New drug development is a high-risk venture, but if successful, will bring great revenues to those willing to accept the risk. In the field of urology, in particular for lower urinary tract symptoms (LUTS), the recent successful landing of drugs (e.g., mirabegron, botulinum toxin A, and tadalafil) has resulted in increased interest in new drug development. Benign prostatic hyperplasia and overactive bladder syndrome, representative LUTS diseases, are attractive targets because of their prevalence and market size in the field of urology. Additionally, the awareness about new stream of research is very important not only because of the market size and economic factors, but also because to keep steady attention to these research for the researcher’s. We have reviewed a selection of new drugs currently under development for the treatment of the two aforementioned diseases and hope to offer urologists an overview of the current situation and future directions in the field of urology.
Botulinum Toxins ; Clinical Trials as Topic ; Hope ; Lower Urinary Tract Symptoms ; Prevalence ; Prostatic Hyperplasia ; Rivers ; Urinary Bladder, Overactive ; Urology

PURPOSE: The chromophobe subtype of renal cell carcinoma (chRCC) has generally been associated with a better prognosis than the clear cell type; however, debate continues as to absolute prognosis as well as the significance of certain prognostic variables. We investigated the significance of pathologic stage and a recently proposed chromophobe tumor grading (CTG) scheme in predicting chRCC outcomes. MATERIALS AND METHODS: All available chRCCs were identified from our surgical pathology archives from 1987-2010. Original slides were reviewed to verify diagnoses and stage, and each case was graded following a novel chromophobe tumor grade system criteria. Disease status was obtained from a clinical outcome database, and cancer specific deaths and recurrences were recorded. RESULTS: Eighty-one cases of chRCC were identified, and 73 had adequate follow-up information available. There were only 3 instances of cancer related recurrence or mortality, which included 1 disease specific mortality and 2 disease recurrences. Pathologic stage and CTG 3 were found to be significantly associated with the recurrences or death from chRCC, but there was no association with CTG 1 and CTG 2. CONCLUSIONS: chRCC is associated with a very low rate of cancer specific events (4.1%) even at a tertiary referral center. In our study, pathologic stage and CTG 3, but not CTG 1 or 2, were significantly associated with the development of these events.
Carcinoma, Renal Cell* ; Diagnosis ; Follow-Up Studies ; Mortality ; Neoplasm Grading* ; Nephrectomy ; Pathology, Surgical ; Prognosis* ; Recurrence ; Tertiary Care Centers

PURPOSE: To evaluate the frequency and clinical characteristics of postoperative hemorrhage as a complication of partial nephrectomy. MATERIALS AND METHODS: The demographics, physical statistics, tumor size, R.E.N.A.L. nephrometry score, operative method, warm ischemic time, and presence of postoperative hemorrhage and its severity and method of intervention were examined in 300 partial nephrectomy patients in two medical centers (Stanford Medical Center and Kyung Hee University Medical Center) between March 2000 and March 2012. RESULTS: Of the 300 subjects, 13 (4.3%) experienced postoperative hemorrhage severe enough to require intervention more invasive than transfusion (Clavien grade III or higher). Univariate analysis of the bleeding and nonbleeding groups showed that whereas age, ischemic time, tumor size and stage, body mass index, American Society of Anesthesiologists class, and operative method did not differ significantly, the exophyticity (E) score was significantly higher for severe postoperative hemorrhage (p=0.04). However, multivariate analysis showed none of the factors to differ significantly. In most of the cases requiring intervention, selective embolization was sufficient, but in one case explorative laparotomy and nephrectomy were required. Clinical characteristics varied significantly among severe hemorrhage cases, with time of onset ranging from the first to the 30th postoperative day and symptoms presenting in a diverse manner, such as gross hematuria and pleuritic chest pain. Computed tomography and angiographic findings were consistent with either arteriovenous fistula or pseudoaneurysms. CONCLUSIONS: Severe hemorrhage after partial nephrectomy is rare. Nonetheless, with the great variability in presenting symptoms and time of onset after surgery, surgeons should exercise great vigilance during the postoperative care of partial nephrectomy patients.
Aneurysm, False ; Arteriovenous Fistula ; Body Mass Index ; Chest Pain ; Demography ; Hematuria ; Hemorrhage ; Humans ; Laparotomy ; Methods ; Multivariate Analysis ; Nephrectomy* ; Postoperative Care ; Postoperative Hemorrhage* ; Risk Factors* ; Warm Ischemia

Purpose: This study aimed to examine the prevalence of surgery for postprostatectomy incontinence (PI) following minimally invasive surgery compared to conventional open surgery for prostate cancer. Methods: This retrospective cohort study used the Florida State Ambulatory Surgery and State Inpatient Databases, 2008 to 2010, radical prostatectomy (RP) patients were identified using International Classification of Diseases (ICD)-9/10 procedure codes and among this cohort, PI was identified also using ICD-9/10 codes. Surgical approaches included minimally invasive (robotic or laparoscopic) versus open (retropubic or perineal) RP. The primary outcome was the overall prevalence of surgery for PI. The secondary outcome was the association of PI requiring anti-incontinence surgery with the surgical approach for RP. Results: Among the 13,535 patients initially included in the study (mean age, 63.3 years), 6,932 (51.2%) underwent open RP and 6,603 (49.8%) underwent minimally invasive RP. The overall prevalence of surgical procedures for PI during the observation period among the all patients who had received RP was 3.3%. The rate of PI surgery for patients receiving minimally invasive surgery was higher than that for patients receiving open surgery (4.8% vs. 3.0%; risk difference, 1.8%; 95% confidence interval, 0.3%–3.4%). The adjusted prevalence of PI surgery for patients who had undergone laparoscopic RP was higher than that for those with retropubic RP (8.6% vs. 3.7%). Conclusions Among patients undergoing RP for prostate cancer, the prevalence of PI surgery is not negligible. Patients undergoing minimally invasive RP had higher adjusted rates for PI surgery compared to open approaches, which was attributed to high rate of PI surgery following laparoscopic approach and low rate of PI surgery following perineal approach. More studies are needed to establish strategies to reduce the rate of PI surgery after RP.

Purpose: This study aimed to examine the prevalence of surgery for postprostatectomy incontinence (PI) following minimally invasive surgery compared to conventional open surgery for prostate cancer. Methods: This retrospective cohort study used the Florida State Ambulatory Surgery and State Inpatient Databases, 2008 to 2010, radical prostatectomy (RP) patients were identified using International Classification of Diseases (ICD)-9/10 procedure codes and among this cohort, PI was identified also using ICD-9/10 codes. Surgical approaches included minimally invasive (robotic or laparoscopic) versus open (retropubic or perineal) RP. The primary outcome was the overall prevalence of surgery for PI. The secondary outcome was the association of PI requiring anti-incontinence surgery with the surgical approach for RP. Results: Among the 13,535 patients initially included in the study (mean age, 63.3 years), 6,932 (51.2%) underwent open RP and 6,603 (49.8%) underwent minimally invasive RP. The overall prevalence of surgical procedures for PI during the observation period among the all patients who had received RP was 3.3%. The rate of PI surgery for patients receiving minimally invasive surgery was higher than that for patients receiving open surgery (4.8% vs. 3.0%; risk difference, 1.8%; 95% confidence interval, 0.3%–3.4%). The adjusted prevalence of PI surgery for patients who had undergone laparoscopic RP was higher than that for those with retropubic RP (8.6% vs. 3.7%). Conclusions Among patients undergoing RP for prostate cancer, the prevalence of PI surgery is not negligible. Patients undergoing minimally invasive RP had higher adjusted rates for PI surgery compared to open approaches, which was attributed to high rate of PI surgery following laparoscopic approach and low rate of PI surgery following perineal approach. More studies are needed to establish strategies to reduce the rate of PI surgery after RP.

Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent because of its tumor selectivity and its ability to induce apoptosis in cancer cells while sparing most normal cells. We evaluated whether docetaxel enhances TRAIL-mediated apoptosis in prostate cancer (PCa) cells and its mechanism. Materials and Methods: LNCap-LN3, PC3, and DU 145 PCa cell lines were used to investigate the effects of TRAIL with docetaxel treatment (dosages, 1, 3, 5, and 10 nmol). To evaluate the mechanism, death receptor 4 (DR4), DR5, enhancer of zeste homolog 2 (EZH2) and E2F1 levels were assessed in PCa cells. Results: Hormone-sensitive LNCap-LN3 showed apoptosis in proportion to the concentration of docetaxel. Castration-resistant PC3 and DU 145 showed no change irrespective of the docetaxel concentration. However, combinations of docetaxel (2 nM) and TRAIL (100 ng/mL) had a significant effect on apoptosis of DU 145 cells. In DU 145 cells, docetaxel reduced EZH2 and elevated expression of DR4. The decrease of EZH2 by docetaxel was correlated with the E2F1 level, which was considered as the promoter of EZH2. DZNep reduced EZH2 and elevated DR4 in all PCa cells. Additionally, DZNep-enhanced TRAIL mediated reduction of PCa cell viability. Conclusions Docetaxel and the EZH2 inhibitor reduced EZH2 and elevated expression of DR4 in all PCa cell lines. Docetaxel-enhanced TRAIL mediated apoptosis in PCa via elevation of DR4 through epigenetic regulation by EZH2. To improve the efficacy of TRAIL for PCa treatment, adding docetaxel or EZH2 inhibitors to TRAIL may be promising.