Kidney stones: flexible ureteroscopy.

INTRODUCTION: The age of peak incidence for stone disease is 20 to 40 years, although stones are seen in all age groups. There is a male to female ratio of 3:2. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of flexible ureteroscopy for the removal of renal stones? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 197 studies. After deduplication and removal of conference abstracts, 118 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 99 studies and the further review of 18 full publications. Of the 18 full articles evaluated, one systematic review and four RCTs were added at this update. We performed a GRADE evaluation for eight PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for four interventions, based on information relating to the effectiveness and safety of: flexible ureteroscopy (combined with snare or basket or laser lithotripsy) versus expectant management, flexible ureteroscopy (combined with snare or basket or laser lithotripsy) versus extracorporeal shockwave lithotripsy, flexible ureteroscopy (combined with snare or basket or laser lithotripsy) versus percutaneous nephrolithotomy.

Sequential intravesical mitomycin plus Bacillus Calmette-Guérin for non-muscle-invasive urothelial bladder carcinoma: translational and phase I clinical trial.

PURPOSE: To determine the safety and toxicities of sequential MMC (mitomycin C) + BCG (bacillus Calmette-Guérin) in patients with non-muscle-invasive bladder cancer (NMIBC) and explore evidence for potentiation of BCG activity by MMC. EXPERIMENTAL DESIGN: A 3 + 3 phase I dose-escalation trial of six weekly treatments was conducted in patients with NMIBC. MMC (10, 20, or 40 mg) was instilled intravesically for 30 minutes, followed by a 10-minute washout with gentle saline irrigation and then instillation of BCG (half or full strength) for 2 hours. Urine cytokines were monitored and compared with levels in a control cohort receiving BCG only. Murine experiments were carried out as described previously. RESULTS: Twelve patients completed therapy, including 3 patients receiving full doses. The regimen was well tolerated with no treatment-related dose-limiting toxicities. Urinary frequency and urgency, and fatigue were common. Eleven (91.7%) patients were free of disease at a mean (range) follow-up of 21.4 (8.4-27.0) months. Median posttreatment urine concentrations of IL2, IL8, IL10, and TNFα increased over the 6-week treatment period. A greater increase in posttreatment urinary IL8 during the 6-week period was observed in patients receiving MMC + BCG compared with patients receiving BCG monotherapy. In mice, intravesical MMC + BCG skewed tumor-associated macrophages (TAM) toward a beneficial M1 phenotype. CONCLUSIONS: Instillation of sequential MMC + BCG is safe tolerable up to 40-mg MMC plus full-strength BCG. This approach could provide improved antitumor activity over BCG monotherapy by augmenting beneficial M1 TAMs.

Impact of nutritional factors on incident kidney stone formation: a report from the WHI OS.

PURPOSE: Increased fluid intake, and decreased dietary sodium and animal protein intake are thought to reduce the risk of kidney stones but the role of calcium intake is controversial. We evaluated the relationship between dietary factors and incident kidney stone formation. MATERIALS AND METHODS: Secondary analysis was done of 78,293 women from the prospective WHI OS (Women's Health Initiative Observational Study) with no history of nephrolithiasis who completed the validated food frequency questionnaire. Multivariate logistic regression was used to determine demographic and dietary factors, and supplement use independently associated with incident kidney stones. RESULTS: Overall 1,952 women (2.5%) reported an incident kidney stone in 573,575 person-years of followup. The risk of incident kidney stones was decreased by 5% to 28% (p = 0.01) with higher dietary calcium intake and by 13% to 31% (p = 0.002) with higher water intake after adjusting for nephrolithiasis risk factors. Conversely higher dietary sodium intake increased the risk of nephrolithiasis by 11% to 61% (p <0.001) after adjustment with the most pronounced effect in women with the highest intake. Higher body mass index independently increased the risk of incident nephrolithiasis (adjusted OR 1.19-2.01, p <0.001). Animal protein intake was not associated with nephrolithiasis on multivariate analysis. CONCLUSIONS: This study adds to the growing evidence underscoring the importance of maintaining adequate fluid and dietary calcium intake. Greater dietary calcium intake significantly decreased the risk of incident kidney stones. In contrast, excess sodium intake increased the risk of incident nephrolithiasis, especially in women with the highest intake. Animal protein intake was not independently associated with nephrolithiasis.

Kidney stones.

INTRODUCTION: The age of peak incidence for stone disease is 20 to 40 years, although stones are seen in all age groups. There is a male to female ratio of 3:2. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions for stone removal in people with asymptomatic kidney stones? What are the effects of interventions for the removal of symptomatic renal stones? What are the effects of interventions to remove symptomatic ureteric stones? What are the effects of interventions for the management of acute renal colic? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antispasmodic drugs, extracorporeal shockwave lithotripsy, intravenous fluids, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, oral fluids, percutaneous nephrolithotomy, and ureteroscopy.

Laterality of nephrocalcinosis in kidney stone formers with severe hypocitraturia.

OBJECTIVE To examine the hypothesis that the distribution of nephrocalcinosis in patients with severe hypocitraturia should be symmetric. PATIENTS AND METHODS Patients with profound hypocitraturia defined as a 24-h urine citrate < 50 mg at the time of initial presentation were identified from the metabolic stone clinic database at our academic medical center. Two independent blinded reviewers evaluated all of the abdominal radiographs for the segmental distribution of macroscopic nephrocalcinosis. RESULTS A total of 44 patients met study criteria, with an equal distribution of males and females and a mean age of 55.4 ± 13.7 years. Mean urinary citrate was 28 ± 11 mg/day. Nephrocalcinosis was present in at least one renal segment in 22 patients (50%). Of the 22 patients with nephrocalcinosis, 9 patients (41%) had unilateral nephrocalcinosis and 13 patients (59%) had bilateral nephrocalcinosis. Of the 35 kidneys with nephrocalcinosis, 14 kidneys (40%) had nephrocalcinosis in only one renal segment, 13 kidneys (37%) had nephrocalcinosis in two segments and eight kidneys (23%) had nephrocalcinosis involving all three segments. CONCLUSIONS Despite the systemic nature of severe hypocitraturia, nephrocalcinosis is frequently asymmetric and focal in nature. This suggests that local factors intrinsic to the renal medullary interstitium, such as vascular injury, must play a role in the formation of nephrocalcinosis. Further study to elucidate these intrinsic local factors may further improve the treatment and prevention of urinary stone disease.

Medical and medical/urologic approaches in acute and chronic urologic stone disease.

Urinary stone disease is a condition with far-reaching implications. Patients with their initial instance of acute renal colic enter the health care system through 2 routes. Severe cases are generally seen in the emergency room, whereas more tolerable cases may be seen by primary care physicians. Patients with urinary stone disease are then managed in the long-term by a urologist. Timely and appropriate treatment of patients with urinary stone disease is essential to prevent the development of sepsis and progressive renal insufficiency. This article reviews the epidemiology, pathogenesis, presentation, and short- and long-term management of acute and chronic urinary stone disease.

Understanding results: P-values, confidence intervals, and number need to treat.

OBJECTIVES: With the increasing emphasis on evidence-based medicine, the urology literature has seen a rapid growth in the number of high-quality randomized controlled trials along with increased statistical rigor in the reporting of study results. P-values, CI, and number needed to treat (NNT) are becoming increasingly common in the literature. This paper seeks to familiarize the reader with statistical measures commonly used in the evidence-based literature. MATERIALS AND METHODS: The meaning and appropriate interpretation of these statistical measures is reviewed through the use of a clinical scenario. RESULTS: The reader will be better able to understand such statistical measures and apply them to the critical appraisal of the literature. CONCLUSIONS: P-values, CI, and NNT each provide a slightly different estimate of statistical truth. Together, they provide a more complete picture of the true effect observed in a study. An understanding of these measures is essential to the critical appraisal of study results in evidence-based medicine.

Obstructive uropathy.

Obstructive uropathy is a relatively common condition in which an anatomic or functional problem causes obstruction to normal urinary flow. Obstructive uropathy becomes more prevalent with increasing age and is most frequent as a result of benign prostatic hyperplasia or neurogenic bladder. The clinical manifestations of obstructive uropathy range from little or no symptoms to acute renal failure. Because its prevalence increases with increasing age, the diagnosis and management of obstructive uropathy is particularly relevant to the geriatric population.

Evaluating the evidence: the methodological and reporting quality of comparative observational studies of surgical interventions in urological publications.

OBJECTIVE: To develop and apply a standardized evaluation form for assessing the methodological and reporting quality of observational studies of surgical interventions in urology. METHODS: An evaluation standard was developed using the Consolidated Standards for Reporting Trials statement and previously reported surgical reporting quality instruments. Consensus scoring among three reviewers was developed using two distinct sets of studies. All comparative observational trials involving therapeutic surgical procedures published in four major urological journals in 1995 and 2005 were randomly assigned to each reviewer. Categories of reporting adequacy included background, intervention, statistical analysis, results and discussion. RESULTS: Twenty-seven articles in 1995 and 62 in 2005 met the inclusion criteria; 90% of studies were retrospective. From 1995 to 2005, the overall reporting quality score increased by 3.9 points (95% confidence interval, CI, 2.7-5.9; P = 0.001), from a mean (SD) of 19.1 (3.9) to 23.0 (4.2) on a scale of 0-42. There were significant improvements in the reporting categories of study background (+0.7 points, 95% CI 0.1-1.3, P = 0.043, 0-8-point scale), intervention (+1.6 points, 0.8-2.3, P = 0.001, 0-9-point scale), and statistical analysis (+0.8 points, 0.2-1.4, P = 0.006, 0-9-point scale). There were smaller and statistically insignificant improvements for results (+0.5 points, -0.3 to 1.2, P = 0.217, 0-10-point scale) and discussion reporting (+0.4 points, -0.1 to 0.8, P = 0.106, 0-6-point scale). CONCLUSIONS: There have been minor improvements in the reporting of observational studies of surgical intervention between 1995 and 2005. However, reporting quality remains suboptimal. Clinical investigators, reviewers and journal editors should continue to strive for transparent reporting of the observational studies representing the bulk of the clinical evidence for urological procedures.

How to use a systematic literature review and meta-analysis.

PURPOSE: This article introduces practicing urologists to the critical appraisal of systematic reviews and meta-analyses to guide their evidence-based clinical practice. MATERIALS AND METHODS: Using a urological clinical case scenario we introduce a 3-step process in evaluating systematic reviews and meta-analyses by considering 1) the validity of the review results, 2) what the results are, and 3) the extent to which the results can and should be applied to patient care. RESULTS: A systematic review seeks to synthesize the medical literature about a specific clinical question using explicit methods to perform a comprehensive literature search, identify and select eligible studies, critically appraise their methods, and judiciously summarize the results considering how they vary with study characteristics. When this summary involves statistical methods, ie a meta-analysis, reviewers can offer a pooled estimate that will have greater precision and will apply more broadly than the individual studies. The quality of the underlying studies, the consistency of results across studies and the precision of the pooled estimate can considerably affect the strength of inference from systematic reviews. CONCLUSIONS: Valid systematic reviews of high quality studies can increase the confidence with which urologists and patients make evidence-based decisions. Thus, urologists need to recognize the inherent limitations, understand the results and apply them judiciously to patient care.

Impact of nerve sparing technique on patient self-assessed outcomes after radical perineal prostatectomy.

PURPOSE: We investigated the impact of nerve sparing technique on erectile function, urinary continence and health related quality of life after radical perineal prostatectomy using a validated self-assessment questionnaire. MATERIALS AND METHODS: The Expanded Prostate Cancer Index Composite questionnaire was administered preoperatively and at defined intervals after surgery to 265 patients who underwent radical perineal prostatectomy at 2 institutions between January 2001 and December 2004. Of these patients 153 (57.7%) and 112 (42.3%) underwent nonnerve sparing and nerve sparing approaches, respectively. Kaplan-Meier analysis was used to determine time to recovery of erectile function (erections firm enough for intercourse) and urinary continence (0 pads per day). RESULTS: Median patient age was 60.6 years. Median followup was 15 months. In multivariate analysis preoperative erectile function (p = 0.005) and preservation of the neurovascular bundle (p = 0.018) were independent predictors of earlier recovery of erectile function, with hazard ratios of 2.3 (95% CI 1.2-4.6) and 4.0 (95% CI 1.5-10.3), respectively. Median time to recovery of urinary continence was 4.8 months in the nerve sparing group and 6.1 months in the nonnerve sparing group (p = 0.001). In multivariate analysis nerve sparing technique (p = 0.001, HR 1.4, 95% CI 1.1-1.9) and age (p = 0.012, HR 1.7, 95% CI 1.3-2.2) were independent predictors of recovery of continence. CONCLUSIONS: This analysis suggests that nerve sparing radical perineal prostatectomy is associated with improved recovery of urinary continence and favorable health related quality of life scores and, therefore, should be considered a viable alternative to other nerve sparing approaches.

The role of early adopter bias for new technologies in robot assisted laparoscopic prostatectomy.

PURPOSE: We determined the potential influence of an early adopter bias in patients undergoing robot assisted laparoscopic prostatectomy. MATERIALS AND METHODS: We compared baseline demographic, clinical and health related quality of life characteristics of patients undergoing 3 different surgical procedures for clinically localized prostate cancer following the introduction of robot assisted laparoscopic prostatectomy at our institution. Patients included in this analysis were participating in a prospective health related quality of life study using the SF-12(R) and Expanded Prostate Cancer Index Composite validated questionnaires. RESULTS: Of 402 patients 159 (39%) underwent robot assisted laparoscopic, 144 (36%) underwent radical perineal and 99 (25%) underwent radical retropubic prostatectomy. There were no statistically significant associations between procedure type and patient age (p = 0.267), race (p = 0.725), number of medical comorbidities (p = 0.490), income (p = 0.056) and level of education (p = 0.495). Mean prostate specific antigen was 5.9 +/- 3.3, 7.3 +/- 5.5 and 5.7 +/- 5.0 ng/ml for robot assisted laparoscopic, radical perineal and radical retropubic prostatectomy, respectively (p = 0.030). The proportion of robot assisted laparoscopic, radical perineal and radical retropubic prostatectomy patients with a final Gleason score of 4-6 was 55%, 45% and 39%, respectively (p = 0.037). The proportion of robot assisted laparoscopic, radical perineal and radical retropubic prostatectomy patients with stage T2 disease was 91%, 68% and 80%, respectively (p = 0.001). Statistically significant associations of higher income and education with higher baseline health related quality of life scores were seen in the sexual and physical domains (each p <0.01). CONCLUSIONS: We failed to find evidence of an early adopter bias for patients undergoing robot assisted laparoscopic prostatectomy. Nevertheless, observational studies comparing robot assisted laparoscopic prostatectomy to radical perineal and radical retropubic prostatectomy should account carefully for patient baseline characteristics to allow meaningful comparisons of surgical outcomes.

Factors associated with the full publication of studies presented in abstract form at the annual meeting of the American Urological Association.

PURPOSE: Many abstracts presented at scientific meetings never come to full text publication, which is a prerequisite for the critical appraisal of a given study for its validity, impact and generalizability. We determined factors associated with the publication of abstracts presented at the American Urological Association national meeting. MATERIALS AND METHODS: All abstracts addressing clinical research accepted for presentation at the 2002 and 2003 meetings of the American Urological Association were reviewed. A comprehensive MEDLINE search was performed for evidence of publication in full manuscript form. Data abstraction and literature searches were done between June 15 and August 30, 2005. Univariate and multivariate analyses were performed to determine the association between abstract characteristics and time to publication. RESULTS: Of the 1,683 abstracts reviewed 740 (44.0%) were published within a median followup of 27.8 months (range 25.9 to 39.7). Time to publication was associated with abstract origin in the United States and the reporting of statistical testing (HR 1.2, 95% CI 1.0-1.4, p=0.040 and HR 1.2, 95% CI 1.1-1.4, p=0.010, respectively). Other variables, such as presentation type, study design, clinical question type and negative outcome, were not predictive. CONCLUSIONS: Nonpublication of research findings is a problematic issue that affects more than half of studies 2 years after presentation at the American Urological Association national meeting. Abstracts from the United States and those providing statistical testing were more likely to be published in full text form. Further efforts are warranted to identify and eliminate factors that hinder publication of research to bring it to the scrutiny of a broad audience of urologists.

Prospective health-related quality-of-life assessment in an initial cohort of patients undergoing robotic radical prostatectomy.

OBJECTIVES: To prospectively assess the health-related quality-of-life outcomes of patients undergoing robot-assisted laparoscopic prostatectomy using a validated patient self-assessment questionnaire. METHODS: Patients undergoing robot-assisted laparoscopic prostatectomy between September 2003 and May 2005 were given the Expanded Prostate Cancer Index Composite questionnaire preoperatively and 1, 3, 6, 9, 12, and 18 months postoperatively. Patients with a minimum follow-up of 3 months were included in the analysis. The mean domain-specific health-related quality-of-life scores +/- SD and the proportion of patients achieving their baseline scores were calculated. Multivariate proportional hazards regression analysis was used to determine the potential prognostic factors for a return to baseline of the domain scores and continence. RESULTS: The median follow-up was 9.5 months. The median time to recovery of the baseline summary scores was 6.6 months (95% confidence interval [CI] 5.9 to 7.2) in the urinary domain, 2.8 months (95% CI 2.0 to 3.7) in the bowel domain, and 3.0 months (95% CI 2.2 to 3.9) in the hormonal domain. The baseline sexual summary score was recovered by 19.2% of patients at 12 months. The median time to return of continence (0 to 1 pads/day) was 4.0 months (95% CI 3.0 to 4.9). The median time to the return of erections firm enough for intercourse was 13.5 months (95% CI 9.9 to 17.1). On multivariate proportional hazards regression analysis, age, body mass index, prostate size, nerve-sparing technique, and number of comorbidities were not significantly associated with the time to recovery of the baseline domain scores or continence. CONCLUSIONS: Patients undergoing robot-assisted laparoscopic prostatectomy have a favorable health-related quality-of-life recovery profile that appears comparable to those of established surgical approaches.