The Journal of Urology

This Month in Adult Urology

William D. Steers — 2010-01-22

In this population based study Nam et al (page 963) from Ontario, Canada reviewed hospital admission rates for complications from prostate biopsy between 1996 and 2005. Of 75,190 men who underwent transrectal ultrasound guided biopsy 45% were diagnosed with prostate cancer. The hospital admission rate for complications within 30 days of the procedure for men without cancer was 1.9%. However, the 30-day hospital admission rate increased from 1% in 1996 to 4.1% in 2005. Thus the probability of being admitted to the hospital within 30 days of having the procedure increased 4-fold between 1996 and 2005 (odds ratio 3.7, 95% CI 2.0–7.0, p <0.0001). Fortunately the overall 30-day mortality rate was 0.09% and did not change during the study period. The authors postulate a variety of reasons for the increase in complication rate, including an increase in antibiotic resistant pathogens and the greater number of needle cores taken at biopsy. They also speculate that mortality has not increased because of improved treatments for sepsis.

This Month in Pediatric Urology

H. Gil Rushton — 2010-01-22

High grade vesicoureteral reflux (VUR) in infants is a distinct entity compared to high grade VUR detected later in childhood because of its greater rate of spontaneous resolution or improvement and relatively frequent congenital renal function abnormalities. Sjostrom et al (page 1177) from Goteborg, Sweden report an observational study of 80 male and 35 female infants diagnosed at a median age of 2.7 months after a urinary tract infection (UTI) in 72% and after an abnormal prenatal ultrasound in 26%. Reflux was grade III in 16% of cases, grade IV in 45% and grade V in 39%. Patients were evaluated with video cystometry, renal scintigraphy and chromium edetic acid clearance scan. Median followup was 36 months. VUR resolved spontaneously in 30 cases and was downgraded to I to II in 14 at a mean of 27 months. Breakthrough UTIs occurred in 54 infants with increasing frequency in higher grades of VUR. General and focal renal abnormalities developed in 72 and 26 patients, respectively. Bladder dysfunction in 48 infants included large capacity with incomplete emptying in 36, overactive bladder in 12 and uncertain dysfunction in 24. Multivariate analysis revealed that renal functional abnormalities, bladder dysfunction and breakthrough UTIs were strong independent negative predictive factors of spontaneous resolution or downgrading of VUR. A child with no bladder dysfunction, breakthrough UTI and renal abnormality had a 91% probability of VUR resolution before age 3 years compared to only a 7% probability if all 3 negative predictors were present.

This Month in Investigative Urology

Karl-Erik Andersson — 2010-01-22

Radical cystectomy is the treatment of choice for muscle invasive bladder cancer and minimally invasive options have been explored to minimize the associated morbidity. Durak et al (page 1227) from New York, New York compared the surgical efficacy and efficiency of a completely suture based procedure with a novel entero-urethral anastomosis device and the EndoGIA™ to create an ileal neobladder. They investigated 2 groups of 7 pigs survived for 8 weeks. In group 1 neobladder construction was performed using a U-shaped segment of ileum and sealed with an EndoGIA. The entero-urethral anastomosis was created with a novel sutureless anastomosis device. All other procedures were completed with standard intracorporeal suturing techniques. Group 2 animals underwent a completely intracorporeal suture technique. Total procedure, and enteroenteric, ileal neobladder, ureteroenteric and entero-urethral anastomosis times were recorded. Immediate postoperative, 2-week and sacrifice cystograms were used to evaluate the newly constructed system.

Paternalism, Probability and Prostate Specific Antigen

Craig Niederberger — 2010-01-19

A recent episode of the radio program “This American Life” narrates the unfortunate plight of a doctor who while a family practice resident counseled a 53-year-old patient whether to have a prostate specific antigen (PSA) assay performed. He explained to his patient the benefits and risks of PSA testing, and the man chose not to have the test. A year and a half passed, and the patient saw another physician who performed PSA screening routinely and without discussion. The worst possible prospect then transpired. The PSA was elevated and a biopsy revealed aggressive carcinoma. Inevitably, the man sued and the family practice residency program was found liable with a million dollar penalty. The radio journalist explained, “At the trial, the patient's attorney argued that (the doctor) shouldn't have given the man a choice to have the PSA test, no matter what the national guidelines said.”

Second Opinions in Pathology

Thomas Wheeler — 2010-01-19

In this issue of The Journal of Urology® 2 groups address the benefits of and need for review of pathological material from patients referred to a tertiary care medical center from outside health care institutions. Kuroiwa et al (page 952) compared their central review of radical prostatectomy data with those at the 50 referring institutions. Although exact concordance of Gleason score on the radical prostatectomy specimen was only slightly greater than the flip of a coin, results were better for pathological staging data, including the presence or absence of extracapsular extension, seminal vesicle invasion, lymph node involvement and positive surgical margins. Notably high volume institutions had a higher rate of concordance with central review than low volume institutions. Lee et al (page 921) studied transurethral resection specimens of bladder tumor referred to Cleveland Clinic and found a 27% to 33% rate of clinically significant discrepancies during the entire study period. These significant errors included lack of cancer in the biopsy material and errors in assessing muscularis propria invasion. These 2 studies make a significant case for central pathology review to compare treatment efficacy among large academic centers and in direct patient treatment decisions.

Prostate Biopsy: A Risk-Benefit Analysis

Stacy Loeb — 2010-01-19

The ideal diagnostic test would be noninvasive with no associated morbidity and 100% sensitivity for the disease of interest. Prostate cancer (CaP) diagnostic tests meet none of these criteria. Prostate biopsy is invasive, has potential associated risks and only samples a limited portion of the prostate, and current imaging modalities are not sufficiently reliable for CaP detection or localization. Nevertheless, transrectal prostate biopsy with about 12 cores remains the current standard for CaP detection at many institutions. According to Urologic Diseases in America Project data 282,640 prostate biopsies were performed in Medicare beneficiaries in 2001, corresponding to an annual rate of 1,601/100,000 men enrolled in Medicare. Although it is generally considered a benign procedure, serious complications may occur and may in fact be increasing in frequency.

A Watershed Year for Interstitial Cystitis

C.A. Tony Buffington — 2010-01-19

A watershed is occurring in our understanding of interstitial cystitis (IC). Recent publications in The Journal of Urology® and others have added explanations of genetic and epigenetic influences, documented the time course of the appearance of comorbid disorders and shown again how much systemic involvement occurs in most patients.

The Top-Down Approach: An Expanded Methodology

Daniel B. Herz — 2010-01-19

The most important reason to image a child after febrile urinary tract infection (UTI) is to identify correctable urinary tract abnormalities and prevent renal complications. Traditionally the focus has been on identifying and treating vesicoureteral reflux (VUR) since historically this is the most common abnormality after childhood febrile UTI. The study by Oh et al (page 1146) in this issue of The Journal of Urology® reinforces this association.

Robotic Prostatectomy

Jeffrey A. Cadeddu, Gagan Gautam, Arieh L. Shalhav — 2010-01-19

The often repeated mantra that robotic surgery must be better because it has 3-dimensional vision, tremor reduction and wristed instrumentation has reached the level of surgical dogma among patients and physicians at the expense of objective data. The result is a prevailing belief that robotic assisted laparoscopic prostatectomy (RALP) is the optimal approach to prostate removal. In fact, it seems urologists and hospitals are in a technology race without pausing to assess the clinical and cost impact to our patients and society. Fortunately, data are available that demonstrate what has always been known and taught in medical school and residency, which is what matters most in surgery is the experience, judgment and results of the surgeon and not the surgical technology used.

Oncological Outcomes After Radical Cystectomy for Bladder Cancer: Open Versus Minimally Invasive Approaches

Daher C. Chade, Vincent P. Laudone, Bernard H. Bochner, Raul O. Parra — 2010-01-18

Purpose: The number of centers performing robotic assisted radical cystectomy has recently increased, spurring greater concerns about oncological outcomes. In this review we summarize the most comprehensive articles published on the oncological outcomes of laparoscopic assisted, robotic assisted and open radical cystectomy.Materials and Methods: A MEDLINE®/PubMed® literature search was conducted in March 2009 to review English language articles published from 1998 onward. Of 217 selected articles on the 3 techniques 19 studies were selected for this review.Results: The laparoscopic series reported recurrence-free survival rates in the range of 83% to 85% at 1 to 2 years and 60% to 77% at 2 to 3 years, while the robotic assisted studies reported recurrence-free survival rates of 86% to 91% at 1 to 2 years. Large open surgery studies showed 62% to 68% recurrence-free survival at 5 years and 50% to 60% at 10 years, with overall survival of 59% to 66% at 5 years and 37% to 43% at 10 years. Overall survival in the laparoscopic cohorts was 90% to 100% at 1 to 2 years and 50% to 87% at 2 to 3 years. Publications reporting robotic cases demonstrated a 90% to 96% overall survival in 1 to 2 years of followup.Conclusions: Despite the surge of centers adopting minimally invasive approaches for radical cystectomy, the long-term effectiveness of these techniques has not yet been proven. This review of recent and landmark articles on open and minimally invasive procedures emphasizes the need for prospective controlled studies and long-term followup data to determine the proper use of laparoscopic and robotic assisted techniques in bladder cancer surgery.

Editorial Comment

Declan G. Murphy — 2010-01-18

The role of robotic assistance in the management of aggressive bladder cancer is far less certain than it is in localized prostate cancer. The clear message from this review is that there are inadequate oncological data at this stage to justify the routine use of minimally invasive approaches over open radical cystectomy. The reported numbers are few and the followup data are short-term.

Editorial Comment

Jose A. Karam, Christopher G. Wood — 2010-01-18

The authors provide a review comparing the oncological outcomes of open, laparoscopic and robotic assisted radical cystectomy with lymph node dissection and urinary diversion. What is readily apparent and intuitively obvious is that longer followup is desperately needed with the minimally invasive approaches before oncological equipoise can be claimed, but even with short followup there are several questions that challenge the future of minimally invasive surgery as a viable treatment option in muscle invasive bladder cancer.

Reply by Authors

2010-01-18

In our review it became clear that longer followup is needed to confirm whether the oncological outcomes of robotic or laparoscopic surgery for bladder cancer are comparable to those of open surgery. Nonetheless, lymph node yield, CSS and RFS rates were as good as those for open surgery at short-term followup. Moreover, in a recent randomized trial comparing robotic to open radical cystectomy a similar number of lymph nodes were removed but significant differences in operative time, estimated blood loss and early recovery measures were noted between the techniques. If these findings are corroborated by similar studies, they may represent a new era in minimally invasive surgery for invasive bladder cancer not unlike that for kidney and prostate cancer.

Post-Prostatectomy Urinary Incontinence: A Confluence of 3 Factors

Kevin R. Loughlin, Michaella M. Prasad — 2010-01-18

Purpose: Urinary incontinence has a significant impact on the quality of life of patients who undergo radical prostatectomy for prostate cancer. We reviewed available published data to analyze the etiology and prevention of this surgical complication.Materials and Methods: A MEDLINE® search of the literature on this topic was performed.Results: There was a wide disparity in the reported rates of urinary incontinence after radical prostatectomy due to various reasons including definitions, patient selection and intraoperative technical factors.Conclusions: Postoperative urinary incontinence has a major impact on patient satisfaction after radical prostatectomy. Attention to factors including patient selection, nuances of the surgical technique, and a more uniform, widespread agreement on the definition and instruments to measure postoperative incontinence is needed to enhance surgical outcomes. In addition, further research is needed to improve the diagnosis and treatment of urinary incontinence after prostate cancer surgery.

Renal Cell Carcinoma Fuhrman Grade and Histological Subtype Correlate With Complete Polymorphic Deletion of Glutathione S-Transferase M1 Gene

2010-01-18

Purpose: We outlined the putative significance of GST in renal cell carcinoma biology by investigating the influence of its deletion polymorphisms on renal cell carcinoma progression.Materials and Methods: Genomic DNA was purified from peripheral blood leukocytes. GSTM1 and GSTT1 genes were polymerase chain reaction amplified and gene fragments were separated by agarose gel electrophoresis. Intact GSTM1 and GSTT1 alleles were identified by the presence of 230 and 480 bp fragments, respectively. Genotypes were associated with clinicopathological variables and survival.Results: Of 147 patients with renal cell carcinoma 80 (54%) had the GSTM1 null and 27 (18%) had the GSTT1 null genotype. The GST genotype distribution did not differ significantly from that in 112 controls without renal cell carcinoma. However, the GSTM1 null genotype was associated with 60% lower odds of the papillary subtype (OR 0.40, 95% CI 0.18 to 0.92, p = 0.032), lower Fuhrman grade (chi-square 9.77, p = 0.008) and a lower risk of metastatic disease in patients with the clear cell subtype (chi-square 4.48, p = 0.034). Of patients with the clear cell subtype those with the GSTM1 null genotype had improved cancer specific survival (p = 0.0412). GSTT1 did not correlate with any pathological variable except age at renal cell carcinoma onset since patients with renal cell carcinoma and the GSTT1 null genotype were significantly younger than their counterparts (mean ± SD age 58.5 ± 14.2 vs 65.4 ± 12.8 years, p = 0.016).Conclusions: GSTM1 deletion polymorphism impacts renal cell carcinoma histological subtype, Fuhrman grade and metastatic behavior while GSTT1 deletion leads to renal cell carcinoma onset at a younger age. In patients with clear cell renal cell carcinoma the GSTM1 null genotype may be associated with better prognosis.

Stereotactic Percutaneous Cryoablation for Renal Tumors: Initial Clinical Experience

2010-01-19

Purpose: Percutaneous imaging guided tumor ablation has an increasingly prominent role as minimally invasive treatment for renal tumors. Precise cryoprobe placement is essential for successful ablation. CT-Nav® is a novel stereotactic surgical navigation system with the potential to achieve precise percutaneous cryoprobe placement while decreasing radiation exposure compared to conventional computerized tomography guided procedures.Materials and Methods: We performed a prospective pilot study to evaluate the technical feasibility, safety and accuracy of the system during renal cryoablation. Patients with enhancing renal masses amenable to renal cryoablation underwent preoperative computerized tomography with a preplaced tracking sensor taped to the body. Using a stereroscopic infrared camera the tracking sensor was located 3-dimensionally and a tracking handle was used to guide the cryoprobe percutaneously based on preoperative preloaded computerized tomography. Demographic and perioperative data were added prospectively to an institutional review board approved database. Immediately after cryoprobe placement computerized tomography was repeated to confirm placement accuracy.Results: A total of 13 tumors in 10 patients were successfully cryoablated with the novel navigational system. Mean tumor size was 2.2 cm. Preoperative biopsy revealed renal cell carcinoma in 9 cases. Mean operative time was 155 minutes. No intraoperative or postoperative complications were noted. Mean length of stay was 9.5 hours. Mean targeting registration error was 4.2 mm.Conclusions: Stereotactic percutaneous cryoablation for renal tumors offers the potential for safe, precise needle placement.

Laparoscopic Renal Cryoablation: 8-Year, Single Surgeon Outcomes

Monish Aron, Kazumi Kamoi, Erick Remer, Andre Berger, Mihir Desai, Inderbir Gill — 2010-01-19

Purpose: We present 5 to 11-year (median 8) oncological outcomes after laparoscopic renal cryoablation.Materials and Methods: Between September 1997 and October 2008 we performed renal cryoablation in 340 patients, of whom 80 treated laparoscopically by a single surgeon before October 2003 had a minimum 5-year followup. Followup involved magnetic resonance imaging on postoperative day 1, at 3, 6 and 12 months, and annually thereafter. Cryolesion biopsy was performed at 6 months. All data were prospectively accrued.Results: In the 80 patients with minimum 5-year followup mean age was 66 years, mean tumor size was 2.3 cm (range 0.9 to 5.0), median American Society of Anesthesiologists score was 3 and mean body mass index was 28 kg/m2. Five patients had local recurrence, 2 had locoregional recurrence with metastasis and 4 had distant metastasis without locoregional recurrence. Six patients died of cancer. In the 55 patients with biopsy proven renal cell cancer at a median followup of 93 months (range 60 to 132) 5-year overall, disease specific and disease-free survival rates were 84%, 92% and 81%, and 10-year rates were 51%, 83% and 78%, respectively. On multivariate analysis previous radical nephrectomy for RCC was the only significant predictor of disease-free and disease specific survival (p = 0.023 and 0.030, respectively).Conclusions: Laparoscopic renal cryoablation is effective oncological treatment for a renal mass in select patients. A disease specific survival rate of 92% at 5 years and 83% at 10 years is possible. Preceding radical nephrectomy for renal cell carcinoma was the only independent factor predicting disease-free and disease specific survival.

Performance of the Chronic Kidney Disease-Epidemiology Study Equations for Estimating Glomerular Filtration Rate Before and After Nephrectomy

2010-01-18

Purpose: Accurate renal function determination before and after nephrectomy is essential for proper prevention and management of chronic kidney disease due to nephron loss and ischemic injury. We compared the estimated glomerular filtration rate using several serum creatinine based formulas against the measured rate based on 125I-iothalamate clearance to determine which most accurately reflects the rate in this setting.Materials and Methods: Of 7,611 patients treated at our institution since 1975 the measured glomerular filtration rate was selectively determined before and after nephrectomy in 268 and 157, respectively. Performance of the Cockcroft-Gault, Modification of Diet in Renal Disease Study, re-expressed Modification of Diet in Renal Disease Study and Chronic Kidney Disease-Epidemiology Study equations, each of which estimates the glomerular filtration rate, were determined using serum creatinine, age, gender, weight and body surface area. The performance of serum creatinine, reciprocal serum creatinine and the 4 formulas was compared with the measured rate using Pearson's correlation, Lin's concordance coefficient and residual plots.Results: Median serum creatinine was 1.4 mg/dl and the median measured glomerular filtration rate was 50 ml per minute per 1.73 m2. The correlation between serum creatinine and the measured rate was poor (−0.66) compared with that of reciprocal serum creatinine (0.78) and the 4 equations (0.82 to 0.86). The Chronic Kidney Disease-Epidemiology Study equation performed with greatest precision and accuracy, and least bias of all equations. Stage 3 or greater chronic kidney disease (125I-iothalamate glomerular filtration rate 60 ml per minute per 1.73 m2 or less) was present in 44% of patients with normal serum creatinine (1.4 mg/dl or less) postoperatively. Such missed diagnoses of chronic kidney disease decreased 42% using the Chronic Kidney Disease-Epidemiology Study equation.Conclusions: Glomerular filtration rate estimation equations outperform serum creatinine and better identify patients with perinephrectomy compromised renal function. The newly developed, serum creatinine based, Chronic Kidney Disease-Epidemiology Study equation has sufficient accuracy to render direct glomerular filtration rate measurement unnecessary before and after nephrectomy for cause in most circumstances.

Editorial Comment

W. Scott McDougal — 2010-01-18

These authors compared equations involving age, weight, gender, race and SCr to calculate GFR vs actual GFR measurements with iothalamate in patients who undergo renal surgery. They conclude that the CKD-EPI GFR estimation is most accurate to calculate GFR in such cases. Although this is technically correct, clinically there is not much difference among the equations. The authors noted that 20%, 21%, 22% and 25% of cases were misclassified using CKD-EPI, reMDRD, MDRD and CG, respectively, which in my opinion is not much different. Looking at the correlation between iGFR and calculated GFR for the various equations, correlation coefficients are relatively poor. The correlation coefficient is helped by the good GFR fit below 20 ml per minute per 1.73 m2 at 1 end of the line, which is what one would expect for GFR measurements comparing any 2 techniques. For GFR in the 30 to 80 ml per minute per 1.73 m2 range the correlation is not particularly good. These values are most problematic from the clinical viewpoint. Had the correlation been expressed as a coefficient of determination, it would be even more apparent that from a clinical viewpoint there can be significant variances using these equations in an individual no matter which equation is used. For example, 1 patient had iothalamate clearance less than 20 ml per minute per 1.73 m2 and calculated GFR about 110 ml per minute per 1.73 m2, a major discrepancy. Although I agree with the final author conclusion that these equations are better than SCr alone and statistically CKD-EPI is the best, clinical judgment is still required to evaluate each case. When the formula GFR does not appear consistent with the clinical situation or GFR must be known with absolute assurance, a clearance measurement (the gold standard) is preferred.

Reply by Authors

2010-01-18

We agree that the CKD-EPIs provide only a modest improvement over the other available formulas for estimating GFR. Importantly for patients with normal renal function, the CKD-EPIs appear to be the best instrument at present. Better tools are needed to more accurately quantify renal function and identify patients at future risk for kidney disease, and much research in this area is ongoing. Nevertheless, the CKD-EPIs are a substantial improvement over serum creatinine alone. We also agree that calculation of GFR should be performed when the creatinine derived estimations do not match the clinical scenario.

Outcome of Stage T2 or Greater Renal Cell Cancer Treated With Partial Nephrectomy

2010-01-18

Purpose: Partial nephrectomy for stage T1 renal cell carcinoma is oncologically efficacious and safe, and may have survival advantages. We describe our experience with partial nephrectomy for T2 or greater renal cell cancer.Materials and Methods: Between 1970 and 2008 approximately 2,300 partial nephrectomies were done at our institution, including 69 for sporadic unilateral advanced stage tumors (pT2 in 32, pT3a in 28 and pT3b in 9). We reviewed outcomes in these patients compared to those in 207 treated with radical nephrectomy matched 3:1 for stage, tumor size, baseline renal function, age and gender.Results: The risk of cancer specific (HR 0.80, 95% CI 0.43–1.50, p = 0.489) and overall (HR 1.11, 95% CI 0.72–1.71, p = 0.642) death was similar for partial nephrectomy. At a median of 3.2 years of followup 15 patients (22%) with partial nephrectomy had metastatic disease vs 69 (33%) with radical nephrectomy (HR 0.74, 95% CI 0.42–1.29, p = 0.29). Four patients (6%) with partial nephrectomy had isolated local recurrence vs 7 (3%) with radical nephrectomy (HR 2.11, 95% CI 0.62–7.22, p = 0.234). In the partial nephrectomy group 12 (17%) and 2 cases (3%) were complicated by urine leak and retroperitoneal bleeding requiring intervention, respectively. The median serum creatinine increase was 9.5% (IQR 0–22) vs 33% (IQR 20–47) for partial vs radical nephrectomy (p <0.001).Conclusions: Partial nephrectomy for T2 or greater renal cell carcinoma preserves renal function and appears to achieve oncological outcomes similar to those of radical nephrectomy. The role of partial nephrectomy in patients with T2–3 tumors and a normal contralateral kidney deserves further consideration and study.

Percent Microscopic Tumor Necrosis and Survival After Curative Surgery for Renal Cell Carcinoma

2010-01-18

Purpose: Tumor necrosis is a potential marker of recurrence and survival after surgery for renal cell carcinoma. We determined whether a correlation exists between the amount (not just the presence/absence) of tumor necrosis, and metastasis-free, disease specific and overall survival after surgery for renal cell carcinoma.Materials and Methods: We identified 841 consecutive patients who underwent partial or radical nephrectomy from 1989 to 2004 for renal cell cancer. Specimens were re-reviewed by a single pathologist (MFS). The tumor necrosis percent was none in 586 cases, less than 50% in 198 and 50% or greater in 55. Grade, stage, subtype, size, gender and age were also analyzed. Variables at p <0.05 on univariate analysis were incorporated into a Cox proportional hazards multivariate model. Metastasis-free, disease specific and overall survival was described using the Kaplan-Meier method and compared with the log rank test.Results: Tumor necrosis was found in 253 specimens (30%). Univariate analysis revealed that the percent and presence of tumor necrosis correlated with metastasis-free, disease specific and overall survival. On multivariate analysis tumor necrosis presence/absence did not remain an independent predictor of disease specific (p = 0.7), metastasis-free (p = 0.7) or overall (p = 0.2) survival. Greater than 50% tumor necrosis was no longer a statistically significant predictor of metastasis-free survival (p = 0.45) but remained significant for disease specific (p = 0.02) and overall (p = 0.01) survival.Conclusions: The presence of 50% or greater tumor necrosis correlates with worse disease specific and overall survival but not metastasis-free survival in patients with renal cell carcinoma. Results support the inclusion of percent tumor necrosis over the presence/absence of tumor necrosis in the risk assessment of patients who undergo surgical treatment for renal cell carcinoma.

Editorial Comment

Allan J. Pantuck — 2010-01-18

Of the wide variety of clinical and pathological prognostic factors that have been proposed as important to assess the risk of death from RCC one of the most potentially attractive histological prognosticators may be TN because of its reported high prognostic value and the fact that it can be assessed at every routine pathological examination without additional cost. Several studies indicate that necrosis is strongly associated with other adverse features, such as high tumor grade and stage, and with worse recurrence and survival outcomes, although there is controversy over whether it serves as an independent prognostic factor as well as its individual contribution to predicting prognosis (reference 15 in article). Adding to this controversy, the predictive accuracy of necrosis may be greater when its extent is assessed quantitatively rather than by simply noting its presence or absence (reference 23 in article). Intuitively this concept is appealing since necrosis may be observed in 0% to 99% of tumor, and increasing percent involvement may be associated with worse pathological factors and prognosis.

Clinical Epidemiology of Nonurothelial Bladder Cancer: Analysis of The Netherlands Cancer Registry

2010-01-18

Purpose: Nonurothelial malignancies represent a small fraction of bladder malignancies and are less extensively studied, resulting in sparse empirical data on these tumors. We sought insight into tumor characteristics and survival.Materials and Methods: Data were obtained from the nationwide Netherlands Cancer Registry on patient and tumor characteristics, and followup in all patients with primary invasive (T1 or greater) bladder tumors in The Netherlands between 1995 and 2006. Data were analyzed using frequency tables. Relative survival analysis was done.Results: We identified 28,807 patients with invasive bladder cancer, of whom 7.7% presented with nonurothelial carcinoma. Mean patient age range at diagnosis of adenocarcinoma and soft tissue tumors was 66.4 years, and 78.3 years at diagnosis of nonspecified tumors. Most histological subtypes were more common in males except squamous cell carcinoma and lymphoma. Muscle invasion was seen in 52.2% of urothelial carcinoma cases vs 87.5%, 71.9% and 89.0% of squamous cell carcinoma, adenocarcinoma and neuroendocrine tumor cases, respectively. For urothelial carcinoma, squamous cell carcinoma and adenocarcinoma women presented at more advanced stage. In the neuroendocrine group this stage difference was the opposite. Survival analysis showed a 5-year relative survival rate of 32.2%, 22.9%, 31.8% and 21.1% for T2 or greater urothelial carcinoma, squamous cell carcinoma, adenocarcinoma and neuroendocrine tumors, respectively.Conclusions: Patients with nonurothelial carcinoma present at more advanced stage and overall have worse survival. Relative survival of muscle invasive adenocarcinoma equals survival of muscle invasive urothelial carcinoma. For stage II and III disease these cases do even better. Muscle invasive squamous cell carcinoma and neuroendocrine tumors show worse survival regardless of stage.

Editorial Comment

Alon Z. Weizer — 2010-01-18

While the incidence of the reported bladder cancer histological subtypes is not new (reference 4 in article), these authors provide RS outcomes in a modern cohort of nonurothelial bladder cancer cases. However, this study falls short on the response to therapy due to the lack of granularity in the data set. Differences in survival by histological subtype may provide further insight into the more common phenomenon of mixed histological findings in bladder cancer cases.

The Role of Pathology Review of Transurethral Bladder Tumor Resection Specimens in the Modern Era

Michael C. Lee, Howard S. Levin, J. Stephen Jones — 2010-01-19

Purpose: The value of pathological reinterpretation of tissue slides has long been questioned. At the Cleveland Clinic subspecialization in genitourinary pathology began in 2003 and has been maintained. We evaluate the role of second review on transurethral bladder tumor resection pathology slides before and after subspecialization and potential impact on treatment.Materials and Methods: Transurethral bladder tumor resection specimens from 78 and 116 patients with bladder cancer in 2002 and 2004, respectively, were reviewed. Initial surgical pathology reports from institutions outside the Cleveland Clinic were compared with review report by a pathologist with genitourinary pathology specialization (HSL). Those cases with differences in diagnosis or staging were then evaluated by a urologist (JSJ) considering current standards of care.Results: The reinterpretation differed substantially from the initial report in 26 of 78 cases (33.3%) in 2002 and in 31 of 116 (26.7%) in 2004 (p = 0.3), resulting in a possible impact on management in 28.2% (22 of 78) in 2002 and 23.3% (27 of 116) in 2004 (p = 0.54). In each year 4 cases diagnosed with bladder cancer elsewhere were determined to have no malignancy. The majority of discrepancies related to the presence of carcinoma in situ in 2002 and to the presence or absence of muscularis propria and/or muscle involvement by carcinoma in 2004.Conclusions: Second review of transurethral bladder tumor resection specimens shows differences of interpretation in 26.7% to 33.3% of cases, which is sufficient to alter management. There was no significant difference in the rate of discrepancies before and after genitourinary pathology subspecialization. Referral centers must assume responsibility for establishing the diagnosis before consultation and/or therapy.

Editorial Comment

William M. Murphy — 2010-01-19

The issues of second opinion and subspecialist vs generalist interpretation are not new but have often been presented in language suggesting that patients will always benefit from the results. The facts that the second reviewer already has the opinion of a pathologist, the subspecialist is not always right and any discrepancy among reviewers may be insufficient to alter patient treatment are not usually emphasized. In this study Lee et al present a balanced account of their experience with institutional review of cases to be managed at their center. They note that the purpose of the review is not so much to detect error as to facilitate patient care by allowing those who will be treating the patient to do so based on the interpretations of their own pathologists.

Editorial Comment

Arthur I. Sagalowsky — 2010-01-19

In-house pathology review of all specimens before treatment of referred patients certainly is a wise best clinical practice for all entities. It is all the more important for malignancies. In the current manuscript the authors show that this practice remains especially important for patients with bladder cancer. There are many reasons why pathology interpretation of bladder cancer results in greater variation between the primary and secondary or tertiary center review than for any other GU malignancy. Limited tissue samples provided by small cup biopsies and electrocautery artifact are 2 common limitations. Misinterpretation of tumor extension into muscularis mucosa as muscularis propria involvement may lead to tumor over staging. Furthermore, it may be difficult for pathologists to distinguish true carcinoma in situ from varying degrees of tissue reaction, inflammation, atypia and dysplasia in any patient with bladder tumor, and particularly in those who have received intravesical therapy.

Risk Factor Analysis in a Contemporary Cystectomy Cohort Using Standardized Reporting Methodology and Adverse Event Criteria

2010-01-18

Purpose: Adverse event reporting is poorly classified and nonstandardized in the urological literature. We report adverse event data and associated risk factors using standardized reporting methods and Common Terminology Criteria for Adverse Events, version 3.0 to minimize interpretation bias and allow reliable comparisons with other populations.Materials and Methods: We retrospectively reviewed consecutive radical cystectomies done for urothelial bladder carcinoma at our institution between January 2004 and September 2006. Adverse events within 90 days postoperatively were recorded. We explored the association of important risk factors with the overall complication rate and specific complications.Results: A total of 283 patients were included in the study. Complete 90-day followup data were available on 90% of patients. Median age was 70 years (IQR 62–75). Median body mass index was 26.8 kg/m2 (IQR 24.4–31.0). At least 1 adverse event was observed in 152 patients (54.0%) and a grade 3–4 adverse event was observed in 40.3%. The most common grade 4 adverse events were myocardial infarction in 3.5% of cases, septic shock in 2.8% and pulmonary embolism in 1.8%. No patient died during followup. An association between body mass index, and any and major adverse events was found after adjusting for confounding variables.Conclusions: More than 50% of patients experience an adverse event after radical cystectomy and 40% are major. Body mass index is independently associated with adverse events in these patients. These findings are important for individualized risk assessment, patient counseling and uniform assessment of quality care.

Editorial Comment

S. Machele Donat — 2010-01-18

Measuring morbidity is a complex process that includes more than commonly reported measures such as blood loss, operative time, death rate, complication rate and length of stay (reference 8 in article). These authors incorporated a standardized grading methodology (Common Terminology Criteria for Adverse Events, version 3.0) to retrospectively assess risk factors predicting complications after RC. BMI was associated with overall complications and a higher risk of major complications. Although they did not categorize complications, the most common complications were in the categories of gastrointestinal (ileus or small bowel obstruction), thromboembolic (pulmonary embolus or deep venous thrombosis), genitourinary related (acute renal failure, leak, stricture, stoma or fistula) and infectious or wound related complications. This finding is similar to that in prior large series (reference 2 in article), suggesting that they may be areas in which we can agree on common procedure specific definitions and mandatory inclusion in future reports. The information is valuable for comparison to other large series and counseling patients preoperatively. It may be useful for designing future preoperative interventions to decrease complication rates.

Adrenal and Renal Physiology, and Medical Renal Disease

W. Scott McDougal — 2010-01-19

A. Amin Nasr, J. Fatani, I. Kashkari, M. Al Shammary and T. Amin Department of Anesthesiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Urological Oncology: Renal, Ureteral and Retroperitoneal Tumors

Fray F. Marshall — 2010-01-22

V. S. Subramanian, A. J. Stephenson, D. A. Goldfarb, A. F. Fergany, A. C. Novick and V. Krishnamurthi Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio

Bladder, Penis and Urethral Cancer, and Basic Principles of Oncology

James E. Montie — 2010-01-22

K. Zieger, C. Wiuf, K. M. Jensen, T. F. Orntoft and L. Dyrskjot Department of Molecular Medicine, Aarhus University Hospital Skejby, Aarhus, Denmark

Prostate Specific Antigen Decrease and Prostate Cancer Diagnosis: Antibiotic Versus Placebo Prospective Randomized Clinical Trial

R.M. Stopiglia, U. Ferreira, M.M. Silva, W.E. Matheus, F. Denardi, L.O. Reis — 2010-01-19

Purpose: Prostate inflammation can lead to an increase in serum prostate specific antigen concentration and confound the use of prostate specific antigen kinetics. Repeat prostate specific antigen measurements after a period of observation or a course of empirical antibiotics are controversial in terms of the optimal approach to reduce the confounding impact on prostate cancer screening. This issue was analyzed in patients with a diagnosis of type IV or asymptomatic prostatitis (National Institutes of Health classification) and high prostate specific antigen.Materials and Methods: We studied 200 men between 50 and 75 years old with a high prostate specific antigen (between 2.5 and 10 ng/dl). Of these patients 98 (49%) had a diagnosis of type IV prostatitis. In a prospective, double-blind trial they were randomized to receive placebo (49 patients, group 1) or 500 mg ciprofloxacin (49 patients, group 2) twice a day for 4 weeks. Prostate specific antigen was determined after treatment and all patients underwent transrectal ultrasound guided biopsy of the prostate.Results: In group 1, 29 (59.18%) patients presented with a decrease in prostate specific antigen and 9 (31%) had cancer on biopsy, while in group 2 there were 26 (53.06%) patients with a decrease in prostate specific antigen and 7 (26.9%) with prostate cancer. There was no statistical difference in either group in relation to prostate specific antigen decrease after treatment or the presence of tumor.Conclusions: A considerable number of patients (49%) were diagnosed with type IV prostatitis and high prostate specific antigen in agreement with the current literature. Of the patients 26.9% to 31% presented with a decrease in prostate specific antigen after the use of antibiotic or placebo and harbor cancer as demonstrated on prostate biopsy. Prostate specific antigen decreases do not indicate the absence of prostate cancer.

Editorial Comment

Sümer Baltacı — 2010-01-19

Although controversial, antibiotics are often prescribed for men with newly increased PSA on the presumption that the patient has subclinical infectious prostatitis. In this randomized, placebo controlled, prospective study the authors evaluated the effect of antibiotics in 98 patients with proven type IV prostatitis and increased PSA. They found that antimicrobial therapy was no more effective than placebo in reducing PSA, and that the proportion of patients with cancer was similar in both groups. There are clearly a number of limitations to this study and the authors address most of them. Considering the power calculation above 80%, the sample size should be at least 130 patients (65 in each group). Therefore, the results should be read cautiously. As recent studies have revealed percent free PSA to be more helpful in suggesting prostate cancer after antibiotic treatment, future studies should include such PSA parameters (reference 25 in article).

Editorial Comment

John N. Krieger — 2010-01-19

Symptomatic prostatitis and urogenital infections acutely increase PSA, and may increase the long-term risk of prostate cancer and lower urinary tract symptoms. Antibiotic treatment of symptomatic infections decreases PSA. However, most patients with prostatitis symptoms do not have active infections.

Reply by Authors

2010-01-19

A vital issue in human research that has been receiving increased attention is the cultural scenario. Health research as a global issue concerns all and clearly manifests global inequality. There are some contrasting behavioral differences among people around the world that must be considered. While much of a cultural matter, Brazil could be one of the wealth of countries underexplored by the global pharmaceutical market, where patients agree to participate in trials for diverse reasons.

Initial Prostate Specific Antigen 1.5 ng/ml or Greater in Men 50 Years Old or Younger Predicts Higher Prostate Cancer Risk

2010-01-18

Purpose: Studies show that initial prostate specific antigen higher than the median in young men predicts a subsequent higher risk of prostate cancer. To our knowledge this relationship has not been studied in patients stratified by race.Materials and Methods: A cohort of 3,530 black and 6,118 white men 50 years or younger with prostate specific antigen 4 ng/ml or less at the first prostate specific antigen screening was retrieved from the prostate center database at our institution. Patients were divided into groups based on initial prostate specific antigen 0.1 to 0.6, 0.7 to 1.4, 1.5 to 2.4 and 2.5 to 4.0 ng/ml. Univariate and age adjusted multivariate logistic regression was done to estimate the cancer RR in these prostate specific antigen groups. We calculated the prostate cancer rate at subsequent followups.Results: Median prostate specific antigen in black and white men was 0.7 ng/ml at age 50 years or less. The prostate cancer rate was not significantly different in the groups with prostate specific antigen less than 0.6 and 0.7 to 1.4 ng/ml in black or white men. Black and white men with initial prostate specific antigen in the 1.5 to 2.4 ng/ml range had a 9.3 and 6.7-fold increase in the age adjusted prostate cancer RR, respectively. At up to 9 years of followup initial prostate specific antigen 1.5 ng/ml or greater was associated with gradually increased detection at followup in black and white men.Conclusions: An initial prostate specific antigen cutoff of 1.5 ng/ml may be better than median prostate specific antigen 0.7 ng/ml to determine the risk of prostate cancer in black and white men 50 years old or younger.

Editorial Comment

M.J. Roobol — 2010-01-18

These authors conclude that a PSA cutoff of 1.5 ng/ml or greater can be used for risk stratification in men 50 years or younger, a group that may benefit from more frequent PSA testing. 1) This study suffers from verification bias. The biopsy rate in PSA subgroups was not known and is likely to differ. 2) Of the men 4% were diagnosed with prostate cancer (96% were not) at a mean of 1.4 years with a total followup of up to 9 years. In a clinical setting these values are 2.3% and 17 years, respectively. We now know that PSA based screening can decrease disease specific mortality but this coincides with considerable over diagnosis even when starting at age 55 years and applying a 4-year screening interval.3 The question is now when and on what basis we label men as at increased risk, keeping in mind the possible consequences of such an approach.

Reply by Authors

2010-01-18

The risk/benefit of PSA screening is an issue and there is a need to develop a method to identify high risk men for periodic PSA screening. Currently the AUA and NCCN guidelines recommend that men should have a baseline PSA test at age 40 years, and that high risk men should start annual screening thereafter. The AUA guidelines consider that men in their forties with a PSA higher than the median (0.6 to 0.7 ng/ml) are at high risk. The NCCN guidelines recommend that men with PSA 1.0 ng/ml or greater should undergo PSA screening more frequently. There is still no definitive evidence supporting these recommendations. Based on our large cohort of men and PSA testing during the last 2 decades, we found that a PSA of 1.5 ng/ml or greater is a better cutoff for identifying high risk men younger than 50 years. This PSA cutoff is higher than that recommended by the AUA and NCCN, and would potentially avoid unnecessary PSA tests and improve cost-effectiveness.

Discrepancy Between Local and Central Pathological Review of Radical Prostatectomy Specimens

2010-01-18

Purpose: Pathological assessment of radical prostatectomy specimens has not been uniform among pathologists. We investigated interobserver variability of radical prostatectomy specimen reviews between local and central pathologists.Materials and Methods: We collated data from 50 institutions on 2,015 patients with cT1c-3 prostate cancer who underwent radical prostatectomy between 1997 and 2005. All radical prostatectomy specimens were retrospectively reevaluated by a central uropathologist. Gleason score, extracapsular extension, seminal vesicle invasion, lymph node involvement, positive surgical margin, year of diagnosis and pathology volume were recorded.Results: The exact concordance rate of Gleason score between local and central review was 54.8%, and under grading and over grading rates at local review were 25.9% and 19.2%, respectively. Spearman's rank correlation coefficient was 0.61 for local and central radical prostatectomy Gleason score. The exact concordance rate of Gleason score 8–10 at local review was significantly lower than that of Gleason score 5–6, 3 + 4 and 4 + 3 at local review (p = 0.011, <0.001 and 0.006). Exact concordance rates between local and central review for extracapsular extension, seminal vesicle invasion, lymph node involvement and positive surgical margin were 82.5%, 97.6%, 99.6% and 87.5%, respectively. High volume institutions and recently diagnosed cohorts showed significantly higher exact concordance rates between local and central review for radical prostatectomy Gleason score and other pathological features (all p <0.001).Conclusions: High volume institutions and recent series show higher concordance between local and central review of radical prostatectomy pathology. However, concordance for high grade Gleason score, extracapsular extension and surgical margin status remains poor. Radical prostatectomy specimens should be reevaluated in a multi-institutional study for more accurate pathological data.

Stage pT0 After Radical Prostatectomy With Previous Positive Biopsy Sets: A Multicenter Study

2010-01-18

Purpose: We analyzed preoperative data, pathological results and followup of pT0 tumors after radical prostatectomy for prostate cancer diagnosed on previous positive biopsy.Materials and Methods: At 6 centers a total of 30 of 7,693 radical prostatectomy specimens were classified as pT0 despite prior biopsy proven prostate cancer. No patients were diagnosed after transurethral prostate resection or received neoadjuvant hormonal treatment. All biopsy cores and radical prostatectomy specimens were reanalyzed by a second pathologist. Followup comprised clinical examination and postoperative prostate specific antigen assay at 1 and 3 months, and every 6 months thereafter.Results: Median patient age was 63 years (range 46 to 73). Median preoperative prostate specific antigen was 7.4 ng/ml (range 1.3 to 23). Of the cases 24 were T1c and 6 were T2a. The median number of biopsy cores was 10 (range 6 to 21) with 1 positive (range 1 to 4). On biopsies median tumor length was 1 mm (range 0.3 to 18) and there was tumor in 11.1% (range 3.4% to 64%). In 25 cases (83.3%) there was only 1 positive biopsy. Gleason score was 3 + 3 in 23 cases and less than 6 in 5 with grade 4 in 2. Only 9 cases filled all nonsignificant tumor criteria. Median specimen weight was 61 gm (range 40 to 160). At a median 82-month followup (range 14 to 226) there was no biochemical progression.Conclusions: After biopsy proven cancer pT0 prostate cancer is an unpredictable pathological finding. Despite its excellent prognosis it has medicolegal repercussions that justify DNA based tissue analysis. There is no evidence that finding focal cancer after extensive prostate resection changes patient prognosis and postoperative treatment.

Increasing Hospital Admission Rates for Urological Complications After Transrectal Ultrasound Guided Prostate Biopsy

2010-01-19

Purpose: Transrectal ultrasound guided prostate biopsy is widely used to confirm the diagnosis of prostate cancer. The technique has been associated with significant morbidity in a small proportion of patients.Materials and Methods: We conducted a population based study of 75,190 men who underwent a transrectal ultrasound guided biopsy in Ontario, Canada, between 1996 and 2005. We used hospital and cancer registry administrative databases to estimate the rates of hospital admission and mortality due to urological complications associated with the procedure.Results: Of the 75,190 men who underwent transrectal ultrasound biopsy 33,508 (44.6%) were diagnosed with prostate cancer and 41,682 (55.4%) did not have prostate cancer. The hospital admission rate for urological complications within 30 days of the procedure for men without cancer was 1.9% (781/41,482). The 30-day hospital admission rate increased from 1.0% in 1996 to 4.1% in 2005 (p for trend <0.0001). The majority of hospital admissions (72%) were for infection related reasons. The probability of being admitted to hospital within 30 days of having the procedure increased 4-fold between 1996 and 2005 (OR 3.7, 95% CI 2.0–7.0, p <0.0001). The overall 30-day mortality rate was 0.09% but did not change during the study period.Conclusions: The hospital admission rates for complications following transrectal ultrasound guided prostate biopsy have increased dramatically during the last 10 years primarily due to an increasing rate of infection related complications.

Editorial Comment

Janet Colli — 2010-01-19

This population based study conducted on more than 75,000 men in Canada analyzed hospitalization due to prostate biopsy complications between 1996 and 2005. The Canadian health care system is nationally run and has the advantage of compiling data on all patients into 1 file.

Editorial Comment

Wade J. Sexton — 2010-01-19

Nam et al present an insightful and careful assessment of complications related to transrectal ultrasound guided prostate biopsies. During a study period of 1 decade postoperative (30-day) hospital admission rates and admission diagnoses were determined from ICD-9 and ICD-10 codes as applied to a data set of more than 75,000 men from a single, government operated health insurance system in Ontario, Canada. The authors found a statistically significant yet concerning trend toward increasing infection related admissions within 30 days of the biopsy, increasing from 1.0% in 1996 to 4.1% in 2005. All cause mortality rates within 30 days from the date of biopsy and admission rates for urinary obstruction or bleeding complications remained steady, or did not change significantly during the study period.

Comparative Study of Inguinal Hernia Repair After Radical Prostatectomy, Prostate Biopsy, Transurethral Resection of the Prostate or Pelvic Lymph Node Dissection

2010-01-18

Purpose: Inguinal hernia is considered one of the major morbidities after radical prostatectomy. We compared inguinal hernia repair rates in patients treated with radical prostatectomy for localized prostate cancer relative to those of 2 nonsurgically treated groups of patients, namely individuals who underwent prostate biopsy or transurethral resection of the prostate, and a surgically treated group of patients who underwent pelvic lymph node dissection, within a large North American database.Materials and Methods: Using the Quebec Health Plan database we identified 5,478 men treated with radical prostatectomy vs 6,933, 7,697 and 532 who underwent prostate biopsy, transurethral resection of the prostate or pelvic lymph node dissection, respectively, between 1990 and 2000. Kaplan-Meier plots graphically explored inguinal hernia repair rates. Univariable and multivariable Cox regression analyses examined variables associated with inguinal hernia repair after either group. Covariates consisted of age, year of treatment and the Charlson comorbidity index.Results: The 1, 2, 5 and 10-year inguinal hernia repair rates after radical prostatectomy were 4.4%, 6.7%, 11.7% and 17.1%, respectively. For the same points after prostate biopsy the rates were 1.7%, 2.9%, 6.1% and 9.8% vs 1.7%, 2.6%, 5.5% and 9.2%, respectively, after transurethral resection of the prostate, and 0.8%, 2.4%, 4.9% and 9.3% after pelvic lymph node dissection (pairwise log rank tests p <0.001). On multivariable Cox regression analyses the rate of inguinal hernia repair was 1.9, 2.1 and 1.7-fold higher for patients who underwent radical prostatectomy vs prostate biopsy, transurethral resection of the prostate and pelvic lymph node dissection, respectively (all p <0.001).Conclusions: Radical prostatectomy predisposes to higher inguinal hernia repair rates than in the 3 examined control groups. A higher rate of inguinal hernia repair after radical prostatectomy warrants consideration in the discussion of radical prostatectomy perioperative complications.

Editorial Comment

Matthew E. Nielsen — 2010-01-18

The authors present a large population based study describing increased rates of clinically significant inguinal hernia, defined by claims for hernia repair, after open radical prostatectomy compared to controls treated with TURP, prostate biopsy or pelvic lymphadenectomy. The finding of an approximately 2-fold risk of inguinal hernia in patients after RP in this context is consistent with previous findings from institutional series and adds clear value to the literature on this subject (references 3, 6 and 7 in article). The design and statistical rigor of this study renders this a significant contribution to our understanding of this phenomenon, given the large population based sample with surgical and nonsurgical controls, and unequivocal identification of cases with claims data from a single payer (surmounting classification and ascertainment biases in previous studies). As the authors acknowledge further study is needed to determine whether this phenomenon is generalizable to patients undergoing laparoscopic prostatectomy, rarely performed in Quebec in this period.

Editorial Comment

Johan Stranne — 2010-01-18

The article addresses the issue of inguinal hernia as a complication to open radical retropubic prostatectomy. Although IH is a complication of open RP, the literature on the subject to date is limited and retrospective in nature. The authors used a large population based cohort of patients treated with RP and compared the incidence of postoperative IH to that of patients who underwent a prostate biopsy, TURP for benign prostatic hyperplasia or pelvic LND. The approach is sound and provides a large, robust material for comparison. However, there is no indication whether LND was performed open or laparoscopically. The incision per se has been suggested to be causative of IH but the incidence after laparoscopic procedures, which should be lower if this is true, is virtually unknown (reference 12 in article). This information on patients treated with LND would add to the understanding of this complication.

Variations Among Experienced Surgeons in Cancer Control After Open Radical Prostatectomy

2010-01-18

Purpose: Complications and functional outcomes after prostate surgery vary among surgeons to a greater extent than may be accounted for by chance. This excessive variation is known as heterogeneity. We explored whether there is also heterogeneity among high volume surgeons with respect to cancer control after surgery.Materials and Methods: The study cohort consisted of 7,725 patients with clinically localized prostate cancer treated with open radical prostatectomy at 4 major American academic medical centers from 1987 to 2003 by 1 of 54 surgeons. We defined biochemical recurrence as serum prostate specific antigen 0.4 ng/ml or greater followed by a higher level. Multivariate random effects models were used to evaluate prostate cancer recurrence heterogeneity among surgeons after adjusting for case mix (prostate specific antigen, pathological stage and grade), surgery year and surgeon experience.Results: We found statistically significant heterogeneity in the prostate cancer recurrence rate independent of surgeon experience (p = 0.002). Seven experienced surgeons had an adjusted 5-year prostate cancer recurrence rate of less than 10% while another 5 had a rate that exceeded 25%. Significant heterogeneity remained on sensitivity analysis adjusting for possible differences in followup, patient selection and stage migration.Conclusions: Patient risk of recurrence may differ depending on which of 2 surgeons is seen even if the surgeons have similar experience levels. Surgical randomized trials are imperative to determine and characterize the roots of these variations.

Editorial Comment

Michael P. Porter — 2010-01-18

These authors report heterogeneity in BCR among 54 surgeons in a large multi-institutional cohort of prostatectomy cases. The observed heterogeneity was not explained by preoperative PSA, stage, grade, surgeon experience or margin status. They conclude that unmeasured surgeon characteristics, namely unmeasured aspects of surgical technique, were the likely cause of the unexplained heterogeneity. However, any characteristic of an individual surgeon that is plausibly related to BCR and not accounted for in the statistical model, eg approaches to patient selection, pathologists assigning grade/stage/margin or grading/staging changes during the course of the surgeon career, is an unmeasured characteristic with the potential to contribute to unexplained heterogeneity in outcome. Thus, the conclusion that unmeasured differences in surgical technique explain the observed heterogeneity in BCR is only 1 of many plausible and perhaps more likely explanations.

Reply by Authors

2010-01-18

We agree that readers should consider a variety of explanations for any result reported in the literature. After adjusting for case mix, recurrence outcomes of individual surgeons varied more than would be expected by chance. The 2 possible types of explanation for this heterogeneity are patient differences and surgeon differences. However, the former assumes equivalency in clinical judgment intent, including goals and approach among surgeons for any given harbored cancer characteristics and, furthermore, equivalency in surgery execution. Reports for other outcomes suggest the latter held true. Our data demonstrate and validate the fact that variations in cancer control exist, and the surgeon is a factor. If the selection question still remains, we can focus on the group with the most established equivalency, that is prostate cancer confined to the gland. In these cases there was significant undesirable heterogeneity in cancer control outcomes among surgeons performing RP.

Definition of Biochemical Recurrence After Radical Prostatectomy Does Not Substantially Impact Prognostic Factor Estimates

Angel M. Cronin, Guilherme Godoy, Andrew J. Vickers — 2010-01-18

Purpose: Biochemical recurrence serves as a surrogate end point after radical prostatectomy. Many definitions of biochemical recurrence are currently used in the research literature. We examined various definitions in a large clinical cohort to explore whether estimation differs by definition.Materials and Methods: The cohort included 5,473 patients who underwent radical prostatectomy from 1985 to 2007 at our cancer center. Separate analysis was done with 12 definitions of biochemical recurrence used in published studies. Cox regression was done to estimate HRs for established predictors. Predictive accuracy was determined using the concordance index.Results: Depending on the definition the recurrence-free probability was 86% to 91% at 3 years and 81% to 87% at 5 years. HRs tended to be smaller for the most inclusive definitions but were fairly similar across all definitions. The univariate HR was 2.1 to 2.4 for log prostate specific antigen, 2.4 to 2.6 for clinical stage T2b vs T2a or less and 9.8 to 15 for biopsy Gleason grade 8 or greater vs 6 or less. Multivariate HRs were more homogeneous across the definitions. The concordance index was 0.79 to 0.83 and 0.83 to 0.87 for the preoperative and postoperative nomograms, respectively.Conclusions: Estimates of risk ratios and predictive accuracy are generally robust to the biochemical recurrence definition. For clinical research, groups using different definitions will come to similar conclusions on prognostic factors. The definition should be factored into studies comparing overall recurrence probabilities.

Editorial Comment

Paul L. Nguyen — 2010-01-18

These authors analyzed the large data set at their institution and reassure us that calculated HRs probably do not substantially depend on which of the 12 published definitions of post-prostatectomy PSA failure is applied, assuming that the data set used is reasonably large. For investigators using smaller data sets the practical advice is to consider a less restrictive definition of failure to increase the number of events and increase the power to detect differences.

Robotic Assisted Laparoscopic Prostatectomy Versus Radical Retropubic Prostatectomy for Clinically Localized Prostate Cancer: Comparison of Short-Term Biochemical Recurrence-Free Survival

2010-01-18

Purpose: We compared biochemical recurrence-free survival of patients who underwent radical retropubic prostatectomy vs robot assisted laparoscopic prostatectomy in concurrent series at a single institution.Materials and Methods: A total of 2,132 patients were treated between June 2003 and January 2008. We excluded from study patients with prior treatment (115), missing data (83) and lymph node involvement (30). The remaining cohort (1,904) was compared based on clinical, surgical and pathological factors. Kaplan-Meier analysis was performed comparing biochemical recurrence after robot assisted laparoscopic prostatectomy and radical retropubic prostatectomy. A Cox proportional hazards model was generated to determine whether surgical approach is an independent predictor of biochemical recurrence.Results: There were 491 radical retropubic prostatectomies (25.9%) and 1,413 robot assisted laparoscopic prostatectomies (74.1%) performed, and median followup was 10 months (IQR 2 to 23). On univariate analysis the robot assisted laparoscopic prostatectomy group was slightly lower risk with lower median prostate specific antigen (5.4 vs 5.8, p <0.01), a lower proportion of pathological grade 7–10 (48.5% vs 54.7%, p <0.01) and lower pathological stage (80.5% pT2 vs 69.6% pT2, p <0.01). The 3-year biochemical recurrence-free survival rate was similar between the robot assisted laparoscopic prostatectomy and radical retropubic prostatectomy groups on the whole as well as when stratified by pathological stage, grade and margin status. On multivariate analysis extracapsular extension (p <0.01), pathological grade 7 or greater (p <0.01) and positive surgical margin (p <0.01) were independent predictors of biochemical recurrence while surgical approach was not.Conclusions: The likelihood of biochemical recurrence was similar between groups when stratified by known risk factors of recurrence. Surgical approach was not a significant predictor of biochemical recurrence in the multivariate model. Our analysis is suggestive of comparable effectiveness for robot assisted laparoscopic prostatectomy, although longer term studies are needed.

Tumor Percent Involvement Predicts Prostate Specific Antigen Recurrence After Radical Prostatectomy Only in Men With Smaller Prostate

2010-01-19

Purpose: We determined the predictive power of tumor percent involvement on prostate specific antigen recurrence in patients when stratified by prostate weight.Materials and Methods: Data on 3,057 patients who underwent radical prostatectomy between 1988 and 2008 was retrieved from our institutional prostate cancer database. Patients with data on tumor percent involvement, prostate volume and prostate specific antigen recurrence were included in analysis. Patients were divided into 3 groups based on prostate volume less than 35, 35 to 45 and greater than 45 cc. The variables tumor percent involvement, age at surgery, race, prostate specific antigen, pathological Gleason score, positive surgical margins, extraprostatic extension, seminal vesicle invasion and surgery year were analyzed using the chi-square and Mann-Whitney tests to determine individual effects on prostate specific antigen recurrence. Tumor percent involvement and prostate specific antigen were evaluated as continuous variables. Significant variables on univariate analysis were included in multivariate Cox regression analysis to compare their effects on prostate specific antigen recurrence.Results: Tumor percent involvement significantly predicted prostate specific antigen recurrence in men with a small prostate (p = 0.006) but not in those with a prostate of greater than 35 cc. Black race was a marginally significant predictor of prostate specific antigen recurrence in men with a medium prostate (p = 0.055). Age at surgery was a predictor of prostate specific antigen recurrence in men with a larger prostate (p = 0.003). Prostate specific antigen, positive surgical margins, seminal vesicle invasion and pathological Gleason score 7 or greater predicted prostate specific antigen recurrence in men with all prostate sizes.Conclusions: In men with a prostate of less than 35 cc tumor percent involvement is an important variable when assessing the risk of prostate specific antigen recurrence. Tumor percent involvement and prostate volume should be considered when counseling patients and determining who may benefit from heightened surveillance after radical prostatectomy.

Editorial Comment

Jonathan I. Epstein — 2010-01-19

Although the prognostic impact of PCa volume is not disputed, only a few studies show that it provides independent prognostic value beyond routinely measured parameters. These few studies have limitations such as 1) predating the PSA era with much more advanced cancer than what is currently identified in the Western world, 2) short followup and 3) a smaller number of cases followed by larger studies from the same institution that fail to show tumor volume as an independent prognosticator. Most series from institutions where there is extensive RP experience show that tumor volume is not an independent predictor of progression after RP. These authors further report that tumor volume measurement in PCa cases is marginal at best. Overall tumor percent only predicted postoperative progression in small prostates and even then it was only weakly predictive compared to other routinely reported variables.

Editorial Comment

Robin T. Vollmer — 2010-01-19

For almost every cancer in every organ tumor size is an important prognostic variable. However, for PCa the way to measure the tumor is not straightforward and a number of methods have evolved, of which the 2 most important are 1) Vc and 2) TPI. TPI is more often prognostic than Vc (reference 4 in article) but they are directly related (TPI = Vc × 100/PV). Thus, it is no surprise to learn, as these authors have, that TPI is significantly higher in smaller prostates. Table 1 results show that all of the usual prognostic variables, such as serum PSA, tumor stage, grade and surgical margin status, are significantly associated with PV. Thus, we may conclude that all of these variables, including TPI, are confounded, as previously documented (reference 4 in article). Deciding which of them is most closely associated with disease recurrence and survival requires careful multivariate statistical analysis of data on many uncensored patients. Thus, I look forward to the followup studies of these authors as their data mature.

The Impact of Positive Surgical Margins on Mortality Following Radical Prostatectomy During the Prostate Specific Antigen Era

2010-01-21

Purpose: The presence of a positive surgical margin at radical prostatectomy has been linked to an increased risk of postoperative biochemical recurrence. We evaluated the impact of margin status on subsequent clinical progression and mortality.Materials and Methods: We reviewed the records of 11,729 patients who underwent prostatectomy between 1990 and 2006. Survival was estimated for patients with vs without a positive margin and compared using the log rank test. Cox proportional hazards regression models were used to analyze the impact of margin status on survival.Results: Overall 3,651 (31.1%) men were identified with a positive margin. Median postoperative followup was 8.2 years (IQR 4.4, 12.1). The 10-year biochemical recurrence-free rate for patients with and without a positive margin was 56% and 77%, respectively (p <0.001), while 10-year local recurrence-free survival was 89% vs 95% (p <0.001). Margin status also stratified systemic progression-free survival (93% vs 97%, p <0.001), cancer specific survival (96% vs 99%, p <0.001) and overall survival (83% vs 88%, p <0.001). On multivariate analysis the presence of a positive margin was associated with increased risk of biochemical recurrence (HR 1.63, 95% CI 1.47–1.80, p <0.0001), local recurrence (HR 1.78, 95% CI 1.45–2.19, p <0.0001) and receipt of salvage therapy (HR 1.79, 95% CI 1.58–2.02, p <0.0001) but was not a significant predictor of systemic progression (p = 0.95), cancer specific death (p = 0.15) or overall mortality (p = 0.16).Conclusions: The presence of a positive margin increased the risk of biochemical recurrence, local recurrence and the need for salvage treatment but was not independently associated with systemic progression, cancer specific death or overall mortality. These results should be considered when evaluating patients for adjuvant therapy.

Editorial Comment

Jesco Pfitzenmaier — 2010-01-21

The authors present a retrospective study on the impact of surgical margins on mortality following radical prostatectomy, demonstrating the significance of surgical margin status in the PSA era. The advantages of this report include the relatively long followup of more than 8 years, and the presentation of cancer specific and overall survival. Most often only BCR is given which does not always translate into clinical progression. They found no independent association with systemic progression, CSS and overall survival on multivariate analysis. Therefore, a followup of more than 10 to 15 years would probably be more adequate to see differences in CSS and overall survival. While discussing CSS and overall survival an important point was the inclusion of adjuvant and salvage therapy strategies in their statistical analysis, which might have influenced the outcomes shown by Bolla et al (reference 18 in article) and Stephenson et al. Because of the findings of this retrospective study the decision to provide adjuvant therapy should be made with caution until the results of randomized trials comparing adjuvant and early salvage treatment after radical prostatectomy, which can be successful, are available (reference 26 in article).

Editorial Comment

Mark J. Mann — 2010-01-21

There are conflicting data regarding the survival benefit of screening for prostate cancer, let alone the identification of positive surgical margins after prostatectomy for prostate cancer. In this article the authors have presented data to suggest that while there may be a greater risk of biochemical recurrence in patients with positive surgical margins after prostatectomy, this does not indicate a risk of decreased overall or cancer specific survival. Although the length of followup after biochemical recurrence is not extensive in the most recent cohort, they call into question the meaning of margins in terms of patient prognosis and treatment. If surgical margins do not make an impact on survival, is treatment, which is not without morbidity, indicated? If the presence of residual cancer in patients does not affect survival, is it possible that cancer would not have affected survival before the bulk was removed? Should margin status be included in prognostic nomograms?

Urological Oncology: Prostate Cancer

Patrick C. Walsh — 2010-01-21

M. J. Zelefsky, W. Shi, Y. Yamada, M. A. Kollmeier, B. Cox, J. Park and V. E. Seshan Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York

Geriatrics

Tomas L. Griebling — 2010-01-22

S. V. Hudson, P. Ohman-Strickland, J. M. Ferrante, G. Lu-Yao, A. J. Orzano and B. F. Crabtree Cancer Institute of New Jersey, UMDNJ/Robert Wood Johnson Medical School, New Brunswick, New Jersey

Prevalence of Urolithiasis in Asymptomatic Adults: Objective Determination Using Low Dose Noncontrast Computerized Tomography

2010-01-21

Purpose: The true prevalence of urolithiasis in asymptomatic adults is unknown. Unenhanced computerized tomography represents the gold standard for detection. We evaluated the prevalence and symptomatic incidence of urolithiasis in a large cohort of asymptomatic adults using noncontrast computerized tomography.Materials and Methods: Low dose noncontrast computerized tomography was performed in 5,047 consecutive asymptomatic adults (mean age 56.9 years, 2,747 women and 2,300 men) between 2004 and 2008. Presence, size and location of urinary calculi were recorded. Screening prevalence as well as the incidence of symptomatic stone disease during a 10-year interval (1997 to 2007) was compared against previously established clinical risk factors.Results: The screening prevalence of asymptomatic urolithiasis was 7.8% (395 of 5,047 adults) with an average of 2.1 stones per case (range 1 to 29) and a mean stone size of 3.0 mm (range 1 to 20). During a 10-year period 20.5% (81 of 395) of patients with stones (1.6% of entire screening cohort) had at least 1 symptomatic episode. Males were more likely to have urolithiasis than females (9.7% vs 6.3%, p <0.001). Diabetes (9.0% vs 7.7%, p = 0.45), obesity (7.6% vs 7.9%, p = 0.72) and age 60 years or older (8.0% vs 7.7%, p = 0.73) did not affect prevalence, but diabetes and obesity did correlate with symptom development (p <0.001 and p <0.05, respectively).Conclusions: This objective population based assessment in a large asymptomatic cohort showed an 8% prevalence of urolithiasis. Most cases were unsuspected and remained asymptomatic. Although there was no correlation between asymptomatic urolithiasis and diabetes, obesity or older age, diabetes and obesity were associated with a higher incidence of symptoms over time.

Stone Forming Risk Factors in Patients With Type Ia Glycogen Storage Disease

2010-01-21

Purpose: Patients with type Ia glycogen storage disease have an increased recurrent nephrolithiasis rate. We identified stone forming risk factors in patients with type Ia glycogen storage disease vs those in stone formers without the disease.Materials and Methods: Patients with type Ia glycogen storage disease were prospectively enrolled from our metabolic clinic. Patient 24-hour urine parameters were compared to those in age and gender matched stone forming controls.Results: We collected 24-hour urine samples from 13 patients with type Ia glycogen storage disease. Average ± SD age was 27.0 ± 13.0 years and 6 patients (46%) were male. Compared to age and gender matched hypocitraturic, stone forming controls patients had profound hypocitraturia (urinary citrate 70 vs 344 mg daily, p = 0.009). When comparing creatinine adjusted urinary values, patients had profound hypocitraturia (0.119 vs 0.291 mg/mg creatinine, p = 0.005) and higher oxalate (0.026 vs 0.021 mg/mg creatinine, p = 0.038) vs other stone formers.Conclusions: Patients with type Ia glycogen storage disease have profound hypocitraturia, as evidenced by 24-hour urine collections, even compared to other stone formers. This may be related to a recurrent nephrolithiasis rate greater than in the overall population. These findings may be used to support different treatment modalities, timing and/or doses to prevent urinary lithiasis in patients with type Ia glycogen storage disease.

Hypocitraturia and Hyperoxaluria After Roux-en-Y Gastric Bypass Surgery

2010-01-21

Purpose: Roux-en-Y gastric bypass surgery is associated with an increased risk of nephrolithiasis but obesity itself is a known risk factor for kidney stones. To assess the mechanism(s) predisposing to nephrolithiasis after Roux-en-Y gastric bypass we compared urinary tract stone risk profiles in patients who underwent the procedure and normal obese individuals.Materials and Methods: In this cross-sectional study urine and serum biochemistry was evaluated in 19 nonstone forming patients after Roux-en-Y gastric bypass and in 19 gender, age and body mass index matched obese controls without a history of nephrolithiasis.Results: Compared with obese controls surgical patients had significantly higher mean ± SD urine oxalate (45 ± 21 vs 30 ± 11 mg daily, p = 0.01) and lower urine citrate (358 ± 357 vs 767 ± 307 mg daily, p <0.01). The prevalence of hyperoxaluria (47% vs 10.5%, p = 0.02) and hypocitraturia (63% vs 5%, p <0.01) was significantly higher in surgical patients, who also had significantly lower urine calcium than obese controls (115 ± 93 vs 196 ± 123 mg daily, p = 0.03). The calcium oxalate urine relative supersaturation ratio was not significantly different between the 2 groups.Conclusions: Almost half of patients with Roux-en-Y gastric bypass without a history of nephrolithiasis showed hyperoxaluria or hypocitraturia. This prevalence was significantly higher than in body mass index matched controls. These risk factors were negated by lower urine calcium excretion in patients with Roux-en-Y gastric bypass.

Randomized Trial of Stone Fragment Active Retrieval Versus Spontaneous Passage During Holmium Laser Lithotripsy for Ureteral Stones

Oscar Schatloff, Uri Lindner, Jacob Ramon, Harry Z. Winkler — 2010-01-20

Purpose: We assessed whether allowing spontaneous passage of small fragments is different from complete intraoperative extraction during semirigid ureteroscopy for ureteral stones.Materials and Methods: A total of 60 patients undergoing ureteroscopy and holmium laser lithotripsy were randomized to intraoperative fragment retrieval (group 1) or exhaustive lithotripsy and spontaneous fragment expulsion (group 2). The primary outcome was differences in unplanned medical and emergency room visits. Other outcomes were the rehospitalization, pain analgesia, time to complete recovery and 30-day stone-free rates.Results: Patients in group 1 were younger (47 vs 54 years, p = 0.05). Other characteristics, including stone burden and site, presentation mode, and ureteral dilation and stent placement rates, did not differ between the groups. Group 2 patients had a higher rate of unplanned visits (3% vs 30%, OR 12.4, 95% CI 1.8–80.3, p = 0.01), a trend toward higher rates of rehospitalization (0% vs 10%, p = 0.24) and the need for ancillary treatment (0% vs 7%, p = 0.49), and a lower stone-free rate (100% vs 87%, p = 0.1). Complications developed in 1 group 1 patient and in 2 in group 2, including 2 with postoperative fever and 1 with mucosal undermining of the guidewire.Conclusions: Not actively retrieving fragments during semirigid ureteroscopy and holmium laser lithotripsy is associated with a higher risk of unplanned medical visits than complete intraoperative extraction. It also shows a tendency toward higher rates of rehospitalization, residual stones and the need for ancillary procedures.

Editorial Comment

Riccardo Autorino, Mark Noble, Robert J. Stein — 2010-01-20

With the development of smaller caliber ureteroscopes and the introduction of improved instrumentation, including the holmium:YAG laser, ureteroscopy has evolved into a safer, more effective treatment modality for ureteral stones. Nevertheless, many unanswered questions remain on the proper approach to optimize stone-free status and minimize periprocedural patient discomfort in this revolutionary ureteroscopic era.

Editorial Comment

Riccardo Bartoletti, Franco Melone — 2010-01-20

HL lithotripsy is now considered the gold standard treatment for ureteral stones but success seems to be related to stone anatomical site, size and hardness, which are intrinsic stone factors. These factors may interfere with operative time and the risk of ureteral wall injury with the subsequent need for ureteral stenting. El-Nahas et al reported their experience with 841 patients with a mean age of 48.5 years in whom ureteral calculi were treated with ureteroscopy (reference 7 in article). The complication rate was 6.7% and the stone-free rate after 1 ureteroscopic intervention was 87%. The current authors confirm that proximal ureteral stones, ureteroscopy done by surgeons other than experienced endourologists, and stone impaction and width are significant factors for unfavorable results. They also report that not actively retrieving fragments after ureteroscopy and HL lithotripsy is associated with a higher risk of unplanned medical visit than complete intraoperative extraction. The take-home message is to plan an appropriate, structured surgical procedure in each case to facilitate prompt recovery after treatment. Nevertheless, unsuccessful cases seem to be related to inadequate evaluation of intrinsic factors, such as site, dimension and hardness of the single stone treated with ureteroscopy and HL lithotripsy. These parameters should be accurately evaluated during patient selection before any necessary surgical treatment.

A Novel Drug Eluting Ureteral Stent: A Prospective, Randomized, Multicenter Clinical Trial to Evaluate the Safety and Effectiveness of a Ketorolac Loaded Ureteral Stent

2010-01-21

Purpose: We evaluated the short-term safety and efficacy of a ketorolac loaded ureteral stent compared to a standard stent (control).Materials and Methods: In this prospective, multicenter, double-blind study patients were randomized 1:1 to ketorolac loaded or control stents after ureteroscopy. The primary end point was an intervention for pain defined as unscheduled physician contact, change in pain medication or early stent removal. Secondary end points included medication use and pain visual analog score. A total of 20 patients underwent serum safety testing for ketorolac levels.Results: None of the safety cohort had detectable serum ketorolac levels. Among the 276 patients there was no difference in primary (9.0% ketorolac loaded vs 7.0% control, p = 0.66) or secondary (22.6% ketorolac loaded vs 25.2% control, p = 0.67) intervention rates. Mean pain pill count at day 3 was lower in the ketorolac loaded stent group than in the control group (p <0.05). A higher number (p = 0.057) of patients with ketorolac loaded (32%) stents used no or limited pain medications compared to controls (22%). A higher number of male patients with ketorolac loaded stents used no pain medication on days 3 and 4 compared to female patients with ketorolac loaded stents, and male and female control patients (p <0.05).Conclusions: The overall safety of the ketorolac loaded stent was confirmed. Although there was no significant difference in primary or secondary intervention rates, a trend toward a treatment benefit was noted for patients receiving drug loaded stents. Specifically young male patients appeared to require less pain medication when the ketorolac loaded stent was used. Future studies with higher drug concentrations or alternative drug eluting stents may prove beneficial.

Editorial Comment

Steve Y. Chung — 2010-01-21

The ureteral stent is a welcome friend for the urologist but a source of pain for patients. This study investigates the potential benefits of ketorolac loaded ureteral stents and the authors have addressed a weak link in endoscopic stone surgery.

Urolithiasis/Endourology

Dean Assimos — 2010-01-21

T. Hermanns, P. Sauermann, K. Rufibach, T. Frauenfelder, T. Sulser and R. T. Strebel Department of Urology, University of Zurich, University Hospital, Zurich, Switzerland

Imaging

Cary Siegel — 2010-01-22

Z. Bozgeyik, E. Kocakoc and F. Sonmezgoz Department of Radiology, Faculty of Medicine, Firat University, Elazig, Turkey

Laparoscopy/New Technology

Jeffrey A. Cadeddu — 2010-01-22

G. Dominguez, L. Durand, J. De Rosa, E. Danguise, C. Arozamena and P. A. Ferraina Department of Surgery, Gastrointestinal Surgery Division, Hospital de Clinicas, Buenos Aires University, Beccar, Buenos Aires, Argentina

Posterior Urethral Stricture After Pelvic Fracture Urethral Distraction Defects in Developing and Developed Countries, and Choice of Surgical Technique

2010-01-21

Purpose: We compared posterior urethral strictures after pelvic fracture urethral distraction defects in India and Italy.Materials and Methods: We retrospectively analyzed the records of patients in India and Italy who underwent repair for posterior urethral stricture after pelvic fracture urethral distraction defect. We investigated etiology, emergency treatment type, the specialist involved in emergency treatment, the type of stricture resulting from trauma and primary repair, posterior urethroplasty techniques and results.Results: Of 255 patients with a median age of 33 years 117 (45.8%) and 138 (54.2%) were evaluated in India and Italy, respectively. In India the most common causes of pelvic fracture urethral distraction defects were pedestrian (35%), motorcycle (26.5%) and bicycle (12.8%) accidents. The most common emergency treatment was suprapubic cystostomy (79.5% of cases). Of the patients 70.1% were treated in emergency fashion by a surgeon and 85.4% had complex posterior urethral strictures. The most common technique was anastomosis with inferior and total pubectomy in 56.4% and 15.3% of cases, respectively. In Italy the etiology was mainly automobile accidents (39.2%). The most common emergency treatment was endoscopic realignment (49.2% of cases). Of the patients 92.7% were treated in emergency fashion by a urologist and 68.1% had simple urethral strictures. Perineal anastomosis and laser urethrotomy were the most used techniques (38.4% and 21.1% of cases, respectively). In India 92 cases (78.6%) were successful and 25 (21.4%) failed while in Italy 120 (86.9%) were successful and 18 (13.1%) failed. Median followup was 74 months (range 12 to 239).Conclusions: Differences in emergency treatment for pelvic fracture urethral distraction defects influence the choice of delayed posterior repair and results.

Transureteroureterostomy Revisited: Long-Term Surgical Outcomes

Markian R. Iwaszko, Amy E. Krambeck, George K. Chow, Matthew T. Gettman — 2010-01-21

Purpose: Transureteroureterostomy is a treatment alternative for ureteral obstruction when more conventionally reconstructive techniques are not feasible. We report on long-term outcomes of patients treated with transureteroureterostomy.Materials and Methods: A retrospective chart review of all patients treated with transureteroureterostomy from January of 1985 to February of 2007 was performed.Results: We identified 63 patients who underwent transureteroureterostomy at our institution. Average treatment age was 31.5 years (range 1 to 83). Transureteroureterostomy was performed for 21 (33%) malignant and 42 (67%) benign indications. Reconstructions were 30 right-to-left (47.6%) and 33 left-to-right (52.4%) with 21 concurrent urinary diversions. There were 16 patients (25.4%) who received radiation before transureteroureterostomy. Postoperative complications occurred in 15 (23.8%) patients and were more common in those undergoing diversion for malignancy. Mean followup was 5.8 years (range 0.1 to 22.2) and 5 patients were lost to followup. Of the 56 patients with followup imaging the transureteroureterostomy was patent in 54 (96.4%) and obstructed in 2 (3.6%). Mean preoperative and recent calculated glomerular filtration rate for this cohort were 62.8 (range 13 to 154) and 71.8 (range 22 to 141) ml per minute, respectively (p = 0.04). Stone disease developed in 8 patients, and was treated with percutaneous nephrolithotomy (2), spontaneous passage (2), ureteroscopy (1) and surveillance (3). Subsequent urological intervention was required for obstruction or revision in 6 (10.3%) patients.Conclusions: We demonstrated the long-term safety and effectiveness of transureteroureterostomy with sustained improvement of renal function compared to preoperative status. Recurrent stricture, distal obstruction and stone disease occur in a small percentage of patients, and can be treated in most with minimal intervention.

Iatrogenic Trapped Penis in Adults: New, Simple 2-Stage Repair

2010-01-21

Purpose: We present a new, 2-stage functional and cosmetic reconstruction of concealed penis in adults with short-term subjective outcomes.Materials and Methods: Patients with excess penile skin removal, shaft tissue scarring and penile retraction with poor functional and cosmetic results underwent 2-stage repair. At stage 1 after a coronal incision and penile degloving an intrascrotal tunnel was formed and the penis was transposed through the scrotum. Three or 4 zero or 2-zero nonresorbable sutures were applied ventral to the penis, crossing through the entire scrotum to ensure complete scrotal skin adhesion to the penis (penile scrotalization). At stage 2 after 6 to 12 weeks the scrotal skin at the penile base was incised bilaterally to separate the skin around the penis from the remaining scrotal skin (penile descrotalization). Evaluation was scheduled 3, 6 and 9 months postoperatively, and annually thereafter.Results: Ten men with concealed penis underwent this 2-stage penile repair, including 8 who were circumcised and 2 who underwent conservative surgery for penile cancer. Mean ± SD operative time was 75 ± 15 minutes for stage 1 and 45 ± 10 minutes for stage 2. No major intraoperative or perioperative complications occurred except superficial scrotal hematoma in 1 patient. At a median followup of 20 months (range 6 to 72) all men were in satisfactory clinical condition and the median patient satisfaction visual analog score was 97 (range 85 to 100). All patients recovered normal spontaneous erection with regular sexual intercourse 4 to 8 weeks after operation 2.Conclusions: This simple, new 2-stage technique seems feasible and effective, and it is well accepted by patients. Further studies are mandatory to confirm preliminary results.

Editorial Comment

Chris Gonzalez — 2010-01-21

These authors describe a 2-stage technique to correct the difficult problem of concealed penis in the adult. Recent literature describes various 1-stage techniques to successfully repair the adult concealed penis, involving genital skin grafts and flaps, scrotoplasty, escutcheonectomy (suprapubic fat removal), penile adhesiolysis and penoscrotal junction anchoring (references 5 and 18 in article). The ease of this 2-stage approach is appealing because of the limited dissection necessary, and the lack of reliance on potentially tenuous skin grafts and penile shaft anchoring techniques. The main issues with this approach, which require more experience to adequately answer, include the level of patient satisfaction with the amount of hair on the penile shaft, sexual function after repair, patient selection parameters for this procedure, and the timing and use of perioperative liposuction. As the authors state, caution must be exercised with penile suspensory ligament sectioning due to the risk of penile instability with erection.

Editorial Comment

Richard A. Santucci — 2010-01-21

These authors describe a technique to treat the child or adolescent with buried penis. It borrows from the extensive knowledge of plastic surgery of the authors and capitalizes on their comfort with using a wide variety of local tissue sources to achieve surgical goals. It offers an advantage over split-thickness skin grafts by providing supple, sensate skin coverage that includes deep tissue layers for a more natural look and feel. However, I am sure that this technique results in a hairy penis, and surgeon and patient must be aware of this fact beforehand. It will work well when buried penis is a cutaneous disease (a penis tethered beneath a skin layer only) but may not work well for adult buried penis with associated morbid obesity.

Penile Dermal Flap in Patients With Peyronie's Disease: Long-Term Results

2010-01-20

Purpose: In 1995 a penile dermal flap was described as an ideal operation for penile curvature due to Peyronie's disease. We report our experience with penile dermal flaps in patients with penile curvature due to Peyronie's disease.Materials and Methods: Between January 2001 and May 2004, 26 potent white men with Peyronie's disease underwent corporoplasty with a penile dermal flap. They were evaluated at 3, 6 and 12 months, and yearly thereafter by determination of penile length changes and residual curvature, and the International Index of Erectile Function-5.Results: At the maximum followup (mean 95 months, range 81 to 108) 22 of 26 patients (85%) were available for examination, of whom 14 (63.6%) had no residual curvature, and 2 (9.1%) and 7 (31.8%) had improved and worse erectile function, respectively. Nine patients (40.9%) had inclusion cysts at the surgical site, including 5 who underwent surgical cyst removal with no cyst recurrence. Only 9 of 22 patients (40.9%) were satisfied with the cosmetic and functional outcome.Conclusions: Despite the attractiveness of the operation to our knowledge no other experience with this technique has been reported. Our results differ from those reported, although we tried to exactly follow the original technique of dermabrading the flap with sandpaper. Based on these results we abandoned the penile dermal flap in patients with Peyronie's disease.

Do Biomechanical Properties of Anterior Vaginal Wall Prolapse Tissue Predict Outcome of Surgical Repair?

Alienor S. Gilchrist, Amit Gupta, Robert C. Eberhart, Philippe E. Zimmern — 2010-01-21

Purpose: We determined the relevance of the biomechanical properties of freshly harvested vaginal tissue during large cystocele repair on clinical outcome at a minimum 1-year followup.Materials and Methods: With institutional review board approval we prospectively studied the biomechanical properties of full thickness vaginal wall tissue from postmenopausal women with symptomatic Baden-Walker prolapse undergoing anterior vaginal wall suspension with cystocele repair from 2002 to 2005. A standardized biomechanical protocol was applied with stress-strain curves for Young's modulus obtained by blinded investigators. Failed repair was defined as recurrence on examination or reoperation for recurrent anterior prolapse.Results: A total of 32 patients (median age 72 years) had a median followup of 34 months (range 12 to 62). Median Young's modulus was statistically different in tissue samples transported in immersed vs moistened media (median 3.8 vs 7.6, p = 0.008). Associations between Young's modulus and clinical variables were described. On followup 7 patients experienced failure of the repair. After controlling for tissue transport protocol no association was seen between Young's modulus and failures (HR 1.1, p = 0.34).Conclusions: This study found no association between Young's modulus and clinical results at long-term followup. This finding suggests that retropubic scarring and pelvic floor muscle properties may be more important for a successful reparative outcome than the intrinsic properties of the vaginal wall.

Trauma, and Genital and Urethral Reconstruction

Allen F. Morey — 2010-01-21

N. Lumen and W. Oosterlinck Department of Urology, Ghent University Hospital, Ghent, Belgium

Diagnostic Urology, Urinary Diversion and Perioperative Care

Richard K. Babayan — 2010-01-22

D. R. Flinn, K. M. Diehl, L. S. Seyfried and P. N. Malani Department of Internal Medicine, Division of Geriatric Medicine, University of Michigan Health System, Ann Arbor, Michigan

Overactive Bladder Medication Adherence When Medication is Free to Patients

2010-01-21

Purpose: We examined overactive bladder medication compliance in a health care system in which patients do not pay for medication.Materials and Methods: Pharmacy dispensing records were reviewed for antimuscarinic agents from January 2003 to December 2006 for the United States Military Health System National Capital Region. Medication nonpersistence, switching and adherence were examined. Kaplan-Meier survival analysis was done to compare medication persistence duration.Results: Overactive bladder medications were dispensed to 7,879 adults. Tolterodine extended release (4,716 patients or 60%) and oxybutynin immediate release (2,003 or 25.5%) were most commonly prescribed. The medication nonpersistence rate, defined as the proportion of patients who never refilled a prescription for antimuscarinics during the study period, was 35.1% (2,760 of 7,858). Of 5,098 patients who refilled a prescription 1,305 changed the medication or dose at least once for a medication switch rate of 25.6%. The overall median medication possession ratio, defined as the total days of medication dispensed except for the last refill divided by the number of days between the first dispense date and the last refill date, was 0.82 in all cases. Men had a significantly higher median medication possession ratio than women (0.86 vs 0.81, p <0.001). Of patients who obtained at least 1 refill women remained on medication longer than men (median 606 vs 547 days, p = 0.01). Patients on tolterodine extended release had a higher medication nonpersistence rate than those on oxybutynin immediate release (0.89 vs 0.68, p <0.01). There was no difference between extended release medications.Conclusions: In a health care system in which patients do not pay for medications 35% of patients did not refill a prescription for overactive bladder medication, similar to previous reports. However, other measures of medication compliance were higher than those published previously in systems with copays.

Does Adenosine Triphosphate Released Into Voided Urodynamic Fluid Contribute to Urgency Signaling in Women With Bladder Dysfunction?

2010-01-21

Purpose: Adenosine triphosphate released from urothelium during stretch stimulates afferent nerves and conveys information on bladder fullness. We measured adenosine triphosphate released during cystometric bladder filling in women with idiopathic detrusor overactivity and stress incontinence (controls), and assessed whether the level of released adenosine triphosphate is related to cystometric parameters.Materials and Methods: Routine cystometry was done in 51 controls and 48 women with detrusor overactivity who were 28 to 87 years old. Voided urodynamic fluid was collected and stored at −30C. Adenosine triphosphate was measured by a bioluminescence assay.Results: Adenosine triphosphate levels were similar in voided urodynamic fluid of controls and patients with detrusor overactivity (p = 0.79). A significant inverse correlation was seen between adenosine triphosphate and maximal cystometric capacity in controls (p = 0.013), and between voided volume and adenosine triphosphate in controls (p = 0.015) and detrusor overactivity cases (p = 0.019). A significant correlation between first desire to void and adenosine triphosphate was also noted in detrusor overactivity cases (p = 0.033) but not in controls (p = 0.58). No correlation was seen between adenosine triphosphate and detrusor pressure during filling or voiding.Conclusions: Adenosine triphosphate measurement in voided urodynamic fluid is a novel approach to understanding signals that may contribute to the urgency sensation (a sudden compelling desire to pass urine). The inverse correlation between adenosine triphosphate in voided urodynamic fluid and first desire to void suggests that adenosine triphosphate has a role in modulating the early filling sensation in patients with detrusor overactivity.

Is Type 2 Diabetes Mellitus a Predictive Factor for Incontinence After Laparoscopic Radical Prostatectomy? A Matched Pair and Multivariate Analysis

2010-01-21

Purpose: We evaluated the effect of diabetes mellitus on incontinence after laparoscopic radical prostatectomy.Materials and Methods: From a series of 2,071 patients 135 with type 2 diabetes mellitus undergoing laparoscopic radical prostatectomy without radiotherapy and with a minimum followup of 24 months were identified. These patients were randomly matched with 135 nondiabetic controls for age, body mass index, preoperative prostate specific antigen, clinical stage, neoadjuvant hormonal therapy, prostate volume, previous surgery, surgeon skills, surgical approach, presence of bladder neck sparing, lymphadenectomy, technique of urethrovesical anastomosis and attempted nerve sparing surgery.Results: Using multivariate analysis age, diabetes mellitus and duration of diabetes mellitus were independent factors for post-prostatectomy incontinence in the whole group. Early continence (0 to 3 months) was observed in 43.7% of patients with diabetes and in 57.8% of nondiabetic controls which was statistically significant (p = 0.02). The rates of continence in patients with diabetes mellitus for 5 or more years at 3, 12 and 24-month evaluations were less than those in patients with diabetes mellitus for less than 5 years, and the difference was statistically significant (36% vs 50%, p = 0.001; 63.9% vs 82.4%, p = 0.02; 91.8% vs 98.6%, p = 0.03, respectively).Conclusions: Patients with type 2 diabetes mellitus need longer to recover continence than nondiabetics after laparoscopic radical prostatectomy. However, type II diabetes mellitus did not affect overall return to continence. Patients with diabetes mellitus for 5 or more years have an almost 5 times increased risk of post-prostatectomy incontinence compared to those with diabetes mellitus for less than 5 years. Diabetic patients should be counseled for the potential negative impact of diabetes mellitus on the recovery of continence after laparoscopic radical prostatectomy.

Urodynamic Effects of Once Daily Tadalafil in Men With Lower Urinary Tract Symptoms Secondary to Clinical Benign Prostatic Hyperplasia: A Randomized, Placebo Controlled 12-Week Clinical Trial

2010-01-20

Purpose: We explored the impact of once daily tadalafil on urodynamic measures in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia via invasive and noninvasive urodynamic studies.Materials and Methods: We conducted a multicenter, randomized, double blind, placebo controlled clinical trial comparing once daily tadalafil 20 mg vs placebo during 12 weeks in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia with or without bladder outlet obstruction. Invasive and noninvasive urodynamics, International Prostate Symptom Score and general safety were assessed. The primary study end point was change in detrusor pressure at maximum urinary flow rate.Results: Urodynamic measures remained largely unchanged during the study with no statistically significant or clinically adverse difference between tadalafil and placebo in change in detrusor pressure at maximum urinary flow rate (mean difference between treatments −2.2 cm H2O, p = 0.33) or any other urodynamic parameter assessed including maximum urinary flow rate, maximum detrusor pressure, bladder outlet obstruction index or bladder capacity (all measures p ≥0.13). Treatment with tadalafil resulted in significant improvements in International Prostate Symptom Score (mean difference between treatments −4.2, p <0.001). Tadalafil was generally well tolerated with the majority of adverse events being mild to moderate in severity and few patients discontinuing due to adverse events (tadalafil 2.0%, placebo 1.0%).Conclusions: Treatment with tadalafil once daily for lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia showed no negative impact on bladder function as measured by detrusor pressure at maximum urinary flow rate or on any other urodynamic parameter assessed. Nonetheless men receiving tadalafil reported significant improvements in International Prostate Symptom Score with an adverse events profile similar to other recent studies of tadalafil for lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia.

Photoselective Prostatic Vaporization for Bladder Outlet Obstruction: 12-Month Evaluation of Storage and Voiding Symptoms

2010-01-21

Purpose: We evaluated voiding and storage symptom evolution in patients treated with prostate photoselective vaporization by a KTP laser.Materials and Methods: Enrolled in the study were 150 consecutive patients with lower urinary tract symptoms due to benign prostatic hyperplasia and a diagnosis of bladder outlet obstruction. Patients underwent prostate photoselective vaporization with the 80 W KTP laser. Baseline parameters included prostate volume, International Prostate Symptom Score with voiding and storage symptom subscores, uroflowmetry, pressure flow study and serum prostate specific antigen. Patients were followed 1, 3, 6 and 12 months after surgery.Results: Mean ± SD patient age was 69.6 ± 10 years. Mean prostate volume was 52 ± 18 ml. Mean International Prostate Symptom Score was 22.3 ± 4, mean maximum urine flow was 9 ± 2.9 ml per second and mean Schäfer obstruction class was 3.6 ± 1. An average of 190 ± 44 kJ were delivered in a mean of 68 ± 24 minutes with an average of 3.6 kJ/ml prostate. The mean number of fibers was 1.2 ± 0.4. Mean catheterization time was 20 ± 8 hours. Retrograde ejaculation was reported in 67% of patients. Prostate specific antigen was significantly decreased at 12 months (2.6 ± 2.3 vs 0.9 ± 0.7 ng/ml, p = 0.001). Storage symptoms decreased by 54.5%, 63.6%, 72.7% and 81.8% at 1, 3, 6 and 12 months, respectively (p <0.001). Voiding symptoms decreased 63.6%, 72.7%, 81.8% and 90.9% at 1, 3, 6 and 12 months, respectively (p <0.001).Conclusions: As shown by a prostate specific antigen significant decrease, proper prostate debulking may be achieved by prostate photoselective vaporization. Significant continuous improvement in storage and voiding symptoms was observed at up to 12-month followup.

Editorial Comment

Anton Ponholzer, Stephan Madersbacher — 2010-01-21

For more than 5 years PVP has been the most popular laser prostatectomy in many industrialized countries. Efficacy and safety were shown in several phase II trials. Limited data on randomized trials vs TURP and initial long-term data with a followup of up to 5 years are now available. These authors add to our knowledge mainly for 2 reasons. 1) Their study included only patients with urodynamically proven obstruction. 2) They report a detailed assessment of storage and voiding symptoms.

Experience With More Than 1,000 Holmium Laser Prostate Enucleations for Benign Prostatic Hyperplasia

Amy E. Krambeck, Shelly E. Handa, James E. Lingeman — 2010-01-21

Purpose: Holmium laser prostate enucleation is a contemporary treatment for benign prostatic hyperplasia. We report our experience with more than 1,000 procedures.Materials and Methods: From June 1998 to March 2009 we performed 1,065 holmium laser prostate enucleations. After receiving institutional review board approval we retrospectively reviewed the database. Reported short-term, intermediate term and long-term results are 0 to 6, 6 to 12 and greater than 12 months, respectively.Results: Bladder stones were present in 50 patients (4.7%) and 87 of the 717 (12.1%) with laboratory studies available had renal insufficiency. Preoperative urinary retention was present in 411 cases (38.7%). Significant preoperative stress and urge incontinence was noted in 8 and 16 patients, respectively. Mean transrectal ultrasound prostate volume was 99.3 gm (range 9 to 391). Mean preoperative American Urological Association symptom score was 20.3 (range 1 to 35) and maximum urinary flow was 8.4 cc per second (range 1.1 to 39.3). Intraoperative or postoperative complications occurred in 24 cases (2.3%). Mean followup was 287 days (range 6 to 3,571). At short-term, intermediate term and long-term followup the mean symptom score was 8.7, 5.9 and 5.3, and maximum urinary flow was 17.9, 19.5 and 22.7 cc per second, respectively. At the most recent followup 3 patients (0.3%) were in urinary retention. One patient with maximum urinary flow 20 cc per second required a second procedure for bleeding prostatic regrowth. Urethral stricture was noted in 9 (0.9%), 11 (1.3%), 4 (1.3%) and 0 patients, and bladder neck contracture was found in 0, 7 (0.8%), 4 (1.3%) and 5 (6.0%) at short-term, intermediate term, long-term and greater than 5-year followup, respectively. At the most recent followup significant stress and urge incontinence was noted in 9 and 6 patients, respectively.Conclusions: Holmium laser prostate enucleation is safe and effective for benign prostatic hyperplasia. The complication rate is low, and incontinence and the need for ancillary procedures are rare for holmium laser prostate enucleation with durable long-term results.

Voiding Function and Dysfunction, Bladder Physiology and Pharmacology, and Female Urology

Alan J. Wein — 2010-01-21

G. A. Digesu, C. Hendricken, R. Fernando and V. Khullar Department of Urogynaecology, St. Mary's Hospital, Imperial College, London, United Kingdom

Socioeconomic Factors, Urological Epidemiology and Practice Patterns

David F. Penson — 2010-01-22

S. Srikrishna, D. Robinson and L. Cardozo Department of Urogynaecology, King's College Hospital, London, United Kingdom

Benign Prostatic Hyperplasia

Steven A. Kaplan — 2010-01-22

K. A. Tikkinen, A. Auvinen, T. M. Johnson, II, J. P. Weiss, T. Keranen, A. Tiitinen, O. Polo, M. Partinen and T. L. Tammela Clinical Research Institute HUCH Ltd., Helsinki, Finland

Sexual Function in Men Born With Classic Bladder Exstrophy: A Norm Related Study

2010-01-21

Purpose: We evaluated erectile function in men born with classic bladder exstrophy using a validated instrument and compared results with those in age matched controls.Materials and Methods: A total of 28 patients born with bladder exstrophy were invited to self-administer an Italian version of the International Index of Erectile Function-15 to assess erectile and orgasmic function, sexual desire and satisfaction, and overall satisfaction. A score of 25 or less of 30 in the erectile function domain was considered diagnostic for erectile dysfunction. Scores in patients with bladder exstrophy were compared with scores in 38 normal controls who self-administered the same questionnaire.Results: A total of 19 men (68%) with a median age of 27.1 years (range 18.3 to 41.2) returned the questionnaire, of whom 11 (58%) presented with erectile dysfunction compared to 9 (23%) age matched controls (p = 0.02). Erectile dysfunction was more common in patients with bladder exstrophy who underwent multiple continence surgeries. Orgasmic function was also significantly lower in patients with bladder exstrophy than in controls (p = 0.001). No difference was observed between the groups in the sexual desire, sexual satisfaction and overall satisfaction domains.Conclusions: Patients born with classic bladder exstrophy appear to have erectile dysfunction and decreased orgasmic function more commonly than normal controls, particularly when they underwent multiple continence surgeries. Sexual desire seems comparable to that of their peers. Eventually patients with bladder exstrophy seem to lead a sexual life that is as satisfactory as that of their peers.

Inflatable Penile Prosthesis Implantation Without Corporeal Dilation: A Cavernous Tissue Sparing Technique

2010-01-21

Purpose: We compared the advantages and disadvantages of initial penile implantation with vs without prior dilation of the corpora cavernosa.Materials and Methods: Patients implanted for the first time with a 700CX™ or an antibiotic coated 700CX InhibiZone™ 3-piece prosthesis by a single surgeon during January 2005 to December 2006 were included in the study. They were randomized to penile implantation without (group 1) or with (group 2) penile dilation. Postoperative pain was measured on the day after surgery and at day 7 postoperatively. Perioperative and postoperative complications were recorded. Residual erectile activity without prosthesis inflation was evaluated using the International Index of Erectile Function at 3-month intervals for 9 months. Patients recorded penile length and girth during maximum sexual stimulation during this time.Results: A total of 100 patients were included in the study. Intraoperative complications occurred in 2 group 1 and 3 group 2 patients. Postoperatively complication rates and types were similar in the 2 groups. Pain was significantly greater in group 2 (p <0.01). Immediately postoperatively, and at 3 and 6 months penile length was significantly greater in group 1 than in group 2 (p <0.05). Mean International Index of Erectile Function scores were higher in group 1 (12, range 10 to 14 vs 7, range 6 to 8).Conclusions: Results suggest that penile dilation is not necessary in primary implantation cases.

Male and Female Sexual Function and Dysfunction; Andrology

Allen Seftel — 2010-01-21

M. Maggio, G. P. Ceda, F. Lauretani, S. Bandinelli, C. Ruggiero, J. M. Guralnik, E. J. Metter, S. M. Ling, G. Paolisso, G. Valenti, A. R. Cappola and L. Ferrucci Department of Internal Medicine and Biomedical Sciences, Section of Geriatrics, University of Parma, Parma, Italy

Male Infertility

Craig Niederberger — 2010-01-25

T. M. Stewart, D. Y. Liu, C. Garrett, N. Jorgensen, E. H. Brown and H. W. Baker Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne IVF Reproductive Services, Royal Women's Hospital, Melbourne, Australia

Urological Oncology: Testis Cancer

Jerome P. Richie — 2010-01-25

D. de Bruin, I. J. de Jong, E. G. Arts, J. Nuver, R. P. Dullaart, W. J. Sluiter, H. J. Hoekstra, D. T. Sleijfer and J. A. Gietema Department of Urology, University of Groningen, University Medical Center, Groningen, The Netherlands

Characterizing Clinicopathological Findings of Transarterial Chemoembolization for Wilms Tumor

2010-01-22

Purpose: We characterized the clinicopathological changes after transarterial chemoembolization for treatment of Wilms tumor.Materials and Methods: A total of 44 consecutive patients with Wilms tumor were randomized to undergo transarterial chemoembolization preoperatively or to undergo surgery only. We compared the clinicopathological findings of resected tumor from the 2 groups.Results: Tumor-free survival at 2 years in the group undergoing transarterial chemoembolization was significantly higher compared to the control group (p <0.01), and tumor related recurrence and deaths within 1 year were significantly lower in the study group than in controls (p <0.01). Average tumor shrinkage was 48.2% in the study group. Average area of necrosis in tumor sections was 63.5% in the study group and 15% in controls (AUC 2.78, p <0.01). Percentage of tumor with moderate to severe interstitial fibrosis was 64% (14 of 22 patients) in the study group and 18% (4 of 22) in controls (AUC 2.72, p <0.01). Comparative rates of percentage of tumor demonstrating grade III to IV lymphocytic infiltration were 73% (16 of 22 patients) and 18% (4 of 22, chi-square 11.6, p <0.01), median mitotic index in tissues 1.4 and 0.19 (AUC 55.7, p <0.01), and median apoptotic index of tumor cells 28.1 and 12.8 per 10 microscopic fields (AUC 109.00, p <0.05). Expression of p53 and Bcl-2 protein did not differ between the groups, but Bax protein expression was significantly higher in the study group (85% vs 40%, p <0.05).Conclusions: Transarterial chemoembolization induces tumor cell necrosis, degeneration and apoptosis, while also boosting interstitial fibrous tissue hyperplasia and lymphocyte infiltration. These histopathological findings could help explain the basis of the better clinical outcome in patients with Wilms tumor who underwent preoperative transarterial chemoembolization.

Editorial Comment

Michael Ritchey — 2010-01-22

Li et al report on their experience with transarterial chemoembolization for treatment of Wilms tumor in children. This modality has been used for other solid tumors, notably unresectable hepatic carcinoma. The authors compare the outcome of patients treated with TACE to a control group treated with primary surgery, reporting data on survival, histological changes and gene expression after TACE.

Predictive Factors for Acute Renal Cortical Scintigraphic Lesion and Ultimate Scar Formation in Children With First Febrile Urinary Tract Infection

Mi Mi Oh, Jun Cheon, Seok Ho Kang, Hong Seok Park, Jeong Gu Lee, Du Geon Moon — 2010-01-22

Purpose: We assessed predictive factors for acute renal cortical scintigraphic lesion and ultimate scar formation in children with a first febrile urinary tract infection.Materials and Methods: A total of 89 girls and 138 boys with a first febrile urinary tract infection were included in the study. We analyzed radiological (ultrasound, dimercapto-succinic acid scintigraphy, voiding cystourethrogram), clinical (age, gender, peak fever, therapeutic delay time) and laboratory (complete blood count with differential count, absolute neutrophil count, blood urea nitrogen, creatinine, urinalysis, Gram's stain, culture, C-reactive protein, erythrocyte sedimentation rate) variables. Dimercapto-succinic acid scintigraphy was performed within 5 days and at 6 months after diagnosis of urinary tract infection. Voiding cystourethrogram was performed after the acute phase of the urinary tract infection. Predictive factors for acute scintigraphic lesion and ultimate scar formation were assessed using logistic regression analysis.Results: Of 227 patients enrolled 140 had a refluxing and 87 a nonrefluxing urinary tract infection. On logistic regression analysis therapeutic delay time (p = 0.001) and presence of reflux (p = 0.011) were predictive of acute scintigraphic lesion and ultimate scar formation (p = 0.001 and p = 0.0001, respectively) in children with a first febrile urinary tract infection.Conclusions: Since vesicoureteral reflux is the common risk factor for acute scintigraphic lesion and ultimate scar formation, voiding cystourethrogram must be considered as an initial study in patients with acute febrile urinary tract infection.

Editorial Comment

Steven J. Skoog — 2010-01-22

It is refreshing to read a clinical study with all of the important clinical variables measured in the entire study population. This article validates the value of VCUG and DMSA renal scan in the evaluation of a first febrile urinary tract infection in an at risk population of infants. The rates of DMSA defined pyelonephritis and renal scarring are similar to other studies but this series has all of the data. Vesicoureteral reflux remains a significant risk factor for APD but more importantly a decisive factor for renal scarring (odds ratio 10.12). Interestingly this scarring risk was independent of reflux grade, decidedly contrary to popular thought, but this finding may reflect a lack of statistical power. Delay in treatment poses a significant risk of APD and later scarring, which contradicts the conclusions of other recent studies. In a time when imaging of infants with UTIs and treatment of VUR have been put to task this study provides the clinician with valid outcomes that will need to be dealt with if one chooses diagnostic and therapeutic nihilism.

Hospitalizations for Pediatric Stone Disease in United States, 2002–2007

2010-01-22

Purpose: Although more common in adults, urolithiasis recently has been occurring with increasing frequency in children. Single institution reviews from 1950 to 1990 revealed that urolithiasis accounts for 1 in 7,600 to 1 in 1,000 pediatric hospitalizations. Stone prevalence and risk factors for hospitalization are less defined in children in North America compared to adults. To identify pediatric hospital admissions due to a diagnosis of urinary stones, we examined Pediatric Health Information System data from 41 freestanding pediatric hospitals.Materials and Methods: We retrospectively studied patients younger than 18 years hospitalized between 2002 and 2007. The Pediatric Health Information System database, a validated collection of pediatric hospital data, was searched for inpatients with a primary ICD-9 diagnosis of urolithiasis.Results: Among more than 2.7 million pediatric inpatients from 2002 to 2007, 3,989 hospitalizations were for 3,815 patients with urolithiasis. In contrast to adults, girls had a 1.5-fold greater likelihood of being hospitalized for stones. More than half of the children (53.1%) were younger than 13 years (mean 12.3, SD 4.23). Most patients (88%) were white. Stone hospitalizations were more common in the North Central region compared to the South. Hospitalizations for stones increased slightly in August and September. Nephrectomy was performed in nearly 1% of stone hospitalizations (29 of 3,170).Conclusions: Children with stones now account for 1 in 685 pediatric hospitalizations in the United States. Surprisingly more than half of the patients are younger than 13 years at hospitalization. Similar to findings in adults, white race and occurrence in late summer months increase the risk of stone hospitalization. However, male gender and geographic location in the Southeast are not risk factors, demonstrating the unique aspects of pediatric stone hospitalization.

Editorial Comment

Luis Guerra — 2010-01-22

In 2000 the expenditure on urolithiasis in the US was estimated at $2.1 billion, which imposes a significant burden on the health care system. The authors evaluated a selected population of children with ICD codes related to urinary stones who required admission to pediatric hospitals in the US. They collected data from the PHIS database and analyzed some clinical/epidemiological features as well as the economical burden resulting from these hospitalizations. Although interesting to read, it seems that the focus of this study is more on health care administration and insurance costs. It lacks the denominator that is the most important information for the urologist. This means that the data on children with urinary stones in the same hospital catchment areas who were not admitted are unknown, as well as all of the associated clinical variables. One must also ponder that these data capture neither all of the patients treated clinically nor all of those who underwent outpatient surgery or ESWL. Although this fact does not compromise the quality or importance of the study, it limits the usefulness of these results in clinical practice.

Bonn Risk Index Based Micromethod for Assessing Risk of Urinary Calcium Oxalate Stone Formation

2010-01-22

Purpose: The Bonn Risk Index has been used to evaluate the risk of urinary calcium oxalate stone formation. According to the original method, risk should be determined based on a 200 ml urine sample taken from a 24-hour collection. We evaluated whether the Bonn Risk Index can also be effectively determined in small urine samples.Materials and Methods: We studied 190 children and adolescents with nocturia and calcium oxalate urolithiasis. Initially Bonn Risk Index was determined according to the original method of Laube. Subsequently Bonn Risk Index was calculated using a computer program controlling a specially designed system to define the time point of induced crystallization based on consecutive urine samples of 1.5, 2.0 and 3.0 ml.Results: No significant differences were found in Bonn Risk Index between values obtained from 200 ml samples and those based on the micromethod with urine samples of 2 and 3 ml.Conclusions: Assessment of risk of urinary calcium oxalate stone formation with Bonn Risk Index in small urine volumes, based on prototype equipment controlled by specialized computer software, is comparable to the original method. This finding facilitates the procedure and improves Bonn Risk Index determination in children.

Hernia After Pediatric Urological Laparoscopy

2010-01-22

Purpose: The incidence of port site hernia following adult laparoscopy is 0.1% to 3.0%. There are no known published reports concerning hernia incidence or related factors after pediatric urological laparoscopic interventions. We present our experience with port site incisional hernias following pediatric urological laparoscopy.Materials and Methods: We reviewed all pediatric urological laparoscopic procedures performed at Children's Medical Center Dallas from 2000 to 2008. A total of 261 cases were identified with followup available in 218 (83.5%). In 187 cases there were sufficient data to evaluate outcomes for each port site separately, and compare the size, location and fascial closure status to hernia development.Results: Median patient age was 6.1 years (range 0.4 to 18.8). A total of 218 patients had a median followup of 5.7 months (range 0.2 to 83.4). Seven hernias (3.2%) were diagnosed at a median of 1.2 months (range 0.1 to 15.1) postoperatively. Patients with hernia were younger than those without hernia, at 1.1 years (range 0.5 to 3.9) vs 6.2 years (0.4 to 18.8, p = 0.04). We analyzed 571 port sites in 187 cases. In 385 ports (67.4%) the fascia was closed. Hernia developed in 4 of 385 ports (1.0%) that were closed and in 3 of 186 (1.6%) that were not closed. No significant relationship was observed between hernia development and port size or location.Conclusions: The incidence of port site hernia after pediatric urological laparoscopy was 3.2%, similar to the reported incidence in adults. While development of hernia after pediatric urological laparoscopy is rare, it is more likely to occur in infants. Due to the low incidence of this complication, it is difficult to draw conclusions regarding contributing factors.

Editorial Comment

Pasquale Casale — 2010-01-22

I congratulate the authors for an honest reporting of their port site hernia complications in a time of minimally invasive surgery growth for pediatric urology. As cited in the article, although many factors are thought to contribute to port site complications in adults, including obesity, diabetes mellitus, smoking status and/or port size and location, there are few data for pediatric port site issues after minimally invasive surgery (reference 10 in article).

Teapot Ureterocystoplasty and Ureteral Mitrofanoff Channel for Bilateral Megaureters: Technical Points and Surgical Results of Neurogenic Bladder

2010-01-22

Purpose: We present the long-term results of simultaneous “teapot” ureterocystoplasty and ureteral Mitrofanoff in patients with bilateral megaureters due to neurogenic bladder, and compare urodynamic results before and after the procedure.Materials and Methods: We treated 13 children (mean age 7.3 years) with end stage neurogenic bladder and refluxing megaureters (mean diameter 5.5 cm) with simultaneous teapot ureterocystoplasty and Mitrofanoff appendicovesicostomy between April 1995 and May 2001. The larger ureter was used for teapot bladder augmentation while keeping its distal 2 cm tubularized. The Mitrofanoff channel was then created using the opposite ureter.Results: Followup ranged from 109 to 169 months (median 121). At the end of the followup period all patients were dry with clean intermittent catheterization and/or voiding. No repeat augmentation was needed and there were no bladder calculi during followup. Median postoperative bladder capacity was 430 ml (IQR 380 to 477), which was increased significantly compared to preoperative evaluations (210 ml, IQR 181 to 230, p = 0.001). During followup bladder compliance also improved significantly (p = 0.001) and serum creatinine level decreased (p = 0.021).Conclusions: Although neurogenic bladder and high grade reflux are poor prognostic factors for ureterocystoplasty, the present modification resulted in enduring bladder augmentation with no calculus formation. Bladders remained compliant with good capacity, presumably because sufficient tissue and blood supply were provided for the augmented flap.

Editorial Comment

Piet Hoebeke — 2010-01-22

Despite the originality of this technique, the patients for whom it is described should nowadays no longer be seen. I understand that there are still places in the world where these patients are encountered. However, in most of these countries application of intermittent catheterization is not an option. This issue is the main criticism of this report. Original? Yes. Applicable? Not in countries with a good medical system where end stage neurogenic bladder is no longer seen, and not in developing countries where intermittent catheterization is not always an option. A further question is whether all patients with end stage neurogenic bladder need continent diversion. Compared to wheelchair bound girls, continent diversion provides less of an advantage for boys with a normal urethra. Thus, this technique is original but probably rarely applicable.

Editorial Comment

Ricardo González — 2010-01-22

The authors are to be congratulated for excellent results with 2 procedures that in most hands give unsatisfactory results, namely ureteral Mitrofanoff and ureterocystoplasty. The authors have done the best they could, given the catastrophic cases they faced. However, the reader should be aware that a child with neurogenic bladder, extreme ureteral dilatation and renal insufficiency represents a failure of medical care, inadequate socioeconomic support or inadequately addressed cultural barriers to proper preventive treatment with adequate surveillance, intermittent catheterization, occasional use of anticholinergic agents and judicious use of antibiotics. I almost never do a ureterocystoplasty, and obtain the best results for a catheterizable channel constructed with appendix, or a reconfigured ileal or sigmoid segment.

Reply by Authors

2010-01-22

We agree that the patients for whom this technique is described no longer exist in developed countries. However, many underdeveloped and developing countries still encounter cases like these and the readers should not always be involved with the problems of developed countries. Additionally, since our institution is the country's referral center for pediatric urology, it is usual to encounter extremes of urological diseases. Furthermore, our patients had undergone surgeries about 2 decades ago and with recent advances in public health in Iran the incidence of such complications is now unlikely.

Predictive Factors for Resolution of Congenital High Grade Vesicoureteral Reflux in Infants: Results of Univariate and Multivariate Analyses

Sofia Sjöström, Ulla Sillén, Ulf Jodal, Louise Sameby, Rune Sixt, Eira Stokland — 2010-01-22

Purpose: We studied variables with impact on cessation of congenital high grade vesicoureteral reflux in univariate analyses and provide a multivariate model for prediction of reflux resolution.Materials and Methods: A total of 80 male and 35 female infants (median age 2.7 months) were included in this prospective observational study. Of the cases 71% were diagnosed after urinary tract infection and 26% after prenatal ultrasound. Reflux was bilateral in 70% of the patients and maximum grade was III in 16%, IV in 45% and V in 39%. The study protocol included repeat videocystometries, renal scintigrams, chromium edetic acid clearances and free voiding observations. Median followup was 36 months.Results: Overall spontaneous reflux resolution, including cases downgraded to grade I to II, was 38%. Variables significantly negatively correlated to resolution were breakthrough febrile urinary tract infection, bladder dysfunction, higher grade of reflux at inclusion, renal abnormality, subnormal renal function, increased bladder capacity, residual urine and passive occurrence of reflux. Multivariate Cox proportional hazard model with stepwise selection identified 3 independent predictors—renal abnormality (hazard ratio 0.45, 95% CI 0.31–0.64, p <0.0001), bladder dysfunction (hazard ratio 0.43, 95% CI 0.29–0.64, p <0.0001) and breakthrough urinary tract infection (hazard ratio 0.38, 95% CI 0.18–0.78, p = 0.009). Performance of the model was evaluated by the receiver operating characteristic curve, with a calculated area under the curve of 83%.Conclusions: Overall resolution rate in congenital high grade vesicoureteral reflux is high during the first years of life. By multivariate analyses renal abnormality, bladder dysfunction and breakthrough febrile urinary tract infection were identified as strong independent negative predictive factors for reflux resolution.

Editorial Comment

Saul P. Greenfield — 2010-01-22

The authors report that infants born with high grade vesicoureteral reflux and 3 findings have a less than 10% chance of having the reflux resolve before age 3 years. These findings are scintigraphic renal abnormality, poor bladder emptying and breakthrough infection. Conversely in the absence of all 3 findings 90% of cases will resolve or improve to a low grade (I to II) by age 3 years. This observation confirms what many may know intuitively, which is that infants with high grade reflux who are least likely to have the condition resolve spontaneously are those with the most abnormal vesicoureteral junctions and associated congenital renal dysplasia. The poor bladder emptying described is consistent with megacystis-megaureter syndrome, which often accompanies high grade reflux. Finally breakthrough infections more readily occur when post-void residual urine volumes are high. While cystoscopic observation of the ureterovesical junction is notoriously subjective, it is probable that infants with these characteristics were born with widely patulous and lateral ureteral orifices with little possibility that growth will result in an antireflux mechanism.

Pediatric Urology

Douglas A. Canning — 2010-01-22

R. Hamid, T. J. Greenwell, J. M. Nethercliffe, A. Freeman, S. N. Venn and C. R. Woodhouse Institute of Urology and University College London Hospital, London, United Kingdom

Congenital Mesoblastic Nephroma

Aaron M. Gruver, Donna E. Hansel, Daniel J. Luthringer, Gregory T. MacLennan — 2010-01-22

Bolande et al were the first to describe congenital mesoblastic nephroma (CMN) based on a study of 8 renal tumors in infants younger than 3 months. Although it is the most common renal tumor in this age group, CMN comprises only 2% to 4% of pediatric renal tumors. Nearly all reported cases occurred in individuals younger than 30 months, including 90% during the first 12 months of life.

Computerized Tomography Reveals Variable Aggressiveness of Transitional Cell Carcinoma of the Bladder and Bladder Diverticulum

Erich K. Lang, Ernest Rudman, Amer Hanano, John Jaworsky — 2010-01-22

A 58-year-old white male presented with gross hematuria. At hospitalization hematocrit was 26, hemoglobin was 9.6 gm and urinalysis revealed greater than 100 red blood cells per high power field with multiple clots. Cytology identified abnormal cells consistent with transitional cell carcinoma, cellular debris and bacteria on high power field. Serum albumin was low, creatinine was 1.4 mg/dl and blood urea nitrogen was 24 mg/dl.

Human Amniotic Fluid as a Potential New Source of Organ Specific Precursor Cells for Future Regenerative Medicine Applications

2010-01-22

Purpose: Human amniotic fluid contains multiple cell types, including pluripotent and committed progenitor cells, and fully differentiated cells. We characterized various cell populations in amniotic fluid.Materials and Methods: Optimum culture techniques for multiple cell line passages with minimal morphological change were established. Cell line analysis and characterization were done with reverse transcriptase and real-time polymerase chain reaction. Immunoseparation was done to distinguish native progenitor cell lines and their various subpopulations.Results: Endodermal and mesodermal marker expression was greatest in samples of early gestational age while ectodermal markers showed a constant rate across all samples. Pluripotent and mesenchymal cells were always present but hematopoietic cell markers were expressed only in older samples. Specific markers for lung, kidney, liver and heart progenitor cells were increasingly expressed after 18 weeks of gestation. We specifically focused on a CD24+OB-cadherin+ population that could identify uninduced metanephric mesenchyma-like cells, which in vivo are nephron precursors. The CD24+OB-cadherin+ cell line was isolated and subjected to further immunoseparation to select 5 distinct amniotic fluid kidney progenitor cell subpopulations based on E-cadherin, podocalyxin, nephrin, TRKA and PDGFRA expression, respectively.Conclusions: These subpopulations may represent different precursor cell lineages committed to specific renal cell fates. Committed progenitor cells in amniotic fluid may provide an important and novel resource of useful cells for regenerative medicine purposes.

Effect of Estrogen on Bladder Nociception in Rats

2010-01-22

Purpose: We assessed the effect of ovariectomy and estrogen replacement on nociceptive responses to bladder distention in a rat model.Materials and Methods: Female Sprague-Dawley rats (Harlan™) underwent ovariectomy or sham surgery. Visceromotor responses (abdominal contractions) to bladder distention were determined 3 to 4 weeks later under isoflurane anesthesia. In rat subsets estrogen was chronically replaced with a subcutaneous estrogen pellet vs a placebo pellet or acutely replaced by subcutaneous injection 24 hours before testing. Effects of estrogen withdrawal were examined in another group of rats by implanting a pellet and explanting the pellet 24 hours before testing. Uterine weight was measured to assess the estrogen dose.Results: Visceromotor responses to bladder distention were significantly less vigorous in ovariectomized rats vs controls. Acute estrogen replacement increased visceromotor responses in these rats but chronic estrogen replacement did not. Sudden chronic estrogen withdrawal resulted in increased visceromotor responses. Uterine weight was consistent with the physiological estrogen dose.Conclusions: Estrogen alone was not sufficient to produce increased nociceptive responses but an acute decrease in estrogen resulted in increased visceromotor responses. These data suggest that the pronociceptive effects of estrogen may be due to a mismatch between peripheral vs central and/or genomic vs nongenomic effects of the hormone, which occur during rapidly decreasing estrogen levels.

CXCR3 Binding Chemokine and TNFSF14 Over Expression in Bladder Urothelium of Patients With Ulcerative Interstitial Cystitis

2010-01-22

Purpose: We investigated the genes responsible for ulcerative interstitial cystitis by DNA microarray analysis and quantitative real-time polymerase chain reaction.Materials and Methods: Bladder urothelial tissues were taken from a site apart from the ulcerative lesion in 9 patients with ulcerative interstitial cystitis and from a normal-looking area in 9 controls, including 7 with bladder carcinoma and 2 with benign prostatic hyperplasia. Total RNA was extracted from bladder samples and gene expression was compared between these 2 groups using Whole Human Genome DNA microarray 44K (Agilent Technologies, Santa Clara, California). Microarray data were analyzed by GeneSpring™ GX software and Ingenuity® Pathway Analysis. Chosen genes were confirmed for altered transcription by quantitative real-time polymerase chain reaction.Results: We identified 564 probes that were significantly expressed in mRNA more than 4-fold vs those in controls using volcano plot analysis (p <0.001). Further network Ingenuity Pathway Analysis of these genes showed the top 3 functions, including 1) cell-to-cell signaling and interaction, and hematological system development and function, 2) inflammatory disease and 3) cellular development. Quantitative real-time polymerase chain reaction confirmed increased mRNA expression of several genes in the bladder samples of patients with ulcerative interstitial cystitis, including CXCR3 binding chemokines (CXCL9, 10 and 11) and TNFSF14 (LIGHT).Conclusions: Our study using DNA microarray analysis followed by quantitative real-time polymerase chain reaction reveals over expression of genes related to immune and inflammatory responses, including T-helper type 1 related chemokines, and cytokines such as CXCR3 binding chemokines and TNFSF14. These genes may be potential interstitial cystitis biomarkers.

Crucial Role of Interferon-γ in Experimental Autoimmune Prostatitis

2010-01-22

Purpose: An autoimmune etiology is proposed in some patients with chronic nonbacterial prostatitis since they show interferon-γ secreting lymphocytes specific to prostate antigens in the periphery and increased interferon-γ in seminal plasma. We investigated the involvement of interferon-γ in an animal model of autoimmune prostatitis.Materials and Methods: Experimental autoimmune prostatitis was studied in the no-obese diabetic and C57Bl/6 (Harlan, Zeist, The Netherlands) susceptible mouse strains, and in the IRF-1 KO and STAT-1 KO mouse strains deficient in transcription factors involved in interferon-γ signaling.Results: Experimental autoimmune prostatitis was characterized by prostate specific interferon-γ secreting cells in the periphery and by T-helper 1 related cytokines in the target organ. Increased interferon-γ and interleukin-12 were observed in the prostate of autoimmune animals while interleukin-10 and interleukin-4 were decreased and unaltered, respectively. The absence of transcription factors involved in the interferon-γ signaling cascade, IRF-1 and STAT-1, made mice resistant to experimental autoimmune prostatitis. IRF-1 KO and STAT-1 KO mice immunized with prostate antigens did not show infiltration or alterations in the prostate. They did not have the typical prostate specific autoimmune response and showed decreased interferon-γ, interleukin-12 and interleukin-10, and augmented interleukin-4 in the prostate.Conclusions: Our results argue for a crucial role of interferon-γ as a key factor in the pathogenesis of the disease. Intense research is promptly required to identify the pathogenic mechanisms underlying chronic prostatitis/chronic pelvic pain syndrome to find a more rational therapy.

Immediate Effect of Kidney Cryoablation on Renal Arterial Structure in a Porcine Model Studied by Imaging Cryomicrotome

2010-01-22

Purpose: Injury to blood microvessels has a crucial role in effective cryoablation for renal masses. We visualized vascular injury induced by a clinically applied cryoablation instrument and established a microvascular diameter threshold for vascular damage.Materials and Methods: In 5 anesthetized pigs 1 kidney each was exposed and 3, 17 gauge cryoneedles were inserted in 1 pole. Tissue was exposed to freezing for 2 × 10 minutes with a 10-minute thaw between freezes. After nephrectomy the arteries were injected with fluorescence dyed casting material and the kidney was frozen to –20C and cut in 40 to 60 μ slices in the imaging cryomicrotome, where fluorescent images of the cutting plane of the bulk were obtained. This resulted in a 3-dimensional image of the arterial tree that was segmented, resulting in unbranched vessel segments. Histograms were constructed with the total segment length per diameter bin plotted as function of diameter.Results: The ablated zone was sharply demarcated on fluorescent and normal light images. Mean ± SD diameter at the peak of the histogram from control areas was 152.4 ± 5.3 μ. Compared to control areas the peak diameter of ablated areas was shifted to a larger diameter by an average of 25.4 ± 2.6 μ.Conclusions: Immediate renal cryoablation injury destroys arteries smaller than 180 μ. Branching structures of larger arteries remain anatomically intact and connected to vascular structures in surrounding tissue.

Complete Ileal Neobladder Intracorporeal Construction With Standard Sutured Technique and Novel Technology

2010-01-22

Purpose: We compared the surgical efficacy and efficiency of a completely suture based procedure with a novel entero-urethral anastomosis device and an EndoGIA™ stapler to create an ileal neobladder.Materials and Methods: Two groups of 7 pigs each were survived for 8 weeks. In group 1 the neobladder was constructed using a U-shaped segment of ileum sealed with the stapler. The entero-urethral anastomosis was created with a novel sutureless anastomosis device. All other procedures were completed with standard intracorporeal suturing techniques. In group 2 animals completely intracorporeal sutured technique was used. Total procedure, and enteroenteric, ileal neobladder, uretero-enteric and entero-urethral anastomosis times were recorded. Cystograms done immediately postoperatively, at 2 weeks and at sacrifice to evaluate the newly constructed system were rated from 0—no leakage to 3—severe leakage.Results: In group 1 vs 2 the overall procedure, and enteroenteric, ileal neobladder, uretero-enteric and entero-urethral anastomoses were completed in 285.3, 32.3, 58.8, 54.2 and 5.5 vs 350.1, 29.9, 139.1, 58.0 and 46.3 minutes, respectively. In groups 1 and 2 the average postoperative cystogram rating was 0.83 and 1.6, respectively (p = 0.63). At 2 weeks and at sacrifice cystograms showed no extravasation in either group. The overall surgical procedure, pouch creation and entero-urethral anastomosis were statistically briefer in group 1 (p = 0.036, 0.01 and 0.039, respectively). Average survival in groups 1 and 2 was 30 (range 4 to 56) and 41 days (range 1 to 56), respectively (p = 0.36). All animals had voiding complications within 1 week after ureteral and urethral catheters were removed. One neobladder ruptured in group 1.Conclusions: Combining stapled ileal neobladder construction and the entero-urethral anastomosis device significantly decreases operative time, pouch creation and urethral anastomoses.

Adipose Derived Stem Cells Ameliorate Hyperlipidemia Associated Detrusor Overactivity in a Rat Model

2010-01-22

Purpose: Adipose tissue derived stem cells can differentiate into muscle and neuron-like cells in vitro. We investigate the usefulness of adipose tissue derived stem cells for overactive bladder in obese hyperlipidemic rats.Materials and Methods: Hyperlipidemia was induced in healthy rats by a high fat diet. The resulting obese hyperlipidemic rats were treated with bladder injection of saline, adipose tissue derived stem cells or tail vein injection of adipose tissue derived stem cells. Bladder function was assessed by 24-hour voiding behavior study and conscious cystometry. Bladder histology was assessed using immunostaining and trichrome staining, followed by image analysis.Results: Serum total cholesterol and low density lipoprotein were significantly higher in obese hyperlipidemic rats than in normal rats (p <0.01). The micturition interval was shorter in saline treated obese hyperlipidemic rats than in normal rats, obese hyperlipidemic rats that received adipose tissue derived stem cells via the tail vein and obese hyperlipidemic rats that received adipose tissue derived stem cells by bladder injection (mean ± SEM 143 ± 28.7 vs 407 ± 77.9, 281 ± 43.9 and 368 ± 66.7 seconds, respectively, p = 0.0084). Bladder wall smooth muscle content was significantly lower in obese hyperlipidemic rats than in normal animals (p = 0.0061) while there was no significant difference between obese hyperlipidemic groups. Nerve content and blood vessel density were lower in controls than in obese hyperlipidemic rats treated with adipose tissue derived stem cells.Conclusions: Hyperlipidemia is associated with increased urinary frequency, and decreased bladder blood vessel and nerve density in rats. Adipose tissue derived stem cell treatment ameliorates these adverse effects and holds promise as a potential new therapy for overactive bladder.

Prostaglandin Receptor EP1 and EP2 Site in Guinea Pig Bladder Urothelium and Lamina Propria

2010-01-22

Purpose: Urothelium has 2 main functions. It is a barrier to urine and has a sensory role. In response to stretch urothelium releases various substances that modulate afferent nerve activity. Recent data on the localization of cyclooxygenase type 1, the enzyme responsible for prostaglandin production, suggests that prostaglandin may have complex local action.Materials and Methods: The bladders of 7 guinea pigs were stained for prostaglandin receptors type 1 and 2, and costained for vimentin and cyclooxygenase I.Results: Prostaglandin receptor type 1 staining was seen in urothelial cells and in the suburothelium. Urothelial staining, which was often punctuate and weak, was detected in all urothelial cell layers, including suburothelial cells. In contrast, strong prostaglandin receptor type 2 staining was seen in the urothelium and in suburothelial cells. Cyclooxygenase I was absent in interstitial cells and umbrella cells with the highest concentration in the basal cell layer.Conclusions: Interstitial cells express prostaglandin receptor types 1 and 2, indicating that they can respond to prostaglandin. Umbrella cells do not express cyclooxygenase I. Cyclooxygenase I was present in basal urothelial cells, making them a possible site of prostaglandin synthesis. Thus, prostaglandin produced by urothelium may target prostaglandin receptor types 1 and 2 in the urothelium and suburothelium. Therefore prostaglandin is hypothesized to have a role in signal regulation in the bladder wall.

Heat Shock Protein and Heat Shock Factor Expression in Sperm: Relation to Oligozoospermia and Varicocele

2010-01-22

Purpose: Varicocele may be associated with normozoospermia or oligozoospermia. Much controversy still exists regarding the diagnosis, management and pathophysiology of spermatogenesis alterations associated with varicocele. The increased temperature induced by varicocele and stress in general may activate heat shock proteins and heat shock factors with a protective function in cells. We analyzed the expression of 5 heat shock proteins and heat shock factors in the sperm of men with normozoospermia and oligozoospermia with or without varicocele.Materials and Methods: We performed a prospective study between June 2008 and February 2009 at an academic clinic in 117 consecutive patients with varicocele and 68 controls without varicocele. Four groups were based on the presence/absence of varicocele and normozoospermia/oligozoospermia. Subjects were studied by history, physical examination, scrotal Doppler ultrasound, semen analysis, reproductive hormone plasma levels and quantitative real-time polymerase chain reaction in RNA extracted from ejaculated sperm to analyze HSP90, HSPA4, HSF1, HSF2 and HSFY expression.Results: Increased HSPA4, HSF1 and HSF2 were observed in the sperm of men with varicocele and in those with oligozoospermia. Levels were maximum when the 2 conditions were present. Increased HSP90 was observed in oligozoospermia cases independent of varicocele. HSFY was up-regulated only in patients with varicocele, especially those with normozoospermia.Conclusions: To our knowledge we describe for the first time the expression of different heat shock proteins and heat shock factors in ejaculated sperm. While some of these proteins are up-regulated in men with oligozoospermia and varicocele, HSFY is up-regulated only in the presence of varicocele and especially in men with normozoospermia. This suggests that it may be a molecular marker of an adequate or inadequate response to the damaging effect of varicocele on spermatogenesis.

Uro-Science

Anthony Atala — 2010-01-22

K. A. Esser, C. E. Harpole, G. S. Prins and A. M. Diamond Department of Physiology, University of Kentucky, Lexington, Kentucky

Re: Transurethral Partial Cystectomy With Continuous Wave Laser for Bladder Carcinoma: Y. Yang, Z.-t. Wei, X. Zhang, B.-F. Hong and G. Guo J Urol 2009; 182: 66–69

Endre Z. Neulander, Tiberiu Katz, Joseph Klein, Jacob Kaneti — 2010-01-22

According to McLuhan, “We shape our tools and thereafter our tools shape us.” Nothing is truer when we look at the continuous change in the field of urology. New means are continuously developed for old problems. We have to change with the new methods developed, and our concepts are changing accordingly.

Re: Genetic Polymorphisms of Matrix Metalloproteinases: Susceptibility and Prognostic Implications for Prostate Cancer: S. T. dos Reis, J. Pontes, Jr., F. E. Villanova, P. M. D. Borra, A. A. Antunes, M. F. Dall'oglio, M. Srougi and K. R. M. Leite J Urol 2009; 181: 2320–2325

Dinesh K. Ahirwar, Rama Devi Mittal — 2010-01-25

This case-control study depicts the association of matrix metalloproteinases (MMPs) 1, 2, 7 and 9 polymorphisms, and susceptibility to prostate cancer (PCa). Although the study provides preliminary evidence to consider MMP polymorphisms as risk factors and prognostic markers for PCa, there are a few important issues that need to be clarified.

Re: Chemoprevention of Prostate Cancer: I. M. Thompson, C. M. Tangen, P. J. Goodman, M. S. Lucia and E. A. Klein J Urol 2009; 182: 499–508

Paul F. Schellhammer — 2010-01-25

Reading this review of the Prostate Cancer Prevention Trial (PCPT) was indeed a urological soul elevating experience. The planning and construction of the PCPT consumed untold hours of thought, energy and meetings. While the trial met its primary end point of reducing the prevalence of prostate cancer, this achievement was buried in the highly publicized possibility that finasteride might induce high Gleason grade. Overcoming initial negative publicity is a monumental challenge, since first impressions provide indelible imprints. However, with the same detailed care that was used in constructing the trial the authors put their shoulders to the data wheel and systematically—and successfully—addressed the high grade induction question and additional questions as well, bringing clarity to the trial results. The unfolding of this entire story and the advances in knowledge it has provided lend support and credibility to the concept of urological clinical trialists and the studies they originate and bring to conclusion.

Reply by Authors

2010-01-25

We appreciate the kind comments. To these we would add an acknowledgment of the individuals who truly deserve all of the credit—the hundreds of investigators and research personnel who dedicated their lives to the study and, even more importantly, the incredible men who enrolled in the PCPT and made the study and its results possible.

Re: Prostate Cancer Severity Among Low Income, Uninsured Men: D. C. Miller, M. S. Litwin, J. Bergman, S. Stepanian, S. E. Connor, L. Kwan and W. J. Aronson J Urol 2009; 181: 579–584

Richard A. Watson — 2010-01-25

This article and the accompanying editorial comment shed welcome light on health care disparities in the diagnosis and treatment of prostate cancer for men in the lower socioeconomic brackets. Statistics for men who are black, Asian or white (Hispanic and non-Hispanic) are scrutinized by category. On the other hand, Native American men—if any at all were recruited for this survey—have been relegated indifferently to the “other” category.

Reply by Authors

2010-01-25

Among the greatest challenges of studying prostate cancer epidemiology in Native Americans are the limited data, which in turn limit our ability to make valid statistical inferences. At the same time Watson is correct that this circumstance does not excuse us from increasing our efforts to understand better the issues related to quality, access and costs of cancer care (prostate and others) among Native Americans. The September 2008 supplement to Cancer presents what are probably the best population based data currently available on this topic.

Re: Efficacy of Selective α1D-Blocker Naftopidil as Medical Expulsive Therapy for Distal Ureteral Stones: X. Sun, L. He, W. Ge and J. Lv J Urol 2009; 181: 1716–1720

T.J. Nirmal — 2010-01-25

The current reappraisal of medical expulsive therapy in the literature questions its efficacy in managing distal ureteral calculi. It is well-known that spontaneous passage rates of distal ureteral calculi 5 mm or smaller approaches 71% to 98%. In the current study the stone expulsion rate in the control group was uncharacteristically low, at 26.7%. This result may have been due to the short followup or an underlying selection bias. Even in the distal ureter stones at the ureterovesical junction have a significantly greater expulsion rate compared to those in a more proximal location. Moreover, even if we take a spontaneous expulsion rate of 60% in the control group, a definitive, high quality, randomized trial with a power of 90% and a type I error of 5% would have required a sample size of at least 110 to prove the study drug efficacious. The basis on which Sun et al have calculated their sample size of 60 is unclear. In the evaluation of flank pain ultrasound and plain x-ray of the kidneys, ureters and bladder have a sensitivity of only 47% and 11%, respectively. Use of unenhanced computerized tomography (sensitivity 99%, specificity 97%) for the measurement and followup would have increased the credibility of this study. The many limitations of this study only prompt us to look forward to larger, well designed, randomized trials to confirm the efficacy of naftopidil as medical expulsive therapy.

Erratum

2010-01-25

Volume 181, Number 5, page 2105: The correct is published below.

The Journal of Urology® Home Study Course 2010 Volume 183/184

2010-01-22

News and Announcements

2010-01-22

Dr. Anton J. Bueschen, Division of Urology, University of Alabama at Birmingham, 1530 3rd Ave. S, FOT 1105, Birmingham, Alabama 35294-3411

Editorial Board

2010-03-01