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Objective: To assess success rates of primary artificial urinary sphincter (AUS) implantation using various objective, subjective, or retreatment definitions.Materials and Methods: We identified 309 male patients who underwent primary AUS placement at the Mayo Clinic from 2010 to 2016. Of those, 214 had not undergone repeat surgery, were sent a mailed survey, and 148 of 214 (69.2%) responded. Eleven definitions of success were evaluated among responders. Associations between the definitions and patient-reported success were assessed via logistic regression and c-statistic.Results: Treatment success rates were highly variable depending on the definition used (14.8%-86.7%). Median follow-up was 24 months (interquartile range [IQR] 8, 40), during which 72% did not undergo reoperation. Among survey respondents, 87% felt at least "much better," and 47% reported surgery was "very successful." Roughly 15% reported zero pad use. Patient-reported success was most strongly associated with the Patient Global Impression of Improvement (PGI-I) score (odds ratio [OR] 0.07, 95% confidence interval [CI] 0.02-0.19; P <.0001; c = 0.88). The largest difference in Michigan Incontinence Symptom Index (M-ISI) score between treatment successes and failures was noted when success was defined by PGI-I as well (success group M-ISI 11 vs failure group M-ISI 24.15; OR 0.48, 95% CI 0.37-0.63; P <.0001; c = 0.97). In terms of pad count, use of a security pad or less was most closely associated with patient-reported success (OR 0.18, 95% CI 0.10-0.35; P <.0001; c = 0.75).Conclusion: The "success rate" after primary AUS implantation varies widely depending on the definition used. Although most patients report that surgery was beneficial, zero pad count was less common. Among definitions evaluated, the PGI-I had the strongest association with patients' evaluation of surgical success. [ABSTRACT FROM AUTHOR]

Objective: To assess the surgeon factors influencing the surgical treatment decisions for symptomatic stone disease. The factors influencing the selection of shock wave lithotripsy (SWL), ureteroscopy, or percutaneous nephrolithotomy to treat symptomatic stone disease are not well studied. Methods: Electronic surveys were sent to urologists with American Medical Association membership. Information on training, practice, and ideal treatment of common stone scenarios was obtained and statistically analyzed. Results: In November 2009, 600 surveys were sent and 180 were completed. High-volume SWL practices (>100 cases annually) were more common in community practice (P < .01), and high-volume ureteroscopy and percutaneous nephrolithotomy practices were more common in academic practice (P = .03). Community practice was associated with SWL selection for proximal urolithiasis and upper pole nephrolithiasis (P < .005). An increasing time since urologic training was associated with SWL selection for proximal urolithiasis and upper pole nephrolithiasis (P < .01). Urologists reporting shock wave lithotriptor ownership were 3-4 times more likely to select SWL for urolithiasis or nephrolithiasis compared with urologists who did not own a lithotripter (P < .01). Routine concern for stent pain and rigid ureteroscope preference (vs flexible) were associated with SWL selection (P < .03). Conclusion: Surgeon factors significantly affected urolithiasis treatment selection. SWL was associated with community urology practice, increasing time since training, shock wave lithotriptor ownership, concern for stent pain, and ureteroscope preference. [Copyright &y& Elsevier]

Background: According to a recent National Comprehensive Cancer Network (NCCN) guidelines update, patients with Gleason score (GS) 3 + 4 prostate cancer (PCa) and "favorable intermediate-risk" (FIR) characteristics might be offered active surveillance (AS). However, the risk of unfavorable disease features and its prediction in this subset of patients is not completely understood. Objective: To identify the risk of unfavorable disease and potential predictors of adverse outcomes among GS 3 + 4 FIR PCa patients. Design, setting, and participants: The study included patients with biopsy GS 3 + 4 and otherwise fulfilling the NCCN low-risk definition (prostate-specific antigen [PSA] <10 ng/ml, cT2a or lower) undergoing radical prostatectomy (RP) from 2006 to 2014 at a single institution. Outcome measurements and statistical analysis Complete information on PSA, PSA density (PSAD), clinical stage, percentage of positive cores, percentage of maximum surface specimen involvement, and RP pathology were available. GS upgrade and downgrade, non-organ-confined and non-specimen-confined disease, unfavorable disease (pT3-T4 and/or pN1 and/or a pGS ≤4 + 3) were the outcomes. Statistical analysis included descriptive statistics and multivariable logistic regression. Results and limitations: A total of 156 patients (13.1%) experienced GS upgrade; 201 (16.9%) were downgraded. Overall, 205 men (17.2%) harbored non-organ-confined disease, and 295 (24.8%) had unfavorable disease. Age (odds ratio [OR]: 1.06), percentage surface involvement (OR: 1.01), and PSAD (OR: 1.83) were the only significant predictors of upgrade. Age (OR: 1.05), clinical stage (OR: 1.74), percentage of positive cores >50% (OR 1.57), percentage of surface area (OR: 1.02), and perineural invasion (OR: 1.89) were significant predictors of unfavorable disease at RP. The retrospective design is a limitation. Conclusions: AS is a possible option for a subset of men with FIR GS 3 + 4. However, clinical models alone have a limited role in GS upgrade prediction, and alternative tools warrant further investigation. Patient summary: Patients with Gleason score 3 + 4 at biopsy, low prostate-specific antigen, and low stage might consider the option of active surveillance, but the use of clinical information alone might be not adequate for thorough risk-adapted counseling. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of incontinence etiology on artificial urinary sphincter (AUS) device outcomes. Materials and Methods: We identified 925 patients who underwent primary AUS placement from 1983 to 2011. The etiology of incontinence was categorized as radical prostatectomy alone, radical prostatectomy with radiation, benign prostate resection, and those with cryotherapy as a salvage prostate cancer treatment. Hazard regression and competing risk analyses were used to determine the association of the etiology of incontinence with device outcomes. Results: The distribution of the 4 etiologies of incontinence included: 598 patients (64.6%) treated with prostatectomy alone, 206 (22.2%) with prostatectomy and pelvic radiation therapy, 104 (11.2%) with benign prostate resection, and 17 (1.8%) with prior cryotherapy. With a median follow-up of 4.9 years (interquartile range, 1.2-8.8 years), there was significant difference in the cumulative incidence of device infection/urethral erosion events between the four etiologies (p=0.003). On multivariable analysis, prior cryotherapy (reference prostatectomy alone; hazard ratio [HR], 3.44; p=0.01), older age (HR, 1.07; p=0.0009) and history of a transient ischemic attack (HR, 2.57; p=0.04) were associated with an increased risk of device infection or erosion. Notably, pelvic radiation therapy with prostatectomy was not associated with an increased risk of device infection or erosion (reference prostatectomy alone, p=0.30). Conclusions: Compared to prostatectomy alone, prior treatment with salvage cryotherapy for recurrent prostate cancer was associated with an increased risk of AUS infection/erosion, whereas radiation (in addition to prostatectomy) was not. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to describe "minimal-touch" technique for primary artificial urinary sphincter placement and evaluate early device outcomes by comparing it with a historical cohort. Materials and methods: We identified patients who underwent primary artificial urinary sphincter placement at our institution from 1983 to 2020. Statistical analysis was performed to identify the rate of postoperative device infection in patients who underwent minimal touch versus those who underwent our traditional technique. Results: 526/2601 total procedures (20%) were performed using our "minimal-touch" approach, including 271/1554 patients (17%) who underwent primary artificial urinary sphincter placement over the study period. Around 2.3% of patients experienced device infection after artificial urinary sphincter procedures. In the "minimal-touch" era, 3/526 patients (0.7%) experienced device infection, including 1/271 (0.4%) of those with primary artificial urinary sphincter placement. In comparison, 46/2075 patients (2.7%) experienced device infection using the historical approach, with 29/1283 (2.3%) of primary artificial urinary sphincter placements resulting in removal for infection. Notably, 90% of device infections occurred within the first 6 months after primary placement. The difference in cumulative incidence of device infections at 12 months did not meet our threshold for statistical significance for either the total cohort of all AUS procedures (primary and revision) or the sub-group of only those patients undergoing primary artificial urinary sphincter placement (Gray K-sample test; P = .13 and .21, respectively). Conclusion: The "minimal-touch" approach for artificial urinary sphincter placement represents an easy-to-implement modification with potential implications on device outcomes. While early results appear promising, longer-term follow-up with greater statistical power is needed to determine whether this approach will lower the infection risk. [ABSTRACT FROM AUTHOR]

Objective To evaluate the incidence, predictors and oncological outcomes of pT0 prostate cancer ( PCa). Methods We conducted a retrospective analysis of 20 222 patients undergoing radical prostatectomy ( RP) for PCa at the Mayo Clinic between 1987 and 2012. Disease recurrence was defined as follow-up PSA >0.4 ng/mL or biopsy-proven local recurrence. Systemic progression was defined as development of metastatic disease on imaging. Comparisons of baseline characteristics between pT0 and non- pT0 groups were carried out using chi-squared tests. Recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Results A total of 62 patients (0.3%) had pT0 disease according to the RP specimen. In univariable analysis, pT0 disease was significantly associated with older age ( P = 0.045), lower prostate-specific antigen ( PSA; P = 0.002), lower clinical stage ( P < 0.001), lower biopsy Gleason score ( P = 0.042), and receipt of preoperative transurethral resection, hormonal and radiation therapies (all P < 0.001). In multivariable analysis, lower PSA levels, lower Gleason score, and receipt of preoperative treatment were independently associated with pT0 (all P < 0.05). Seven patients (11%) with pT0 PCa developed disease recurrence over a median follow-up of 10.9 years. All seven patients had preoperative treatment(s) and three had recurrence with a PSA doubling time of <9 months. Compared with non- pT0 disease, pT0 disease was associated with longer recurrence-free survival ( P < 0.05). Only one (1.6%) patient with pT0 disease developed systemic progression. Conclusions pT0 stage PCa is a rare phenomenon and is associated with receipt of preoperative treatment and features of low-risk PCa. Although pT0 has a very favourable prognosis, some men, especially those who received preoperative treatment, experience a small but non-negligible risk of disease recurrence and systemic progression. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of the body mass index (BMI) as it relates to the predictive value of the preoperative prostate-specific antigen (PSA) level regarding the tumor volume at radical prostatectomy. Stage migration with the widespread use of PSA screening is well documented; however, the association between the PSA level and tumor volume is less defined. Additionally, the effect of obesity on the serum PSA level might cause relative hemodilution and account for the decreased predictive ability of the PSA level to determine the tumor volume in the modern era. Methods: We identified 14 293 patients who had undergone radical prostatectomy for prostate cancer from 1987 to 2007 and had a documented BMI. Using the clinicopathologic variables, we examined the relationship among the BMI, preoperative PSA level, and tumor volume at radical prostatectomy using multiple linear regression analysis. Results: An elevated BMI was associated with an increased pathologic Gleason score (P < .0001), increased tumor volume (P < .0001), and increased prostate size (P < .0001). The preoperative PSA level correlated significantly with the tumor volume (P < .0001). No significant correlation was found between the BMI and preoperative PSA level (P = .39). On multivariate analysis, controlling for the BMI, the preoperative PSA level remained a significant predictor of the tumor volume (P < .0001). The interaction between the preoperative PSA level and BMI in the prediction of the tumor volume was not statistically significant (P = .56), suggesting that the BMI does not affect the association between the PSA level and tumor volume. Conclusion: Our results have shown that the predictive ability of the PSA level for tumor volume is not affected by the BMI. There does not appear to be a need to correct the serum PSA level in relation to the BMI when used in preoperative prediction models of the tumor volume. [ABSTRACT FROM AUTHOR]

Study Type – Prognosis (individual cohort series) Level of Evidence 2b OBJECTIVE To evaluate the influence of the pathological Gleason score on the predictive value of the prostate-specific antigen (PSA) doubling time (DT), as this variable predicts a patient’s risk of disease progression both before and after definitive therapy for prostate cancer, and there is an inverse correlation between the Gleason score and PSA production. PATIENTS AND METHODS We evaluated all men treated with radical prostatectomy (RP) between 1990 and 1999 who did not receive neoadjuvant or adjuvant therapy. We identified 2296 patients who had multiple PSA values available before RP, and 1323 who had biochemical recurrence after RP and had at least two PSA values available before starting secondary therapy. Systemic progression and cancer-specific survival (CSS) rates were estimated using the Kaplan-Meier method and Cox proportional hazard regression models. RESULTS A PSA DT of <18 vs >18 months predicted a lower 10-year systemic progression-free survival for patients with tumours having a pathological Gleason score of <7 (98% vs 99%, P = 0.005), 7 (82% vs 91%, P = 0.003) and 8–10 (57% vs 73%, P = 0.042). A PSA DT after RP of <12 months was significantly associated with a lower 10-year systemic progression-free survival for patients with tumours having a Gleason score of <7 (77% vs 94%, P < 0.001) and 7 (61% vs 86%, P < 0.001), but not 8–10 (61% vs 75%, P = 0.11). The ability of PSA DT before and after RP to predict systemic progression and CSS decreased with increasing Gleason score. CONCLUSIONS The PSA DT remains associated with outcome both before and after RP across increasing pathological Gleason scores, although the predictive ability of PSA DT is diminished in Gleason 8–10 cancers. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the perioperative complications and early oncological results in a comparative study matching open radical retropubic (RRP) and robot-assisted radical prostatectomy (RARP) groups. PATIENTS AND METHODS From August 2002 to December 2005 we identified 294 patients undergoing RARP for clinically localized prostate cancer. A comparison RRP group of 588 patients from the same period was matched 2:1 for surgical year, age, preoperative prostate-specific antigen level, clinical stage and biopsy Gleason grade. Perioperative complications were compared. Patients completed a standardized quality-of-life questionnaire. Pathological features were assessed and Kaplan-Meier estimates of biochemical progression-free survival (PFS) were compared. RESULTS There was no significant difference in overall perioperative complications between the RARP and RRP groups (8.0% vs 4.8%, P = 0.064). Wound herniation was more common after RARP (1.0% vs none, P = 0.038), and development of bladder neck contracture was more common after RRP (1.2% vs 4.6%; P < 0.018). The hospital stay was less after RARP (29.3% vs 19.4%, P = 0.004, for a stay of 1 day). At the 1-year follow-up there was no significant difference in continence (RARP 91.8%, RRP 93.7%, P = 0.344) or potency (RARP 70.0%, RRP 62.8%, P = 0.081) rates. The biochemical PFS was no different between treatments at 3 years (RARP 92.4%, RRP 92.2%; P = 0.69). CONCLUSION There was no significant difference in overall early complication, long-term continence or potency rates between the RARP and RRP techniques. Furthermore, early oncological outcomes were similar, with equivalent margin positivity and PFS between the groups. [ABSTRACT FROM AUTHOR]

Background: The authors evaluated the long-term outcomes of men with prostate cancer and very high (> or =50 ng/mL) preoperative serum prostate-specific antigen (PSA) values that were treated with radical prostatectomy.Methods: This study included 236 men with preoperative serum PSA values > or =50 ng/mL who underwent radical retropubic prostatectomy between 1987 and 2004. For comparison, the study cohort was divided into 2 groups: patients with PSA levels between 50 and 99 ng/mL and patients with PSA levels > or =100 ng/mL. Biochemical recurrence was defined as a single postoperative serum PSA value of 0.4 ng/mL or greater. Systemic disease progression was defined as the development of a local recurrence or systemic metastases, and any death resulting from prostate cancer or its treatment was defined as a cancer-specific mortality.Results: Biochemical recurrence-free survival rates in the groups of patients with a PSA level 50 to 99 ng/mL and > or =100 ng/mL were 43% and 36% at 10 years, respectively. Systemic progression-free survival rates in the PSA 50 to 99 ng/mL and PSA > or =100 ng/mL groups were 83% and 74% at 10 years, respectively. Estimated overall cancer-specific survival was 87% at 10 years.Conclusions: Patients with prostate cancer and a serum PSA level > or =50 ng/mL have very high-risk prostate cancer that carries a high likelihood of being pathologically advanced. Although the probability of realizing long-term survival in these high-risk patients is less than in patients with more favorable disease, 10-year survival outcomes remain excellent and argue for aggressive management of these cases. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate whether the clinical and pathological outcomes after radical retropubic prostatectomy (RRP) have changed since the advent of prostate-specific antigen (PSA) testing for patients with Gleason 8–10 cancers. PATIENTS AND METHODS We identified 584 men treated with RRP between 1988 and 2001 for pathological Gleason 8–10 tumours. Patients were divided for analysis by year of surgery, i.e. early (1988–93), mid (1994–97) and late PSA era (1998–2001). Survival rates after RRP were estimated using the Kaplan-Meier method, and the effect of clinicopathological factors on outcome was analysed using Cox proportional hazard regression models. RESULTS The median preoperative PSA level decreased from 15 ng/mL in the early to 10 ng/mL in the late PSA era ( P < 0.001), while the rate of organ-confined disease increased from 22.9% to 35.1% ( P = 0.007). However, the 7-year biochemical recurrence-free (37% vs 45%, P = 0.087) and cancer-specific survival (89% to 91%, P = 0.73) did not change significantly from the early to the late PSA era. Increased preoperative PSA level ( P < 0.001), seminal vesicle invasion ( P < 0.001) and positive lymph nodes ( P = 0.02) were associated with biochemical recurrence. Seminal vesicle invasion ( P = 0.005), positive nodes ( P < 0.001) and positive surgical margins ( P = 0.03) predicted death from cancer. CONCLUSION Although the pathological features of Gleason 8–10 cancers have become more favourable over the PSA era, survival has not changed. This lack of improvement in clinical outcome probably reflects the inherent biological aggressiveness of these cancers. While RRP provides long-term cancer control in a subset of these patients, continued investigation of multi-modal treatment options is warranted. [ABSTRACT FROM AUTHOR]

Prostate size exhibits considerable variation among men. Recent evidence from computational, pathologic, and radiologic studies has suggested that enlarged prostates may confer protection against the development of aggressive prostate cancer. In theory, small prostates provide a relatively androgen resistant milieu compared to large prostates, and cancers that develop in smaller glands may be more likely to be androgen resistant and thus aggressive. Nonetheless, the relationship between prostate size and perioperative and oncological outcomes remains uncertain. To address this gap, we studied the association between pathologic prostate specimen weight and perioperative and long-term oncologic outcomes after radical prostatectomy. This study queried the Mayo Clinic's prospectively maintained prostatectomy registry from 1986 to 2017. This study included patients with non-metastatic pathologically confirmed prostate adenocarcinoma and excluded patients that had undergone prior BPH therapy or had previously been taking androgen deprivation therapy. Prostate size was determined using pathologic specimen weight. Prostate sizes were grouped into multiples of 25gm. Multivariable cox analysis evaluated biochemical recurrence after controlling for age, PSA, grade, stage, surgical year, surgical approach, and adjuvant therapy. Using 0-25gm prostates as the reference group, several multivariable logistic regressions were conducted to assess the odds of positive surgical margins, incontinence, and erectile dysfunction at the one-year postoperative mark. In a cohort of 19,160 patients undergoing radical prostatectomy, most patients had prostates between 0-50gm (81%), while 13.6%, 3.44%, and 1.80% had prostate sizes of 50-75gm, 75-100gm, and 101+gm, respectively. Patients with larger prostates had higher PSAs and had a lower incidence of positive surgical margins (Table 1). They also had a lower incidence of complete nerve sparing, post-operative potency without medications at 1-year, and post-operative continence at 1-year. On multivariable regression analysis (Figure 1), increasing prostate size was associated with lower risk of positive margins, reduced biochemical recurrence and increased risk of incontinence at 1-year. However, the risk of post-operative impotence at 1-year did not significantly vary by prostate size. Larger prostates had a lower risk of positive surgical margins, and despite adjusting for margin status and other pathological variables, they were associated with a lower risk of biochemical recurrence. There was no significant independent association of prostate size with post-operative functional outcomes. This information can be useful for individualizing surgical counseling. It also supports the hypothesis that smaller prostates developing in a relatively androgen deficient milieu may form more aggressive cancers than those that develop in larger prostates. Further research to understand the biologic basis of this observation is warranted. [ABSTRACT FROM AUTHOR]

Purpose: The associations between metabolic syndrome (MetS) and prostate cancer (CaP) outcomes following radical prostatectomy (RP) are not clear. This study aims to understand the role of MetS in influencing oncological outcomes at RP.Materials and Methods: Patients who underwent RP for CaP at our institution from 2000 to 2010 were identified; MetS prior to RP was ascertained with a modified version of the IDF-AHA/NHLBI using ICD-9 codes. Histopathological outcomes included surgical margins, pathological stage, and Gleason score (GS) upgrading. Long-term outcomes included biochemical recurrence (BCR), local recurrence, systemic progression, and CaP-specific mortality. Multivariable adjusted logistic regression and Cox proportional hazards regression assessed the association between MetS status and histopathological and long-term outcomes, respectively.Results: Of 8,504 RP patients, 1,054 (12.4%) had MetS at the time of RP. MetS patients were older, had higher biopsy GS, but lower pre-op prostatic specific antigen (PSA), higher pathological GS, and larger prostate volume. Adjusted logistic regression suggested an association between MetS and positive margins (odds ratio [OR] = 1.22, P = 0.025) and GS upgrading (OR = 1.28, P = 0.002). There was evidence of an increased risk of local recurrence (hazard ratio [HR] = 1.33, P = 0.037) and CaP-specific mortality (HR = 1.58, P < 0.001) for MetS patients. There was no evidence to suggest an association with BCR or systemic progression.Conclusion: Men with MetS are at higher risk of GS upgrade and positive surgical margins at surgery, local recurrence, and CaP-specific mortality. Pathological stage, BCR, and systemic progression were not associated with MetS. Our data may be useful in patients' counseling, especially when active surveillance is an option. [ABSTRACT FROM AUTHOR]

Objective: Artificial urinary sphincter (AUS) device failure or revision can be due to multiple etiologies including erosion, infection, mechanical malfunction, and urethral atrophy. However, few studies have evaluated factors that predispose patients to urethral atrophy. Here, we sought to identify preoperative and perioperative risk factors associated with urethral atrophy in men undergoing primary artificial urinary sphincter (AUS) placement for stress urinary incontinence. Material and methods: From 1987 to 2013, 1829 AUS procedures were performed at our institution. A total of 1068 patients underwent primary AUS placement and were the focus of our study. Multiple clinical and surgical variables were evaluated for a potential association with revision for atrophy. Those found to be associated with atrophy and relevant competing risks were further evaluated on multivariable analysis. Results: With a median follow-up of 4.2 years (IQR 1.3-8.1), 89 men (8.3%) had urethral atrophy requiring reoperation. Median time to revision was 4.5 years (IQR 1.9-7.6). On univariable analysis, only smaller cuff size (4.0-cm versus 4.5-cm; HR 3.1, p=0.04) was associated with an increased rate of urethral atrophy. Notably, patient age at the time of surgery (p=0.62), body mass index (0.22), and smoking status (p=1.00) were not associated with a risk of atrophy. On multivariable analysis smaller urethral cuff size remained significant (HR 2.8, 95% CI 1.1-7.1; p=0.01). Conclusion: Revision surgery for urethral atrophy was performed in approximately 8% of men undergoing primary AUS placement. Utilization of a smaller AUS cuff size appears to be an independent factor associated with increased rate of urethral atrophy. [ABSTRACT FROM AUTHOR]

Objective: Artificial urinary sphincter malfunctions can occur in any of the individual components. Preoperative identification of the malfunctioning component can be valuable for patient counseling and surgical planning. The optimal strategy for repair of failed artificial urinary sphincter components is debated given the relative rarity of the situation. The aim of the present study was to evaluate the relationship of time to failure with failed artificial urinary sphincter component and to compare our outcomes of specific component versus complete device replacement. Methods: From 1983 to 2011, 1805 artificial urinary sphincter procedures were carried out at Mayo Clinic (Rochester, Minnesota, USA), of which 1072 patients underwent primary artificial urinary sphincter placement. Clinical variables, including time to failure, were evaluated for association with component failure. Bootstrap analysis was used to estimate the differences in time to reach a fixed percentage of component failure. Results: A total of 115 patients experienced device failure at a median follow up of 4.2 years. Urethral cuff, abdominal reservoir, scrotal pump and tubing malfunction occurred in 53 (4.9%), 26 (2.4%), 11 (1%) and 25 (2.3%) patients, respectively. Increasing age at the time of primary surgery was protective of cuff malfunction (hazard ratio 0.97, P = 0.04). Time to 3% urethral cuff failure outpaced other component failures (P < 0.05). Secondary failure‐free rates after whole device versus specific component revisions were comparable (P = 0.38). Conclusions: Clinical predictors for artificial urinary sphincter failure continue to be difficult to establish. Although single component versus entire device replacement have similar outcomes, if pursuing single component revision, we recommend cuff‐first interrogation in devices in place for >3 years, as this represents the most likely component to fail. [ABSTRACT FROM AUTHOR]

In the present report we aimed to analyze the incremental value of preoperative magnetic resonance imaging (MRI), in addition to clinical variables and clinically-derived nomograms, in predicting outcomes radical prostatectomy (RP). All Mayo Clinic RP patients who underwent preoperative 1.5-Tesla MRI with endo-rectal coil from 2003 to 2013 were identified. Clinical and histopathological variables were used to calculate Partin estimates and Cancer of the Prostate Risk Assessment (CAPRA) score. MRI results in terms of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph-node invasion (N+) were recorded. Using RP pathology as gold standard, we developed multivariate logistic regression models based on clinical variables, Partin Tables, and CAPRA score, and assessed their predictive accuracy before and after the addition of MRI results. Five hundred and one patients were included. MRI + clinical models outperformed clinical-based models alone for all outcomes. Comparing Partin and Partin + MRI predictive models, the areas under the curve were 0.61 versus 0.73 for ECE, 0.75 versus 0.82 for SVI, and 0.82 versus 0.85 for N+. Comparing CAPRA and CAPRA + MRI models, the areas under the curve were 0.69 versus 0.77 for ECE, 0.75 versus 0.83 for SVI, and 0.82 versus 0.85 for N+. Our data show that MRI can improve clinical-based models in prediction of nonorgan confined disease, particularly for ECE and SVI. Patient summary Magnetic resonance imaging, together with clinical information, can be useful in preoperative assessment before radical prostatectomy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of diabetes and obesity on artificial urinary sphincter (AUS) outcomes.Materials and Methods: From 1987 to 2011, men with available diabetes and body mass index (BMI) information (568 of 954) undergoing primary AUS placement at our institution were evaluated. The incidence of all-cause reintervention, mechanical failure, atrophy, and erosion or infection was assessed using the Kaplan-Meier method. Multivariable analyses evaluated the association between clinical characteristics and AUS outcomes.Results: In total, 90 (16%) men had diabetes. Median follow-up among alive men without AUS event was 5.9 years. Diabetics had a greater 5-year incidence of erosion/infection (13% vs 8%; P = .025). On multivariable analysis, diabetes was independently associated with an increased risk of erosion/infection (hazard ratio [HR] = 2.26; P = .02); whereas greater BMI was associated with a reduced risk of erosion or infection (obese: HR = 0.39; P = .02; overweight: HR = 0.57; P = .07). Accordingly, in diabetics, greater average postoperative glucose level (176 mg/dL vs 153 mg/dL; P = .04) and use of nonantibiotic coated devices (13 of 62 vs 1 of 28; P = .035) was associated with a greater incidence of erosion or infection. There was no difference in social continence (≤1 pad/day) (45% vs 57%; P = .29) or high-level satisfaction (95% vs 90%; P = .43) among diabetics vs nondiabetics. However, with greater BMI (<25, 25 to <30, and ≥30), there was a decrease in ≤1 pad/day usage (62% vs 61% vs 49%; P = .02).Conclusion: We found that the presence of diabetes was independently associated with a 2.3-fold increased risk of AUS erosion or infection. These findings warrant the consideration of additional periprocedural measures to reduce the risk of this devastating complication. [ABSTRACT FROM AUTHOR]

Objective To evaluate the impact of patient age on device outcomes among patients undergoing primary artificial urinary sphincter. Methods A total of 1081 male patients who underwent primary artificial urinary sphincter placement from 1983 to 2011 were analyzed, including 91 men (8%) who were aged >80 years at the time of surgery. Revisions and explanations were compared between men stratified by decade of life. Hazard ratios adjusting for competing risks were used to determine the association with age and artificial urinary sphincter device outcomes (infection/erosion, urethral atrophy and malfunction), while overall device failure was estimated using Kaplan-Meier and Cox regression analysis. Results Patients aged >80 years were more likely to have coronary disease ( P = 0.009), diabetes mellitus ( P = 0.04), hypertension ( P = 0.002) and lower body mass index ( P < 0.0001). On multivariable analysis, patients aged >80 years were significantly more likely to experience device erosion or infection compared with a reference of patients aged <60 years (hazard ratio 4.13; P = 0.046), whereas there was no difference in those patients aged 60-70 years or 70-80 years compared with the reference group ( P = 0.56 and 0.45). There was no significant difference in overall device survival between the age-stratified groups ( P = 0.26). Conclusions Although overall artificial urinary sphincter device survival is similar, patients aged >80 years are more likely to experience erosion or infection compared with younger patients. Despite this, the overall device failure rate is low, and artificial urinary sphincter might be considered for appropriately selected and counseled octogenarians. [ABSTRACT FROM AUTHOR]

Background The presence of a positive surgical margin (PSM) at radical prostatectomy (RP) has been linked to an increased risk of biochemical recurrence and receipt of secondary therapy; however, its association with other oncologic end points remains controversial. Objective To evaluate the association of primary Gleason grade (GG) at the site of PSM with subsequent clinical progression and mortality among patients with Gleason score (GS) 7 prostate cancer (PCa). Design, setting, and participants We identified 1036 patients who underwent RP between 1996 and 2002. A single uropathologist re-reviewed all specimens noted to have a PSM to record GG at the margin. Outcome measurements and statistical analysis Survival was estimated using the Kaplan-Meier method. Cox models were used to analyze the association of margin primary GG with outcome. Results and limitations Overall, 338 men (33%) had a PSM; of those, 242 had PSM GG3 and 96 had PSM GG4. Median postoperative follow-up was 13 yr. Compared with men with PSM GG3 or a negative SM, we noted that men with PSM GG4 had significantly worse 15-yr systemic progression-free survival (74% vs 90% vs 93%, respectively; p < 0.001) and cancer-specific survival (86% vs 96% vs 97%, respectively; p = 0.002). On multivariable analysis, the presence of PSM GG4 was associated with increased risks of systemic progression (hazard ratio [HR]: 2.77; p = 0.003) and death from PCa (HR: 3.93; p = 0.02) among men with a PSM. Limitations include the relatively small rate of disease recurrence. Conclusions PSM primary GG4 was independently associated with adverse oncologic outcomes among men with GS7 PCa. Pending external validation, GG at the PSM may be considered for inclusion in pathologic reports and risk stratification following RP. Patient summary Among patients with Gleason grade 7 prostate cancer and a positive surgical margin at the time of prostatectomy, we found that higher Gleason grade at the margin was associated with worse oncologic outcomes. [ABSTRACT FROM AUTHOR]

Objective: Our objective is to assess the outcomes of patients with prostate cancer (PCa) diagnoses undergoing holmium laser enucleation of the prostate (HoLEP). Methods: From 2009 to 2012, 450 patients underwent HoLEP at our institution. We performed a retrospective review of these patients to identify those with PCa. Results: PCa was diagnosed in 57 (12.7%) HoLEP patients: 11 (19.2%) preoperatively, 43 (75.4%) in the operative specimen, and 3 (5.4%) during follow-up. Mean time to PCa development in the postoperative group was 16 months (9-23). There was no difference in patient characteristics for those diagnosed with PCa at the time of HoLEP or in the postoperative period. There were 5 patients with a Gleason score (GS)>8 and 52 with GS<8 PCa. In the operative group, 39 (91%) elected for active surveillance and 4 (9%) elected to have cancer treatment. In subgroup analysis, men diagnosed with GS>8 intraoperatively or postoperatively had significantly elevated preoperative, postoperative, and percent change prostate-specific antigen (PSA) levels when compared to patients diagnosed GS≤7 ( P=0.01, 0.02, and 0.01, respectively). There were no complications, all voided spontaneously, and one patient had persistent incontinence. Conclusion: HoLEP for the treatment of lower urinary tract symptoms (LUTS) in selectively chosen men with known PCa can safely improve urination. Furthermore, PCa is diagnosed at the time of or post HoLEP in nearly 12% of patients. Those patients with persistently elevated post HoLEP PSA levels or low percent change PSA levels should raise suspicion for high GS PCa. Finally, HoLEP does not preclude active surveillance or treatment for PCa when appropriate. [ABSTRACT FROM AUTHOR]

Abstract: Background: Assessment of overall health is a critical component in the evaluation of patients presenting with clinically localized prostate cancer. Estimated glomerular filtration rate (eGFR) has been associated with increased risk of cardiovascular and overall mortality. Therefore, the objective of our study was to evaluate the impact of baseline renal function on oncologic outcomes and overall survival following radical prostatectomy. Materials and methods: We identified 10,099 patients who underwent radical prostatectomy at our institution from 1990 to 2004 with a preoperative serum creatinine available for analysis. eGFR was calculated by the chronic kidney disease-epidemiology formula (CKD-EPI) and reported as ml/min per 1.73 m2. Patients were then classified according to their eGFR: <30, 30–59, 60–89, 90–119, and 120–150 ml/min/1.73 m2. Multivariate Cox proportional hazard regression models were used to analyze the impact of eGFR on postoperative outcomes. Results: At the time of surgery, 25 patients (0.1%) had an eGFR <30 ml/min/1.73 m2, 2,398 (23.7%) between 30 and 60, 7,097 (70.3%) between 60 and 90, and 605 (6.0%) patients had an eGFR >90. eGFR was not associated with oncologic outcomes, including biochemical recurrence, systemic progression or cancer-specific survival (P > 0.05 for all). However, eGFR was strongly associated with all-cause mortality and non-prostate cancer death. On multivariate analysis, after controlling for age, BMI, prostate-specific antigen doubling time (PSA), Gleason score, and clinical stage, eGFR remains a statistically significant predictor of all-cause mortality. Conclusions: Assessment of eGFR is an important metric in the overall evaluation of patient health and should be considered in combination with patient age and other medical comorbidities when selecting the initial treatment of prostate cancer. While prostate cancer-specific outcomes do not appear to be impacted by renal function, overall survival is decreased in those with lower and higher than normal eGFR. [Copyright &y& Elsevier]

Objectives To examine the ability of standard and saturation transrectal prostate biopsy techniques to predict appropriate candidates for active surveillance. Methods Between 2005 and 2007, 500 consecutive patients underwent transrectal ultrasound-guided biopsy by a standard template (12 cores) or saturation template (≥18 cores, median 27 cores), with subsequent radical prostatectomy. Using the criteria of Gleason score ≤6, clinical stage T1 or T2a, prostate-specific antigen <10 and ≤33% of cores involved, 218 patients were potential candidates for active surveillance. Pathology results from the prostatectomy specimens were used to determine the accuracy of each biopsy technique. Biochemical failure after prostatectomy was evaluated using logistic and Cox proportional hazards regression. Results A standard biopsy was carried out for 124 patients and saturation biopsy for 94 patients. There was no statistically significant difference between the groups in terms of median age ( P = 0.14), preoperative prostate-specific antigen ( P = 0.52) and clinical stage ( P = 0.23). Similar rates of Gleason score ≥7 at the time of radical prostatectomy were found, with 14% for standard biopsy and 15% for saturation biopsy ( P = 0.70). Upstaging was shown in two standard biopsy patients (1.6%) and no saturation biopsy patients ( P = 0.62). A multivariate analysis adjusting for prior prostate biopsy, preoperative prostate-specific antigen and clinical stage showed no difference in the rate of upgrading based on biopsy technique ( P = 0.26). During follow up, 5-year biochemical failure-free survival estimates were not significantly different ( P = 0.11). Conclusions In men with prostate cancer, standard and saturation transrectal prostate biopsies techniques are equally predictive of candidates for active surveillance. [ABSTRACT FROM AUTHOR]

Background To evaluate the impact of adjuvant hormonal therapy after radical prostatectomy on overall survival in high-risk prostate cancer patients, stratified by comorbidity status. Methods We identified 1247 patients who underwent radical prostatectomy from 1988 to 2004 for high-risk prostate cancer, as defined by National Comprehensive Cancer Network classification. Comorbidity status was stratified by Charlson Comorbidity Index as 0, 1 or >2, as well as by the presence or absence of cardiovascular disease. Overall survival was estimated by the Kaplan- Meier method, and compared within each comorbidity category/adjuvant hormonal therapy strata with the log-rank test. Results Median patient age was 65 years, and the median postoperative follow up was 11.2 years. In total, 419 patients (34%) received adjuvant hormonal therapy. The distribution of Charlson Comorbidity Index was 0, 1 and ≥2 in 861 (69%), 244 (20%) and 142 (11%) patients, respectively. The 10-year overall survival for patients who received adjuvant hormonal therapy versus those who did not was 75% versus 82% ( P = 0.54) for patients with Charlson Comorbidity Index = 0, 72% versus 76% ( P = 0.83) with Charlson Comorbidity Index = 1, and 70% versus 68% ( P = 0.33) with Charlson Comorbidity Index ≥2. Meanwhile, 155 (12%) patients had cardiovascular disease, and the 10-year overall survival for patients with cardiovascular disease who received adjuvant hormonal therapy was 72%, compared with 76% without adjuvant hormonal therapy ( P = 0.97). On multivariate analysis, receipt of adjuvant hormonal therapy was not associated with non-prostate cancer mortality ( P = 0.24). Conclusions Adjuvant hormonal therapy after radical prostatectomy for high-risk prostate cancer does not increase non-prostate cancer mortality, even among patients with multiple comorbidities. Additional studies are warranted to determine optimal multimodal treatment approach for high-risk patients. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Despite a lack of randomised controlled trials, most men with locally advanced prostate cancer are recommended to undergo external beam radiotherapy (EBRT), often combined with long-term androgen-deprivation therapy (ADT). Many of these men are not offered radical prostatectomy (RP) by their treating urologist. Additionally, it is know that EBRT with long-term ADT does provide good cancer control (88% at 10 years). We have previously published intermediate-term follow-up of a large series of men treatment with RP for cT3 prostate cancer. We report long-term follow-up of a large series of men treated with RP as primary treatment for cT3 prostate cancer. Our study shows that with long-term follow-up RP provides excellent oncological outcomes even at 20 years. While most men do require a multimodal treatment approach, many men can be managed successfully with RP alone. OBJECTIVE To present long-term survival outcomes after radical prostatectomy (RP) for patients with cT3 prostate cancer, as the optimal treatment for patients with clinical T3 prostate cancer is debated., PATIENTS AND METHODS We identified 843 men who underwent RP for cT3 tumours between 1987 and 1997., Survival was estimated using the Kaplan-Meier method., Cox proportional hazards regression models were used to evaluate the association of clinicopathological features with outcome, RESULTS The median (range) postoperative follow-up was 14.3 (0.1-23.5) years., Down-staging to pT2 disease occurred in 26% (223/843) at surgery., Local recurrence-free, systemic progression-free and cancer-specific survival for men with cT3 prostate cancer after RP was 76%, 72%, and 81%, respectively, at 20 years., On multivariate analysis, increasing RP Gleason score (hazard ratio [HR] 1.8; P= 0.01), non-diploid chromatin content (HR 1.8; P= 0.01), positive surgical margins (HR 2.1; P= 0.007), and seminal vesicle invasion (HR 2.1; P= 0.005) were associated with a significant risk of prostate cancer death, while a more recent year of surgery was associated with a decreased risk of cancer-specific mortality (HR 0.88; P= 0.01), CONCLUSIONS RP affords accurate pathological staging and may be associated with durable cancer control for cT3 prostate cancer, with 20 years of follow-up presented here., RP as part of a multimodal treatment strategy therefore remains a viable treatment option for patients with cT3 tumours. [ABSTRACT FROM AUTHOR]

Objective: Medullary sponge kidney (MSK) is a disorder characterized by tubular dilation of renal collecting ducts and cystic dilation of medullary pyramids that has been associated with stone disease. The significance of nephrolithiasis and the mechanisms by which it occurs are incompletely understood. We describe clinical and metabolic features of nephrolithiasis in a cohort of patients with MSK. Methods: Records were reviewed of 56 patients, all with radiographic diagnosis of medullary sponge kidney and data collected pertaining to presentation, stone events and recurrences, stone composition, and metabolic profile to perform a descriptive study with median 3.7 years follow-up. Results: Nephrolithiasis was confirmed radiographically in 39/56 patients (69.6%). No patient without evidence of nephrolithiasis developed a stone event, whereas 13/39 (33%) of those with nephrolithiasis developed a recurrent stone event. Stones were composed of calcium oxalate monohydrate, calcium oxalate dihydrate, calcium phosphate apatite, and uric acid. Metabolic profile was obtained for 26 of 39 (67%) stone-forming patients demonstrating abnormalities in 22/26 (84.6%). These included hypercalciuria, 58% (15/26); low urine volume, 35% (9/26); hyperuricosuria, 27% (7/26); hypocitraturia, 19% (5/26); elevated urine sodium, 15% (4/26); and hyperoxaluria, 12% (3/26). Conclusion: Many patients with MSK have no evidence of nephrolithiasis. Among those who do, recurrence is common, and metabolic profile and composition are varied as in the general stone-forming population. [ABSTRACT FROM AUTHOR]

BACKGROUND: The long-term survival of patients with high-risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen-deprivation therapy (ADT). METHODS: In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate-specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow-up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer-specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk-regression model. RESULTS: The 10-year cancer-specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51-1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68-1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all-cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25-2.05; P = .0002). CONCLUSIONS: RRP alone and EBRT plus ADT provided similar long-term cancer control for patients with high-risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality-of-life and noncancer mortality will be necessary to determine the optimal management approach for these patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The natural history of biochemical recurrence (BCR) after radical retropubic prostatectomy (RRP) is variable and does not always translate into systemic progression or prostate cancer (PCa) death. Objective: To evaluate long-term clinical outcomes of patients with BCR and to determine predictors of disease progression and mortality in these men. Design, setting, and participants: We reviewed our institutional registry of 14 632 patients who underwent RRP between 1990 and 2006 to identify 2426 men with BCR (prostate-specific antigen [PSA] levels ≥0.4ng/ml) who did not receive neoadjuvant or adjuvant therapy. Median follow-up was 11.5 yr after RRP and 6.6 yr after BCR. Intervention: RRP. Measurements: Patients were grouped into quartiles according to time from RRP to BCR. Survival after BCR was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression models were used to analyze clinicopathologic variables associated with systemic progression and death from PCa. Results and limitations: Median systemic progression-free survival (PFS) and cancer-specific survival (CSS) had not been reached after 15 yr of follow-up after BCR. Cancer-specific mortality 10 yr after BCR was 9.9%, 9.3%, 7.8%, and 4.7% for patients who experienced BCR <1.2 yr, 1.2–3.1 yr, 3.1–5.9 yr, and >5.9 yr after RRP, respectively (p =0.10). On multivariate analysis, time from RRP to BCR was not significantly associated with the risk of systemic progression (p =0.50) or cancer-specific mortality (p =0.81). Older patient age, increased pathologic Gleason score, advanced tumor stage, and rapid PSA doubling time (DT) predicted systemic progression and death from PCa. Limitations included retrospective design, varied utilization of salvage therapies, and the inclusion of few patients with positive lymph nodes. Conclusions: Only a minority of men experience systemic progression and death from PCa following BCR. The decision to institute secondary therapies must balance the risk of disease progression with the cost and morbidity of treatment, independent of time from RRP to BCR. [Copyright &y& Elsevier]

Objectives: To investigate the effect of preoperative total serum calcium on disease progression after radical prostatectomy (RP). Elevated total serum calcium has been linked to death from prostate cancer in the National Health and Nutrition Examination Surveys I and II. However, these findings have not been studied in a large cohort of patients with prostate cancer. Methods: We identified 10 532 consecutive patients who had undergone RP from 1990 to 2004 for prostate cancer. Total serum calcium levels were available for 7648 (72.6%) of these patients within 90 days before RP. Postoperative survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression models were used to analyze the ability of serum calcium to predict biochemical recurrence, systemic progression, and cancer-specific survival. Results: The median patient age at surgery was 64 years. The median total serum calcium level was 9.4 mg/dL (range 6.8-11.2). On univariate analysis, the total serum calcium level was not significantly associated with any clinical or pathologic variables, including tumor stage, preoperative prostate-specific antigen, Gleason score, tumor volume, surgical margins, or lymph node status. Furthermore, the serum calcium level was not significantly associated with biochemical failure, systemic progression, or prostate cancer death on univariate or multivariate analysis. Conclusions: The total serum calcium level was not predictive of cancer outcomes in patients who had undergone RP. Additional investigations of the preoperative disease predictors after RP for patients with nonmetastatic disease might be better directed toward other markers. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the impact of adjuvant androgen deprivation therapy (ADT) on survival in patients with seminal vesicle invasion (pT3b) at radical prostatectomy. PATIENTS AND METHODS We reviewed 12 115 patients who underwent radical prostatectomy between 1987 and 2002 to identify patients with pT3bN0 prostate cancer who received adjuvant ADT ( n = 191). These patients were matched by clinical and pathological variables to a group of patients with pT3b prostate cancer who did not receive adjuvant ADT. Median postoperative follow-up was 10 years. Clinical endpoints included biochemical progression-free survival (BPFS), local recurrence-free survival (LRFS), systemic progression-free survival (SPFS), cancer-specific survival (CSS) and overall survival. RESULTS Patients who underwent adjuvant ADT experienced improved 10-year BPFS (60% vs 16%, P < 0.001), LRFS (87% vs 76%, P = 0.002), SPFS (91% vs 78%, P = 0.004) and CSS (94% vs 87%, P = 0.037). Overall survival was not significantly different between groups (75% vs 69%, P = 0.12). Both luteinizing hormone-releasing hormone agonists (hazard ratio, 0.26; 95% CI, 0.15-0.46; P < 0.001) and bilateral orchiectomy (hazard ratio, 0.13; 95% CI, 0.06-0.31; P < 0.001) improved BPFS. When stratified by type of ADT (hormonal therapy vs orchiectomy), there was no difference in survival outcomes. CONCLUSIONS Adjuvant ADT improves local, and systemic control after radical prostatectomy for pT3b prostate cancer. There is no difference in survival between patients receiving medical hormonal therapy vs patients undergoing orchiectomy. Given the lack of improvement in overall survival, continued investigation is needed to identify the cohort of pT3b patients at highest risk for cancer progression and therefore most likely to benefit from a multimodal treatment approach. [ABSTRACT FROM AUTHOR]

Large DNA rearrangements account for about 8% of disease mutations and are more common in duplicated genomic regions, where they are difficult to detect. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2. PKD1 is located in an intrachromosomally duplicated region. A tuberous sclerosis gene, TSC2, lies immediately adjacent to PKD1 and large deletions can result in the PKD1/TSC2 contiguous gene deletion syndrome. To rapidly identify large rearrangements, a multiplex ligation-dependent probe amplification assay was developed employing base-pair differences between PKD1 and the six pseudogenes to generate PKD1-specific probes. All changes in a set of 25 previously defined deletions in PKD1, PKD2 and PKD1/TSC2 were detected by this assay and we also found 14 new mutations at these loci. About 4% of the ADPKD patients in the CRISP study were found to have gross rearrangements, and these accounted for about a third of base-pair mutation negative families. Sensitivity of the assay showed that about 40% of PKD1/TSC contiguous gene deletion syndrome families contained mosaic cases. Characterization of a family found to be mosaic for a PKD1 deletion is discussed here to illustrate family risk and donor selection considerations. Our assay improves detection levels and the reliability of molecular testing of patients with ADPKD.Kidney International (2008) 74, 1468–1479; doi:10.1038/ki.2008.485; published online 24 September 2008 [ABSTRACT FROM AUTHOR]

Abstract: Objective: Recent studies have shown a relative risk reduction in the incidence of prostate cancer in patients taking metformin. However, there are conflicting findings on the effect of metformin on established cases of prostate cancer. In this study we evaluated the effect of metformin on survival and pathologic outcomes in established prostate cancer. Materials and methods: We retrospectively identified 12,052 patients who underwent radical prostatectomy between 1997 and 2010 at Mayo Clinic. Among these, 885 (7.3%) were diabetics, including 323 taking and 562 not taking metformin. Kaplan-Meier method was utilized to calculate rates of biochemical recurrence (BCR), systemic progression (SP), and all-cause mortality (ACM). Cox models were used to estimate the metformin hazard ratio (HR) adjusted for clinical and pathologic variables. Results and conclusions: Median follow-up was 5.1 years. In univariate analysis, metformin HR (95% confidence intervals) was not significant for BCR (1.13 [0.84, 1.52]; P = 0.40), SP (1.37 [0.69, 2.72]; P = 0.37), and ACM (1.32 [0.84, 2.05]; P = 0.23). After adjusting for covariates of interest, the HRs for metformin among diabetics remained nonsignificant for BCR (0.91 [0.67, 1.24]; P = 0.55), SP (0.83 [0.39, 1.74]; P = 0.62); and ACM (1.16 [0.73, 1.86]; P = 0.53). No significant difference was seen between metformin users and nonusers in the final pathologic Gleason score (P = 0.33), stage (P = 0.1), rate of positive surgical margins (P = 0.29), or tumor volume (P = 0.76). Metformin use was not associated with a risk reduction in BCR, SP, or ACM. Besides presenting survival data, our results describing metformin's effect on final pathology are unique. [Copyright &y& Elsevier]

Abstract: Objectives: Determining clinicopathologic features that stratify the risk of disease progression in patients with seminal vesicle invasion at radical prostatectomy remains critical for patient counseling, clinical trial enrollment, and the judicious application of secondary therapies. Then, we evaluated the prognostic significance of concomitant extracapsular extension (ECE) in patients with seminal vesicle invasion and negative lymph nodes at radical prostatectomy. Methods: We identified 1,132 patients who underwent prostatectomy between 1987 and 2009 and were found to have pT3bN0 disease. Median postoperative follow-up was 10.6 years (interquartile range, 5.9–15.3). Survival was estimated using the Kaplan-Meier method and compared for patients with and without ECE with the log-rank test. The association of ECE with outcome was evaluated using Cox proportional hazards regression models. Results: A total of 693 (61%) patients were noted to have ECE. Compared with pT3bN0 patients without ECE, patients with pT3bN0 tumors and ECE had a significantly worse 15-year biochemical recurrence-free survival (29% vs. 39%; P<0.001), systemic progression-free survival (71% vs. 81%; P<0.001), cancer-specific survival (80% vs. 89%; P<0.001), and overall survival (50% vs. 63%; P<0.001). On multivariate analysis, the presence of ECE was associated with significantly increased risks of systemic progression (hazard ratio [HR], 1.56; P=0.006), death from prostate cancer (HR, 1.71; P=0.01), and all-cause mortality (HR, 1.35; P=0.007). Meanwhile, adjuvant hormonal therapy, which was received by 334 patients (29.5%), was associated with significantly decreased risks of systemic progression (HR, 0.50; P=0.0004) and cancer death (HR, 0.57; P=0.03), but not all-cause mortality (HR, 0.81; P=0.09). Limitations included retrospective design and nonstandardized application of secondary treatments. Conclusions: The presence of ECE in patients with pT3bN0 prostate cancer is associated with increased risks of systemic progression and cancer death. Pending validation, ECE may be incorporated into risk stratification or staging classification or both. Meanwhile, these patients continue to represent ideal candidates for adjuvant therapy trials. [Copyright &y& Elsevier]