<abstract>Aim: To evaluate the efficacy of biofeedback therapy in patients with chronic pelvic pain syndrome (CPPS). Methods: From November 2001 to April 2002, patients visiting the Urological Outpatient Clinic ...<abstract>Aim: To evaluate the efficacy of biofeedback therapy in patients with chronic pelvic pain syndrome (CPPS). Methods: From November 2001 to April 2002, patients visiting the Urological Outpatient Clinic of this Hospital were evaluated by means of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and classified by the NIH classification standard. Sixty-two patients of CPPS category Ⅲwere involved in this study. All patients had been treated by conventional approaches such as antibiotics and alpha-blockers for more than half a year without any improvement. The expressed prostatic secretion results were as follows: WBC 5 to 9/high power field, lipid +-+++and bacterial culture negative. Their NIH-CPSI were 12-40. All the 62 cases complained of micturitional irritation (frequency, urgency, splitted stream and sense of residual urine), 32 cases, of pain or discomfort at the testicular, penile, scrotal, pelvic or rectal region and 13 cases, of white secretion-dripping. The patients were treated by the Urostym Biofeedback equipment (Laborie Co., Canada) 5 times a week for 2 weeks with a stimulus intensity of 15 mA-23 mA and duration of 20 minutes. Results: Sixty patients were significantly improved or cured, while no significant improvement in the remaining 2. No apparent side effect was observed. The NIH-CPSI dropped to 6 to 14 with an average reduction of 21 (P<0.01). In the 60 improved cases, pain was relieved after 2-3 treatment courses and other symptoms disappeared after 4-5 courses. Conclusion: Biofeedback therapy is a safe and effective treatment for CPPS. Large randomized clinical trials are needed to confirm its efficacy and to explore the mechanism of action.展开更多
The aim of this review was to systematically compare the outcomes of enhanced recovery after surgery(ERAS)with standard care(SC)after radical cystectomy.We performed a systematic search of PubMed,Ovid?Web of Science,a...The aim of this review was to systematically compare the outcomes of enhanced recovery after surgery(ERAS)with standard care(SC)after radical cystectomy.We performed a systematic search of PubMed,Ovid?Web of Science,and the Cochrane Library to identify studies published until September 2017 which involved a comparison of ERAS and SC.A meta-analysis was performed to assess the outcomes of ERAS versus SC.Sixteen studies including 8 prospective and 8 retrospective trials met the eligibility criteria.A total of 2100 participants were assigned to ERAS(1258 cases)or SC(842 cases).The time to first flatus passage[WMD=-0.95 days,95%Cl(-1.50,-0.41),P=0.0006],time until return to a regular diet[WMD=-2.15 days,95%Cl(-2.86,—1.45),P<0.00001]and the length of hospital stay[WMD=-3.75 days,95%Cl(-5.13,-2.36),P<0.00001]were significantly shorter,and the incidence of postoperative complications[OR=0.60,95%Cl(0.44,0.83),P=0.002],especially postoperative paralytic ileus[OR=0.43,95%Cl(0.30,0.62),P<0.00001]and cardiovascular complications[OR=0.28,95%Cl(0.09,0.90),P=0.03]was significantly lower in the ERAS group than those in the SC group.This meta-analysis demonstrated that ERAS was associated with a shorter time to first flatus passage,return of bowel fimction,and the length of hospital stay than SC in patients undergoing radical cystectomy,as well as a lower rate of postoperative complications,especially paralytic ileus and cardiovascular complications.展开更多
Renal cell cancer(RCC)remains one of the most lethal types of cancer in adults.Micro RNAs(mi RNAs)play key roles in the pathogenesis of RCC.The role of mi R-206 in RCC has not been fully understood.The purpose of this...Renal cell cancer(RCC)remains one of the most lethal types of cancer in adults.Micro RNAs(mi RNAs)play key roles in the pathogenesis of RCC.The role of mi R-206 in RCC has not been fully understood.The purpose of this study was to examine the role of mi R-206 in the regulation of proliferation and metastasis of RCC and the possible mechanism.mi R-206 expression was detected by reverse transcription?quantitative polymerase chain reaction(RT-q PCR)in RCC cell lines(786-O and OS-RC-2 cells)and clinical samples.MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]method,colony formation and transwell assay were used to detect the tumor-suppressing ability of mi R-206 in RCC.Luciferase assay was performed to verify the precise target of mi R-206.The results showed that the expression of mi R-206 was significantly down-regulated in RCC tissues and cells.The expression level of cyclin G-associated kinase(GAK),a master regulator of tumor proliferation and metastasis,was up-regulated with the decrease in mi R-206 in RCC tissues as well as RCC cell lines.In addition,the mi R-206 inhibitor promoted the proliferation,migration and invasion of 786-O and OS-RC-2 cells.Bioinformatics combined with luciferase and Western blot assays revealed that mi R-206 inhibited the expression of GAK.Moreover,mi R-206 regulates RCC cell growth partly through targeting GAK.Our study indicated that mi R-206 functions as a tumor suppressor in regulating the proliferation,migration and invasion of RCC by directly targeting GAK,and it holds promises as a potential therapeutic target for RCC.展开更多
Aim:To study the relaxation mechanisms of tetrandrine(Tet)on the corpus cavernosum smooth muscle.Methods: The corpus cavernosum smooth muscle cells from New Zealand white rabbits were cultured in vitro.[Ca^(2+)]_i was...Aim:To study the relaxation mechanisms of tetrandrine(Tet)on the corpus cavernosum smooth muscle.Methods: The corpus cavernosum smooth muscle cells from New Zealand white rabbits were cultured in vitro.[Ca^(2+)]_i was measured by Fluorescence Ion Digital Imaging System,using Fluo-2/AM as a Ca^(2+)-sensitive fluorescent indicator. Results:Tet(1,10 and 100 μmol/L)had no effect on the resting [Ca^(2+)]_i(P>0.05).In the presence of extracellular Ca^(2+)(2.5 mmol/L),Tet(1,10 and 100 μmol/L)inhibited [Ca^(2+)]_i elevation induced by high K^+ and phenylephrine(PE) in a concentration-dependent manner(P<0.05).In calcium free solution containing egtaic acid,Tet(1 and 10 μmol/L) had no inhibitory effects on [Ca^(2+)]_i elevation induced by PE(P>0.05).However,Tet(100μmol/L)inhibited [Ca^(2+)]_i elevation induced by PE(P<0.05).Conclusion:Tet inhibited the Ca^(2+)influx from the extracellular site via voltage- activated Ca^(2+)channel and α_1-adrenoceptor-operated Ca^(2+)channel.At a high concentration,Tet might inhibit the cytosolic calcium pool release in cultured corpus cavernosum smooth muscle cells.This inhibitory action on [Ca^(2+)]_i might be one of the relaxation mechanisms of Tet on the corpus cavernosum smooth muscle.(Asian J Androl 2006 Jul;8:405-409)展开更多
The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial showed improvement in overall survival(OS)and other efficacy endpoints with apalutamide plus androgen de...The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial showed improvement in overall survival(OS)and other efficacy endpoints with apalutamide plus androgen deprivation therapy(ADT)versus ADT alone in patients with metastatic castration-sensitive prostate cancer(mCSPC).As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer,a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation.Event-driven endpoints were OS,and time from randomization to initiation of castration resistance,prostate-specific antigen(PSA)progression,and second progression-free survival(PFS2)on first subsequent therapy or death.Efficacy endpoints were assessed using the Kaplan–Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity.Participating Asian patients received once-daily apalutamide 240 mg(n=111)or placebo(n=110)plus ADT.After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide,apalutamide reduced the risk of death by 32%(hazard ratio[HR]:0.68;95%confidence interval[CI]:0.42–1.13),risk of castration resistance by 69%(HR:0.31;95%CI:0.21–0.46),PSA progression by 79%(HR:0.21;95%CI:0.13–0.35)and PFS2 by 24%(HR:0.76;95%CI:0.44–1.29)relative to placebo.The outcomes were comparable between subgroups with low-and high-volume disease at baseline.No new safety issues were identified.Apalutamide provides valuable clinical benefits to Asian patients with mCSPC,with an efficacy and safety profile consistent with that in the overall patient population.展开更多
Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is...Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml^-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA〉4.0 ng ml^-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1.展开更多
Background: Currently available evaluation criteria lbr penile tumescence and rigidity have been fraught with controversy. In tiffs study, we sought to establish normative Chinese evaluation criteria lbr penile tumes...Background: Currently available evaluation criteria lbr penile tumescence and rigidity have been fraught with controversy. In tiffs study, we sought to establish normative Chinese evaluation criteria lbr penile tumescence and rigidity by utilizing audiovisual sexual stimulation and RigiScanTM test (AVSS-Rigiscan test) with the administration of phosphodiesterase-5 inhibitor. Methods: A total of 1169 patients (aged 18-67 years) complained of erectile dysfunction (ED) underwent AVSS-RigiScan test with the administration of phosphodiesterase-5 inhibitor. A total of 1078 patients whose final etiological diagnosis was accurate by means of history, endocrine, vascular, and neurological diagnosis, International Index of Erectile Function 5 questionnaire, and erection hardness score were included in the research. Logistic regression model and receiver operating characteristic curve analysis were performed to determine the cutoffvalue of the RigiScanTM data. Then, the multivariable logistic analysis was used in the selected variables. Results: A normal restllt is defined as one erection with basal rigidity over 60% sustained for at least 8.75 rain, average event rigidity of tip at least 43.5% and base at least 50.5%, average maximum rigidity of tip at least 62.5% and base at least 67.5%, △tumescence (increase of tumescence or maxinaum-mininaum tumescence) of tip at least 1.75 cm and base at least 1.95 cm, total tumescence time at least 29.75 rain, and times of total tumescence at least once. Most importantly, basal rigidity over 60% sustained for at least 8.75 min, average event rigidity of tip at least 43.5%, and base at least 50.5% would be the new normative Chinese evaluation criteria for penile tumescence and rigidity. By multivariable logistic regression analysis, six significant RigiScanTM parameters including times of total tumescence, duration of erectile episodes over 60%, average event rigidity of tip, Atumescence of tip, average event rigidity of base, and Atunaescence of base contribute to the risk model of ED. In logistic regression equation, predict value P 〈 0.303 was considered as psychogenic ED. The sensitivity and specificity of the AVSS-RigiScan test with the administration ofphosphodiesterase-5 inhibitor in discriminating psychogenic from organic ED was 87.7% and 93.4%,, respectively. Conclusions: This study suggests that AVSS-RigiScan test with oral phosphodiesterase-5 inhibitors can objectively assess penile tumescence and rigidity and seems to be a better modality in differentiating psychogenic from organic ED. ttowever, due to the limited sample size, bias cannot be totally excluded.展开更多
Our previous studies have demonstrated that erectile function was preserved in aged transgenic rats (TGR) harboring the human tissue kallikrein 1 (hKLK1), while the molecular level of hKLK1 on corporal fibrosis to...Our previous studies have demonstrated that erectile function was preserved in aged transgenic rats (TGR) harboring the human tissue kallikrein 1 (hKLK1), while the molecular level of hKLK1 on corporal fibrosis to inhibit age-related erectile dysfunction (ED) is poorly understood. Male wild-type Sprague-Dawley rats (WTR) and TGR harboring the hKLK1 gene were fed to 4- or 18-month-old and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR), and aged TGR (aTGR). Erectile function of all rats was assessed by cavernous nerve electrostimulation method. Masson's trichrome staining was used to evaluate corporal fibrosis in the corpus cavernosum. We found that the erectile function of rats in the aWTR group was significantly lower than that of other two groups. Masson's trichrome staining revealed that compared with those of the yWTR and aTGR groups, the ratio of smooth muscle cell (SMC)/collagen (C) was significantly lower in the aWTR group. Immunohistochemistry and Western blotting analysis were performed, and results demonstrated that expression of a-SMA was lower, while expressions of transforming growth factor-β1 (TGF-β1), RhoA, ROCK1, p-MYPT1, p-LIMK2, and p-cofilin were higher in the aWTR group compared with those in other two groups. However, LIMK2 and cofilin expressions did not differ among three groups. Taken together, these results indicated that the RhoA/ROCK1/LIMK/cofilin pathway may be involved in the corporal fibrosis caused by advanced age, and hKLK1 may reduce this corporal fibrosis by inhibiting the activation of this pathway to ameliorate age-related ED.展开更多
Ethnicity might be associated with treatment outcomes in advanced prostate cancer.This study aimed to evaluate the efficacy and safety of androgen deprivation therapy(ADT)combined with apalutamide in East Asians with ...Ethnicity might be associated with treatment outcomes in advanced prostate cancer.This study aimed to evaluate the efficacy and safety of androgen deprivation therapy(ADT)combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer(mCSPC).The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial was conducted at 260 sites in 23 countries.This subgroup analysis included patients enrolled in 62 participating centers in China,Japan,and Korea.Radiographic progression-free survival(PFS),time to prostate-specific antigen(PSA)progression,and PSA changes from baseline were compared between groups in the East Asian population.The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups,respectively.The 24-month radiographic PFS rates were 76.1%and 52.3%in the apalutamide and placebo groups,respectively(apalutamide vs placebo:hazard ratio[HR]=0.506;95%confidence interval[CI],0.302–0.849;P=0.009).Median time to PSA progression was more favorable with apalutamide than placebo(HR=0.210;95%CI,0.124–0.357;P<0.001).Median maximum percentages of PSA decline from baseline were 99.0%and 73.9%in the apalutamide and placebo groups,respectively.The most common adverse event(AE)was rash in the apalutamide group,with a higher rate than that in the placebo group(37.3%vs 9.1%).The most common grade 3 or 4 AEs were rash(12[10.9%])and hypertension(12[10.9%])for apalutamide.The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.展开更多
We performed a meta-analysis to compare treatment with a combination of solifenacin plus tamsulosin oral controlled absorption system (TOCAS) with placebo or TOCAS monotherapy. The aim of the meta-analysis was to cl...We performed a meta-analysis to compare treatment with a combination of solifenacin plus tamsulosin oral controlled absorption system (TOCAS) with placebo or TOCAS monotherapy. The aim of the meta-analysis was to clarify the efficacy and safety of the combination treatments method for lower urinary tract symptoms (LUTS). We searched for trials of men with LUTS that were randomized to combination treatment compared with TOCAS monotherapy or placebo. We pooled data from three placebo-controlled trials meeting inclusion criteria. Primary outcomes of interest included changes in International Prostate Symptom Score (IPSS) and urinary frequency. We also assessed postvoid residual, maximum urinary flow rate, incidence of urinary retention (UR), adverse events. Data were pooled using random or fixed effect models for continuous outcomes and the ManteI-Haenszel method to generate risk ratio. Reductions in IPSS storage subscore and total urgency and frequency score (TUFS) were observed with solifenacin 6 mg plus TOCAS compared with placebo (P 〈 0.0001 and P 〈 0.0001, respectively). Reductions in IPSS storage subscore and TUFS were observed with solifenacin 9 mg plus TOCAS compared with placebo (P= 0.003 and P = 0.0006, respectively). Reductions in TUFS was observed with solifenacin 6 mg plus TOCAS compared with TOCAS (P = 0.01). Both combination treatments were well tolerated, with low incidence of UR. Solifenacin 6 mg plus TOCAS significantly improved total IPSS, storage and voiding symptoms compared with placebo. Solifenacin 6 mg plus TOCAS also improved storage symptoms compared with TOCAS alone. There was no additional benefit of solifenacin 9 mg compared with 6 mg when used in combination with TOCAS.展开更多
文摘<abstract>Aim: To evaluate the efficacy of biofeedback therapy in patients with chronic pelvic pain syndrome (CPPS). Methods: From November 2001 to April 2002, patients visiting the Urological Outpatient Clinic of this Hospital were evaluated by means of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and classified by the NIH classification standard. Sixty-two patients of CPPS category Ⅲwere involved in this study. All patients had been treated by conventional approaches such as antibiotics and alpha-blockers for more than half a year without any improvement. The expressed prostatic secretion results were as follows: WBC 5 to 9/high power field, lipid +-+++and bacterial culture negative. Their NIH-CPSI were 12-40. All the 62 cases complained of micturitional irritation (frequency, urgency, splitted stream and sense of residual urine), 32 cases, of pain or discomfort at the testicular, penile, scrotal, pelvic or rectal region and 13 cases, of white secretion-dripping. The patients were treated by the Urostym Biofeedback equipment (Laborie Co., Canada) 5 times a week for 2 weeks with a stimulus intensity of 15 mA-23 mA and duration of 20 minutes. Results: Sixty patients were significantly improved or cured, while no significant improvement in the remaining 2. No apparent side effect was observed. The NIH-CPSI dropped to 6 to 14 with an average reduction of 21 (P<0.01). In the 60 improved cases, pain was relieved after 2-3 treatment courses and other symptoms disappeared after 4-5 courses. Conclusion: Biofeedback therapy is a safe and effective treatment for CPPS. Large randomized clinical trials are needed to confirm its efficacy and to explore the mechanism of action.
基金grants from the Natural Science Foundation of Hubei Province,China(No 2016CFB619)Clinical Research Physician Program of Tongji Medical College,HUST(No.5001540017).
文摘The aim of this review was to systematically compare the outcomes of enhanced recovery after surgery(ERAS)with standard care(SC)after radical cystectomy.We performed a systematic search of PubMed,Ovid?Web of Science,and the Cochrane Library to identify studies published until September 2017 which involved a comparison of ERAS and SC.A meta-analysis was performed to assess the outcomes of ERAS versus SC.Sixteen studies including 8 prospective and 8 retrospective trials met the eligibility criteria.A total of 2100 participants were assigned to ERAS(1258 cases)or SC(842 cases).The time to first flatus passage[WMD=-0.95 days,95%Cl(-1.50,-0.41),P=0.0006],time until return to a regular diet[WMD=-2.15 days,95%Cl(-2.86,—1.45),P<0.00001]and the length of hospital stay[WMD=-3.75 days,95%Cl(-5.13,-2.36),P<0.00001]were significantly shorter,and the incidence of postoperative complications[OR=0.60,95%Cl(0.44,0.83),P=0.002],especially postoperative paralytic ileus[OR=0.43,95%Cl(0.30,0.62),P<0.00001]and cardiovascular complications[OR=0.28,95%Cl(0.09,0.90),P=0.03]was significantly lower in the ERAS group than those in the SC group.This meta-analysis demonstrated that ERAS was associated with a shorter time to first flatus passage,return of bowel fimction,and the length of hospital stay than SC in patients undergoing radical cystectomy,as well as a lower rate of postoperative complications,especially paralytic ileus and cardiovascular complications.
文摘Renal cell cancer(RCC)remains one of the most lethal types of cancer in adults.Micro RNAs(mi RNAs)play key roles in the pathogenesis of RCC.The role of mi R-206 in RCC has not been fully understood.The purpose of this study was to examine the role of mi R-206 in the regulation of proliferation and metastasis of RCC and the possible mechanism.mi R-206 expression was detected by reverse transcription?quantitative polymerase chain reaction(RT-q PCR)in RCC cell lines(786-O and OS-RC-2 cells)and clinical samples.MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]method,colony formation and transwell assay were used to detect the tumor-suppressing ability of mi R-206 in RCC.Luciferase assay was performed to verify the precise target of mi R-206.The results showed that the expression of mi R-206 was significantly down-regulated in RCC tissues and cells.The expression level of cyclin G-associated kinase(GAK),a master regulator of tumor proliferation and metastasis,was up-regulated with the decrease in mi R-206 in RCC tissues as well as RCC cell lines.In addition,the mi R-206 inhibitor promoted the proliferation,migration and invasion of 786-O and OS-RC-2 cells.Bioinformatics combined with luciferase and Western blot assays revealed that mi R-206 inhibited the expression of GAK.Moreover,mi R-206 regulates RCC cell growth partly through targeting GAK.Our study indicated that mi R-206 functions as a tumor suppressor in regulating the proliferation,migration and invasion of RCC by directly targeting GAK,and it holds promises as a potential therapeutic target for RCC.
文摘Aim:To study the relaxation mechanisms of tetrandrine(Tet)on the corpus cavernosum smooth muscle.Methods: The corpus cavernosum smooth muscle cells from New Zealand white rabbits were cultured in vitro.[Ca^(2+)]_i was measured by Fluorescence Ion Digital Imaging System,using Fluo-2/AM as a Ca^(2+)-sensitive fluorescent indicator. Results:Tet(1,10 and 100 μmol/L)had no effect on the resting [Ca^(2+)]_i(P>0.05).In the presence of extracellular Ca^(2+)(2.5 mmol/L),Tet(1,10 and 100 μmol/L)inhibited [Ca^(2+)]_i elevation induced by high K^+ and phenylephrine(PE) in a concentration-dependent manner(P<0.05).In calcium free solution containing egtaic acid,Tet(1 and 10 μmol/L) had no inhibitory effects on [Ca^(2+)]_i elevation induced by PE(P>0.05).However,Tet(100μmol/L)inhibited [Ca^(2+)]_i elevation induced by PE(P<0.05).Conclusion:Tet inhibited the Ca^(2+)influx from the extracellular site via voltage- activated Ca^(2+)channel and α_1-adrenoceptor-operated Ca^(2+)channel.At a high concentration,Tet might inhibit the cytosolic calcium pool release in cultured corpus cavernosum smooth muscle cells.This inhibitory action on [Ca^(2+)]_i might be one of the relaxation mechanisms of Tet on the corpus cavernosum smooth muscle.(Asian J Androl 2006 Jul;8:405-409)
基金The study was funded by Janssen Pharmaceutical Ltd.Writing assistance was provided by Katherine A Lyseng-Williamson and Kerry Dechant,ISMPP CMPP^(TM),on behalf of Content Ed Net,and was funded by Janssen Pharmaceutical Ltd.Janssen Pharmaceutical Ltd.is not involved in the process of experimental design,results,or discussion,and has no competing interests with this study.
文摘The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial showed improvement in overall survival(OS)and other efficacy endpoints with apalutamide plus androgen deprivation therapy(ADT)versus ADT alone in patients with metastatic castration-sensitive prostate cancer(mCSPC).As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer,a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation.Event-driven endpoints were OS,and time from randomization to initiation of castration resistance,prostate-specific antigen(PSA)progression,and second progression-free survival(PFS2)on first subsequent therapy or death.Efficacy endpoints were assessed using the Kaplan–Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity.Participating Asian patients received once-daily apalutamide 240 mg(n=111)or placebo(n=110)plus ADT.After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide,apalutamide reduced the risk of death by 32%(hazard ratio[HR]:0.68;95%confidence interval[CI]:0.42–1.13),risk of castration resistance by 69%(HR:0.31;95%CI:0.21–0.46),PSA progression by 79%(HR:0.21;95%CI:0.13–0.35)and PFS2 by 24%(HR:0.76;95%CI:0.44–1.29)relative to placebo.The outcomes were comparable between subgroups with low-and high-volume disease at baseline.No new safety issues were identified.Apalutamide provides valuable clinical benefits to Asian patients with mCSPC,with an efficacy and safety profile consistent with that in the overall patient population.
文摘Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml^-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA〉4.0 ng ml^-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1.
文摘Background: Currently available evaluation criteria lbr penile tumescence and rigidity have been fraught with controversy. In tiffs study, we sought to establish normative Chinese evaluation criteria lbr penile tumescence and rigidity by utilizing audiovisual sexual stimulation and RigiScanTM test (AVSS-Rigiscan test) with the administration of phosphodiesterase-5 inhibitor. Methods: A total of 1169 patients (aged 18-67 years) complained of erectile dysfunction (ED) underwent AVSS-RigiScan test with the administration of phosphodiesterase-5 inhibitor. A total of 1078 patients whose final etiological diagnosis was accurate by means of history, endocrine, vascular, and neurological diagnosis, International Index of Erectile Function 5 questionnaire, and erection hardness score were included in the research. Logistic regression model and receiver operating characteristic curve analysis were performed to determine the cutoffvalue of the RigiScanTM data. Then, the multivariable logistic analysis was used in the selected variables. Results: A normal restllt is defined as one erection with basal rigidity over 60% sustained for at least 8.75 rain, average event rigidity of tip at least 43.5% and base at least 50.5%, average maximum rigidity of tip at least 62.5% and base at least 67.5%, △tumescence (increase of tumescence or maxinaum-mininaum tumescence) of tip at least 1.75 cm and base at least 1.95 cm, total tumescence time at least 29.75 rain, and times of total tumescence at least once. Most importantly, basal rigidity over 60% sustained for at least 8.75 min, average event rigidity of tip at least 43.5%, and base at least 50.5% would be the new normative Chinese evaluation criteria for penile tumescence and rigidity. By multivariable logistic regression analysis, six significant RigiScanTM parameters including times of total tumescence, duration of erectile episodes over 60%, average event rigidity of tip, Atumescence of tip, average event rigidity of base, and Atunaescence of base contribute to the risk model of ED. In logistic regression equation, predict value P 〈 0.303 was considered as psychogenic ED. The sensitivity and specificity of the AVSS-RigiScan test with the administration ofphosphodiesterase-5 inhibitor in discriminating psychogenic from organic ED was 87.7% and 93.4%,, respectively. Conclusions: This study suggests that AVSS-RigiScan test with oral phosphodiesterase-5 inhibitors can objectively assess penile tumescence and rigidity and seems to be a better modality in differentiating psychogenic from organic ED. ttowever, due to the limited sample size, bias cannot be totally excluded.
文摘Our previous studies have demonstrated that erectile function was preserved in aged transgenic rats (TGR) harboring the human tissue kallikrein 1 (hKLK1), while the molecular level of hKLK1 on corporal fibrosis to inhibit age-related erectile dysfunction (ED) is poorly understood. Male wild-type Sprague-Dawley rats (WTR) and TGR harboring the hKLK1 gene were fed to 4- or 18-month-old and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR), and aged TGR (aTGR). Erectile function of all rats was assessed by cavernous nerve electrostimulation method. Masson's trichrome staining was used to evaluate corporal fibrosis in the corpus cavernosum. We found that the erectile function of rats in the aWTR group was significantly lower than that of other two groups. Masson's trichrome staining revealed that compared with those of the yWTR and aTGR groups, the ratio of smooth muscle cell (SMC)/collagen (C) was significantly lower in the aWTR group. Immunohistochemistry and Western blotting analysis were performed, and results demonstrated that expression of a-SMA was lower, while expressions of transforming growth factor-β1 (TGF-β1), RhoA, ROCK1, p-MYPT1, p-LIMK2, and p-cofilin were higher in the aWTR group compared with those in other two groups. However, LIMK2 and cofilin expressions did not differ among three groups. Taken together, these results indicated that the RhoA/ROCK1/LIMK/cofilin pathway may be involved in the corporal fibrosis caused by advanced age, and hKLK1 may reduce this corporal fibrosis by inhibiting the activation of this pathway to ameliorate age-related ED.
基金This study was funded by Janssen Pharmaceutical Ltd.,which designed the study.
文摘Ethnicity might be associated with treatment outcomes in advanced prostate cancer.This study aimed to evaluate the efficacy and safety of androgen deprivation therapy(ADT)combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer(mCSPC).The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial was conducted at 260 sites in 23 countries.This subgroup analysis included patients enrolled in 62 participating centers in China,Japan,and Korea.Radiographic progression-free survival(PFS),time to prostate-specific antigen(PSA)progression,and PSA changes from baseline were compared between groups in the East Asian population.The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups,respectively.The 24-month radiographic PFS rates were 76.1%and 52.3%in the apalutamide and placebo groups,respectively(apalutamide vs placebo:hazard ratio[HR]=0.506;95%confidence interval[CI],0.302–0.849;P=0.009).Median time to PSA progression was more favorable with apalutamide than placebo(HR=0.210;95%CI,0.124–0.357;P<0.001).Median maximum percentages of PSA decline from baseline were 99.0%and 73.9%in the apalutamide and placebo groups,respectively.The most common adverse event(AE)was rash in the apalutamide group,with a higher rate than that in the placebo group(37.3%vs 9.1%).The most common grade 3 or 4 AEs were rash(12[10.9%])and hypertension(12[10.9%])for apalutamide.The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
文摘We performed a meta-analysis to compare treatment with a combination of solifenacin plus tamsulosin oral controlled absorption system (TOCAS) with placebo or TOCAS monotherapy. The aim of the meta-analysis was to clarify the efficacy and safety of the combination treatments method for lower urinary tract symptoms (LUTS). We searched for trials of men with LUTS that were randomized to combination treatment compared with TOCAS monotherapy or placebo. We pooled data from three placebo-controlled trials meeting inclusion criteria. Primary outcomes of interest included changes in International Prostate Symptom Score (IPSS) and urinary frequency. We also assessed postvoid residual, maximum urinary flow rate, incidence of urinary retention (UR), adverse events. Data were pooled using random or fixed effect models for continuous outcomes and the ManteI-Haenszel method to generate risk ratio. Reductions in IPSS storage subscore and total urgency and frequency score (TUFS) were observed with solifenacin 6 mg plus TOCAS compared with placebo (P 〈 0.0001 and P 〈 0.0001, respectively). Reductions in IPSS storage subscore and TUFS were observed with solifenacin 9 mg plus TOCAS compared with placebo (P= 0.003 and P = 0.0006, respectively). Reductions in TUFS was observed with solifenacin 6 mg plus TOCAS compared with TOCAS (P = 0.01). Both combination treatments were well tolerated, with low incidence of UR. Solifenacin 6 mg plus TOCAS significantly improved total IPSS, storage and voiding symptoms compared with placebo. Solifenacin 6 mg plus TOCAS also improved storage symptoms compared with TOCAS alone. There was no additional benefit of solifenacin 9 mg compared with 6 mg when used in combination with TOCAS.