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Purpose: CellDetect® is a unique platform technology comprising a proprietary plant extract and 3 dyes that enables color discrimination between malignant (red) and benign (green) cells based on specific metabolic alterations exclusive to the former. Preclinical studies and clinical trials demonstrated the applicability of the new technology in many cell culture lines and various cancers. We explored its performance characteristics in bladder cancer., Materials and Methods: We performed an open label, 2-step study at tertiary medical centers. The study enrolled patients with newly diagnosed or a history of urothelial carcinoma. Step 1 involved staining archived biopsies. Slides were evaluated by 2 independent pathologists, who determined the concordance of the new staining technology with the hematoxylin and eosin based diagnosis. Step 2 included staining urine specimens with the new method and comparing findings to the patient final diagnosis and the results of standard urine cytology., Results: A total of 58 archived biopsies were collected. The concordance of staining using the new platform technology with the hematoxylin and eosin based diagnosis was 100%. The new method applied to 44 urine smears showed 94% sensitivity and 89% specificity to detect urothelial carcinoma. Compared to standard urine cytology the new technology had overall superior sensitivity (94% vs 46%), particularly for low grade tumors (88% vs 17%, each p <0.005). There was no significant difference in specificity between the 2 staining techniques., Conclusions: Findings show the capability of CellDetect to accurately identify urothelial carcinoma. This indicates that the technology can be further developed to provide an alternative urine cytology test with diagnostic value that may have significant clinical benefits., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We assessed the risk of upper urinary tract obstruction and tumor recurrence following ureteral orifice resection during transurethral resection of bladder tumor., Materials and Methods: We reviewed the medical records of patients treated with transurethral resection of bladder tumors involving the ureteral orifice from 2008 to 2011. Patients with preoperative hydronephrosis or prior ipsilateral nephrectomy and those in whom a ureteral stent was placed during the procedure were excluded from analysis. Study end points were clinical or radiographic evidence of upper urinary tract obstruction and disease recurrence., Results: The study group included 65 men (82%) and 14 women (18%) in whom a total of 84 orifice resections were performed. Hydronephrosis was observed in 11 patients (13%) during a median followup of 15 months (IQR 7-26). Hydronephrosis was secondary to muscle invasive disease in 5 patients (6%) and it resolved spontaneously in 3 (4%). In the remaining 3 patients (4%) overt stricture was detected at the ureterovesical junction, requiring endoscopic intervention. One patient was diagnosed with recurrent tumor in the upper urinary tract. The estimated bladder disease recurrence rate was 28% at 1 year and 54% at 2 years. Corresponding disease progression rates were 4% and 12%, respectively., Conclusions: Ureteral orifice resection during transurethral resection of bladder tumor is rarely associated with detrimental renal obstruction or an increased risk of tumor recurrence in the upper urinary tract. New onset hydronephrosis is mostly attributable to muscle invasive disease or temporary obstruction. However, the few cases of overt stricture underscore the importance of meticulous followup with imaging., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Urostomy care requires manual skills and emotional adaptation. We identified predictors of self-stomal care and their impact on quality of life after urostomy creation in patients with an ileal conduit., Materials and Methods: A telephone questionnaire was administered to patients treated with urostomy creation in 2005 to 2010. Assessment included demographic data, stomal care patient education data and quality of life parameters., Results: The study population included 65 patients, including 20% females and 80% males. Mean age was 72 years (range 40 to 88). Mean followup was 30 months (range 6 to 74). Of the patients 97% received stomal specific patient education preoperative but only 32 (49%) felt satisfactorily skilled in stomal care upon hospital discharge. Of the patients 34 (52%) self-managed the urostomy, including 85% of females but only 44% of males (p = 0.009). Predictors of long-term self-stomal care were patient perception that questions before surgery were answered (p = 0.04), better bag replacement training (p = 0.001) and early stomal care skill (p <0.001). Self-stomal care was associated with a higher quality of life score and an improved psychological impact score. On multivariate analysis female gender (OR 15.9, p = 0.008) and higher postoperative education score (OR 5.8, p <0.001) predicted self-stomal care. Preoperative education quality (β = 0.44, p <0.001) and self-stomal handling (β = 0.25, p = 0.02) predicted higher quality of life and an improved psychological impact score., Conclusions: Only half of the patients with an ileal conduit care for the urostomy independently. Female gender, better patient education and early proficiency in stomal care predict long-term self-stomal care. An association exists between self-stomal care and improved quality of life., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We characterized the clinical presentation and outcome of patients on hemodialysis diagnosed with urothelial carcinoma of the bladder., Materials and Methods: Patients treated for bladder cancer while undergoing maintenance hemodialysis were identified by querying the medical registry of a university affiliated hospital between 1999 and 2010. Clinical, pathological and treatment related data were retrieved and characterized. The study end points were recurrence-free, progression-free and overall survival., Results: A total of 15 patients met study criteria. Median age at hemodialysis onset was 67 years (IQR 62, 74). Median dialysis duration before the bladder cancer diagnosis was 36 months (IQR 12, 60). Hematuria and bloody urethral discharge were the most common clinical manifestations. Tumors were generally large and multifocal. Of the patients 66% had invasive disease (T1 or greater) at presentation and 73% had high grade tumors. There were no adverse sequelae after transurethral resection or intravesical therapy. Two of the 4 patients treated with total urinary exenteration died soon after surgery and 1 had a grade IV complication. At a median followup of 18 months the estimated recurrence-free survival rate was 54% at 1 year, and 43% each at 2 and 3 years. The progression-free survival rate was 78%, 56% and 42%, and the overall survival rate was 66%, 45% and 23% at 1 to 3 years, respectively., Conclusions: Bladder cancer diagnosed in patients on hemodialysis often harbors aggressive histological features at presentation. Conservative therapy in patients with noninvasive tumors appears to be well tolerated while urinary tract exenteration is associated with high morbidity and mortality. The prognosis of patients with invasive cancer is generally dismal., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The role of neoadjuvant chemotherapy before surgery in patients with muscle invasive bladder cancer remains debated and the need for tools to identify patients who would benefit from chemotherapy is pertinent. We previously published a preoperative algorithm to predict nonorgan confined disease. This algorithm included tumor markers (CEA, CA 125 and CA 19-9) as well as clinical parameters. In this study we validated the accuracy of this algorithm in an independent, external cohort., Materials and Methods: We used the Toronto Biobank to measure preoperative serum levels of CEA, CA 125 and CA 19-9 in 76 consecutive patients with clinically organ confined bladder cancer (cT2 or less) who underwent radical cystectomy. Clinical parameters were retrieved from our prospective bladder information system database and incorporated into our marker based algorithm. A numerical score was generated for each patient and a previously published cutoff was used to predict the presence of nonorgan confined disease. The accuracy of the model was quantified with the area under the curve, and the positive and negative predictive values were calculated., Results: On pathological evaluation 38 patients (50%) had nonorgan confined tumors. The AUC of the algorithm was 0.79 (95% CI 0.69-0.89). The positive and negative predictive values were 79% (95% CI 71-87) and 74% (95% CI 66-82), respectively., Conclusions: We externally validated a pre-cystectomy model to predict pathological stage. The algorithm may possibly aid in selecting patients who would benefit from neoadjuvant chemotherapy before cystectomy., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We assessed the perspectives of patients with testicular cancer on the placement of a prosthesis at orchiectomy and identified predictors of long-term satisfaction., Materials and Methods: Consecutive patients who underwent radical orchiectomy for testicular cancer in 1995 to 2009 were asked to complete a telephone questionnaire covering background demographics, subjective assessment of implant characteristics, impact of the prosthesis on daily and sexual activities, and overall satisfaction with outcome., Results: A total of 98 patients completed the interview, of whom 86 (87%) received a prosthesis. Median interval from surgery to interview was 6 years and most men were married or engaged in a steady relationship. The majority found the prosthesis to be of appropriate weight and size. The main complaints were firm consistency (70%) and high scrotal position (39%), both of which were significantly associated with lesser patient satisfaction (p = 0.03) and regret of the decision to accept an implant (p = 0.02). Approximately 15% of patients indicated the prosthesis interfered with physical exercise or sexual activity. Younger age at surgery was associated with a greater likelihood of accepting a prosthesis but not with long-term satisfaction. Overall the outcome was rated good to excellent in 77% of cases., Conclusions: Patients with testicular cancer scheduled to undergo orchiectomy should be offered a testicular prosthesis, and reassured that complications are few and that expected long-term satisfaction is fair. Optimizing the texture of the implant and its position in the scrotum may improve outcome. However, patients should be counseled about possible adverse implications in terms of physical exercise or sexual activity., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Long-term prostate cancer specific mortality after radical prostatectomy is poorly defined in the era of widespread screening. An understanding of the treated natural history of screen detected cancers and the pathological risk factors for prostate cancer specific mortality are needed for treatment decision making., Materials and Methods: Using Fine and Gray competing risk regression analysis we modeled clinical and pathological data, and followup information on 11,521 patients treated with radical prostatectomy at a total of 4 academic centers from 1987 to 2005 to predict prostate cancer specific mortality. The model was validated on 12,389 patients treated at a separate institution during the same period. Median followup in the modeling and validation cohorts was 56 and 96 months, respectively., Results: The overall 15-year prostate cancer specific mortality rate was 7%. Primary and secondary Gleason grade 4-5 (each p<0.001), seminal vesicle invasion (p<0.001) and surgery year (p=0.002) were significant predictors of prostate cancer specific mortality. A nomogram predicting 15-year prostate cancer specific mortality based on standard pathological parameters was accurate and discriminating with an externally validated concordance index of 0.92. When stratified by patient age at diagnosis, the 15-year prostate cancer specific mortality rate for pathological Gleason score 6 or less, 3+4, 4+3 and 8-10 was 0.2% to 1.2%, 4.2% to 6.5%, 6.6% to 11% and 26% to 37%, respectively. The 15-year prostate cancer specific mortality risk was 0.8% to 1.5%, 2.9% to 10%, 15% to 27% and 22% to 30% for organ confined cancer, extraprostatic extension, seminal vesicle invasion and lymph node metastasis, respectively. Only 3 of 9,557 patients with organ confined, pathological Gleason score 6 or less cancer died of prostate cancer., Conclusions: Poorly differentiated cancer and seminal vesicle invasion are the prime determinants of prostate cancer specific mortality after radical prostatectomy. The prostate cancer specific mortality risk can be predicted with remarkable accuracy after the pathological features of prostate cancer are known., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: A vesicourethral anastomotic leak after radical prostatectomy is a common postoperative sequela. Rarely additional intervention is required for a persistent or high output urinary leak. We describe a novel solution to this uncommon complication., Materials and Methods: With the patient under general or spinal anesthesia the technique included 19Fr rigid cystoscopy in a partially distended bladder and insertion of 5Fr Single J® ureteral stents over a hydrophilic guidewire under fluoroscopic guidance. The 2 stents were exteriorized via the urethra beside an 18Fr Foley catheter. We monitored urine output and the relative amount of leak. The Jackson-Pratt drains were removed after leakage decreased to 50 ml or less per day. All patients underwent cystogram to ascertain leak resolution before stent removal. Time to continence was estimated using Kaplan-Meier analysis., Results: Seven of 1,480 patients (0.5%) required intervention for a prolonged or high output anastomotic leak after radical prostatectomy. Mean time from surgery to stent insertion was 6.2 days (range 2 to 12). Stents were retained an average of 9 days (range 6 to 11), enabling complete resolution of the leak within a mean±SD of 1.8±0.9 days. Median time to recovery of urinary continence was 20±1.7 weeks., Conclusions: Temporary urinary diversion with exteriorized ureteral stents via the urethra is a safe, effective solution for a prolonged or high output anastomotic leak after radical prostatectomy. Recovery of urinary continence may be delayed in this setting but long-term urinary function appears to be unaffected in most patients., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We assessed the long-term outcome of laser endoureterotomy for benign ureteral stricture., Materials and Methods: From a database of 69 patients who underwent retrograde laser endoureterotomy from October 2001 to June 2007 we identified 35 with a benign ureteral stricture. Clinical characteristics, operative results and functional outcomes were investigated. Success was defined as symptomatic improvement and radiographic resolution of obstruction., Results: Median followup was 27 months (range 10 to 72). All except 1 patient were followed at least 16 months. All patients completed clinical followup and 33 completed imaging. Of 35 patients 29 (82%) were symptom-free during followup and 26 of 33 (78.7%) were free of radiographic evidence of obstruction. All except 1 failure occurred within less than 9 months postoperatively. The success rate was higher for nonischemic strictures (100% vs 64.7%, p = 0.027) and tended to be higher for strictures 1 cm or less (89.4% vs 64.2%, p = 0.109)., Conclusions: Holmium laser endoureterotomy is effective for benign ureteral stricture in well selected patients. Most failures occur within less than 9 months after surgery, which may indicate a need for closer followup during postoperative year 1. Factors that might may outcome are ischemia and stricture length.

Purpose: Standard treatment for testicular germ cell tumor is radical orchiectomy. Several groups have suggested an organ sparing approach in patients with bilateral tumors or tumor in a solitary testis. We determined the prevalence of multifocality in testicular germ cell tumor cases., Materials and Methods: Orchiectomy specimens from 145 consecutive patients treated for testicular germ cell tumor between 1995 and 2006 were included in the study. In the current series slides were reviewed by a single dedicated uropathologist. Multifocality was defined as 1 of 4 distinct pathological entities, including 1) distinct tumor focus conspicuously separable from the main tumor mass, 2) microinvasive tumor characterized by a single or small groups of malignant germ cells scattered within the normal interstitial parenchyma, 3) extra tumor vascular invasion and 4) rete testis invasion by pagetoid tumor spread., Results: Multifocality was identified in 48 patients (33%), of whom 17 (12%) had an additional distinct tumor focus, 21 (14%) had microinvasive tumor, 17 had extra tumor vascular invasion and 2 had rete testis invasion by pagetoid tumor spread. Multifocality was more prevalent in men with smaller tumors and seminomatous histology (pure seminoma or as part of a mixed germ cell tumor). Multifocality was present in 63% of men with an index mass of 2 cm or less in diameter. Study limitations include potential pathological sampling errors resulting from the retrospective design., Conclusions: Multifocality is a frequent finding in testicular germ cell tumor cases that is associated with small mass size and seminomatous histology. Data suggest that additional invasive tumor outside the index mass may be present in up to 63% of men considered potential candidates for organ sparing surgery.

Purpose: We evaluated the prognostic roles of metastasectomy and an established risk stratification system in patients with disease recurrence following nephrectomy for nonmetastatic renal cell carcinoma., Materials and Methods: A retrospective analysis was performed in 129 patients with localized renal cell carcinoma treated with partial or radical nephrectomy and subsequently diagnosed with disease recurrence. At recurrence a previously validated risk score based on Karnofsky performance status, interval from nephrectomy, and serum hemoglobin, calcium and lactate dehydrogenase was used to categorize patients as being at favorable, intermediate or poor risk. Survival from time of recurrence was assessed based on risk categorization and metastasectomy., Results: Median time from nephrectomy to recurrence was 16 months. The risk score was strongly associated with median survival and the 2-year survival rate, including 73 months and 81% for favorable risk, 28 months and 54% for intermediate risk, and 6 months and 11% for poor risk, respectively (log rank <0.001). Metastasectomy performed in 44 patients (34%) was found to be of clinical benefit across the various risk categories (interaction analysis p = 0.8). On multivariate analysis a better risk category and metastasectomy were each independently associated with more favorable survival (each p <0.001). When combined, they provided 6 risk categories with an estimated 2-year survival of 0% to 93%., Conclusions: The clinical course in patients with recurrent renal cell carcinoma following nephrectomy can be variable. It is independently impacted by an objectively determined risk score and whether the patient undergoes metastasectomy.

Purpose: The prognostic significance and optimal management of positive surgical margins following partial nephrectomy remain ill-defined. We combine data from 2 tertiary care intuitions, and report predictors of positive surgical margins and long-term oncological outcomes for patients with positive surgical margins., Materials and Methods: Clinical, pathological and followup data on 1,344 patients undergoing 1,390 partial nephrectomies for kidney cancer were analyzed. Patients with positive surgical margins on final pathology were treated expectantly. Univariate and multivariable logistic regression models were fit to determine clinicopathological features associated with positive surgical margins. The Kaplan-Meier method was used to estimate freedom from local disease recurrence and metastatic progression. Cox proportional hazards models were used to assess whether positive surgical margin predicted local recurrence or metastatic disease adjusting for tumor size, pathological stage, histological subtype and presence of a solitary kidney., Results: Positive surgical margins were documented in 77 cases (5.5%). Decreasing tumor size and presence of a solitary kidney carried a significantly higher risk of positive surgical margins. The overall 10-year probability of freedom from local disease recurrence was 93% (95% CI 89, 95) and from metastatic progression 93% (95% CI 90, 95), with no significant difference between patients with positive vs negative margins (p = 0.97 and 0.18, respectively). Positive surgical margins were not associated with an increased risk of local recurrence or metastatic disease., Conclusions: Positive surgical margins in partial nephrectomy specimens do not uniformly portend an adverse prognosis. While every effort should be taken to ensure clear margins, our data suggest that select patients with a positive surgical margin can be safely offered vigilant monitoring without compromising long-term disease-free survival.

Purpose: Transurethral bladder tumor resection is associated with imperfect clinical staging and incomplete tumor removal. Transurethral prostate resection may be complicated by inadvertent damage to the urinary sphincter, bladder neck and trigone. We performed a multicenter pilot and feasibility study of a novel working element for resectoscopes designed to improve the efficacy and safety of transurethral endoscopic surgery., Materials and Methods: An innovative working element for resectoscopes was developed to convert the standard in/out linear/axial movement at the handgrip into a side-to-side, bidirectional, lateral rotating motion. The device is compatible with current optical technology and conventional electrocautery generators, and it has been granted marketing approval. It consists of variably sized cutting loops designed for transurethral resection of bladder tumors and the prostate. To date 80 patients with bladder cancer (38) or benign prostatic hyperplasia (42) have undergone surgery with this instrument at our 3 clinical sites., Results: No safety concerns were evident. When used during transurethral bladder tumor resection, lateral resection at the base of the tumor enabled accurate depth of penetration into the bladder wall, which may decrease the risk of bladder perforation and improve pathological assessment of tumor invasion. During transurethral prostate resection this novel tool facilitated dissection of adenoma adjacent to the verumontanum and prostatovesical junction, which may decrease the risk of sphincteric damage and bladder neck injury., Conclusions: A novel resectoscope is currently under prospective clinical investigation to establish its surgical and pathological efficacy, ease of use and side effect profile. Current data suggest that the learning curve is mild, its use is safe and it provides distinct advantages when used for transurethral resection of bladder tumors and the prostate.

Purpose: We evaluated risk factors for positive soft tissue surgical margins and the impact of soft tissue surgical margins on metastatic progression and disease specific survival in patients treated with radical cystectomy for bladder cancer., Materials and Methods: A total of 1,589 patients who underwent radical cystectomy for primary urothelial cancer at our institution were included in the study. Several variables were analyzed including gender, age, use of perioperative chemotherapy, tumor stage, tumor grade, presence of carcinoma in situ, pathological vascular invasion, bladder pathology, status of soft tissue surgical margins, lymph node status, number of lymph nodes removed and number of positive lymph nodes. End points were freedom from progression to metastases and disease specific survival., Results: Positive soft tissue surgical margins were detected in 67 patients (4.2%). Risk factors for positive soft tissue surgical margins were female gender (p = 0.04), pathological stage, vascular invasion in the radical cystectomy specimen, lymph node metastases (all p < or = 0.001) and median number of positive lymph nodes (p = 0.002). In addition, nonpure transitional cell carcinoma histology (p = 0.001) was associated with positive soft tissue surgical margins. In the 5 years after cystectomy, rates of disease specific survival for the negative and positive soft tissue surgical margin groups were 72% (95% CI 69-75) and 32% (95% CI 19-54), respectively. On multivariate analysis disease specific death was associated with tumor stage, positive soft tissue surgical margins, vascular invasion, presence of positive lymph nodes, number of nodes removed and number of positive nodes., Conclusions: Risk factors for positive soft tissue surgical margins are female gender, locally advanced cancer, presence of vascular invasion and mixed histology. Patients with positive soft tissue surgical margins have poor prognosis, and positive soft tissue surgical margins were found to be independently associated with disease specific death.

Purpose: Oxidative damage has been linked to prostate carcinogenesis but its role in disease development and progression remains elusive. We investigated associations between indexes of oxidative stress with localized and advanced prostate cancer. Specifically we assessed the susceptibility of serum lipids to copper induced peroxidation (oxidizability)., Materials and Methods: Serum oxidizability, and levels of alpha-tocopherol, malonyldialdehyde and uric acid were assessed in samples from 79 patients with prostate cancer, including 42 with localized and 37 with metastatic disease receiving androgen deprivation therapy, and 25 control subjects. Oxidizability was assayed by continuous spectroscopic monitoring of the accumulation of peroxidation products. The lag preceding oxidation, that is the delay between the induction and propagation of the reaction, served as a measure of the resistance of serum lipids to oxidation., Results: Compared to control subjects patients with localized prostate cancer had no difference in oxidative stress indexes, whereas those with metastatic disease had a shorter lag preceding oxidation and increased malonyldialdehyde (p <0.05), each reflecting a state of high oxidative stress. In patients with prostate cancer the probability of disease progression from localized to advanced state increased with a shorter lag preceding oxidation (p <0.001), increased malonyldialdehyde (p <0.03) and decreased uric acid (p <0.04). Localized and metastatic disease was associated with increased rather than decreased alpha-tocopherol (p <0.008 and <0.005, respectively)., Conclusions: Patients with advanced prostate cancer are subject to high oxidative stress, as determined by increased susceptibility of serum lipids to peroxidation. This association was not detected in patients with localized cancer and it is not attributable to altered levels of alpha-tocopherol.

Purpose: Standardized criteria are lacking to define high risk, clinically localized prostate cancer before definitive treatment. Reliance on simple risk stratification schemes to define high risk cancers has led many physicians and patients toward therapeutic nihilism, inappropriately selecting androgen deprivation instead of definitive local therapy. Of patients undergoing radical prostatectomy we identified those at high risk based on 8 previously described definitions. We examined pathological characteristics and prostate specific antigen outcomes., Materials and Methods: The study population included 4,708 men treated with radical prostatectomy alone between 1985 and 2004. Estimates of prostate specific antigen relapse for patients at high risk were generated with the Kaplan-Meier method. Cox proportional hazards regression was used to estimate the HR for recurrence in high risk vs nonhigh risk cohorts., Results: Depending on the definition used patients at high risk composed 3% to 38% of the study population. The proportion of patients with extracapsular extension, seminal vesicle invasion and lymph node metastasis among men with high risk cancer was 35% to 71%, 10% to 33% and 7% to 23%, respectively. Of the high risk tumors 22% to 63% proved to be confined to the prostate pathologically. While patients at high risk had a 1.8 to 4.8-fold increased hazard of prostate specific antigen relapse, their 5-year relapse-free probability after radical prostatectomy alone was 49% (95% CI 39 to 58) to 80% (95% CI 77 to 83). Of patients at high risk who had relapse 25% across all definitions experienced relapse more than 2 years after surgery and in 26% to 39% prostate specific antigen doubling time at recurrence was 10 months or greater., Conclusions: Patients diagnosed with high risk cancer by currently available definitions do not have a uniformly poor prognosis after radical prostatectomy. Many cancers classified clinically as high risk are actually confined to the prostate pathologically. The risk of extraprostatic disease and prostate specific antigen relapse varies greatly depending on the definition used.

Purpose: Interest has emerged in urinary biomarkers to replace or alternate with followup cystoscopies for routine bladder cancer surveillance. We assessed whether patients would accept a urine biomarker assay over flexible cystoscopy for monitoring bladder cancer., Materials and Methods: We enrolled 200 consecutive patients previously diagnosed with superficial bladder tumors who were undergoing outpatient flexible cystoscopy as followup. Immediately after cystoscopy each patient completed a pain intensity numerical rating and was interviewed. The standard gamble method was applied to determine the minimal accepted diagnostic accuracy at which a urine test would be favored over cystoscopy for bladder surveillance. Clinical and demographic data with potential to affect patient preferences were analyzed., Results: Of the 200 patients 75% would accept the results of a urine test as a replacement for cystoscopy only if it was capable of detecting more than 95% of recurrent bladder tumors and an additional 21% would accept it if the urine test was at least 90% to 95% accurate. Anxiety associated with the possibility of missing cancer was the major determinant of the minimal accepted accuracy. While male gender and higher pain intensity at cystoscopy were associated with willingness to accept a small level of uncertainty on univariate and multivariate analyses, the risk of progression to muscle invasion and the convenience of followup did not appear to affect patient preferences., Conclusions: From the patient perspective a urinary biomarker would likely require 95% or greater diagnostic accuracy to supplant cystoscopies for routine bladder surveillance. Inadequate sensitivity may be the major impediment to general acceptance of urinary biomarkers in this setting.

Purpose: The emergence of laparoscopic nephron sparing surgery has rekindled interest in the impact of warm renal ischemia on renal function. To provide data with which warm renal ischemia can be compared we analyzed short-term and long-term changes in the glomerular filtration rate after temporary cold renal ischemia., Materials and Methods: In patients undergoing open nephron sparing surgery the estimated glomerular filtration rate was assessed preoperatively, early in the postoperative hospital stay, and 1 and 12 months after surgery using the abbreviated Modification of Diet in Renal Disease Study equation. We separately analyzed 70 patients with a solitary kidney and 592 with 2 functioning kidneys. The end point was the percent change from the baseline glomerular filtration rate. A linear regression model was used to test the association between the glomerular filtration rate change, and ischemia time, patient age, tumor size, estimated blood loss and intraoperative fluid administration., Results: Median cold ischemia time was 31 minutes in patients with a solitary kidney and 35 minutes in those with 2 kidneys. Compared to patients with 2 kidneys those with a solitary kidney had a significantly lower preoperative estimated glomerular filtration rate (p < 0.001), which decreased a median of 30% during the early postoperative period, and 15% and 32% 1 and 12 months after surgery, respectively. In patients with 2 kidneys the corresponding glomerular filtration rate decreases were 16%, 13% and 14%, respectively. On multivariate analyses in each group cold ischemia duration and intraoperative blood loss were significantly associated with early glomerular filtration rate changes. However, 12 months after surgery age was the only independent predictor of a glomerular filtration rate decrease in patients with 2 kidneys., Conclusions: Cold renal ischemia during nephron sparing surgery is a significant determinant of the short-term postoperative glomerular filtration rate. Longer clamping time is particularly detrimental in patients with a solitary kidney but it does not appear to influence long-term renal function. Patients of advanced age may be less likely to recover from acute ischemic renal injury.

Purpose: Prostate specific antigen velocity 2.0 ng/ml per year or greater in the year before prostate cancer diagnosis is associated with cancer specific survival following radical prostatectomy and radiation therapy. We evaluated the relationship between prediagnosis prostate specific antigen velocity and cancer progression following primary radiation therapy., Materials and Methods: We analyzed the records of 24,893 men from a community based prostate cancer screening study and identified 237 with clinically localized prostate cancer who elected primary radiation therapy. Our final cohort consisted of 130 men, including 83 treated with external beam radiation and 47 treated with brachytherapy. Patient specific variables at diagnosis were analyzed for their value in predicting biochemical progression using American Society for Therapeutic and Radiation Oncology criteria., Results: Mean followup +/- SD was 64 +/- 35 months. Prostate specific antigen at diagnosis, family history of prostate cancer and prediagnosis prostate specific antigen velocity 2.0 ng/ml per year or greater were associated with cancer progression following brachytherapy or external beam radiation. Of men with prostate specific antigen velocity 2.0 ng/ml per year or greater 38% had cancer progression compared to 12% with prostate specific antigen velocity less than 2.0 ng/ml per year (OR 4.3, p = 0.003). The 6-year progression-free survival estimate was 57% in men with prostate specific antigen velocity 2.0 ng/ml per year or greater and 82% in men with prostate specific antigen velocity less than 2.0 ng/ml per year (p < 0.001). On multivariate analysis absolute prostate specific antigen at diagnosis and prostate specific antigen velocity 2.0 ng/ml per year or greater were independently associated with cancer progression in men treated with external beam radiation therapy or brachytherapy., Conclusions: Men with a prediagnosis prostate specific antigen velocity of 2.0 ng/ml per year or greater are at increased risk for cancer progression following brachytherapy or external beam radiation compared to men with a prostate specific antigen velocity of less than 2.0 ng/ml per year.

Purpose: We assessed the safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients., Materials and Methods: We retrospectively reviewed the charts of 697 patients treated with bacillus Calmette-Guerin instillations at our institution from 1991 to 2004. In 24 patients (3.5%) an underlying comorbidity directly affecting the immune system was diagnosed before bacillus Calmette-Guerin administration or steroids were administered at least 6 weeks before and at the time of bacillus Calmette-Guerin instillations. The immunosuppressive effect of steroids was assessed by the percent of lymphocytes. End points were the bacillus Calmette-Guerin response at 6 months, defined as normal cystoscopy, cytology and biopsy when available, and treatment related toxicity., Results: Four patients (17%) had active lymphoma or chronic lymphocytic leukemia during bacillus Calmette-Guerin administration and 21 (88%) had a concurrent condition for which oral steroids (11), inhaled steroids (14) or oral and inhaled steroids (4) were administered. Patients treated with oral steroids had a lower percent of lymphocytes than patients treated with inhaled steroids and 15 age matched patients with high risk superficial bladder cancer and no steroid treatment (12.3% vs 17.5% and 18.6%, respectively). The overall bacillus Calmette-Guerin response rate at 6 months was 58%. Ten of the 24 patients had disease recurrence and 3 had disease progression at a median followup of 63.5 months (IQR 19.5, 89). One patient treated with oral steroids had self-limited febrile disease and worsening of myalgia 48 hours after his third bacillus Calmette-Guerin cycle. No other systemic adverse event following bacillus Calmette-Guerin therapy was recorded and all patients completed scheduled treatments., Conclusions: Intravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids. The bacillus Calmette-Guerin response rate at 6 months and the side effects profile associated with bacillus Calmette-Guerin therapy in these patients were comparable to those in patients with no evidence of immunosuppression. Further studies are warranted to assess the safety and efficacy of bacillus Calmette-Guerin instillations in critically immunocompromised patients.

Purpose: Conservative treatment of upper urinary tract tumors has been popularized during the last decade. Like in bladder cancer management, localized adjuvant therapy has been advocated to reduce the risk of disease recurrence or progression. In this study we tested the feasibility of creating vesicoureteral reflux (VUR) using a Double-J stent (Medical Engineering Corp., New York, New York) as a measure of efficacy for intravesical adjuvant treatment of the ureter and renal collecting system., Materials and Methods: The cohort included 100 consecutive patients in whom a Double-J stent was inserted for renal obstruction. All the patients underwent cystography in the supine position by retrograde filling of the bladder with a 50% dilute solution of 300 mgI/ml iopromide in serial increments of 50 ml up to a maximum of 350 ml. A total of 41 patients underwent cystography immediately following stent insertion (early group) and 59 patients with indwelling stents underwent cystography before further endourological intervention (late group). The presence of VUR and the level along the ureter and renal collecting system were assessed fluoroscopically., Results: Overall VUR was detected in 56 patients (56%), specifically 11 of the 41 (27%) in the early group and 45 of the 59 (76%) in the late group (p <0.001). There was no correlation between stent diameter or length and VUR, or between patient sex, age or particular side and the likelihood of reflux. Mean minimal intravesical volume required to obtain reflux was 171 +/- 11 ml, which was significantly higher in the early (255 +/- 21 ml) than in the late (146 +/- 11 ml) cystogram group. In 24 of the 56 patients (43%) with VUR, there was complete visualization of the entire ureter and renal collecting system. However, 15 patients (26%) had opacified renal pelves and calices without concomitant visualization of the ureters, whereas 7 patients (31%) had reflux to the ureter without opacification of the renal pelvis., Conclusions: VUR is not a guaranteed consequence of Double-J stent placement. Therefore, when upper urinary tract instillation with the Double-J technique is considered, a cystogram should be performed first to confirm the occurrence of reflux, determine the intravesical volume required to induce reflux and ascertain that the pertinent section of the ureter or pelvicaliceal system from which the tumor was initially removed is opacified during study. An interval that remains to be defined should be allowed between stent insertion and VUR assessment.

Purpose: We report a single center experience with emergency urological consultations and interventions during cesarean sections, and provide several guidelines for the intraoperative diagnosis and management of urological trauma in this specific clinical setting., Materials and Methods: From 1996 to 2003 urological consultations were required in 29 of 10,439 abdominal deliveries (0.3%). Patient files were reviewed for obstetric, surgical and followup data., Results: In 20 patients (69%) cesarean section was done on an emergency basis for fetal distress or placental abruption. Of the 29 urological consults 12 (42%) were for inadvertent cystotomy and 17 (58%) were for suspected injuries to the ureter. Patients with inadvertent cystotomy underwent concomitant assessment of ureteral patency by direct insertion of ureteral catheters through the ureteral orifice. Ureteral obstruction was identified in 1 case and promptly repaired by dissecting the ureter and releasing offending sutures that were angulating the ureter and occluding the lumen. Patients with suspected ureteral damage and an intact bladder were studied by endoscopic means (14) or direct surgical dissection and exposure of the ureter (3). Endoscopic assessment was performed by cystoscopic inspection of stained urine flow from the orifices following the administration of intravenous dye (indigo carmine) or by retrograde ureteral catheterization. One patient was found to have incomplete ureteral transection, which was repaired primarily over a self-retaining ureteral stent., Conclusions: Key factors to obtain optimal results in the management of urological injuries during cesarean sections are the early recognition and immediate repair of damage. Ureteral catheterization via a cystoscope or directly through the orifices should be considered the modality of choice to assess ureteral intactness. Algorithms for urological assessment in this clinical setting are provided.

Purpose: In this retrospective review we characterize the outcomes of patients treated for transitional cell carcinoma in a bladder diverticulum., Materials and Methods: Between 1986 and 2001, 39 patients were treated for tumors in a bladder diverticulum. All patients underwent initial transurethral resection of the tumor. Based on cystoscopic evaluation, bimanual examination and computerized tomography findings, tumors were classified as superficial (Ta, Tis), superficially invasive confined to diverticulum (T1) or extra diverticular (T3+). Patients with superficial or superficially invasive disease were treated either conservatively with repeat transurethral resection, or with partial or radical cystectomy. Patients with extra diverticular extension were treated with partial or radical cystectomy when amenable to surgical extirpation. Predictors of outcome were assessed by univariate and multivariate analyses. End point was overall and disease-specific survival., Results: Of our cohort of 39 patients 13 (33%) presented with superficial disease, 13 (33%) with superficially invasive tumors and 13 (33%) with invasive (extra diverticular) disease. Actuarial 5-year disease specific survival for the cohort was 72 +/- 5.4%. Significant differences in 5-year disease specific survival were observed among patients presenting with superficial tumors (83 +/- 9%), superficially invasive tumors (67 +/- 7%) and extra diverticular disease (45 +/- 14%). Of the patients presenting with T1 tumors the primary mode of treatment did not correlate with outcome. In a multivariate model clinical staging was the only independent predictor of outcome and concomitant carcinoma in situ reached borderline significance., Conclusions: Our data support a conservative approach for tumors confined to the bladder diverticulum, provided complete removal is feasible and close surveillance ensues.

Purpose: The impact of orthotopic urinary diversion on the quality of cystectomy and ensuing cancer control has not been adequately studied. We analyzed our experience with this clinical problem., Materials and Methods: The records of 214 patients who underwent cystectomy and orthotopic diversion for bladder cancer were retrospectively evaluated and compared with those of 269 treated with an ileal conduit. Analyzed end points included overall and cancer specific survival. We specifically assessed the patterns of relapse and their association with pathological findings at cystectomy in the neobladder group., Results: No cancer specific survival difference was identified in the neobladder and ileal conduit cohorts when adjusting for pathological stage. Patterns of relapse in 62 of the 214 patients with a neobladder (29%) included local recurrence in 23 (11%), distant recurrence in 19 (9%), and combined local and distant recurrence in 18 (8%). Urethral recurrence was rare (2%). Of 10 patients (4.6%) diagnosed with upper tract recurrence 6 and 4 initially had relapse in the ureteroenteric anastomosis and renal pelvis, respectively. Five of the 6 patients with anastomotic relapse had evidence of disease in the intramural or juxtavesical ureter that was removed en bloc with the cystectomy specimen. Only 1 patient required neobladder takedown after such anastomotic recurrence., Conclusions: These results indicate that neobladders do not compromise the quality of preceding cystectomy or interfere with management in the presence of local or distant disease relapse. Our data suggest that involvement of the intramural or juxtavesical ureteral segment at cystectomy irrespective of surgical margin status may identify patients at higher risk for anastomotic recurrence, which is associated with an ominous prognosis.

Purpose: Bladder neck invasion by prostate cancer in radical prostatectomy specimens is uncommon and, thus, its influence on disease recurrence has not been well defined. Consequently the classification of bladder neck invasion in the TNM staging system is controversial. We studied our cohort of patients with stage pT4 disease and bladder neck invasion to clarify the true clinical behavior and prognostic significance of bladder neck invasion in radical prostatectomy specimens., Materials and Methods: The study group consisted of 4,090 consecutive patients treated with radical prostatectomy at one of our institutions between 1983 and 2001. Median followup was 53.1 months (range 1 to 189). After excluding from analysis patients treated with neoadjuvant androgen withdrawal or preoperative irradiation 72 of the remaining 2,571 (2.8%) with bladder neck invasion were classified with stage pT4 disease and their specimens were reviewed. Progression-free probability was determined by Kaplan-Meier analysis. Using the Cox proportional hazards model the independent prognostic significance of bladder neck invasion was assessed after controlling for pretreatment prostate specific antigen, final Gleason sum, extracapsular extension, surgical margins status, seminal vesicle invasion and lymph node involvement., Results: Of the 72 patients categorized with stage pT4 disease 14 (19%) had poorly differentiated Gleason sum 8 to 10 cancer, 38 (53%) had established extracapsular extension, 24 (33%) had seminal vesicle invasion and 8 (11%) had lymph node involvement. However, 26 patients (36%) had cancer confined to the prostate and 28 (39%) had negative surgical margins except for the bladder neck site. The mean 5-year progression-free probability plus or minus SD in all stage pT4 cases was 68% +/- 7%, which was better than in cases of seminal vesicle invasion (52% +/- 5%, log rank test p = 0.0156) but worse than in those of extracapsular extension (84% +/- 4.1%). Univariate analysis of the stage pT4 cohort revealed that higher prostatectomy Gleason sum, more extensive extracapsular extension and seminal vesicle invasion were significantly associated with an adverse prognosis. However, in a multivariate model that included all radical prostatectomy cases the finding of bladder neck invasion or stage pT4 disease did not independently predict prostate specific antigen recurrence., Conclusions: Stage pT4 disease comprises a heterogeneous group of tumors with various pathological features and inconsistent outcomes. Assigning the pT4 stage to cases of microscopic bladder neck invasion provides no independent ability for predicting disease progression after adjusting for other adverse disease features. Due to this and previously reported data the definition of stage pT4 disease should be modified in the next version of the TNM staging system.

Purpose: The natural history and prognosis of bladder cancer in young patients is not well defined. We analyzed our experience with such patients., Materials and Methods: The medical records of 74 patients presenting with transitional cell carcinoma of the bladder at 40 years and younger were reviewed and compared with those of 75 patients diagnosed with bladder transitional cell carcinoma at 65 years old and older., Results: Median followup was 28.1 months (range 1 to 155) and 34.7 (range 1 to 178) in young and old patients, respectively. Initial stage distribution was similar with 80% of patients presenting with superficial disease. No difference was observed in the disease-free progression or disease-free recurrence rate among the groups in patients initially presenting with stage Ta, Tis or T1 tumors. A significantly higher proportion of older versus younger patients underwent cystectomy (54% versus 23%). We did not observe a difference in pathological stage distribution or the rate of extravesical disease in young and old patients (47% and 45%, respectively). Younger patients who ultimately underwent radical cystectomy had significantly lower disease-free survival, mainly due to a higher rate of distant metastases than in the older group (41% versus 24%). The rate of local recurrence was similar., Conclusions: Bladder transitional cell carcinoma in young adults has a clinical stage distribution and natural history similar to that in older patients. Our study suggests that a subset of young patients who ultimately undergo radical cystectomy have particularly aggressive tumors, portending a poor outcome.