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1.
Investig Clin Urol ; 61(1): 19-27, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942459

RESUMO

Purpose: This study aimed to evaluate the clinical efficacy of enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients using real-world data from Korean patients. Materials and Methods: We retrospectively reviewed the medical records of 199 chemotherapy-naïve patients with mCRPC at 13 tertiary centers in Korea between 2014 and 2017. All patients received enzalutamide daily and 89 patients received concurrent androgen deprivation therapy (ADT). Results: The median age of the patients was 74 years. Initial results showed that 81.5% of the patients had Gleason score ≥8 and 33.3% of the patients had European Cooperative Oncology Group Performance Status 0. The overall mortality rate was 12%. The median OS was not archieved and 76.7% of patients were alive at 30 months. Median time until PSA progression was 6 months. The overall survival rate at 2 years was significantly higher (84.6% vs. 71.7%, p=0.015) and the duration of PSA progression-free survival was significantly longer (8.0 vs. 4.6 months, p=0.008) in patients receiving concurrent ADT than in those receiving enzalutamide alone. The incidence of adverse events of grade 3 or higher was 1.7%. Multivariate Cox proportional hazard analysis indicated that ADT administered concurrently with enzalutamide significantly improved the overall survival (hazard ratio, 0.346; 95% confidence interval, 0.125-0.958). Conclusions: Enzalutamide is effective and safe for chemotherapy-naïve patients with mCRPC. Furthermore, the overall survival was significantly higher in patients receiving enzalutamide and concurrent ADT than in patients receiving enzalutamide alone.

2.
Investig Clin Urol ; 61(1): 28-34, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942460

RESUMO

Purpose: Several strategies of prostate biopsy (PBx) have been introduced to improve prostate cancer (PCa) detection rates. However, studies comparing cancer detection rates (CDRs) according to biopsy methods in real-world practice are scarce. This study aimed to investigate CDRs according to the biopsy methods for patients with prostate-specific antigen (PSA) <10.0 ng/mL. Materials and Methods: From 2006 to 2015, patients who underwent PBx were initially selected. All patients were categorized according to the biopsy methods performed (magnetic resonance imaging targeted biopsy [MR-TBx], 12+2 hypoechoic lesion target biopsy, saturation biopsy [sPBx], extended biopsy, and 12-core PBx). The CDR of MR-TBx was compared to that of sPBx and other protocols. Volume per core (VPC) was defined as prostate volume divided by the number of biopsy cores. Patients previously diagnosed with PCa were excluded. Results: Of the 1,598 patients (median PSA, 5.41 ng/mL), 401 (25.1%) were diagnosed with PCa. Among the biopsy methods, MR-TBx has the highest CDR and proportion of Gleason score ≥7 (3+4). Biopsy methods, VPC, age, prostate volume, and PSA were associated with PCa detection. In the sub-analysis for initial biopsy, MR-TBx had no significant difference with sPBx, but had higher CDR than the other biopsy protocols. For repeat biopsy, VPC, rather than the biopsy method, was associated with CDR. Conclusions: This study reaffirmed the efficacy of MR-TBx on CDR in real-world practice. In cases with barriers to performing magnetic resonance imaging, VPC might be useful for adjusting the optimal number of biopsy cores in repeat biopsy.

3.
World J Urol ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925552

RESUMO

PURPOSE: The delivery of precision medicine is a primary objective for both clinical and translational investigators. Patients with newly diagnosed prostate cancer (PCa) face the challenge of deciding among multiple initial treatment modalities. The purpose of this study is to utilize artificial neural network (ANN) modeling to predict survival outcomes according to initial treatment modality and to develop an online decision-making support system. METHODS: Data were collected retrospectively from 7267 patients diagnosed with PCa between January 1988 and December 2017. The analyses included 19 pretreatment clinicopathological covariates. Multilayer perceptron (MLP), MLP for N-year survival prediction (MLP-N), and long short-term memory (LSTM) ANN models were used to analyze progression to castration-resistant PCa (CRPC)-free survival, cancer-specific survival (CSS), and overall survival (OS), according to initial treatment modality. The performances of the ANN and the Cox-proportional hazards regression models were compared using Harrell's C-index. RESULTS: The ANN models provided higher predictive power for 5- and 10-year progression to CRPC-free survival, CSS, and OS compared to the Cox-proportional hazards regression model. The LSTM model achieved the highest predictive power, followed by the MLP-N, and MLP models. We developed an online decision-making support system based on the LSTM model to provide individualized survival outcomes at 5 and 10 years, according to the initial treatment strategy. CONCLUSION: The LSTM ANN model may provide individualized survival outcomes of PCa according to initial treatment strategy. Our online decision-making support system can be utilized by patients and health-care providers to determine the optimal initial treatment modality and to guide survival predictions.

4.
Am J Health Behav ; 44(1): 90-99, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31783936

RESUMO

Objectives: Androgen-deprivation therapy (ADT) for prostate cancer (PCa) is associated with reduced physical function and quality of life (QoL). We investigated the impact of a structured lifestyle intervention on the promotion of physical activity (PA) and reduction of sedentary behavior (SB), and its effect on QoL in men on ADT. Methods: Patients with advanced PCa on long-term ADT were randomized to the intervention (N = 11) or a control arm (N = 10) between February 2018 and May 2019. The intervention group received a structured lifestyle intervention including motivational text messages for 8 weeks (maintenance visit at week 12). At each visit, self-report measures and accelerometer data were used to assess PA and SB, and questionnaires were used to measure QoL, life satisfaction, anxiety, and depression. Results: Significantly greater improvements in QoL and depression compared to baseline were reported in the intervention group compared to the control group. In addition, the intervention group also showed a significantly greater increase in self-reported light, as well as moderate-to-vigorous PA, and reduction in self-reported SB. Conclusions: Given its inherent advantage in improving QoL and reducing depression, a lifestyle intervention program should be offered to patients on ADT.

5.
BJU Int ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31868997

RESUMO

OBJECTIVES: To document the management of advanced prostate cancer including diagnosis, prognosis, treatment, and care, in real-world practice in Asia using the United in Fight against prOstate cancer (UFO) registry. PATIENTS AND METHODS: We established a multi-national, longitudinal, observational registry of patients with prostate cancer presenting to participating tertiary care hospitals in eight Asian countries. A total of 3636 eligible patients with existing or newly diagnosed high-risk localised prostate cancer (HRL), non-metastatic biochemically recurrent prostate cancer (M0), or metastatic prostate cancer (M1), were consecutively enrolled and are being followed-up for 5 years. Patient history, demographic and disease characteristics, treatment and treatment decisions, were collected at first prostate cancer diagnosis and at enrolment. Patient-reported quality of life was prospectively assessed using the European Quality of Life-five Dimensions, five Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy for Prostate Cancer questionnaires. In the present study, we report the first interim analysis of 2063 patients enrolled from study start (15 September 2015) until 18 May 2017. RESULTS: Of the 2063 enrolled patients, 357 (17%), 378 (19%), and 1328 (64%) had HRL, M0 or M1 prostate cancer, respectively. The mean age at first diagnosis was similar in each group, 56% of all patients had extracapsular extension of their tumour, 28% had regional lymph node metastasis, and 53% had distant metastases. At enrolment, 62% of patients had at least one co-morbidity (mainly cardiovascular disease or diabetes), 91.8% of M1 patients had an Eastern Cooperative Oncology Group performance score of <2 and the mean EQ-5D-5L visual analogue score was 74.6-79.6 across cohorts. Treatment of M1 patients was primarily with combined androgen blockade (58%) or androgen-deprivation therapy (either orchidectomy or luteinising hormone-releasing hormone analogues) (32%). Decisions to start therapy were mainly driven by treatment guidelines and disease progression. Decision to discontinue therapy was most often due to disease progression (hormonal drug therapy) or completion of therapy (chemotherapy). CONCLUSION: In the UFO registry of advanced prostate cancer in Asia, regional differences exist in prostate cancer treatment patterns that will be explored more deeply during the follow-up period; prospective follow-up is ongoing. The UFO registry will provide valuable descriptive data on current disease characteristics and treatment landscape amongst patients with prostate cancer in Asia.

6.
Medicine (Baltimore) ; 98(51): e18505, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861036

RESUMO

Targeted biopsy with multiparametric magnetic resonance imaging and hypoechoic lesions on transrectal ultrasound has been implemented to increase prostate cancer detection rate.We compared the detection abilities of systematic prostate biopsy, hypoechoic lesion-targeted biopsy (HL-TBx), and cognitive magnetic resonance imaging-targeted biopsy (MRI-TBx) in patients with suspected prostate cancer. Between September 2014 and August 2016, 193 patients with a prostate-specific antigen level of 3 to 10 ng/mL underwent HL-TBx or MRI-TBx. In patients who refused magnetic resonance imaging examination before prostate biopsy, HL-TBx was performed. We compared cancer detection rates and pathologic outcomes between systematic prostate biopsy and HL-TBx or MRI-TBx.The cancer detection rates for HL-TBx and MRI-TBx were 40.8% and 43.8%, respectively, without a significant difference (P = .683). Of the 81 patients diagnosed with prostate cancer, most patients (77 patients, 95.1%) were diagnosed with prostate cancer by systematic prostate biopsy. The detection ability for prostate cancer was significantly better for systematic prostate biopsy than for HL-TBx or MRI-TBx (P < .001).The detection abilities for clinically significant prostate cancer similar between HL-TBx and systematic prostate biopsy. Systematic prostate biopsy alone should be recommended for detection prostate cancer in patients with a prostate-specific antigen ≤10 ng/mL.


Assuntos
Próstata/patologia , Neoplasias da Próstata/diagnóstico , Idoso , Biópsia/métodos , Imagem de Difusão por Ressonância Magnética , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Estudos Retrospectivos
7.
Oxid Med Cell Longev ; 2019: 1825018, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772699

RESUMO

Calcineurin inhibitors (CNIs) are the most popular immunosuppressants in organ transplantation, but nephrotoxicity is a major concern. The common mechanism underlying chronic CNI nephropathy is oxidative stress, and the process of chronic CNI nephropathy is similar to that of aging. Current studies provide evidence that antiaging Klotho protein plays an important role in protecting against oxidative stress, and its signaling is a target for preventing oxidative stress-induced aging process. In this review, we focus on the association between Klotho and oxidative stress and the protective mechanism of action of Klotho against oxidative stress in chronic CNI nephropathy. In addition, we discuss the delivery strategy for Klotho in CNI-induced nephropathy.

8.
Yonsei Med J ; 60(12): 1129-1137, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31769243

RESUMO

PURPOSE: Local treatment has become a treatment option for patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). Subgroup analyses based on a history of cerebrovascular disease (CVD) were performed to evaluate the impact thereof on overall survival (OS) after local treatment. MATERIALS AND METHODS: A retrospective analysis was performed for 879 patients with de novo mHSPC between August 2003 and November 2016. Patients were stratified according to prior CVD history and the type of initial treatment: androgen-deprivation therapy (ADT) alone versus local treatment consisting of radical prostatectomy (RP) or radiation therapy (RT) with ADT, with or without metastasis-directed therapy. The primary outcome was OS assessed by Kaplan-Meier analysis and Cox-regression models. RESULTS: Of 879 patients, 660 (75.1%) men underwent ADT alone, and 219 (24.9%) men underwent RP or RT with ADT, with or without metastasis-directed therapy. The median follow-up was 38 months. Multivariable analysis showed CVD history to be associated with a higher risk of overall mortality (p=0.001). In the overall cohort and in patients without a history of CVD, patients who underwent local treatment exhibited higher OS than men who received ADT alone (all p<0.001). However, the survival benefit conferred by local treatment was not seen in patients with a history of CVD (p=0.324). OS was comparable between patients who received RP and RT (p=0.521). CONCLUSION: Local treatment with or without metastasis-directed therapy may provide OS advantages for mHSPC patients without a history of CVD. Further prospective studies are needed to address these important concerns.

9.
Investig Clin Urol ; 60(6): 442-446, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31692911

RESUMO

Purpose: The impact of family history on the diagnosis of the prostate cancer among Asian population remains controversial. We evaluated whether a positive family history of the prostate cancer in Korean men is associated with the diagnosis and aggressiveness of the prostate cancer. Materials and Methods: Patients who underwent a transrectal ultrasound-guided prostate biopsy from March 2015 to September 2017 were evaluated. Information on family history was obtained via a self-administered questionnaire. The presence of prostate cancer and clinically significant prostate cancer (Gleason score ≥7) was evaluated according to the presence of a family history. Results: Of 602 patients (median age, 68.3 years; median prostate-specific antigen level, 6.28 ng/mL), 41 (6.8%) patients had a family history of prostate cancer. Family history was a significant factor for detecting prostate cancer (odds ratio [OR], 2.99; 95% confidence interval [CI], 1.330-6.704; p=0.008). In multivariate analysis for predicting clinically significant prostate cancer, family history was a significant predictor (OR, 6.32; 95% CI; 2.790-14.298; p<0.001). Conclusions: A family history of prostate cancer in Korean men was a significant factor for predicting prostate cancer. Moreover, significant differences in the aggressive features of the disease were identified between patients with and without a family history.

10.
Transplant Proc ; 51(10): 3297-3303, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31732215

RESUMO

BACKGROUND: Graft biopsy is the gold standard for the differential diagnosis of graft dysfunction. The time interval between transplant surgery and biopsy often provides clinicians with diagnostic clues. However, the clinicopathologic features of late graft biopsy, especially those obtained at more than 5 years after kidney transplant, are not well understood. MATERIALS AND METHODS: We retrospectively collected graft biopsy tissues obtained from kidney transplant recipients who underwent indication biopsy between February 2012 and March 2017. Patients were divided according to their post-transplant period, and their clinical characteristics, pathologic diagnosis, and Banff scores were compared across groups. RESULTS: A total of 410 indication biopsy specimens obtained from 321 kidney transplant recipients were analyzed in this study. Overall, the incidence of T cell-mediated rejection, borderline rejection, and BK virus-associated nephropathy decreased while that of antibody-mediated rejection, nonspecific interstitial fibrosis and tubular atrophy, and glomerulonephritis increased over time. Most samples obtained over 5 years after kidney transplant exhibited chronic glomerular and tubulointerstitial injuries irrespective of their pathologic diagnosis. In patients whose post-transplant period was less than 5 years, urine protein-to-creatinine ratio was significantly elevated in the glomerulonephritis and chronic active antibody-mediated rejection groups only. In contrast, patients who underwent graft biopsy more than 5 years after kidney transplant showed significantly high levels of proteinuria irrespective of the pathologic diagnosis, and there was no statistical difference between groups. CONCLUSION: We demonstrated that the etiology of graft dysfunction is largely influenced by the biopsy time point.

11.
Korean J Intern Med ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31739654

RESUMO

Background/Aims: It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. Methods: We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. Results: The nephrotoxicity in the HM- and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-associated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM- and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2'-deoxyguanosine and manganese- dependent superoxide dismutase expression) and apoptotic cell death (terminal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM- and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM- and AA-treated mice in the short-term and long-term studies. Conclusions: The nephrotoxic potential of HM containing AA was similar to that of AA itself.

12.
Medicine (Baltimore) ; 98(45): e17931, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702677

RESUMO

When making clinical decisions concerning additional treatment for patients who have undergone radical prostatectomy (RP), adverse laboratory/pathological features are considered major factors. We investigated and compared the prognostic efficacy of adverse laboratory/pathological features in predicting overall survival (OS) and biochemical failure (BCF) in these patients.The Korean Prostate Cancer Database was used to identify patients undergoing RP between May 2001 and April 2013. Patients with incomplete clinicopathological data or positive lymphadenectomy results were excluded. Finally, 4486 patients included in the final analysis were categorized based on their adverse laboratory/pathological features.Adverse pathological features and detectable prostate-specific antigen (PSA) levels 6 weeks after surgery were observed in 1977 (44.1%) and 634 (14.1%) patients, respectively. PSA levels, pathological Gleason score ≥8, adverse pathological features [positive surgical margin (PSM), seminal vesicle invasion (SVI), and extracapsular extension (ECE)], and adverse laboratory features (detectable PSA levels after 6 weeks) together were significant predictors of BCF-free survival (BCFFS). SVI was identified as a predictor of OS. Additionally, patients with ECE, PSM, and detectable PSA levels after 6 weeks, but without SVI, showed similar OS to those without ECE, PSM, and detectable PSA levels after 6 weeks and with SVI (log-rank test, P = .976).We successfully stratified patients based on adverse laboratory/pathological features after RP and demonstrated that these are important prognostic factors for OS and BCFFS. Additionally, we identified the criteria for selecting appropriate patients for undergoing additional treatment based on OS and BCFFS.


Assuntos
Biomarcadores Tumorais/sangue , Gradação de Tumores , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Humanos , Masculino , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Prostatectomia/mortalidade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Sistema de Registros , Glândulas Seminais/patologia
13.
Kidney Res Clin Pract ; 38(4): 509-516, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31640307

RESUMO

Background: Cancer rates are increasing not only in the general population but also in patients with end-stage renal disease. We investigated the changing pattern of pretransplant malignancy in kidney transplant recipients over 5 decades. Methods: We reviewed 3,748 kidney transplant recipients between 1969 and 2016. We divided patients into three groups (1969-1998, 1999-2006, 2007-2016) based on the era of the cancer screening system used throughout the nation. We analyzed the incidence and pattern of pretransplant malignancy among the three groups. We also evaluated recurrent and de novo malignancy in these patients compared to patients without pretransplant malignancy. Results: A total of 72 patients exhibited pretransplant malignancy (1.9%). There were no cases of pretransplant cancer until 1998, but the rate of pretransplant malignancy gradually increased to 1.1% during 1999-2006 and further increased to 4.3% thereafter. The most frequent types of pretransplant malignancy changed from the bladder, liver, and stomach cancers to thyroid cancer and renal cell carcinoma. There were no de novo cases, but there were three cases of recurrent cancer in patients with pretransplant malignancy; the recurrence rate among kidney transplant recipients with pretransplant malignancy was not significantly different from the incidence rate of de novo malignancy among kidney transplant recipients without pretransplant malignancy (4.2% vs. 6.9%, P = 0.48). Conclusion: The incidence of pretransplant malignancy in kidney transplantation candidates is gradually increasing, and recent increases were accompanied by changes in cancer types. Pretransplant malignancy may not be a hindrance to kidney transplantation because of the low incidence of posttransplant recurrence and de novo malignancy.

14.
Medicine (Baltimore) ; 98(42): e17635, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626149

RESUMO

This study aimed to investigate the metabolic syndrome-related risk factors for the development of benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS) in healthy men.A total of 4880 healthy men who underwent transrectal ultrasonography at our hospital during routine health examinations were included in this study. Those who had undergone a prior biopsy or surgery for prostate disease, were suspected of having urinary tract infection, or were taking BPH/LUTS or metabolic syndrome medications were excluded. BPH/LUTS was defined as an International Prostate Symptom Score (IPSS) of ≥8 and a prostate volume (PV) of ≥30 cm.The subjects had a mean age of 54.1 years, PV of 29.2 cm, prostate-specific antigen (PSA) level of 1.20 ng/mL, and IPSS of 9.2. The annual PV growth rate was 0.48 cm/year. Age, body mass index (BMI), PSA, basal metabolic rate, apolipoprotein A-1, fasting blood glucose, high-density lipoprotein (HDL) cholesterol levels were significant predictive factors for PV. Age, PSA, apolipoprotein B, fasting blood glucose, cholesterol, HDL, and low-density lipoprotein (LDL) levels were predictors of BPH/LUTS at the initial health examination. A decreased fat mass and LDL level were a significant risk factor for the development of BPH/LUTS within 5 years in men without a BPH/LUTS diagnosis at the initial examination.Metabolic syndrome-related variables were strongly associated with BPH/LUTS and by decreasing fat mass and LDL levels, development of BPH/LUTS could be prevented within 5 years in healthy Korean men.


Assuntos
LDL-Colesterol/sangue , Sintomas do Trato Urinário Inferior/etiologia , Síndrome Metabólica/complicações , Hiperplasia Prostática/etiologia , Medição de Risco/métodos , Idoso , Biomarcadores/sangue , Biópsia , Glicemia/metabolismo , Índice de Massa Corporal , Progressão da Doença , Endossonografia , Seguimentos , Humanos , Incidência , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/epidemiologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Próstata/diagnóstico por imagem , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/epidemiologia , Reto , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco
15.
PeerJ ; 7: e7795, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592197

RESUMO

Background: To identify the factors associated with lower urinary tract symptoms (LUTS), we investigated associations between psychological factors, including depression and sleep disorders, and LUTS using the National Health and Nutrition Examination Survey (NHANES) database. Materials and Methods: The NHANES database was examined for the period of 2005 to 2008. Men older than 40 years, who had completed questionnaires surveying their kidney/urologic, prostate, mental health, and sleep conditions were included in this study. LUTS was defined as the presence of two or more of the following symptoms: incomplete emptying, urinary hesitancy, urinary frequency, and nocturia. Multivariable models using logistic regression were used to compare groups of men with or without LUTS. Results: Of 1,820 participants, 110 (6.1%) men reported depression, and 235 (12.9%) presented with LUTS. Men with LUTS were older and had a significantly higher prevalence of depression and unemployment. Sleep disorder was not associated with LUTS. Multivariable logistic regression models demonstrated that men reporting moderate depression had the highest age-adjusted odds (odds ratio = 5.89, 95% CI [3.44-10.11]; p < 0.001) of reporting clinical LUTS. Conclusions: A significant association was observed between LUTS and depression, and between LUTS and employment status. Although the pathophysiology of these relationships is unclear, physicians should consider multi-disciplinary evaluation and treatment approaches for LUTS.

16.
Lancet Oncol ; 20(11): 1518-1530, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31578173

RESUMO

BACKGROUND: In the phase 3 TITAN study, the addition of apalutamide to androgen deprivation therapy (ADT) significantly improved the primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer. We aimed to assess health-related quality of life (HRQOL) in TITAN, including pain and fatigue. METHODS: In this randomised, placebo-controlled, double-blind, phase 3 study, patients with metastatic castration-sensitive prostate cancer (defined as not receiving ADT at the time of metastatic disease progression) aged 18 years and older, receiving continuous ADT (selected at the investigator's discretion), and with an Eastern Cooperative Oncology Group performance status score of 0 or 1 were randomly assigned (1:1), using an interactive web response system, to receive oral apalutamide (four 60 mg tablets, once daily) or matching placebo. Previous localised disease treatment or previous docetaxel for metastatic castration-sensitive prostate cancer were allowed. Randomisation was stratified by Gleason score at diagnosis, region, and previous docetaxel treatment. Randomisation was done using randomly permuted blocks (block size of four). Investigators, research staff, sponsor study team, and patients were masked to the identities of test and control treatments. Patient-reported outcomes were prespecified exploratory endpoints and were the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EuroQoL 5D questionnaire 5 level (EQ-5D-5L). BPI and BFI were completed for 7 consecutive days (days -6 to 1 inclusive of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed during cycles 1-7, then every other cycle until the end of treatment, and at months 4, 8, and 12 in follow-up. Analyses were based on the intention-to-treat population. Missing patient-reported outcome assessments were calculated as the expected number of assessments for a visit minus the actual number of assessments received for that visit. For time-to-event endpoints, when median values could not be calculated because less than 50% of patients had degradation, 25th percentiles were compared. This study is registered with ClinicalTrials.gov, number NCT02489318, and is ongoing. FINDINGS: Between Dec 9, 2015, and July 25, 2017, 1052 eligible patients were enrolled randomly assigned to apalutamide (n=525) or placebo (n=527). Data cutoff for this analysis of patient-reported outcomes was Nov 23, 2018. Median follow-up for time to pain-related endpoints ranged from 19·4 to 22·1 months. Patients were mostly asymptomatic at baseline: on the BPI-SF pain severity scale of 0-10, median pain scores (indicating worst pain in the past 24 h) were 1·14 (IQR 0-3·17) in the apalutamide group and 1·00 (0-2·86) in the placebo group, and median worst fatigue scores on the BFI were 1·29 (IQR 0-3·29) in the apalutamide group and 1·43 (0·14-3·14) in the placebo group. Patient experience of pain and fatigue (intensity and interference) did not differ between the groups for the duration of treatment. Median time to worst pain intensity progression was 19·09 months (95% CI 11·04-not reached) in the apalutamide group versus 11·99 months (8·28-18·46) in the placebo group (HR 0·89 [95% CI 0·75-1·06]; p=0·20). Median time to pain interference progression was not reached in either group (95% CI 28·58-not reached in the apalutamide group; not reached-not reached in the placebo group). 25th percentiles for time to pain interference progression were 9·17 months (5·55-11·96) in the apalutamide group and 6·24 months (4·63-7·43) in the placebo group (HR 0·90 [95% CI 0·73-1·10]; p=0·29). FACT-P total scores and EQ-5D-5L data showed preservation of HRQOL in both groups. The median time to deterioration as determined by FACT-P total score was 8·87 months (95% CI 4·70-11·10) in the apalutamide group and 9·23 months (7·39-12·91) in the placebo group (HR 1·02 [95% CI 0·85-1·22]; p=0·85). INTERPRETATION: Apalutamide with ADT is a well-tolerated and effective option for men with metastatic castration-sensitive prostate cancer. The combination significantly improves survival outcomes compared with ADT alone while maintaining HRQOL despite additive androgen blockade. FUNDING: Janssen Research & Development.

17.
Aging (Albany NY) ; 11(15): 5548-5569, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400753

RESUMO

The antioxidant function of Klotho is well-documented as a regulatory factor implicated in countering the aging process. This study investigated whether ginseng upregulates Klotho and its antiaging signaling in a setting of calcineurin inhibitor-induced oxidative stress. Although tacrolimus treatment reduced Klotho level in the serum and kidney, ginseng treatment was found to reverse the levels. Tacrolimus-induced oxidative stress was reduced by ginseng treatment, with functional and histological improvements. Effect of ginseng on Klotho-induced manganese superoxide dismutase signaling pathway during tacrolimus treatment in mice revealed that ginseng suppressed phosphatidylinositol 3-kinase/serine-threonine kinase Akt-mediated phosphorylation of forkhead box protein O3a and promoted the binding of forkhead box protein O3a to manganese superoxide dismutase promoter. In the mitochondria, ginseng reduced mitochondrial reactive oxygen species production, mitochondrial membrane potential, and oxygen consumption rate, whereas blocking phosphatidylinositol 3-kinase activity with LY294002 enhanced them. These findings together suggested that ginseng attenuated tacrolimus-induced oxidative stress via signaling between Klotho and the phosphatidylinositol 3-kinase/serine-threonine kinase Akt/forkhead box protein O3a-related antioxidant pathway.

18.
Korean J Intern Med ; 34(5): 1091-1099, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31408925

RESUMO

BACKGROUND/AIMS: Membranous nephropathy (MN) is the most common primary glomerular disease diagnosed in older patients. Few reports describe the clinical outcomes in older patients with idiopathic MN. METHODS: The outcomes of 135 patients with histologically proven MN were analyzed. 'Older' was defined as 60 years of age or older at the time of the renal biopsy. The rates of complete remission (CR), progression to end-stage renal disease (ESRD) and infection were compared between older and younger patients. RESULTS: The cumulative event rate for achieving CR was inferior (p = 0.012) and that for requiring renal replacement was higher (p = 0.015) in older patients, and they had a greater risk of infection (p = 0.005). Older age was a significant predictor of a lower rate of CR (adjusted odds ratio [OR], 0.51; 95% confidence interval [CI], 0.26 to 0.98), and was a robust predictor of infection (adjusted OR, 5.27; 95% CI, 1.31 to 21.20). Conservative treatment was associated with a lower remission rate (p = 0.036) and corticosteroid treatment was less effective in achieving CR (p = 0.014), in preventing progression to ESRD (p = 0.013) and in reducing infection (p = 0.033) in older patients. Cyclosporine treatment had similar clinical outcomes with regard to CR, ESRD progression, and infection in older patients. CONCLUSION: Older age was independently associated with inferior rates of CR and greater risk of infection. Treatment modalities affected the outcomes of older patients differently in that cyclosporine treatment is predicted to be more useful than corticosteroids.

19.
Sci Rep ; 9(1): 11899, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417160

RESUMO

Prostate-specific antigen (PSA) kinetics predicts survival in castration-resistant prostate cancer (CRPC); however, the influence of prior treatment on this relationship is unclear. Patients with CRPC were stratified according to time to PSA nadir and time to CRPC progression to investigate their prognostic significance on prostate cancer-specific survival (PCSS) and whether PSA kinetics may serve as prognosticators regardless of prior local treatment. This multicenter retrospective study included 295 patients diagnosed with CRPC between September 2009 and November 2017. PSA kinetics during androgen-deprivation therapy (ADT) including %PSA decline, PSA nadir level, time to PSA nadir, and time to CRPC progression was investigated. Subgroup analysis was performed according to the prior history of local curative treatment. Patients who did not receive prior local treatment with ≥6 months to PSA nadir and <12 months to CRPC, showed lower PCSS rates than those with <6 months to PSA nadir (23.3% vs. 45.3%; p = 0.031) and ≥12 months to CRPC (20.0% vs. 47.8%; p = 0.001). In patients who had received local treatment, PSA kinetic parameters did not influence PCSS. Our results indicate that time to PSA nadir and time to CRPC progression are prognosticators of PCSS in patients with CRPC who did not previously receive curative local treatment.

20.
World J Urol ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31456018

RESUMO

PURPOSE: Lower urinary tract symptoms in men have previously been attributed to obstruction from an enlarged prostate. However, several factors in addition to prostate volume have been identified as impacting urine flow. Prostatic apex shape is one factor that has not been evaluated. This study evaluates the relationship between prostatic apex shape and voiding symptoms and urine flow. METHODS: A retrospective, exploratory data review was conducted for 806 healthy men who underwent routine transrectal ultrasonography at our hospital, and data for 329 patients with uroflowmetric measurements were reviewed for the confirmatory study. Patients were categorized into four groups according to the prostatic apex shape on midsagittal ultrasonography. The association between prostatic apex shape and voiding symptoms was investigated. International Prostate Symptom Score (IPSS) and uroflowmetry were measured, and the associations between IPSS, uroflowmetry, and prostatic apex shape were analyzed. RESULTS: Patients in group 4 (356/806, 44.2%), whose prostatic apex did not overlap the membranous urethra anteriorly or posteriorly, had a significantly lower incidence of moderate and severe lower urinary tract symptoms compared to other groups. There was a significant relationship between prostatic apex shape and total International Prostate Symptom Score. Patients in group 3, whose prostatic apex overlapped posteriorly with the membranous urethra, had lower maximum flow rates on uroflowmetry. There were significant correlations between the maximum flow rate and independent factors including age, intravesicle prostatic protrusion, and prostatic apex shape. CONCLUSIONS: Prostatic apex shape is an independent risk factor for voiding symptom severity and low maximum flow rate.

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