus/genética , Infecções por Polyomavirus/virologia , Neoplasias Cutâneas/virologia , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/virologia
4.
Medicine (Baltimore) ; 98(39): e16965, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574795

RESUMO

This study presents the postoperative pregnancy rate of women with recurrent endometriosis and evaluates the predictive value of the endometriosis fertility index (EFI) for the pregnancy.A total of 107 women who wished to conceive after surgery for recurrent endometriosis from January 2007 to December 2016 were included. The EFI score was calculated postoperatively. The receiver operator characteristic (ROC) curve was plotted to determine the most promising contributor to predicting pregnancy, and Kaplan-Meier (K-M) analysis was used to estimate the cumulative pregnancy rate (CPR).A total of 61 pregnancies were registered in 58 women and the remaining 49 patients failed to become pregnant. The EFI score was strongly associated with the postoperative fertility prognosis. The CPRs during the first 2 and 3 years postoperatively were 51.86% and 66.38%, respectively, and increased to 71.98% within the first 5 years postoperatively in patients with EFI scores ≥5. However, the CPR was 26.00% during the first 2 years after surgery in individuals with EFI scores <5, and there was no increase in the CRP thereafter.Women suffering from recurrent endometriosis still experienced a probability of natural pregnancy, especially patients with EFI scores ≥5. The EFI score had good predictive power for postoperative pregnancy in these patients.


Assuntos
Endometriose/cirurgia , Fertilização , Índice de Massa Corporal , Endometriose/complicações , Feminino , Seguimentos , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Estimativa de Kaplan-Meier , Valor Preditivo dos Testes , Gravidez , Taxa de Gravidez , Curva ROC , Recidiva , Técnicas de Reprodução Assistida , Estudos Retrospectivos
5.
Medicine (Baltimore) ; 98(39): e17296, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574852

RESUMO

The angiotensin-receptor-neprilysin inhibitor (ARNI) reduced cardiovascular deaths and heart failure hospitalization in patients with heart failure of reduced ejection fraction (HFrEF). Its role in non-HFrEF patients was not clear. This study aims to answer this question.In this retrospective study, we enrolled 928 patients diagnosed with non-HFrEF, 492 of them received angiotensin converting enzyme inhibitor (ACEI) and the rest 436 received angiotensin-receptor-neprilysin inhibitor. Outcomes were compared by Kaplan-Meier survival analysis and various clinical parameters were investigated using Cox multivariable analysis, followed by interaction analysis. Minnesota living with heart failure Questionnaire (MLHFQ) was employed as one of the criteria to assess heart failure outcome.The cardiovascular (CV) death or HF hospitalization at 24 months occurred in 49 patients in ACEI group compared with 31 in ARNI group (Hazard Ratio (HR): 1.231, 95% confidence Interval (CI): 1.080-2.460, P = .031). And ARNI showed better prognosis of HF hospitalization (HR: 1.283, 95%CI: 1.065-1.360, P = .038). Cumulative Kaplan-Meier estimates of endpoints, ARNI could reduce the incidence of CV death or HF hospitalization (P = .042) and HF hospitalization (P = .035). The stratified analysis revealed that participants with age less than 70 years old had a lower incidence of CV death or HF hospitalization (HR: 1.194, 95%CI: 1.011-1992, P = .031) after treated with ARNI. Patients received diuretics could benefit from ARNI (HR: 1.383, 95%CI: 1.082-1.471, P = .019). Similar results were also observed in patients with heart rate lower than 90 bpm (HR: 1.556, 95%CI: 1.045-2.386, P = .003) and patients with atrial fibrillation history (HR: 1.873, 95%CI: 1.420-2.809, P = .011). ARNI could improve the quality of life both from the total, emotional and physical aspects.ARNI is an efficacy treatment strategy to improve the outcome and quality of life in patients with non-HFrEF.


Assuntos
Antagonistas de Receptores de Angiotensina , Insuficiência Cardíaca , Hospitalização/estatística & dados numéricos , Neprilisina/antagonistas & inibidores , Qualidade de Vida , Volume Sistólico , Idoso , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/efeitos adversos , China/epidemiologia , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/psicologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Função Ventricular Esquerda
6.
Braz J Med Biol Res ; 52(9): e8204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482974

RESUMO

Sarcopenia remains poorly managed in clinical practice due to the lack of simple and accurate screening tools. This study aimed to identify the cutoff values of the SARC-F questionnaire and Ishii's score using the variables age, grip strength, and calf circumference in older inpatients in China to compare the accuracy of the two methods and to explore their predictive ability for adverse outcomes (rehospitalization, falls, fracture, and death). Hospitalized patients (n=138) aged ≥60 years were included. The accuracy of the two tools was evaluated using the reference diagnosis recommended by the Asian Working Group on Sarcopenia (assessing patients with measurements of muscle mass, handgrip strength, and usual gait speed). Follow-up data were obtained by telephone and clinical visits combined with the inpatient medical record system after discharge for at least one year. The results showed that the SARC-F score reached the highest Youden's index when a score of 3 was set as the cutoff value. Ishii's score presented a higher accuracy than SARC-F (area under the receiver operating curve: 0.78 vs 0.64, P=0.01). The Kaplan-Meier survival analysis demonstrated a higher cumulative incidence of rehospitalization in sarcopenic individuals compared to non-sarcopenic individuals according to SARC-F (log-rank test, P<0.001). Cox analysis revealed that SARC-F was an independent risk factor for rehospitalization (adjusted hazard ratio: 4.23, 95%CI: 2.12-9.79, P<0.001). The SARC-F and Ishii's scores might facilitate the early detection of sarcopenia and help identify older adults at risk for adverse outcomes in clinical practice.


Assuntos
Índice de Massa Corporal , Avaliação Geriátrica/métodos , Força da Mão/fisiologia , Sarcopenia/diagnóstico , Inquéritos e Questionários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pacientes Internados , Estimativa de Kaplan-Meier , Masculino , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Sarcopenia/fisiopatologia
7.
JAMA ; 322(11): 1054-1065, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31529008

RESUMO

Importance: Vaginal hysterectomy with suture apical suspension is commonly performed for uterovaginal prolapse. Transvaginal mesh hysteropexy is an alternative option. Objective: To compare the efficacy and adverse events of vaginal hysterectomy with suture apical suspension and transvaginal mesh hysteropexy. Design, Setting, Participants: At 9 clinical sites in the US Pelvic Floor Disorders Network, 183 postmenopausal women with symptomatic uterovaginal prolapse were enrolled in a randomized superiority clinical trial between April 2013 and February 2015. The study was designed for primary analysis when the last randomized participant reached 3 years of follow-up in February 2018. Interventions: Ninety-three women were randomized to undergo vaginal mesh hysteropexy and 90 were randomized to undergo vaginal hysterectomy with uterosacral ligament suspension. Main Outcomes and Measures: The primary treatment failure composite outcome (re-treatment of prolapse, prolapse beyond the hymen, or prolapse symptoms) was evaluated with survival models. Secondary outcomes included operative outcomes and adverse events, and were evaluated with longitudinal models or contingency tables as appropriate. Results: A total of 183 participants (mean age, 66 years) were randomized, 175 were included in the trial, and 169 (97%) completed the 3-year follow-up. The primary outcome was not significantly different among women who underwent hysteropexy vs hysterectomy through 48 months (adjusted hazard ratio, 0.62 [95% CI, 0.38-1.02]; P = .06; 36-month adjusted failure incidence, 26% vs 38%). Mean (SD) operative time was lower in the hysteropexy group vs the hysterectomy group (111.5 [39.7] min vs 156.7 [43.9] min; difference, -45.2 [95% CI, -57.7 to -32.7]; P = <.001). Adverse events in the hysteropexy vs hysterectomy groups included mesh exposure (8% vs 0%), ureteral kinking managed intraoperatively (0% vs 7%), granulation tissue after 12 weeks (1% vs 11%), and suture exposure after 12 weeks (3% vs 21%). Conclusions and Relevance: Among women with symptomatic uterovaginal prolapse undergoing vaginal surgery, vaginal mesh hysteropexy compared with vaginal hysterectomy with uterosacral ligament suspension did not result in a significantly lower rate of the composite prolapse outcome after 3 years. However, imprecision in study results precludes a definitive conclusion, and further research is needed to assess whether vaginal mesh hysteropexy is more effective than vaginal hysterectomy with uterosacral ligament suspension. Trial Registration: ClinicalTrials.gov Identifier: NCT01802281.


Assuntos
Histerectomia Vaginal/métodos , Telas Cirúrgicas , Prolapso Uterino/cirurgia , Útero/cirurgia , Idoso , Feminino , Seguimentos , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Histerectomia Vaginal/efeitos adversos , Estimativa de Kaplan-Meier , Ligamentos/cirurgia , Pessoa de Meia-Idade , Pós-Menopausa , Complicações Pós-Operatórias , Telas Cirúrgicas/efeitos adversos , Resultado do Tratamento , Vagina/cirurgia
8.
J Cancer Res Clin Oncol ; 145(10): 2495-2506, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31494736

RESUMO

PURPOSE: Histology samples are important for the appropriate administration of tumor type-specific cytotoxic and molecular-targeted therapies for the treatment of non-small cell lung cancer (NSCLC). When biopsy samples lack a definite morphology, a diagnosis can be selected from three subtypes based on immunohistochemistry (IHC) results, as follows: favor adenocarcinoma (ADC), favor squamous cell carcinoma (SQC), or not otherwise specified (NOS)-null. In terms of patient outcome, however, the validity of IHC-based classifications remains unknown. METHODS: A large series of 152 patients with advanced NSCLC whose diagnoses had been made based on morphological findings and who had been homogeneously treated were enrolled. We used IHC staining (TTF-1, SP-A, p40, and CK5/6) to examine tumor samples and refined the diagnoses. We then analyzed the pathological subgroups according to the IHC staining results. RESULTS: IHC profiling resulted in 50% of the cases being classified as favor ADC, 31% being classified as favor SQC, and 19% being classified as NOS-null groups. Compared with the favor ADC and favor SQC groups, the NOS-null group had a significantly poorer outcome. Pemetrexed-containing platinum regimens produced a response rate similar to that of other platinum doublet regimens in the favor ADC group (44% vs. 46%), whereas it produced a poorer response in the favor SQC group (0% vs. 52%) and the NOS-null group (0% vs. 24%). The favor ADC group tended to have a higher percentage of EGFR positivity and ALK positivity than the favor SQC group (25% vs. 11% and 7% vs. 0%, respectively). CONCLUSIONS: These findings support the use of immunohistological subtyping of NSCLC biopsy specimens to select patient-appropriate treatments.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Biópsia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento , Adulto Jovem
9.
BMJ ; 366: l5125, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562117

RESUMO

OBJECTIVE: To investigate whether fenofibrate as add-on to statin treatment reduce persistent cardiovascular risk in adults with metabolic syndrome in a real world setting. DESIGN: Propensity matched cohort study. SETTING: Population based cohort in Korea. PARTICIPANTS: 29 771 adults with metabolic syndrome (≥40 years) receiving statin treatment. 2156 participants receiving combined treatment (statin plus fenofibrate) were weighted based on propensity score in a 1:5 ratio with 8549 participants using statin only treatment. MAIN OUTCOME MEASURE: Primary outcome was composite cardiovascular events including incident coronary heart disease, ischaemic stroke, and death from cardiovascular causes. RESULTS: The incidence rate per 1000 person years of composite cardiovascular events was 17.7 (95% confidence interval 14.4 to 21.8) in the combined treatment group and 22.0 (20.1 to 24.1) in the statin group. The risk of composite cardiovascular events was significantly reduced in the combined treatment group compared with statin group (adjusted hazard ratio 0.74, 95% confidence interval 0.58 to 0.93; P=0.01). The significance was maintained in the on-treatment analysis (hazard ratio 0.63, 95% confidence interval 0.44 to 0.92; P=0.02). The risk of incident coronary heart disease, ischaemic stroke, and cardiovascular death was lower in the combined treatment group than statin group but was not significant. Participant characteristics did not appear to be associated with the low risk of composite cardiovascular events with combined treatment. CONCLUSION: In this propensity weighted cohort study of adults with metabolic syndrome, the risk of major cardiovascular events was significantly lower with fenofibrate as add-on to statin treatment than with statin treatment alone.


Assuntos
Doenças Cardiovasculares , Fenofibrato/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Adulto , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Causas de Morte , Estudos de Coortes , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Avaliação de Resultados (Cuidados de Saúde) , Pontuação de Propensão , República da Coreia/epidemiologia , Fatores de Risco
10.
Medicina (B Aires) ; 79(4): 280-283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487248

RESUMO

The purpose of the study was to evaluate the outcome of patients under 18 months diagnosed with neuroblastoma. Between April 2006 and December 2013, 45 consecutive patients followed in Hospital de Pediatría Garrahan, were retrospectively reviewed. With a median age of 9.3 months (1-18 months) N-myc amplification was detected in 5 out of 38 patients, 1p deletion (del1p) in 4 patients, and 11q aberration in one patient. With a median follow-up of 53 (range: 6-109 months), at 24 months the event free survival (EFS) of all patients was 83% (SE 6%) and overall survival (OS) of 88% (SE 5%). Significant difference was found in OS and EFS between patients with stages L1, L2 and Ms vs. stage M (p = 0.01 and p = 0.01 respectively). EFS for each stage: L1 85% (SE 7%), L2 100%, MS 100%, vs. M 55% (SE 16%). OS: L1 90% (SE 6%), L2 100%, MS 100%, vs. M 66% (SE 15%). OS and EFS results are similar to those reported in international studies. However, better identification of biological prognostic factors will warr ant accurate staging and consequently an appropriate treatment.


Assuntos
Antineoplásicos/administração & dosagem , Neuroblastoma/diagnóstico , Neuroblastoma/tratamento farmacológico , Protocolos Antineoplásicos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Neuroblastoma/mortalidade , Prognóstico , Estudos Retrospectivos
11.
Medicine (Baltimore) ; 98(36): e16705, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490362

RESUMO

Deregulation of miR-153 has recently been observed in several common human cancer, while miR-153 serves an oncogene or tumor suppressive role in different cancer types. Previously, miR-153 has been identified to be overexpressed in prostate cancer. miR-153 played an important role in promoting proliferation of human prostate cancer cells and presented a novel mechanism of microRNA-mediated direct suppression of phosphatase and tensin homolog (PTEN) expression in prostate cancer cells. Until now, little is known about the clinical significance of miR-153 expression in prostate cancer.The miR-153 expression in 143 pairs of prostate cancer and adjacent non-cancerous prostate tissues was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Student t test was conducted for intergroup comparison. Pearson correlation test was used for correlation analysis. Survival curves were carried out by the Kaplan-Meier method and evaluated using the log-rank test. Multivariable Cox proportional hazard risk regression model was performed to screen the independent factor affected the prognosis of prostate cancer patients.qRT-PCR analysis showed that the expression of miR-153 was significantly increased in the prostate cancer tissues in comparison with the adjacent noncancerous prostate tissues (P < .001). The high expression of miR-153 in prostate cancer tissues is closely correlated with aggressive clinical pathological parameters such as lymph node metastasis (P = .001); bone metastasis (P < .001); Gleason score (P < .001); and tumor-node-metastasis (TNM) stage (P < .001). Prostate cancer patients with a high expression of miR-153 had an evidently lower 5-year overall survival as compared with those with a low expression of miR-153 (P = .019). Notably, the multivariate Cox regression analysis indicated that miR-153 expression was an independent factor for predicting the 5-year overall survival of prostate cancer patients (hazard ratio [HR] = 2.481, 95% confidence interval [CI]: 1.582-10.727; P = .018).Our study demonstrated that high miR-153 expression was significantly associated with a poor overall survival independently of other factors in prostate cancer. Therefore, miR-153 may be an available biomarker for prostate cancer prognosis.


Assuntos
MicroRNAs/biossíntese , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
Medicine (Baltimore) ; 98(36): e16937, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490377

RESUMO

Metadherin (MTDH), also known as astrocyte elevated gene-1 (AEG-1), is an oncoprotein closely related to the development of breast cancer. However, few studies have been done on the expression and clinical significance of MTDH in human epidermal growth factor receptor-2 (HER-2) positive breast cancer patients.This study aimed to investigate the expression of MTDH in locally advanced HER-2 positive breast cancer, and evaluate the clinical significance of MTDH in predicting the prognosis of patients with HER-2 positive advanced breast cancer who received the neoadjuvant chemotherapy plus trastuzumab.In 144 HER-2 positive breast cancer tissues, 79 cases showed high expression of MTDH and 65 cases showed low expression. The expression of MTDH in locally advanced HER-2 positive breast cancer tissues was correlated with TNM stage, lymph node metastasis, Miller-Payne (MP) grade, and pathologic complete response (pCR) status (P < .05), but was not correlated with patient age, estrogen receptor (ER) expression level, progesterone receptor (PR) expression level, and Ki-67 expression level (P > .05). Kaplan-Meier univariate analysis revealed a negative correlation between MTDH expression and the disease-free survival (DFS) and overall survival (OS) in the post-operative patients with locally advanced HER-2 positive breast cancer (log rank test: P < .001). By using the COX proportional hazard regression model, it was found that MTDH expression, TNM stage, lymph node metastasis, and Ki-67 expression were closely related to DFS in patients. The hazard ratio (HR) of high MTDH expression was 1.816 (95% CI: 1.165-2.829). In addition, MTDH expression, TNM stage, and lymph node metastasis were also closely related to the OS of patient. The HR of the high expression of MTDH was 2.512 (95% CI: 1.472-4.286). The expression of MTDH in tumor tissues of patients with HER2-positive locally advanced breast cancer was significantly elevated, which was related to the poor pathological features.High MTDH expression was closely correlated with poor prognosis of patients and was an important factor affecting tumor progression.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Moléculas de Adesão Celular/biossíntese , Receptor ErbB-2/biossíntese , Trastuzumab/uso terapêutico , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Receptores Estrogênicos/biossíntese , Receptores de Progesterona/biossíntese
13.
Tumour Biol ; 41(9): 1010428319863627, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500540

RESUMO

Stratification of colorectal cancer for better management and tangible clinical outcomes is lacking in clinical practice. To reach this goal, the identification of reliable biomarker(s) is a prerequisite to deliver personalized colorectal cancer theranostics. Osteopontin (SPP1) is a key extracellular matrix protein involved in several pathophysiological processes including cancer progression and metastasis. However, the exact molecular mechanisms regulating its expression, localization, and molecular functions in cancer are still poorly understood. This study was designed to investigate the SPP1 expression profiles in Saudi colorectal cancer patients, and to assess its prognostic value. Hundred thirty-four (134) archival paraffin blocks of colorectal cancer were collected from King Abdulaziz University Hospital, Saudi Arabia. Tissue microarrays were constructed, and automated immunohistochemistry was performed to evaluate SPP1 protein expression patterns in colorectal cancer. About 20% and 23% of our colorectal cancer samples showed high SPP1 cytoplasmic and nuclear expression patterns, respectively. Cytoplasmic SPP1 did not correlate with age, gender, tumor size, and location. However, significant correlations were observed with tumor grade (p = 0.008), tumor invasion (p = 0.01), and distant metastasis (p = 0.04). Kaplan-Meier survival analysis showed a significantly lower recurrence rate in patients with higher SPP1 cytoplasmic expression (p = 0.05). At multivariate analysis, high SPP1 cytoplasmic expression was an independent favorable prognostic marker (p = 0.02). However, nuclear SPP1 expression did not show any prognostic value (p = 0.712). Our results showed a particular SPP1 prognostic relevance that is not in line with most colorectal cancer previous studies that may be attributed to the molecular pathophysiology of our colorectal cancer cohort. Saudi Arabia has both specific genomic makeup and particular environment that could lead to distinctive molecular roots of cancer. SPP1 has several isoforms, tissue localizations and molecular functions, signaling pathways, and downstream molecular functions. Therefore, a more individualized approach for CRC studies and particularly SPP1 prognosis outcomes' assessment is highly recommended toward precision oncology.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Recidiva Local de Neoplasia/genética , Osteopontina/genética , Idoso , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Medicina de Precisão , Prognóstico , Arábia Saudita/epidemiologia
14.
Anticancer Res ; 39(9): 4947-4955, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519600

RESUMO

BACKGROUND/AIM: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) plays an important role in the adhesion, invasion, and metastasis of tumor cells. Although emerging evidence suggests that IMP3 promotes tumor progression in several malignancies, the expression of IMP3 and its prognostic implication in adenocarcinoma of the ampulla of Vater (AVAC) has not been clarified to date. MATERIALS AND METHODS: The IMP3 expression status in 87 AVAC tissues was examined using immunostaining, and its association with various clinicopathological features and outcome of patients with AVAC was investigated. RESULTS: The vast majority (87.4%) of AVAC cases displayed at least focal cytoplasmic and membranous IMP3 immunoreactivity in tumor cells, whereas IMP3 expression was consistently absent from normal biliary epithelial cells. Tumor-specific IMP3 expression was associated with submucosal and pancreatic invasion, which were not identified in the corresponding hematoxylin and eosin-stained slides. This finding led to up-staging of the pathological tumor stage in two cases of well-differentiated AVAC. In addition, high IMP3 expression was significantly associated with a poorly differentiated histology (p=0.026). Survival analyses revealed that high IMP3 expression independently predicted shorter recurrence-free (p=0.003) and overall (p=0.029) survival. CONCLUSION: Our study demonstrated tumor-specific IMP3 expression in AVAC, which will be helpful in determining invasion depth and tumor extent in patients with well-differentiated tumors, as well as indicating worse survival of patients with AVAC. Our data highlight IMP3 expression status as a potential diagnostic and prognostic marker for AVAC.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Ampola Hepatopancreática/patologia , Neoplasias do Ducto Colédoco/genética , Neoplasias do Ducto Colédoco/mortalidade , Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação a RNA/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adulto , Idoso , Biomarcadores Tumorais , Neoplasias do Ducto Colédoco/diagnóstico , Neoplasias do Ducto Colédoco/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Proteínas de Ligação a RNA/genética , Carga Tumoral
15.
N Engl J Med ; 381(12): 1103-1113, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31475793

RESUMO

BACKGROUND: There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease. METHODS: In a multicenter, open-label trial conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority. RESULTS: The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority). CONCLUSIONS: As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease. (Funded by the Japan Cardiovascular Research Foundation; AFIRE UMIN Clinical Trials Registry number, UMIN000016612; and ClinicalTrials.gov number, NCT02642419.).


Assuntos
Fibrilação Atrial/tratamento farmacológico , Doença das Coronárias/terapia , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Ponte de Artéria Coronária , Doença das Coronárias/complicações , Quimioterapia Combinada/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Modelos de Riscos Proporcionais , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Rivaroxabana/efeitos adversos
16.
JAMA ; 322(9): 834-842, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479138

RESUMO

Importance: The optimal international normalized ratio (INR) to prevent venous thromboembolism (VTE) in warfarin-treated patients with recent arthroplasty is unknown. Objective: To determine the safety and efficacy of a target INR of 1.8 vs 2.5 for VTE prophylaxis after orthopedic surgery. Design, Setting, and Participants: The randomized Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis enrolled 1650 patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions: In a 2 × 2 factorial design, participants were randomized to a target INR of 1.8 (n = 823) or 2.5 (n = 827) and to either genotype-guided or clinically guided warfarin dosing. For the first 11 days of therapy, open-label warfarin dosing was guided by a web application. Main Outcomes and Measures: The primary outcome was the composite of VTE (within 60 days) or death (within 30 days). Participants underwent screening duplex ultrasound postoperatively. The hypothesis was that an INR target of 1.8 would be noninferior to an INR target of 2.5, using a noninferiority margin of 3% for the absolute risk of VTE. Secondary end points were bleeding and INR values of 4 or more. Results: Among 1650 patients who were randomized (mean age, 72.1 years; 1049 women [63.6%]; 1502 white [91.0%]), 1597 (96.8%) received at least 1 dose of warfarin and were included in the primary analysis. The rate of the primary composite outcome of VTE or death was 5.1% (41 of 804) in the low-intensity-warfarin group (INR target, 1.8) vs 3.8% (30 of 793) in the standard-treatment-warfarin group (INR target, 2.5), for a difference of 1.3% (1-sided 95% CI, -∞ to 3.05%, P = .06 for noninferiority). Major bleeding occurred in 0.4% of patients in the low-intensity group and 0.9% of patients in the standard-intensity group, for a difference of -0.5% (95% CI, -1.6% to 0.4%). The INR values of 4 or more occurred in 4.5% of patients in the low-intensity group and 12.2% of the standard-intensity group, for a difference of -7.8% (95% CI, -10.5% to -5.1%). Conclusions and Relevance: Among older patients undergoing hip or knee arthroplasty and receiving warfarin prophylaxis, an international normalized ratio goal of 1.8 compared with 2.5 did not meet the criterion for noninferiority for risk of the composite outcome of VTE or death. However, the trial may have been underpowered to meet this criterion and further research may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01006733.


Assuntos
Anticoagulantes/administração & dosagem , Artroplastia de Quadril , Artroplastia do Joelho , Coeficiente Internacional Normatizado , Tromboembolia Venosa/prevenção & controle , Varfarina/administração & dosagem , Idoso , Anticoagulantes/efeitos adversos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Tromboembolia Venosa/mortalidade , Varfarina/efeitos adversos
17.
Anticancer Res ; 39(9): 4681-4685, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519567

RESUMO

BACKGROUND/AIM: S100A8 is a chemoattractant known to be associated with metastatic niche formation. Herein, we evaluated the prognostic value of S100A8 in patients with clear cell renal cell carcinoma (CCRCC). MATERIALS AND METHODS: A total of 152 CCRCC patients who have undergone nephrectomy were enrolled. The expression of S100A8 was assessed immunohistochemically using tissue microarray (TMA) blocks of CCRCC. Using statistical analysis, the relationship between S100A8 expression and clinicopathological factors was evaluated. RESULTS: Among 152 TMA cores, 21 (6.9%) showed higher S100A8 expression. S100A8 expression was significantly increased in cores of patients with higher T stage (≥2, p<0.001) and higher Fuhrman nuclear grade (≥3, p<0.001). Multivariate analysis confirmed that high expression of S100A8 was significantly correlated to poor disease-free survival (hazard ratio, 2.601; 95% confidence interval (CI), 1.020-6.628; p-value=0.045). CONCLUSION: S100A8 expression may have a prognostic value in CCRCC reflecting TNM staging and Fuhrman nuclear grade.


Assuntos
Biomarcadores Tumorais , Calgranulina A/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Expressão Gênica , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Calgranulina A/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico
18.
Anticancer Res ; 39(9): 4687-4698, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519568

RESUMO

BACKGROUND/AIM: Propagermanium (PG) inhibits the CCL2/CCR2 axis, and has been shown to function as an immune modulator. This study investigated its anti-tumor mechanism in patients with refractory cancers. MATERIALS AND METHODS: Five healthy volunteers and 23 patients with refractory oral (n=8) or gastric (n=15) cancer received PG (30 mg/day). We performed flow cytometry (FCM) of peripheral blood mononuclear cells and in vitro killing assays. RESULTS: FCM revealed that CD16+/CD56Dim NK cells (i.e., mature, cytolytic subset) increased, and the apoptosis induction rate of cancer cells increased after PG administration. Among gastric cancer patients, median OS was 172.0 days. Two patients showed complete remission of lung or liver metastasis. Survival of patients with oral cancer also tended to be prolonged. CONCLUSION: PG induces NK cell maturation, and may potentiate anti-tumor activity.


Assuntos
Antineoplásicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Neoplasias/imunologia , Neoplasias/mortalidade , Compostos Organometálicos/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Humanos , Estimativa de Kaplan-Meier , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Tomografia Computadorizada por Raios X
19.
Anticancer Res ; 39(9): 4933-4940, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519598

RESUMO

BACKGROUND: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). MATERIALS AND METHODS: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. RESULTS: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. CONCLUSION: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Variação Genética , Interleucina-2/genética , Adulto , Idoso , Alelos , Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/imunologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Imunomodulação , Interleucina-2/sangue , Interleucina-2/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Prognóstico , Medição de Risco
20.
Anticancer Res ; 39(9): 4977-4985, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519604

RESUMO

BACKGROUND/AIM: To evaluate whether factors related to the clinical staging of lymph node (LN) metastasis diagnosed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (PET/CT) correspond to poor survival in esophageal squamous cell cancer (ESCC) patients treated with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 69 patients with curative intent and no prior treatment for ESCC or simultaneous treatment for synchronous cancers were investigated. A maximum standardized uptake value (SUVmax) on the highest image pixel in the LN ≥2.5 was considered positive. Location of the involved LN and its impact on survival were analyzed. RESULTS: In the univariate analysis of location, metastasis of the abdominal site, regional abdominal LN, and left gastric LN station negatively affected overall survival (OS) and disease-free survival (DFS). Other adverse clinical factors influencing OS included T4, clinical stage IVA and body mass index <21.2. In terms of DFS, a further unfavorable factor was primary tumor SUVmax ≥10.4. Abdominal site LN metastasis affected both OS and DFS in multivariate analysis. CONCLUSION: LN metastasis diagnosed by PET/CT in abdominal sites was an independent predictor affecting both OS and DFS in ESCC patients who underwent curative CCRT.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Resultado do Tratamento
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