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PURPOSE: To assess adherence to combination therapy comprising α-adrenergic blocker (AB) and 5α-reductase inhibitor (5ARI) for benign prostatic hyperplasia (BPH) in a real-world setting and whether lower urinary tract symptoms (LUTS) will relapse after discontinuing one medication from long-term combination therapy. METHODS: BPH/LUTS patients receiving initial AB +5ARI combination therapy for at least 1 year between January 2012 and January 2017 were retrospectively analyzed. The patients were classified into DC-AB group (n = 65, AB discontinued) and DC-5ARI group (n = 77, 5ARI discontinued) and followed up. Clinical effects were assessed at baseline and annually using the International Prostatic Symptoms Score (IPSS), quality of life (QoL) index, total prostate volume (TPV), maximal flow rate (Qmax), and prostate-specific antigen (PSA) level. RESULTS: Of total 1783 patients, 809 (45.4%) patients were identified with more than 1-year combination therapy. After withdrawal of one medication from combination therapy, the TPV progression (27.6% vs. - 10.8%; P < 0.001) and the requirement for prostate surgery (14.3% vs. 6.1%; P = 0.038) were significantly higher in the DC-5ARI group than in the DC-AB group. The rate of resuming combination therapy was significantly higher in the DC-5ARI group than in the DC-AB group (38.9% vs. 23.0%; P = 0.009). CONCLUSIONS: Adherence to combination BPH therapy is relatively low. Although patients adhered to combination therapy for more than 1 year, a higher risk of requiring prostate surgery or resuming combination therapy was observed in patients who discontinued 5ARI.
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Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Quimioterapia Combinada , Inibidores de 5-alfa Redutase/uso terapêutico , Antagonistas Adrenérgicos alfa/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Oxirredutases/uso terapêuticoRESUMO
BACKGROUND: Contradictory data have been reported about the association between testosterone levels and the levels of low-density lipoprotein cholesterol (LDL). OBJECTIVES: The aim of this study was to elucidate the association between testosterone and LDL levels. MATERIALS AND METHODS: A cross-sectional study was conducted that included 7268 men who had participated in a health examination. Men who took agents that influence serum lipid profiles within the previous 6 months were excluded. A full metabolic work-up and serum testosterone level checks were performed. The main outcome measures included the testosterone level and testosterone <3.5 ng/ml prevalence of each decile of LDL and their polynomial trendlines and the odds ratio (OR) of testosterone <3.5 ng/ml according to the LDL level. RESULTS: The polynomial trendline suggests the inverse association of testosterone with the deciles of triglycerides, the positive association of testosterone with the deciles of high-density lipoprotein cholesterol and the inverted U-shaped association between testosterone and the deciles of LDL. The polynomial trendline suggests a U-shaped curvilinear relationship between the deciles of LDL and the prevalence of testosterone <3.5 ng/ml. The adjusted ORs of testosterone <3.5 ng/ml in men in the lowest and highest deciles were significantly higher than those of men in the 10th-90th deciles of LDL (OR [95% CI], < 10th LDL: 1.4[1.2-1.8]; 10th - 90th LDL: 1.0 [reference]; >90th LDL: 1.3[1.0-1.6]), which reinforces the U-shaped curvilinear relationship between LDL levels and the prevalence of testosterone <3.5 ng/ml. DISCUSSION AND CONCLUSION: Further research is needed to elucidate the association of very low or very high LDL concentrations with circulating testosterone in men.
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Congêneres da Testosterona , Testosterona , Masculino , Humanos , Estudos Transversais , Triglicerídeos , LDL-ColesterolRESUMO
BACKGROUND: Osteoporosis is a progressive skeletal disease associated with an increased risk of bone fracture. This study aimed to estimate the cost-effectiveness of denosumab for osteoporotic fracture prevention compared to bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and selective estrogen receptor modulators (raloxifene) in a cohort of postmenopausal women with osteoporosis. METHODS: A Markov model was used to evaluate the cost and effectiveness of denosumab versus comparators. The model had a cycle length of 6 months and was run from the age of 68 years to individual patients' lifetime or the age of 100 years. The health states considered in the model were well, hip fracture, vertebral fracture, wrist fracture, other osteoporotic fracture, post-hip fracture, post-vertebral fracture, and death. Recent local data were used as inputs for the model parameters. A discount rate of 4.5% was applied to both costs and outcomes. RESULTS: From the perspective of the healthcare system, denosumab was cost-effective or cost-saving compared to all comparators, considering one unit of Korea's gross domestic product per capita, USA dollar (USD) 34,870. Denosumab was cost-saving compared to ibandronate (oral) and raloxifene. Compared to alendronate, denosumab was cost-effective with an incremental cost-effectiveness ratio (ICER) of USD 767.10 per quality-adjusted life year (QALY). The ICER of denosumab vs. ibandronate IV, risedronate, and zoledronate was USD 685.63, USD 1,469.71, USD 4,668.53 per QALY, respectively. CONCLUSIONS: The findings of this analysis suggest that denosumab is a cost-effective therapeutic option for preventing fractures in postmenopausal women with osteoporosis in South Korea.
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OBJECTIVE: There are little data on the endogenous testosterone effect on hemoglobin or hematocrit. Moreover, these data are limited by a cross-sectional study design, a small participant number, and no adjustment for confounding factors. Therefore, the present study was conducted to address the aforementioned limitations of previous studies using a large dataset and propensity score matched analysis. MATERIALS AND METHODS: Men who underwent health check-up were analyzed. Participants were divided into two groups using the cut-off testosterone value of 3.5 or 3.0 ng/ml according to a previous definition of testosterone deficiency. Using the cutoff testosterone value of 3.5 ng/ml, 966 cases (testosterone levels <3.5 ng/ml) and 7402 controls (testosterone level ≥3.5 ng/ml) were included, but following propensity score matching, there were 966 cases and 1932 controls. Using the cutoff testosterone value of 3.0 ng/ml, 444 cases (testosterone levels <3.0 ng/ml) and 7924 controls (testosterone level ≥3.0 ng/ml) were included, but following propensity score matching, there were 444 cases and 888 controls. RESULTS: After matching, the groups were evenly distributed with respect to age, body mass index, estimated glomerular filtration rate, hypertension, and diabetes in both data sets. After matching, the mean Hb and Hct were significantly lower and the incidence of anemia was significantly greater in the case compared to the control in both data sets. The relative risk of anemia in the case was 2.4 compared to the control in both data sets. CONCLUSION: Screening for anemia in patients with testosterone deficiency would be needed and vice versa.
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Anemia , Testosterona , Anemia/epidemiologia , Anemia/etiologia , Índice de Massa Corporal , Estudos Transversais , Hemoglobinas , Humanos , Masculino , Pontuação de PropensãoRESUMO
PURPOSE: We assessed the relationship between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED) using propensity score matching. METHODS: Data from 8727 middle-aged men who had undergone health checkups were analyzed. The National Institutes of Health Chronic Prostatitis Symptoms Index (NIH-CPSI), the International Index of Erectile Function-5 (IIEF), the Premature Ejaculation Diagnostic Tool (PEDT), testosterone measurement, basic blood chemistry, and metabolic syndrome (MetS) assessment were performed in this study. Of the 8727 men considered, 7181 formed the cohort for propensity score matching, including 597 men with moderate to severe prostatitis-like symptoms (case) and 6584 men with no prostatitis-like symptoms (control); ultimately, however, members of the case and control groups were matched at a 1:1 ratio by propensity score. RESULTS: After matching, the variables of age, testosterone, PEDT and MetS were evenly distributed between the groups. After matching, the mean IIEF score of the case group was significantly lower than that of the control group (17.2 ± 5.5 vs. 14.7 ± 5.3; P < 0.001). Additionally, the severity of ED was significantly greater in the case group (no, mild, mild to moderate, moderate, and severe, respectively: 27.5%, 30.2%, 24.6%, 13.1%, and 4.7% in the control group; 10.7%, 27.0%, 33.0%, 18.9%, and 10.4% in the case group; P < 0.001). Finally, the rate of moderate to severe ED was significantly higher in the case group than in the control group (17.8% vs. 29.3%; P < 0.001). CONCLUSION: Moderate to severe prostatitis-like symptoms were significantly and independently correlated with ED in middle-aged men.
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Disfunção Erétil/complicações , Prostatite/complicações , Correlação de Dados , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Índice de Gravidade de DoençaRESUMO
BACKGROUND: To compare the safety and efficacy of open simple prostatectomy (OSP) and robotic simple prostatectomy (RSP) for the treatment of large benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 52 patients who underwent OSP (n = 23) and RSP (n = 29) between January 2005 and March 2019 at a single institution. The preoperative status of the patients, complications related to surgery, and the functional outcomes of the surgery were analyzed. RESULTS: There were no significant differences in the preoperative total prostate volume, transitional volume, prostate-specific antigen value, and age between the two groups. Postoperative improvements in the International Prostate Symptom Score, maximum urinary flow rate, and postvoid residual were significant and similar for both groups. There were no significant differences between the two groups regarding surgery duration and resected prostate volume. The majority of patients in both groups had the urethral Foley catheter removed within the planned 10 day postoperative period, with the exception of two patients in the OSP group who had prolonged indwelling Foley catheter placement because of persistent hematuria. Postoperative hematocrit changes were significantly lower in the RSP group (RSP: 7.8 ± 4.1%, OSP: 14.2 ± 4.9%, P < 0.001). Seven patients (30.4%) who underwent OSP and two patients (6.9%) who underwent RSP were transfused because of significant intraoperative bleeding. Two patients from the RSP group who received transfusion comprised the first two cases that underwent RSP treatment. During the follow-up period, two patients (one patient in the OSP group and one patient in the RSP group) underwent transurethral incision of the bladder neck for bladder neck contracture. CONCLUSION: Both OSP and RSP can produce excellent outcomes after surgery. However, complications of bleeding are significantly less prevalent in RSP, suggesting that RSP can replace conventional OSP.
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INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have recently been proposed as easily accessible inflammatory biomarkers and as surrogate markers for metabolic disease, cardiovascular disease, and malignancies, including prostate cancer. However, scant studies have investigated the association of NLR, PLR, and LMR with benign prostatic hyperplasia (BPH). METHODS: Data from 8,727 middle-aged men who had participated in a health checkup were analyzed. BPH was defined as prostate volume ≥30 mL, International Prostate Symptom Score > 7, and maximal flow rate <15 mL/s. Propensity score matching was considered for 269 men with BPH (cases), and 7,136 men with no BPH (controls), but ultimately, propensity scores were matched at a 2:1 ratio of controls to cases (538 men in the control group and 269 men in the case group). RESULTS: After propensity score matching, age, International Index of Erectile Function-5, testosterone, and number of metabolic syndrome component variables were evenly distributed and did not differ significantly between the groups. After matching, PLR and LMR were not significantly different between the 2 groups. However, NLR was significantly higher in the case group than in the control group (median [interquartile range]: 1.4 [1.1; 1.8] vs. 1.5 [1.2; 1.9]; p = 0.024) after matching. CONCLUSION: High NLR was significantly associated with the presence of BPH. Our results suggest the possible effect of inflammation on BPH development. A prospective study is needed to investigate the potential role of NLR as a candidate biomarker of BPH.
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Plaquetas , Linfócitos , Monócitos , Neutrófilos , Hiperplasia Prostática/diagnóstico , Estudos de Casos e Controles , Bases de Dados Factuais , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Pontuação de Propensão , Hiperplasia Prostática/sangueRESUMO
Background: Percutaneous aspiration with sclerotherapy (PAS) and laparoscopic marsupialization (LM) are minimally invasive treatment modalities for renal cysts. We aimed to compare the efficacy and cost/effectiveness of LM and PAS for the treatment of simple symptomatic renal cysts. Methods: Data were prospectively collected from three health care institutions in which 80 patients with symptomatic simple renal cysts underwent a single session of PAS with 95% ethanol (PAS group, n = 40) or underwent LM under general anesthesia (LM group, n = 40) between March 2012 and May 2016. We compared the patient profile, duration of procedure, duration of hospital stay, radiological and symptomatic success rates, treatment costs, and incidence of complications between the two groups. Results: At the 6-month follow-up, the radiological success rate in the LM group was significantly greater than that in the PAS group (97.5% versus 60%; P < .001). The symptomatic success rate was comparable in the two groups (95% versus 90%; P = .675). The treatment failure rate did not significantly differ between the two groups (5.0% versus 17.5%, P = .154). The mean total cost in the PAS and LM groups was 1256 USD and 2343 USD, respectively (P = .001). No significant between-group difference was noted regarding the overall complication rate (P = .615). Conclusions: Both LM and PAS are effective and safe procedures for the treatment of symptomatic simple renal cysts. A single session of PAS seems to be a cost-effective method for the management of symptomatic simple renal cysts.
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Cistos/terapia , Nefropatias/terapia , Laparoscopia , Escleroterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Cistos/diagnóstico por imagem , Cistos/cirurgia , Etanol/uso terapêutico , Feminino , Custos de Cuidados de Saúde , Humanos , Nefropatias/diagnóstico por imagem , Nefropatias/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/economia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Soluções Esclerosantes/uso terapêutico , Escleroterapia/efeitos adversos , Escleroterapia/economia , Sucção/efeitos adversos , Sucção/economia , Resultado do TratamentoRESUMO
Hernias of pelvic floor are very rare condition, and herniations of ureter into sciatic foramen are extremely rare condition which is globally reported only by 32 cases. Clinical aspects of ureterosciatic hernias appeared variously according to the degree of hydronephrosis, inflammation and infection of kidney due to ureter obstruction. Herein, we report our experience of laparoscopic repair in a patient with ureterosciatic hernia combined urosepsis.
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Hérnia/complicações , Herniorrafia/métodos , Laparoscopia/métodos , Sepse/etiologia , Doenças Ureterais/cirurgia , Idoso , Diagnóstico Diferencial , Feminino , Hérnia/diagnóstico , Humanos , Diafragma da Pelve , Sepse/diagnóstico , Tomografia Computadorizada por Raios X , Doenças Ureterais/complicações , Doenças Ureterais/diagnóstico , UrografiaRESUMO
PURPOSE: Heat shock protein (HSP) 27 protects the cell by controlling apoptosis and immune reactions, and c-FLIP (cellular-FLICE inhibitory protein) inhibits apoptosis by inhibiting caspase-8 activity. We investigated the relationship of HSP27 and c-FLIP expression to prostate-specific antigen, Gleason score sum (GSS), and pathologic stage. MATERIALS AND METHODS: Samples from 163 patients between May 2004 and April 2010 were analyzed: 83 from patients that had underwent a radical prostatectomy, and 80 from those that underwent transurethral resection of the prostate to alleviate urinary symptoms from benign prostate hyperplasia. c-FLIP and HSP27 expression were observed by immunohistochemistry staining. Samples with less than 5% expression-positive cells were scored as 1, with 5%-50% were scored as 2, and with more than 50% were scored as 3. Local reactions were identified as 0.5 and evaluated. RESULTS: Both the presence of HSP27 within the tumor and the number of cancer cells positive for HSP27 were significantly correlated to GSS and pathologic stage (p<0.001, p=0.001, p<0.001, p<0.001). The same was true for c-FLIP expression (p<0.001). GSS was more highly correlated to HSP27 expression than to c-FLIP expression (r=0.814 for HSP27, r=0.776 for c-FLIP), as was pathologic stage (r=0.592 for HSP27, r=0.554 for c-FLIP). CONCLUSIONS: In prostate cancer, higher GSS and a more advanced pathologic stage were associated with a higher likelihood of having a HSP27-positive tumor and more HSP27-positive tumor cells. HSP27 expression was correlated with GSS and prostate cancer stage. A more advanced pathologic stage corresponded to a higher likelihood of having a c-FLIP-positive tumor and more c-FLIP-positive tumor cells. HSP27 expression had a higher correlation with prostate cancer stage and GSS than c-FLIP expression did.
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Biomarcadores Tumorais/metabolismo , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Prostatectomia/métodos , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Ressecção Transuretral da PróstataRESUMO
Using the Korean public health insurance database, we analyzed patients diagnosed as benign prostatic hyperplasia (BPH) from 2004 to 2008. Age and year-specific amount and seasonal variation of hospital visits (HV), duration of treatment (DT), the total and per capita amount of insurance payment (TAIP, PCIP) were evaluated. A total of 12,088,995 HV were studied. Total HV increased 1.7 times and DT almost doubled in 2008 compared to those in 2004. HV, DT, and TAIP showed linearly increasing patterns year by year. In a time series analysis, HV increased in winter and demonstrated seasonality in a 12-month cycle. In a Poisson regression analysis, the annual variations of HV, DT, TAIP, and PCIP were different by age groups. In patients older than 40 yr, HV significantly increased 1.10-1.16 times compared to that of the previous year. DT markedly increased in their 60s and 80s patients. The rate of increase in PCIP was steeper in patients 50 yr and older than in the others.Health care utilization due to BPH was rapidly increasing in Korea and it was remarkable in the elderly population. Seasonal variation of HV demonstrated that health care utilization increased in winter.
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Seguro Saúde/economia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Hiperplasia Prostática/economia , Hiperplasia Prostática/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Humanos , Seguro Saúde/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/terapia , República da Coreia/epidemiologia , Estudos Retrospectivos , Estações do Ano , Adulto JovemRESUMO
PURPOSE: The aim of this study was to define the clinical significance of transurethral resection of the prostate (TURP) in patients with benign prostate hyperplasia (BPH) and an elevated prostate-specific antigen (PSA) level. METHODS: We retrospectively evaluated patients with BPH, lower urinary tract symptoms (LUTS; International Prostate Symptom Score [IPSS]≥8), an elevated serum PSA level (≥4 ng/mL), and previous negative transrectal ultrasonography (TRUS) guided prostate biopsy. The PSA level after TURP was monitored by long-term follow-up. The tumor detection rate on resected prostate tissue, IPSS, maximal urinary flow rate (Qmax), and postvoid residual urine (PVR) were analyzed. RESULTS: One-hundred and eighty-six patients were enrolled. Histological examination of resected tissue by TURP revealed prostate cancer in 12 of these patients (6.5%). Among 174 patients without prostate cancer, the mean PSA level and the PSA normalization rate in 112 patients followed up at postoperative day (POD) 3 months were 1.26±0.13 ng/mL and 94.6%, respectively. The mean PSA level and the PSA normalization rate were 1.28±1.01 ng/mL and 95.7% in 47 patients at 1st year, 1.17±0.82 ng/mL and 97.1% in 34 patients at second years, and 1.34±1.44 ng/mL and 97.2% in 36 patients at third years of TURP. One patient showed a dramatic increase in the PSA level was diagnosed with prostate cancer at 7 years after TURP. IPSS, quality of life, Qmax, and PVR were improved significantly at POD 3 months compared to baseline (P<0.05), respectively. CONCLUSIONS: TURP significantly reduced the serum PSA level, which was maintained for at least 3 years. This could be helpful to screen the prostate cancer using PSA value in the patient with previous negative biopsy and elevated PSA. In addition, TURP improves IPSS, Qmax, and PVR in patients with BPH, moderate LUTS, and an elevated PSA level.
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PURPOSE: We retrospectively investigated the effect of transurethral resection of the prostate (TURP) on the basis of the degree of obstruction seen in preoperative urodynamic study in patients with benign prostatic hyperplasia (BPH) who complained of lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: The subjects of this study were 285 patients who were diagnosed with BPH with LUTS and who subsequently underwent TURP. The Abrams-Griffiths number was calculated from the urodynamic results to divide the patients into the following groups: unobstructed, equivocal, and obstructed. There were 26 patients (9.1%) in the unobstructed group, 98 patients (34.4%) in the equivocal group, and 161 patients (56.5%) in the obstructed group. The preoperative and postoperative uroflowmetry, residual urine, International Prostate Symptom Score (IPSS), and quality of life (QoL) score were compared between the three groups to evaluate the outcome of the treatment. RESULTS: The reduction in the IPSS was 14.4 in the obstructed group, which was higher than the reductions of 12.7 in the equivocal group and 9.5 in the unobstructed group, but this difference was not statistically significant (p=0.227). The QoL score was also not significantly different across the three groups (p=0.533). The postoperative maximum flow rate was significantly improved in all three groups. The obstructed group had an improvement of 7.8±7.2 mL/s, which was higher than the improvement of 3.7±6.2 mL/s in the unobstructed group (p=0.049) but was not significantly different from the improvement of 5.6±6.9 mL/s in the equivocal group (p=0.141). CONCLUSIONS: TURP led to an improvement in the maximum flow rate and LUTS even in BPH patients without BOO. Therefore, TURP can be expected to improve LUTS in BPH patients without definite urodynamic obstruction.
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PURPOSE: To investigate the learning curve and outcomes of robot-assisted laparoscopic radical prostatectomy (RALP) performed by a relatively lower volume surgeon at a secondary training hospital. MATERIALS AND METHODS: The medical records and the surgery video recordings of 100 patients who underwent RALP by a single surgeon between March 2010 and January 2013 were reviewed. The first 10 cases were grouped into period 1, cases 11 to 40 into period 2, cases 41 to 70 into period 3, and cases 71 to 100 into period 4. The interval between the operations, the operative time for each step of the surgery, the total console time, and the operative outcomes were investigated. RESULTS: The mean interval between surgeries was 10.6±9.3 days. The console time decreased progressively after the first 10 cases and reached under 3 hours after 75 cases. The time taken to begin dissection of the dorsal vein complex, for the division of the bladder neck, for lateral dissection with neurovascular bundle preservation, and for apex dissection decreased significantly with experience, although the time for vesicourethral anastomosis did not. The margin-positive rate of stage T2 patients was 27.4% (20/73), and the transfusion rate was 50% in period 1 patients and 3.3% in period 4 patients. No major complications occurred. CONCLUSIONS: It is difficult to shorten the learning curve of surgeons in secondary training hospitals owing to the smaller number of cases and the irregular surgical intervals. Although the operation time was relatively longer, the surgical outcome and complication rates were comparable with those of surgeons at larger hospitals.
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We evaluated effect of dual gene silencing of Hsp27 and c-FLIP in doxazosin-induced apoptosis of PC-3 cell. After transfection using Hsp27 and c-FLIP siRNA mixture (dual silencing), doxazosin treatment was done at the concentrations of 1, 10, and 25 µ M. We checked apoptosis of PC-3 cells with and TUNEL staining. We also checked interaction between Hsp27 and C-FLIP in the process of apoptosis inhibition. Spontaneous apoptotic index was 5% under single gene silencing of Hsp27 and c-FLIP and 7% under dual silencing of Hsp27 and c-FLIP. When doxazosin treatment was added, apoptotic indices increased in a dose-dependent manner (1, 10, and 25 µ M): nonsilencing 10, 27, and 52%; Hsp27-silencing: 14, 35, and 68%; c-FLIP silencing: 21, 46, and 78%; dual silencing: 38, 76, and 92%. While c-FLIP gene expression decreased in Hsp27- silenced cells, Hsp27 gene expression showed markedly decreased pattern in the cells of c-FLIP silencing. The knockout of c-FLIP and Hsp27 genes together enhances apoptosis even under 1 µ M, rather than low concentration, of doxazosin in PC-3 cells. This finding suggests a new strategy of multiple knockout of antiapoptotic and survival factors in the treatment of late-stage prostate cancer refractory to conventional therapy.
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Apoptose/efeitos dos fármacos , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética , Doxazossina/administração & dosagem , Proteínas de Choque Térmico HSP27/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Sinergismo Farmacológico , Inativação Gênica , Terapia Genética/métodos , Humanos , Masculino , Neoplasias da Próstata/patologia , Resultado do TratamentoRESUMO
PURPOSE: We investigated the effects of mirodenafil, a phosphodiesterase-5 inhibitor developed in South Korea, on the female rat bladder in a partial bladder outlet obstruction (BOO) model. MATERIALS AND METHODS: Thirty-six female Sprague-Dawley rats were divided into four groups: the control group, BOO without medication group, BOO with mirodenafil 1 mg/kg group, and BOO with mirodenafil 4 mg/kg group. Mirodenafil was administered orally for 2 weeks after the induction of BOO. Two weeks after BOO, the rats in each group underwent cystometry under urethane anesthesia. After cystometry, the bladder was excised to perform immunohistochemical staining for connexin 43. RESULTS: The three BOO groups showed significant increases in mean bladder weight compared with the control group. Baseline pressure, threshold pressure, and maximum contraction pressure were not significantly different between the four groups. Although the contraction interval was decreased in all BOO groups compared with the control group, it was prolonged in the two groups treated with mirodenafil compared with the untreated BOO group. In the immunohistochemical examination, connexin 43 staining intensity in the lamina propria increased in the three BOO groups compared with the control group. The two groups treated with mirodenafil, however, showed decreased connexin 43 staining compared with the untreated BOO group. CONCLUSIONS: Mirodenafil may increase the contraction intervals of female rat bladders in a partial BOO model. Decreasing bladder overactivity by mirodenafil may be related to intracellular communication mechanisms involving connexin 43.
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PURPOSE: We evaluated the efficacy of alfuzosin for the treatment of ureteral calculi less than 10 mm in diameter after extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A randomized, single-blind clinical trial was performed prospectively by one physician between June 2010 and August 2011. A total of 84 patients with ureteral calculi 5 to 10 mm in diameter were divided into two groups. Alfuzosin 10 mg (once daily) and loxoprofen sodium 68.1 mg (as needed) were prescribed to group 1 (n=41), and loxoprofen sodium 68.1 mg (as needed) only was prescribed to group 2 (n=44). The drug administration began immediately after ESWL and continued until stone expulsion was confirmed up to a maximum of 42 days after the procedure. RESULTS: Thirty-nine of 41 (95.1%) patients in group 1 and 40 of 43 (93.0%) patients in group 2 ultimately passed stones (p=0.96). The number of ESWL sessions was 1.34±0.65 and 1.41±0.85 in groups 1 and 2, respectively (p=0.33). The patients who required analgesics after ESWL were 8 (19.5%) in group 1 and 13 (30.2%) in group 2 (p=0.31). Visual analogue scale pain severity scores were 5.33±1.22 and 6.43±1.36 in groups 1 and 2, respectively (p=0.056). The time to stone expulsion in groups 1 and 2 was 9.5±4.8 days and 14.7±9.8 days, respectively (p=0.005). No significant adverse effects occurred. CONCLUSIONS: The use of alfuzosin in combination with ESWL seems to facilitate stone passage and to reduce the time of stone expulsion but does not affect the stone-free rate.
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PURPOSE: We investigated the treatment outcomes according to neuropathic bladder sphincter dysfunction (NBSD) type after oral oxybutynin (OBT) treatment in children with NBSD caused by myelodysplasia. METHODS: Among 334 pediatric patients who were diagnosed with NBSD caused by myelodysplasia, only children treated with oral OBT for more than 1 year with pre- and post-treatment urodynamic studies and dimercaptosuccinic acid (DMSA) were retrospectively reviewed. We compared pre- and post-treatment urodynamic parameters including maximum cystometric capacity (MCC), MCC/estimated bladder capacity (EBC), and compliance by NBSD type in children. We also compared renal scarring on pre- and post-treatment DMSA by NBSD type in children. RESULTS: Our study population was comprised of 81 children (45 boys and 36 girls), with a mean age of 4.2 ± 3.4 years. The mean follow-up duration was 4.5 (range 1.0-15.1) years. After OBT treatment, MCC was increased significantly in all types of NBSD from 110.3 ± 62.2 to 202.3 ± 103.9 ml (p < 0.05), compliance was significantly improved from 6.4 ± 6.1 to 11.1 ± 9.6 ml/cmH2O (p < 0.05), but MCC/EBC was slightly decreased from 75.2 ± 46.9 to 69.8 ± 33.3 % (p = 0.40). Sub-analyzed by NBSD type, the pre-treatment compliance of children with acontractile detrusor with spastic sphincter (n = 16) was markedly decreased compared with other types of NBSD. Acontractile detrusor with spastic sphincter demonstrated the worst renal deterioration on DMSA. CONCLUSIONS: Although increases in MCC/EBC were limited, oral OBT treatment markedly improved MCC and compliance in all NBSD types. Children who had acontractile detrusor with spastic sphincter had a relatively high probability of renal deterioration and required specific attention.
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Ácidos Mandélicos/administração & dosagem , Defeitos do Tubo Neural/complicações , Bexiga Urinaria Neurogênica/terapia , Administração Oral , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Antagonistas Muscarínicos/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/fisiopatologia , UrodinâmicaRESUMO
INTRODUCTION: The aim was to evaluate the changes of androgen receptor (AR) expression quantitatively and to identify influence of AR on cancer related survival markers in LNCap cell line. MATERIALS AND METHODS: We compared expressions of AR, heat shock protein 27 (HSP27), clusterin (CLU), glucose-related protein 78 (GRP78), and cellular FLICE-like inhibitory protein (c-FLIP) and their genes between es-LNCaP (less than 33 times subcultured, L-33), ls-LNCaP (over 81 times subcultured, H-81), and si-LNCaP (AR siRNA transfected ls-LNCaP) by Western blotting and RT-PCR. RESULTS: The expressions of AR, HSP27, CLU, GRP78, and c-FLIP were increased in ls-LNCaP compared with es-LNCaP (AR, 157%; HSP27, 132%; CLU, 146%; GRP78, 138%; c-FLIP, 152%). However, in si-LNCaP cell line, protein expressions were reversed to the level of es-LNCaP cell lines (25, 102, 109, 98, and 101%), and gene expressions on real-time PCR were also reversed to the expression level of es-LNCaP (ls-LNCaP: 179, 156, 133, 123, and 167%; si-LNCaP: 22, 93, 103, 112, and 107%). CONCLUSIONS: This finding suggests that androgen receptor can be related to the increased expression of cancer related survival markers such as HSP27, GRP78, CLU, and c-FLIP in late stage prostate cancer, and also inhibition of AR gene can be a therapeutic target in this stage of cancer.