The effect of increasing doses of saw palmetto fruit extract on serum prostate specific antigen: analysis of the CAMUS randomized trial.

PURPOSE: Saw palmetto extracts are used to treat lower urinary tract symptoms in men despite level I evidence that saw palmetto is ineffective in reducing these lower urinary tract symptoms. We determined whether higher doses of saw palmetto as studied in the CAMUS (Complementary and Alternative Medicine for Urologic Symptoms) trial affect serum prostate specific antigen levels. MATERIALS AND METHODS: The CAMUS trial was a randomized, placebo controlled, double-blind, multicenter, North American trial conducted between June 5, 2008 and October 10, 2012, in which 369 men older than 45 years with an AUA symptom score of 8 to 24 were randomly assigned to placebo or dose escalation of saw palmetto, which consisted of 320 mg for the first 24 weeks, 640 mg for the next 24 weeks and 960 mg for the last 24 weeks of this 72-week trial. Serum prostate specific antigen levels were obtained at baseline and at weeks 24, 48 and 72, and were compared between treatment groups using the pooled t test and Fisher's exact test. RESULTS: Serum prostate specific antigen was similar at baseline for the placebo (mean ± SD 1.93 ± 1.59 ng/ml) and saw palmetto groups (2.20 ± 1.95, p = 0.16). Changes in prostate specific antigen during the study were similar, with a mean change in the placebo group of 0.16 ± 1.08 ng/ml and 0.23 ± 0.83 ng/ml in the saw palmetto group (p = 0.50). In addition, no differential effect on serum prostate specific antigen was observed between treatment arms when the groups were stratified by baseline prostate specific antigen. CONCLUSIONS: Saw palmetto extract does not affect serum prostate specific antigen more than placebo, even at relatively high doses.

Randomized controlled trial of oxybutynin extended release versus placebo for urinary symptoms during intravesical Bacillus Calmette-Guérin treatment.

PURPOSE: Intravesical bacillus Calmette-Guérin is used to decrease recurrence rates of nonmuscle invasive urothelial carcinoma. Irritative urinary symptoms are a common side effect of treatment and frequently limit treatment tolerance. While anticholinergic medications may be used for symptom prophylaxis, to our knowledge they have not been evaluated in a randomized controlled trial. MATERIALS AND METHODS: A total of 50 bacillus Calmette-Guérin naïve patients were randomized to 10 mg extended release oxybutynin daily or placebo starting the day before 6 weekly bacillus Calmette-Guérin treatments. A questionnaire assessing urinary symptoms (frequency, burning on urination, urgency, bladder pain, hematuria), systemic symptoms (flu-like symptoms, fever, arthralgia) and medication side effects (constipation, blurred vision, dry mouth) was recorded daily throughout the therapeutic course. A linear mixed repeated measures model tested the differences between each point and baseline score. RESULTS: The treatment group had a greater increase in urinary frequency and burning on urination compared to placebo (p = 0.004 and p = 0.04, respectively). There were no significant differences between groups for other urinary symptoms, which increased in severity after bacillus Calmette-Guérin but concomitantly returned to baseline in both groups. The treatment group experienced increases in fever, flu-like symptoms, dry mouth and constipation compared to placebo (p <0.0001, p = 0.0008, p = 0.045 and p = 0.001, respectively). There were otherwise no significant differences in nonurinary symptoms or medication adverse reactions. CONCLUSIONS: Oxybutynin increased urinary frequency and burning on urination compared to placebo in patients receiving intravesical bacillus Calmette-Guérin treatment. Our results do not support the routine use of oxybutynin as prophylaxis against urinary symptoms during bacillus Calmette-Guérin therapy.

Is there a financial disincentive to perform partial nephrectomy?

PURPOSE: Despite the explicit endorsement of the American Urological Association guidelines of partial nephrectomy as the treatment of choice for T1a renal cell carcinoma, a considerable underuse of nephron sparing surgery characterizes general practice patterns in the United States. We explored possible financial disincentives associated with partial nephrectomy that may contribute to this important quality of care deficit. MATERIALS AND METHODS: A PubMed® query on perioperative outcomes identified 10 series on open or laparoscopic radical nephrectomy and 16 on open, laparoscopic or robot-assisted partial nephrectomy. Mean operative time and hospital length of stay were calculated for each group. Using these data in conjunction with Health Care Financing Administration data on physician work time, which guides the current Resource-Based Relative Value Scale Medicare fee schedule, we calculated global physician time expenditure and hourly Medicare reimbursement rates for each of these 5 surgical services. RESULTS: Mean±SD operative time for open and laparoscopic radical nephrectomy, and open, laparoscopic and robot-assisted partial nephrectomy was 180.7±24.7 minutes (95% CI 119.3-242.0) in 3 studies, 178.8±16.5 (95% CI 163.5-194.1) in 7, 226.0±36.9 (95% CI 187.2-264.8) in 6, 227.9±40.2 (95% CI 185.8-270.1) in 6 and 227.9±37.8 (95% CI 167.7-288.1) in 4, respectively (p=0.028). Mean length of stay (days) after open and laparoscopic radical nephrectomy, and open, laparoscopic and robot-assisted partial nephrectomy was 5.8±0.7 days (95% CI 4.0-7.7) in 3 studies, 2.5±1.1 (95% CI 1.4-3.6) in 6, 5.8±0.4 (95% CI 5.3-6.2) in 5, 2.9±0.3 (95% CI 2.6-3.3) in 6 and 2.8±1.0 (95% CI 1.2-4.4) in 4, respectively (p<0.001). The hourly reimbursement rate was calculated at $200.61, $242.03, $185.66, $231.27 and $231.97 for open and laparoscopic radical nephrectomy, and open, laparoscopic and robot-assisted partial nephrectomy, respectively. Hence, open partial nephrectomy emerged as the lowest paying of these procedures. CONCLUSIONS: Inferior compensation for open partial nephrectomy relative to that of laparoscopic or open radical nephrectomy may impede the dissemination of nephron sparing surgery for small renal masses. This may occur particularly in a general practice setting, where the expertise required for laparoscopic or robot-assisted partial nephrectomy may be lacking. We propose rectifying this inequity to facilitate wider use of nephron sparing surgery in the clinically appropriate setting.

Limited use of surveillance imaging following nephrectomy for renal cell carcinoma.

OBJECTIVES: To evaluate the utilization of follow-up imaging after nephrectomy for renal cell carcinoma (RCC) in nationally representative data. PATIENTS AND METHODS: Using Surveillance, Epidemiology, End Results data linked to Medicare records, we identified patients with RCC who received nephrectomy from 1991 to 2007. Patients were stratified by tumor stage. Postoperative chest and abdominal imaging (including chest x-ray, computed tomography scan, and magnetic resonance imaging; abdominal ultrasound, computed tomography scan, and magnetic resonance imaging) was assessed. Observed surveillance imaging frequency was compared to published protocols. Predictors of initial and continued yearly surveillance imaging were identified. RESULTS: Agreement between observed imaging frequency and evidence-based surveillance protocols was low, particularly for patients with T2-T4 disease. For patients who were not censored before 13 months, initial abdominal and chest surveillance imaging was obtained in 69% and 78% of patients, respectively. By year 5, 28% and 39% of patients with high-risk disease (T3 or T4), as compared to 21% and 25% of patients with low to moderate risk disease (T1 and T2), received yearly surveillance abdominal and chest imaging, respectively. High-risk disease was predictive of initial chest (odds ratio [OR] = 1.38) and abdominal (OR = 1.6) imaging, as well as continued yearly chest (hazard ratio [HR] = 0.73) and abdominal (HR = 0.74) imaging surveillance. For abdominal imaging, more contemporary year of surgery was predictive of initial (1997-2001, OR = 1.6; 2002-2007, OR = 2.4) and continued yearly surveillance (1997-2001, HR = 0.82; 2002-2007; HR = 0.67). CONCLUSIONS: In the Medicare population, surveillance imaging is performed in a limited number of patients following nephrectomy for RCC. However, increasing tumor stage is predictive of both increased chest and abdominal imaging surveillance.

Prostate cancer chemoprevention.

Prostate cancer is a leading cause of morbidity and mortality in men and has significant treatment-associated complications. Prostate cancer chemoprevention has the potential to decrease the morbidity and mortality associated with this disease. Chemoprevention research to date has primarily focused on nutrients and 5 alpha-reductase inhibitors (5ARIs). A large randomized trial (SELECT) found no favorable effect of selenium or vitamin E on prostate cancer prevention. Two large randomized placebo controlled trials (the PCPT and REDUCE trials) have been published and have supported the role of 5ARIs in prostate cancer chemoprevention; however, these trials also have prompted concerns regarding the increase in high-grade disease seen with treatment and have not been approved by the US Food and Drug Administration (FDA) for chemoprevention. Conclusive evidence for the chemopreventive benefit of nutrients or vitamins is lacking, whereas the future role of 5ARIs remains to be clarified.

Robot-assisted partial nephrectomy: off-clamp technique.

Robot-assisted partial nephrectomy (RAPN) has been established as a viable alternative to open and laparoscopic partial nephrectomy for small renal tumors. Multiple variations in surgical technique have been described to reduce warm ischemia time (WIT). We present our off-clamp technique for RAPN. From August 2007 to January 2012, off-clamp RAPN was performed on 47 tumors in 39 patients. WIT was 0 minutes in all cases. The mean operative time was 147 minutes (SD=58); the mean and median estimated blood loss were 219 mL (SD=253) and 150 mL (range 50-1500), respectively; the mean length of stay was 1.9 days (SD=1.1). There were no intraoperative complications, and results for all surgical margins were negative. In experienced hands, our off-clamp technique for RAPN is a safe and feasible technique that eliminates WIT.

Laparoscopic prostatectomy for prostate cancer: continued role in urology.

The purpose of this article is to provide an update on the current literature evaluating outcomes with laparoscopic prostatectomy. The reported perioperative, oncologic, and functional outcomes with this approach are reviewed and comparisons are made to the open and robotic-assisted approaches.

Overdiagnosis of prostate cancer.

This chapter addresses issues relevant to prostate cancer overdiagnosis. Factors promoting the overdiagnosis of prostate cancer are reviewed. First is the existence of a relatively large, silent reservoir of this disease, as can be seen by evaluating autopsy studies and histologic step-sectioning results of prostates removed for other causes. The second main factor responsible for prostate cancer overdiagnosis is fairly widespread prostate-specific antigen and digital rectal examination-based screening, which has been fairly widely practiced in the United States for the past 20 years among heterogeneous groups of men. This has resulted in the identification of many men from this reservoir who otherwise may never have been diagnosed with symptomatic prostate cancer and is substantially responsible for the current annual incidence to mortality ratio for prostate cancer of approximately 6 to 1. Finally, the relatively indolent natural history and limited cancer-specific mortality as reported in a variety of contemporary randomized screening and treatment trials is reviewed. We attempt to quantitate the proportion of newly diagnosed prostate cancers that are overdiagnosed using various trial results and models. We explore the impact of prostate cancer overdiagnosis in terms of patient anxiety and the potential for overtreatment, with its attendant morbidity. We explore strategies to minimize overdiagnosis by targeting screening and biopsy only to men at high risk for aggressive prostate cancer and by considering the use of agents such as 5-alpha reductase inhibitors. Future prospects to prevent overtreatment, including better biopsy and molecular characterization of newly diagnosed cancer and the role of active surveillance, are discussed.

Off-clamp robot-assisted partial nephrectomy for complex renal tumors.

BACKGROUND AND PURPOSE: Considering the potential impact of warm ischemia time (WIT) on renal functional outcomes after robot-assisted partial nephrectomy (RAPN), many techniques that reduce or eliminate WIT have been studied. We present our institutional experience and progression using one such technique-off-clamp RAPN-as well as the results of this technique in the management of complex cases. PATIENTS AND METHODS: A retrospective chart review of 65 patients undergoing off-clamp RAPN was performed, 15 of whom underwent off-clamp RAPN for 26 complex tumors. Complex features included hilar location, completely endophytic growth, and ipsilateral multifocality. In all cases, hilar vessels were dissected but not clamped. RESULTS: Mean tumor size was 2.5 cm (standard deviation; [SD]=1.4), while mean nephrometry score was 8.7 (SD=1.5). One (7%) intraoperative complication occurred. Mean estimated blood loss was 403 mL (SD=381), mean operative time was 190 minutes (SD=68), and WIT was 0 minutes in all cases. Mean length of stay was 1.8 days (SD=0.9), with one patient needing a postoperative blood transfusion (Clavien II complication). Final pathology results demonstrated clear-cell carcinoma (n=16), papillary carcinoma (n=4), angiomyolipoma (n=1), oncocytoma (n=2), and cystic nephroma (n=3). Margins were negative for tumor for 96% (25/26) of resected masses. Estimated glomerular filtration rate (eGFR) decreased by an average of 3.1 mL/min/1.73 m(2) (SD=9.8, P=0.24), at a mean follow-up of 177 days (SD=296). Five patients with radiographic follow-up of at least 6 months have no evidence of disease recurrence. CONCLUSIONS: Off-clamp RAPN can be safely and effectively performed even in the case of complex tumors, but occurs with higher estimated blood loss. Minimal changes in eGFR were experienced by patients undergoing off-clamp RAPN at an average follow-up of roughly 6 months. Longer follow-up and direct comparison with conventional clamped RAPN technique are needed to establish the efficacy of off-clamp RAPN in complex cases.

Renal functional and perioperative outcomes of off-clamp versus clamped robot-assisted partial nephrectomy: matched cohort study.

OBJECTIVE: To evaluate the potential benefit of performing off-clamp robot-assisted partial nephrectomy as it relates to renal functional outcomes, while assessing the safety profile of this unconventional surgical approach. METHODS: Twenty-nine patients who underwent off-clamp robot-assisted partial nephrectomy for suspected renal cell carcinoma at Washington University between March 2008 and September 2011 (group 1) were matched to 29 patients with identical nephrometry scores and comparable baseline renal function who underwent robot-assisted partial nephrectomy with hilar clamping during the same period (group 2). The matched cohorts' perioperative and renal functional outcomes were compared at a mean 9-month follow-up. RESULTS: Mean estimated blood loss was 146.4 mL in group 1, versus 103.9 mL in group 2 (P = .039). Mean hilar clamp time was 0 minutes in group 1 and 14.7 minutes in group 2. No perioperative complications were encountered in group 1; 1 Clavien-2 complication (3.4%) occurred in group 2 (P = 1.000). At 9-month follow-up, mean estimated glomerular filtration rate in group 1 was 79.9 versus 84.8 mL/min/1.73 m(2) preoperatively (P = .013); mean estimated glomerular filtration rate in group 2 was 74.1 versus 85.8 mL/min/1.73 m(2) preoperatively (P < .001). Hence, estimated glomerular filtration rate declined by a mean of 4.9 mL/min/1.73 m(2) in group 1 versus 11.7 mL/min/1.73 m(2) in group 2 (P = .033). CONCLUSION: Off-clamp robot-assisted partial nephrectomy is associated with a favorable morbidity profile and relatively greater renal functional preservation compared to clamped robot-assisted partial nephrectomy. Nevertheless, the benefit is small in renal functional terms and may have very limited clinical relevance.

2D versus 3D visualization: impact on laparoscopic proficiency using the fundamentals of laparoscopic surgery skill set.

INTRODUCTION: We compared the impact of two-dimensional (2D) versus three-dimensional (3D) visualization on both objective and subjective measures of laparoscopic performance using the validated Fundamentals of Laparoscopic Surgery (FLS) skill set. SUBJECTS AND METHODS: Thirty-three individuals with varying laparoscopic experience completed three essential drills from the FLS skill set (peg transfer, pattern cutting, and suturing/knot tying) in both 2D and 3D. Participants were randomized to begin all tasks in either 2D or 3D. Time to completion and number of attempts required to achieve proficiency were measured for each task. Errors were also noted. Participants completed questionnaires evaluating their experiences with both visual modalities. RESULTS: Across all tasks, greater speed was achieved in 3D versus 2D: peg transfer, 183.4 versus 245.6 seconds (P<.0001); pattern cutting, 167.7 versus 209.3 seconds (P=.004); and suturing/knot tying, 255.2 versus 329.5 seconds (P=.031). Fewer errors were committed in the peg transfer task in 3D versus 2D (P=.008). Fourteen participants required multiple attempts to achieve proficiency in one or more tasks in 2D, compared with 7 in 3D. Subjective measures of efficiency and accuracy also favored 3D visualization. The advantage of 3D vision persisted independent of participants' level of technical expertise (novice versus intermediate/expert). There were no differences in reported side effects between the two visual modalities. Overall, 87.9% of participants preferred 3D visualization. CONCLUSIONS: Three-dimensional vision appears to greatly enhance laparoscopic proficiency based on objective and subjective measures. In our experience, 3D visualization produced no more eye strain, headaches, or other side effects than 2D visualization. Participants overwhelmingly preferred 3D visualization.

Off-clamp robot-assisted partial nephrectomy: initial Washington University experience.

BACKGROUND AND PURPOSE: Because of the impact warm ischemia time may have on renal function, various surgical techniques have been proposed to minimize or eliminate warm ischemia. The purpose of this study is to evaluate our initial renal functional outcomes of off-clamp robot-assisted partial nephrectomy (RAPN), while assessing the safety profile of this unconventional surgical approach. PATIENTS AND METHODS: We performed a retrospective review of our off-clamp RAPN experience between August 2007 and January 2012. All patients with baseline and postoperative serum creatinine determinations were included. Patient demographics, operative information, perioperative outcomes, and renal functional outcomes were evaluated for this cohort. RESULTS: Forty-two patients with a mean age of 59.9 years (standard deviation [SD]=12) had a median follow-up of 100 days (range 1-1007 days). In all cases, warm ischemia time was 0 minutes. Mean operative time was 143 minutes (SD=59), and median estimated blood loss was 138 mL (range 50-1500 mL). No intraoperative complications were encountered, and all surgical margins were negative. Our postoperative complication rate was 14.3%. At the most recent follow-up, the mean estimated glomerular filtration rate (eGFR) was 76.2 mL/min/1.73 m(2) (SD=27.6), compared with 78.5 mL/min/1.73 m(2) (SD=28.9) preoperatively (P=0.11). Therefore, the mean eGFR decline of 2.3 mL/min/1.73 m(2) (SD=9.1) was not significant. CONCLUSIONS: Off-clamp RAPN is associated with minimal morbidity and minimal decline in renal function on short-term follow-up. Further studies and continued monitoring of renal function are needed to determine if off-clamp RAPN provides any advantage in renal function preservation relative to the traditional RAPN with vascular clamping.

Short echo time in vivo prostate ¹H-MRSI.

Visualization of short echo time (TE) metabolites in prostate magnetic resonance spectroscopic imaging is difficult due to lipid contamination and pulse timing constraints. In this work, we present a modified pulse sequence to permit short echo time (TE=40ms) acquisitions with reduced lipid contamination for the detection of short TE metabolites. The modified pulse sequence employs the conformal voxel MRS (CV-MRS) technique, which automatically optimizes the placement of spatial saturation planes to adapt the excitation volume to the shape of the prostate, thus reducing lipid contamination in prostate magnetic resonance spectroscopic imaging (MRSI). Metabolites were measured and assessed using a modified version of LCModel for analysis of in vivo prostate spectra. We demonstrate the feasibility of acquiring high quality spectra at short TEs, and show the measurement of short TE metabolites, myo-inositol, scyllo-inositol, taurine and glutamine/glutamate for both single and multi-voxel acquisitions. In single voxels experiments, the reduction in TE resulted in 57% improvement in the signal-to-noise ratio (SNR). Additional 3D MRSI experiments comparing short (TE=40 ms), and long (TE=130 ms) TE acquisitions revealed a 35% improvement in the number of adequately fitted metabolite peaks (775 voxels over all subjects). This resulted in a 42 ± 24% relative improvement in the number of voxels with detectable citrate that were well-fitted using LCmodel. In this study, we demonstrate that high quality prostate spectra can be obtained by reducing the TE to 40 ms to detect short T2 metabolites, while maintaining positive signal intensity of the spin-coupled citrate multiplet and managing lipid suppression.

Description of a multicenter safety checklist for intraoperative hemorrhage control while clamped during robotic partial nephrectomy.

BACKGROUND: The adoption of robotic assistance has contributed to the increased utilization of partial nephrectomy for the management of renal tumors. However, partial nephrectomy can be technically challenging because of intraoperative hemorrhage, which limits the ability to identify the tumor margin and may necessitate the conversion to open surgery or radical nephrectomy. To our knowledge, a comprehensive safety checklist does not exist to guide surgeons on the management of hemorrhage during robotic partial nephrectomy. We developed such an safety checklist based on the cumulative experiences of high volume robotic surgeons. METHODS: A treatment safety checklist for the management of hemorrhage during robotic partial nephrectomy was collaboratively developed based on prior experiences with intraoperative hemorrhage during robotic partial nephrectomy. RESULTS: Reducing the risk of hemorrhage during robotic partial nephrectomy begins with reviewing the preoperative imaging for renal vasculature and tumor anatomy, with a focus on accessory vessels and renal tumor proximity to the renal hilum. During hilar exposure, an attempt is made to identify additional accessory renal arteries. The decision is then made on whether to clamp the hilum (artery +/- vein). If bleeding is encountered during resection, management is based on whether the bleeding is suspected to be arterial or from venous backbleeding. Operative maneuvers that may increase the chance of success are highlighted in safety checklists for arterial and venous bleeding. CONCLUSIONS: Safely performing robotic partial nephrectomy is dependent on attention to prevention of hemorrhage and rapid response to the challenge of intraoperative bleeding. Preparation is essential for maximizing the chance of success during robotic partial nephrectomy.

Outcomes of pT0N0 at radical cystectomy: The Canadian Bladder Cancer Network experience.

INTRODUCTION: : Radical cystectomy is the standard treatment for muscle invasive bladder cancer. We assessed clinical outcomes in patients found to have no evidence of disease (i.e., pT0N0) following radical cystectomy. METHODS: : We collected and pooled a database of 2287 patients who underwent radical cystectomy between 1993 and 2008 in eight centres across Canada. Of this number, 135 patients were found to have pT0N0 bladder cancer at the time of cystectomy. Survival data and prognostic variables were analyzed using Kaplan-Meier method and Cox proportional hazard regression analysis. RESULTS: : Median patient age was 66 years with a mean follow-up of 42 months. Clinical stage distribution was Tis 8.9%, Ta 1.5%, T1 20.7%, T2 45.2%, T3 5.2%, and T4 5.2%. The five-year recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were 83%, 96%, and 88%, respectively. The 10-year RFS, DSS and OS were 66%, 92%, and 70%, respectively. On Cox proportional regression analysis, no variables were associated with disease recurrence and only patient age was associated with overall survival. INTERPRETATION: : Patients with pT0N0 pathology after cystectomy have excellent outcomes with high five- and 10-year RFS, DSS and OS. However, there is still a risk of tumour recurrence in this patient population and thus postoperative surveillance is still required.