Active Surveillance for Men Younger than 60 Years or with Intermediate-risk Localized Prostate Cancer. Descriptive Analyses of Clinical Practice in the Movember GAP3 Initiative.

Background: Active surveillance (AS) is a management option for men diagnosed with low-risk prostate cancer. Opinions differ on whether it is safe to include young men (≤60 yr) or men with intermediate-risk disease. Objective: To assess whether reasons for discontinuation, treatment choice after AS, and adverse pathology at radical prostatectomy (RP; N1, or ≥GG3, or ≥pT3) differ for men ≤60 yr or those with European Association of Urology (EAU) intermediate-risk disease from those for men >60 yr or those with EAU low-risk disease. Design setting and participants: We analyzed data from 5411 men ≤60 yr and 14 959 men >60 yr, 14 064 men with low-risk cancer, and 2441 men with intermediate-risk cancer, originating from the GAP3 database (21 169 patients/27 cohorts worldwide). Outcome measurements and statistical analysis: Cumulative incidence curves were used to estimate the rates of AS discontinuation and treatment choice. Results and limitations: The probability of discontinuation of AS due to disease progression at 5 yr was similar for men aged ≤60 yr (22%) and those >60 yr (25%), as well as those of any age with low-risk disease (24%) versus those with intermediate-risk disease (24%). Men with intermediate-risk disease are more prone to discontinue AS without evidence of progression than men with low-risk disease (at 1/5 yr: 5.9%/14.2% vs 2.0%/8.8%). Adverse pathology at RP was observed in 32% of men ≤60 yr compared with 36% of men >60 yr (p = 0.029), and in 34% with low-risk disease compared with 40% with intermediate-risk disease (p = 0.048). Conclusions: Our descriptive analysis of AS practices worldwide showed that the risk of progression during AS is similar across the age and risk groups studied. The proportion of adverse pathology was higher among men >60 yr than among men ≤60 yr. These results suggest that men ≤60 yr and those with EAU intermediate-risk disease should not be excluded from opting for AS as initial management. Patient summary: Data from 27 international centers reflecting daily clinical practice suggest that younger men or men with intermediate-risk prostate cancer do not hold greater risk for disease progression during active surveillance.

Urine and Serum Metabolomics Analyses May Distinguish between Stages of Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is a heterogeneous disease that is usually asymptomatic until late in the disease. There is an urgent need for RCC specific biomarkers that may be exploited clinically for diagnostic and prognostic purposes. Preoperative fasting urine and serum samples were collected from patients with clinical renal masses and assessed with ¹H NMR and GCMS (gas chromatography-mass spectrometry) based metabolomics and multivariate statistical analysis. Alterations in levels of glycolytic and tricarboxylic acid (TCA) cycle intermediates were detected in RCC relative to benign masses. Orthogonal Partial Least Square Discriminant Analysis plots discriminated between benign vs. pT1 (R2 = 0.46, Q2 = 0.28; AUC = 0.83), benign vs. pT3 (R2 = 0.58, Q2 = 0.37; AUC = 0.87) for ¹H NMR-analyzed serum and between benign vs. pT1 (R2 = 0.50, Q2 = 0.37; AUC = 0.83), benign vs. pT3 (R2 = 0.72, Q2 = 0.68, AUC = 0.98) for urine samples. Separation was observed between benign vs. pT3 (R2 = 0.63, Q2 = 0.48; AUC = 0.93), pT1 vs. pT3 (R2 = 0.70, Q2 = 0.54) for GCMS-analyzed serum and between benign vs. pT3 (R2Y = 0.87; Q2 = 0.70; AUC = 0.98) for urine samples. This pilot study suggests that urine and serum metabolomics may be useful in differentiating benign renal tumors from RCC and for staging RCC.

Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification.

PURPOSE: Conventional ultrasound systems operate at 6 to 9 MHz and serve as the standard of care to guide prostate biopsies. We present a protocol using a novel high resolution (29 MHz) transrectal prostate micro-ultrasound system. This protocol includes a scoring system to assess the risk of prostatic carcinoma and enable real-time targeted biopsies. MATERIALS AND METHODS: The ExactVu™ system is currently being used in a multisite, 2,000-patient, randomized clinical trial. Cine loops of 400 biopsies from this trial were used to create the PRI-MUS™ (prostate risk identification using micro-ultrasound) protocol and risk scale. Validation was performed in an independent, pathology blinded set of 100 cines. Three of the 5 investigators performing this validation were familiar with micro-ultrasound but naïve to the PRI-MUS protocol and they received only 1 hour of training. RESULTS: Each increase in risk score demonstrated a 10.1% increase (95% CI 9.3-10.8) in the probability of clinically significant cancer. The risk score also increased with Gleason sum and cancer length with a slope of 0.15 (95% CI 0.09-0.21) and 0.58 (95% CI 0.43-0.73), respectively. Sensitivity and specificity were 80% and 37%, respectively, and the mean ± SD ROC AUC was 60% ± 2%. The protocol was more accurate for detecting high grade disease (Gleason sum greater than 7) with a peak AUC of 74% (mean 66%). CONCLUSIONS: The new resolution of the micro-ultrasound platform paired with the PRI-MUS protocol shows promise for real-time visualization of suspicious lesions and targeting of biopsies. The improved performance of the protocol in more significant disease is consistent with the focus of the field on decreasing insignificant diagnoses and detecting high risk disease early.

The use of regenerative medicine in the management of invasive bladder cancer.

Muscle invasive and recurrent nonmuscle invasive bladder cancers have been traditionally treated with a radical cystectomy and urinary diversion. The urinary diversion is generally accomplished through the creation of an incontinent ileal conduit, continent catheterizable reservoir, or orthotopic neobladder utilizing small or large intestine. While radical extirpation of the bladder is often successful from an oncological perspective, there is a significant morbidity associated with enteric interposition within the genitourinary tract. Therefore, there is a great opportunity to decrease the morbidity of the surgical management of bladder cancer through utilization of novel technologies for creating a urinary diversion without the use of intestine. Clinical trials using neourinary conduits (NUC) seeded with autologous smooth muscle cells are currently in progress and may represent a significant surgical advance, potentially eliminating the complications associated with the use of gastrointestinal segments in the urinary reconstruction, simplifying the surgical procedure, and greatly facilitating recovery from cystectomy.

Characteristics of positive surgical margins in robotic-assisted radical prostatectomy, open retropubic radical prostatectomy, and laparoscopic radical prostatectomy: a comparative histopathologic study from a single academic center.

Studies detailing differences in positive surgical margin among open retropubic radical prostatectomy, laparoscopic radical prostatectomy, and robotic-assisted laparoscopic radical prostatectomy are lacking. A retrospective review of all prostatectomies with positive surgical margin performed at our center in 2007 disclosed 99 cases, 6 (5%) of which were reinterpreted cases as having negative margins. Ninety-three cases were, therefore, included, corresponding to 37 retropubic radical prostatectomies, 19 laparoscopic radical prostatectomies, and 37 robotic-assisted laparoscopic radical prostatectomies. The relationship of positive surgical margin characteristics to clinicopathologic parameters and biochemical recurrence was assessed. The most commonly found positive surgical margin site was the apex/distal third in all groups (62% retropubic prostatectomies, 79% laparoscopic prostatectomies, 60% robotic-assisted prostatectomies). Total linear length of positive surgical margin sites was significantly correlated with preoperative prostate-specific antigen, preoperative prostate-specific antigen density, pT stage, and tumor volume (P ≤ .001). We found no significant differences among the 3 groups with respect to total linear length, number of foci, laterality, or location of positive surgical margin. The rate of biochemical recurrence was also comparable in the 3 groups. On univariate analyses, biochemical recurrence was significantly associated with preoperative prostate-specific antigen values, preoperative prostate-specific antigen density, Gleason score, number of positive surgical margins, and total linear length of positive surgical margin (P ≤ .02). Only preoperative prostate-specific antigen density and number of positive surgical margin foci were statistically significant (P ≤ .03) independent predictors of biochemical recurrence. We found no significant difference in positive surgical margin characteristics or biochemical recurrence among the 3 radical prostatectomy modalities. Preoperative prostate-specific antigen density and number of positive surgical margin foci were the only independent predictors of biochemical recurrence.

Metabolomics and bladder cancer.

Diagnosis of bladder cancer is primarily made based on clinical presentation and then by direct visualization with cystoscopy. Despite the massive investments recently made to identify urinary-based assays that are able to diagnosis urothelial carcinoma, urine cytology and cystoscopy still remain the gold standard. Recently proof of principle studies have shown that noninvasive urine-based metabolomics, using high pressure liquid chromatography (HPLC) and nuclear magnetic resonance (NMR), may be able to accurately diagnosis bladder cancer. This review discusses the published studies investigating metabolomics and bladder cancer and the future potential of this developing field.

Microperforations of surgical gloves in urology: minimally invasive versus open surgeries.

INTRODUCTION: Surgical glove integrity is important in preventing wound infections and reducing patient mortality. Rates of perforations have been studied in many surgical subspecialties, but glove perforations specific to urology have not been investigated previously. This study aims to determine the incidence of glove perforations during urological surgeries and to investigate differences between open, laparoscopic, and endoscopic procedures. MATERIALS AND METHODS: A total of 180 gloves were collected from various urological procedures performed at our institution: 59 from endoscopic, 72 from laparoscopic, and 49 from open cases. The gloves were tested for defects by both the water load test and electrical conductance testing. The frequency of defects for each type of procedure along with the length of wear, surgeon experience, and glove brand was analyzed. RESULTS: Glove defects were detected in 29% of all cases. Microperforations encompassed the majority of the glove defects (23.3%) and were detected in 15.2%, 25.0 %, and 30.6% of the endoscopy, laparoscopic and open surgical cases, respectively. The frequency of perforations noted in the minimally invasive procedures was significantly different across the groups (p < 0.01). There was no statistical significant correlation between glove defects and operation time, surgeon experience, and glove brand. CONCLUSIONS: The rates of glove perforation (29%) in urological procedures were higher than expected. Given the high rates of glove perforations found, double gloving in urological surgeries may offer a solution to the increased risk for cross contamination from microscopic perforations.

Incidence and risk factors for inguinal and incisional hernia after laparoscopic radical prostatectomy.

OBJECTIVES: To examine the risk of postoperative hernia development in men undergoing transperitoneal and extraperitoneal laparoscopic radical prostatectomy (LRP). Open radical retropubic prostatectomy increases the risk of postoperative inguinal hernia development within the first 2 postoperative years. It is less clear to what extent minimally invasive radical prostatectomy techniques affect the incidence of hernia development. METHODS: A total of 651 LRP patients were mailed follow-up surveys regarding hernia development. Of these 651 patients, 378 responded (58%). Of the 378 patients, 308 had complete medical records for review. The mean follow-up for the fully evaluable cohort was 33.9 months (median 29.5, range 3-87). The potential risk factors for hernia (ie, previous hernia, age, surgical approach, pelvic lymph node dissection, bladder neck contracture, and operative time) were evaluated as categorical and/or continuous variables and using the univariate Cox proportional hazard ratio and Kaplan-Meier analyses. Preoperatively diagnosed inguinal hernias were repaired laparoscopically at LRP. RESULTS: The incidence of postoperative inguinal hernia was 5.2% (16 of 308). After transperitoneal LRP (n = 122), 7.4% (9/122) reported an inguinal hernia, a few (29%) of which occurred within 2 years after LRP. After extraperitoneal LRP (n = 186), only 3.8% (7/186) reported an inguinal hernia, all of which occurred within 2 years after LRP. Kaplan-Meier analysis, however, demonstrated no effect of the surgical approach on the inguinal hernia incidence (P = .65). No risk factor was significantly associated with the postoperative hernia risk. One incisional hernia was noted (0.3%, 1 of 308), at a 5-mm extraperitoneal port site. Of the 308 men in the present study, 21 (6.8%) had undergone synchronous hernia repair, with no recurrences. CONCLUSIONS: The incidence of inguinal hernia after LRP was similar, regardless of the laparoscopic approach, and was comparable or lower than the risk noted in published open radical retropubic prostatectomy series. No specific risk factors for post-LRP inguinal hernia development were identified.

The T-786-->C mutation in endothelial nitric oxide synthase is associated with hypertension.

Although the pathogenic mechanisms involved in predisposing individuals to hypertension are not well defined, evidence is accumulating that suggests a strong genetic transmission. Animal studies and some clinical investigations have revealed that aberrant NO production may be an important contributing factor. Indeed, a missense mutation in the endothelial NO gene caused by a Glu298Asp alteration has been strongly associated with essential hypertension, coronary artery spasm, and myocardial infarction. Recently, another point mutation caused by a T-786-->C transition in the 5'-flanking region of the endothelial NO synthase gene has been identified and, like the Glu298Asp mutation, is associated with coronary artery spasm. The present study was conducted to determine the effect of the T-786-->C point mutation on hypertension. We investigated the interaction between the endothelial NO synthase T-786-->C polymorphism and blood pressure in a large (n=705) clinically healthy population. Allele frequencies for the T and C alleles were 62% and 38%, translating into 39%, 46% and 15% of the population having the T/T, T/C, and C/C genotypes, respectively, for the T-786-->C point mutation. Subjects with the C/C genotype had significantly higher systolic blood pressures and were 2.16(95% confidence interval, 1.3 to 3.7) more likely to be hypertensive. Therefore, the -786 C/C genotype in NO synthase is a significant contributing factor for increasing the risk of essential hypertension.