Long-term tadalafil once daily in Chinese men with erectile dysfunction: a 2-year final analysis of a post-marketing, multicenter, randomized, open-label trial.

The long-term safety and effectiveness of once-daily tadalafil is crucial, but limited data are available in Chinese patients with erectile dysfunction (ED). In this post-marketing, multicenter, randomized, open-label trial with 2-year follow-up, 635 ED cases were randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months, of whom 580 continued once-daily tadalafil 5 mg for 21 months. Treatment-emergent adverse events in the 12-month and 24-month period were similar, with the most common being viral upper respiratory tract infection, upper respiratory tract infection, and headache. Significant improvement from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) score was detected at month 12 (least squares mean [LSM] change: 7.9, 95% confidence interval [CI]: 7.5-8.4, P < 0.001) and was maintained to month 24 (LSM change: 8.6, 95% CI: 8.1-9.0, P < 0.001). The proportions of patients regaining normal erectile function (IIEF-EF score ≥26) were 43.7% and 48.0% at months 12 and 24, respectively. Global Assessment Questionnaire results showed improved erection function in 97.5% of patients and improved ability to engage in sexual activity in 95.9% of patients at month 12; these values were 96.1% and 95.0% at month 24, respectively. The quality of sexual life score based on the Sexual Life Quality Questionnaire (SLQQ) was increased by 52.2% at month 12 and by 55.3% at month 24 (both P < 0.001). The treatment satisfaction score determined by SLQQ (mean ± standard deviation) was 62.4 ± 21.0 at month 12 versus 65.9 ± 20.2 at month 24. Two-year daily application of tadalafil 5 mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

Is use of vitamin K antagonists associated with the risk of prostate cancer?: A meta-analysis.

BACKGROUND: Vitamin K antagonists (VKAs) may have potential antitumor effects in prostate cancer. However, the findings of observational studies are inconsistent. The purpose of the present study was to estimate the quantitative association between VKAs use and prostate cancer risk by combining the results of all eligible observational studies. METHODS: PubMed and Web of Science database were searched from inception until May, 2018. A DerSimonian random-effects model was used to combine the studies. Study heterogeneity was measured using the chi-squared and I statistics. RESULTS: Six eligible studies were eventually included in our meta-analysis. There was an inverse but not statistically significant association between ever use of VKAs and the risk of prostate cancer (relative risk [RR] 0.84, 95% confidence interval [CI] 0.70-1.01, P = .063) with large heterogeneity across studies (P < .001 for heterogeneity, I = 94.6%). When analysis restricted to long term of VKAs user (>3 years), the pooled risk estimate was 0.83 (0.77-0.90) without obvious heterogeneity (P = .597, I = 0.0%). CONCLUSION: This meta-analysis indicates that VKAs use may be associated with a decreased risk of prostate cancer, especially in long-term users.

Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction: interim results of a multicenter, randomized, open-label trial.

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.

[Diagnosis and treatment of prostatic malignant mesenchymal tumors: Analysis of 20 cases].

OBJECTIVE: To explore the diagnosis, treatment, and prognosis of prostatic malignant mesenchymal tumors (PMMT). METHODS: We retrospectively analyzed the clinical and follow-up data about 20 cases of PMMT and reviewed the literature relevant to the diagnosis, treatment, and prognosis of the disease. RESULTS: Based on the results of pathology and immunohistochemistry, the 20 PMMT cases included leiomyosarcoma (n = 7), rhabdomyosarcoma (n = 5), prostatic stromal sarcoma (n = 3), chondrosarcoma (n = 1), and undifferentiated PMMT (n = 4). Twelve of the patients were treated by radical prostatectomy (3 concurrently by sigmoid colostomy and 1 by cystostomy), 2 by pelvic tumor resection following arterial embolization, 1 by total pelvic exenteration, 1 by colostomy with pelvic lymph node biopsy, and 4 by conservative therapy because of metastasis to the lung, pelvis and bone. Of the 20 patients, 9 died of systemic metastasis within 3 months after treatment, 3 died at 6, 7, and 14 months, respectively, 3 survived with tumor for 5, 11, and 12 months, respectively, 2 survived without tumor for 12 and 24 months so far, all subjected to periodic chemotherapy postoperatively, and 3 lost to follow-up. CONCLUSION: PMMT is a tumor of high malignancy and rapid progression, for which transrectal ultrasound-guided biopsy remains the main diagnostic method. The clinical stage of the tumor is an important factor influencing its prognosis and the survival rate of the patients can be improved by early diagnosis and combined therapy dominated by radical prostatectomy.

External iliac vein - transplant ureteral fistula combined with renal cell carcinoma: an unusual case of hematuria.

Iliac vein-ureteral fistula is a rare cause of hematuria. The diagnosis of an iliac vein-ureteral fistula can be elusive even with the use of multiple methods. With regards to the treatment, there appears to be a shift in management from primarily open surgical to primarily angiographic management. We present a unique case of an external iliac vein - transplant ureteral fistula. A 48 year-old female complained of recurrent gross hematuria. She underwent transplant nephrectomy and radical left nephrectomy because of rejection of transplanted kidney and cystic renal cell carcinoma when the hematuria arose for the first time. Ten months later, the hematuria recurred again, and cystoscopy showed bleeding from the right transplant ureteral orifice. Open exploration confirmed the diagnosis of external iliac vein - transplant ureteral fistula. Diagnostic difficulties and treatment dilemma of such a rare cause of hematuria are also discussed.

[Comparison of ultrasound-guided transrectal and transperineal prostate biopsies in clinical application].

OBJECTIVE: To compare the positive rates and complications of ultrasound-guided transrectal and transperineal prostate biopsies. METHODS: We retrospectively analyzed 156 cases of ultrasound-guided transrectal (n = 97) and transperineal (n = 59) prostate biopsy, and compared the positive rate and post-biopsy complications between the two approaches. RESULTS: The positive rates in the transrectal and transperineal groups were 48.4% and 44.1%, respectively, with no significant difference between the two approaches according to different PSA levels (P >0.05). No statistically significant differences were observed between the transrectal and transperineal groups in the post-biopsy incidence rates of such complications as hematuria (54.6% vs 42.4%, P >0.05), lower urinary tract symptoms (17.5% vs 22.0%, P >0.05), dysuria (9.3% vs 6.8%, P >0.05), and acute urinary retention (7.2% vs 6.8%, P >0.05). However, the incidence rates of post-biopsy infection and rectal bleeding were remarkably higher (15.5% vs 3.4%, P<0.05 and 50.5% vs 3.4%, P >0.01) while that of perineal swelling markedly lower in the former than in the latter (3.1% vs 13.6%, P <0.05). CONCLUSION: Transrectal and transperineal biopsies are both effective for the diagnosis of prostate cancer. Since their complications vary, the choice between the two methods depends on the specific condition of the patient.

Upper urinary tract inverted papillomas: Report of 10 cases.

The aim of the study was to review the clinical features and treatments of 10 (9 males and 1 female; age range, 61-73 years; median age, 67 years) upper urinary tract inverted papilloma (IP) cases between 1995 and 2010. The clinical syndromes, diagnostic procedures, treatments and results of the follow-up were evaluated. The results showed that the site of tumor development was the ureter in 6 cases and the renal pelvis in 4 cases. It was also identified that 7 tumors developed on the left side and 3 developed on the right side of the ureter and renal pelvis, respectively. A nephroureterectomy was performed in the first 6 cases, while a partial ureterectomy was performed in 3 cases and a local resection was performed endoscopically in 1 case. All but 2 tumors were solitary, ranging from 5 to 30 mm in diameter. Occurrence in association with transitional cell carcinoma was identified in one case. All 10 patients were subject to follow-up (range, 19-120 months; median, 59 months), during which no recurrence was found. Local excision is considered as adequate treatment when upper urinary tract IP is diagnosed according to strictly defined criteria.

A panel of five circulating microRNAs as potential biomarkers for prostate cancer.

BACKGROUND: Circulating microRNA (miRNAs) have been shown to have the potential as noninvasive diagnosis markers in several types of cancers. In this study, we investigated whether circulating miRNAs could be used in the diagnosis of prostate cancer (CaP) in a Chinese patient population. METHODS: Illumina's Human v2 miRNA microarray was used to analyze miRNAs levels in a small set of patients [25 CaP, 17 benign prostatic hyperplasia (BPH)] in an effort to identify CaP-specific miRNAs. The identified miRNAs were further examined by quantitative real-time PCR (qRT-PCR) in the same small set of patients. After the training phase of screening and selecting, the candidate miRNAs were validated in a larger independent cohort (80 CaP, 44 BPH, and 54 healthy controls) with qRT-PCR in the verification phase. RESULTS: Five miRNAs were confirmed by qRT-PCR analysis in validation sets. Receiver operating characteristic (ROC) curve analysis showed all 5 miRNAs had diagnostic value. More importantly, further principal component analysis indicated component 1 extracted from expression data of the 5 miRNAs could differentiate CaP from BPH and healthy controls with high diagnosis performance, with an AUC of 0.924 and 0.860, respectively. CONCLUSIONS: Our data suggested that circulating miRNAs could serve as biomarkers for CaP, and compared to single miRNA, the 5 miRNAs panel can accurately discriminate CaP from BPH and healthy controls with high sensitivity and specificity, and therefore, combined with routine PSA test, these 5 CaP-specific miRNAs may help improve CaP diagnosis in clinical application.

Exogenous p27KIP1 expression induces anti-tumour effects and inhibits the EGFR/PI3K/Akt signalling pathway in PC3 cells.

p27 is a cyclin-dependent kinase inhibitor that regulates the progression of cells from G(1) to S phase of the cell cycle. Loss of p27 has been associated with disease progression and with an unfavourable outcome in prostate cancer. In this study, we investigated whether exogenous p27 expression in the human androgen-independent prostate cancer PC3 cell line had any effect on cell growth, and we studied the molecular mechanisms involved. p27 expression was restored in PC3 cells by plasmid delivery. Cell proliferation and apoptosis were assessed in PC3 cells transfected with p27. We also investigated the effects of p27 on the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway in PC3 cells. By restoring p27 expression in PC3 cells, we observed that p27 reduced proliferation and induced arrest in G(0)/G(1) phase. Moreover, p27-transfected PC3 cells underwent apoptosis, as shown by flow cytometric analysis and western blotting analysis of Bcl-2, Bax, Bad, caspase-3 and poly(ADP-ribose)polymerase expression. Furthermore, the p27-induced anti-tumour action correlated with inhibition of the EGFR/PI3K/Akt signalling pathway, as confirmed by western blotting analysis and densitometry of EGFR, PI3K (p85), Akt and p-Akt(S473) expression. Our results suggest that exogenous expression of p27 inhibits the proliferation of PC3 cells through induction of G(1) arrest and apoptosis, and this process correlates with inhibition of the EGFR/PI3K/Akt signalling pathway.

Expression of Nkx3.1 enhances 17beta-estradiol anti-tumor action in PC3 human prostate cancer cells.

AIM: To explore whether the anti-tumor action of 17beta-estradiol is enhanced by re-expression of the homeodomain transcription factor Nkx3.1 in PC3 human prostate cancer cells. METHODS: PC3 cells were stably transfected with pcDNA3.1-Nkx3.1-His vector, which carries a full-length cDNA of human Nkx3.1. The PC3 cells stably transfected with vector pcDNA3.1 were set as a control. The expression of Nkx3.1 protein in the cells was confirmed by Western blot analysis. The effect of Nkx3.1 on cell proliferation of PC3 cells was examined with MTT assay. The antiproliferative and apoptotic effects of 17beta-estradiol alone or in combination with Nkx3.1 were estimated on PC3 cells by using MTT growth tests and flow cytometric analyses. The expression of apoptosis-related proteins was analyzed using Western blotting. RESULTS: The plasmid carrying Nkx3.1 gene induced high expression of Nkx3.1 protein in PC3 cells. The re-expression of exogenous Nkx3.1 did not cause a significant reduction in cellular proliferation, whereas the expression of Nkx3.1 enhanced the 17beta-estradiol anti-proliferative effect in PC3 cells. Nkx3.1 expression promoted 17beta-estradiol-induced apoptosis of PC3 cells, as shown by analysis of Bcl-2, Bax, Caspase-3 and poly (ADP-ribose) polymerase expression. CONCLUSION: The present study demonstrates that re-expression of Nkx3.1 enhances 17beta-estradiol anti-tumor action in PC3 human prostate cancer cells. The in vitro study suggests that re-expression of Nkx3.1 is worthy of further consideration as an adjuvant treatment of androgen independent prostate cancer with estrogen anti-tumor therapies.

[Sexual-nerve-Sparing radical cystectomy: experience with 32 cases].

OBJECTIVE: To evaluate the effect of sexual-nerve-sparing radical cystectomy. METHODS: Thirty-two male patients were treated with sexual-nerve-sparing radical cystectomy in our hospital in the past 5 years. The age of the patients ranged from 38 to 72 years, with the course of the disease ranging from 2 days to 20 years. All of them were potent preoperatively. Radical cystectomy was performed antegradely and retrogradely with the neurovascular bundle spared. RESULTS: The patients were followed up for 6 to 54 months, 3 achieved sexual activity of Grade I, 6 Grade II and 23 Grade III after the operation. The recovery time of erectile function ranged from 2 to 14 months, averaging at 4. 5 months. CONCLUSION: Whenever condition suits, sexual-nerve-sparing radical cystectomy is to be strongly recommended.

[Inverted urothelial papilloma: report of 151 cases].

OBJECTIVE: To investigate the clinical features, pathology, diagnosis and treatment of inverted urothelial papilloma. METHODS: A total of 151 cases of urothelial inverted papilloma were analysed retrospectively. Of the cases, 134 were male and 17 were female, with a mean age of 54 years old. Most patients complained of painless gross hematuria. The diagnosis could be established mainly by ultrasonic, intravenous urography, retrograde pyelography, cystoscope and pathology. Among them, 7 cases who had the papilloma at upper urinary tract underwent nephroureterectomy except one. One hundred and forty-four cases had the papilloma at low urinary tract, with 124 treated by transurethral bladder tumor resection (TURBT), among which 11 cases accompanying benign prostatic hyperplasia were treated by transurethral prostatic resection, 3 by transurethral resection of prostatic urethral tumor, 15 by partial cystectomy, 2 by total cystectomy. RESULTS: One hundred and eighteen cases were followed up 1 year to 12.5 years (mean 6.3 years). Intravesical recurrence was found in 5 cases. Of them 2 cases developed malignance in 8 and 30 months postoperatively, and 1 case underwent total cystectomy. CONCLUSIONS: Inverted urothelial papilloma is a benign tumor, which appears male predominant. Most of the lesions are found in the bladder. TURBT is the preferred treatment choice for inverted papilloma of the bladder. Although this disease has a good prognosis, regular follow-up observations are necessary.