Search

Objectives . To compare the clinicopathologic characteristics of urothelial carcinoma (UC), urothelial carcinoma with squamous differentiation (UCSD), and squamous cell carcinoma (SCC) of the bladder, which have been suggested to differ in terms of risk factors, immunophenotype, and prognosis. Methods . We evaluated the clinicopathologic features of radical cystectomy specimens between 1980 and 2015 with a diagnosis of SCC, UCSD, and UC. PD-L1 immunohistochemistry (clinically available clones 22C3, SP142, and SP263) was performed on SCC and UCSD. Multivariate Cox regression was used to identify prognostic factors. Kaplan-Meier curves were plotted to assess cancer-specific survival (CSS). Results . Of the 1478 cases, there were 1126 UC (76%), 217 UCSD (15%), and 135 SCC (9%). Bladder cancer was more common in men than women (80% vs 20%, P  < .0001). However, a higher proportion of SCC and UCSD occurred in women (SCC-36%, UCSD-22%, UC-18%). Women were significantly more likely to be never smokers in all 3 cohorts (UC: 45% vs 16%, UCSD: 44% vs 12%, SCC: 40% vs 18%, P  < .0001). Patients with SCC and UCSD were at a higher pathologic stage (>pT2) at the time of cystectomy (UCSD-74%, SCC 71%, UC-44%, P  < .0001) and had worse CSS compared to patients with UC ( P  = 0.006). SCC had higher PD-L1 scores (all clones) than UCSD ( P  < .0001). PD-L1 22C3 ( P  = .02, HR: 0.36) and SP142 scores ( P  = .046, HR: 0.27) predicted CSS on Kaplan-Meier analysis for SCC cases. Conclusions . UC, UCSD, and SCC are associated with different risk factors, gender distributions, and clinical outcomes. PD-L1 is expressed in SCC and UCSD, suggesting some patients may benefit from targeted therapy.

Bacillus Calmette-Guérin (BCG) is the most widely used vaccine worldwide and has been used to prevent tuberculosis for a century. BCG also stimulates an anti-tumour immune response, which urologists have harnessed for the treatment of non-muscle-invasive bladder cancer. A growing body of evidence indicates that BCG offers protection against various non-mycobacterial and viral infections. The non-specific effects of BCG occur via the induction of trained immunity and form the basis for the hypothesis that BCG vaccination could be used to protect against the severity of coronavirus disease 2019 (COVID-19). This Perspective article highlights key milestones in the 100-year history of BCG and projects its potential role in the COVID-19 pandemic., (© 2021. Springer Nature Limited.)

Introduction: We aimed to identify preoperatively available patient variables associated with increased mortality within 30 and 90 days of radical cystectomy (RC) for localized urothelial carcinoma (UC), and to evaluate temporal trends in early mortality rates., Methods: We reviewed the National Cancer Database to identify patients who underwent RC for UC between 2006 and 2013. Preoperatively available patient-specific demographics and mortality rates at 30 and 90 days postoperatively were analyzed. Univariable and multivariable logistic regression analyses were performed to examine factors associated with 30- and 90-day mortality., Results: We identified 37 366 patients who underwent RC between 2006 and 2013. Overall mortality rates remained stable over time. From 2006-2013, 936 patients (2.5%) and 2554 patients (6.8%) died of any cause within 30 and 90 days post-RC, respectively. On multivariable analysis, increased age, higher clinical T and N stage, increased Charlson-Deyo comorbidity classification, African-American race, lower hospital volume, non-academic centers, lower patient income, and absence of insurance were each significantly associated with increased early mortality after RC (p<0.05). The protective effect of higher hospital volume was similar regardless of patient's age, clinical stage, or comorbidity status., Conclusions: Our study identified patient-specific variables that are significantly associated with increased early mortality after RC. These findings can be used in counselling to identify ideal candidates for RC to decrease patient harm. Furthermore, early mortality rates after RC have remained stable over time, indicating that ongoing quality improvement is essential to improve outcomes.

Objective: To evaluate the clinical features, pathologic features, and prevalence of human papilloma virus (HPV) in squamous cell carcinoma (SCC) of the bladder. SCC of the bladder is known to be associated with conditions that cause chronic inflammation/irritation. The literature is inconsistent regarding the association of HPV with pure SCC of the bladder., Methods: A multi-institutional study identified cases of SCC of the bladder. Pure squamous histology and the absence of urothelial carcinoma in situ were required for inclusion. Clinical and pathologic features were collected, and tissues were evaluated for high-risk HPV using p16 immunohistochemistry and in situ hybridization., Results: We identified 207 cases of SCC of the bladder. Risk factors for bladder cancer included smoking (133/207, 64%) and chronic bladder irritation (83/207, 40%). The majority (155/207, 75%) of patients had > pT2 disease. Mean tumor size was 5.6 ± 3.0 cm and 36/207 (17%) patients had lymph node positive disease. p16 immunohistochemistry was positive in 52/204 (25%) cases but high-risk HPV was identified with in situ hybridization in only 1 (0.5%) case. Tumor size, stage, number of lymph nodes removed, number of positive lymph nodes, lymphovascular invasion, perineural invasion, and positive margins each were associated with cancer-specific mortality when adjusted for demographic factors. A multivariate analysis of variable importance further revealed sex and race as important factors in predicting cancer-specific mortality., Conclusion: SCC of the bladder is an aggressive histologic subtype. Although bladder SCC can express p16, it is not typically associated with high-risk HPV, although rare cases can occur., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Bladder cancer has the sixth highest incidence in the United States. Treatment of metastatic bladder cancer is difficult, and mortality is certain. There are certain pathways in cancer growth and progression that are important in bladder cancer development. Recently, the estrogen pathway has been found to be a potential target for therapy., Methods: We identified 410 patients treated with radical cystectomy for urothelial cell carcinoma between 1990 and 1994. We obtained representative paraffin-embedded tissue blocks for 336 (82.0%) of these cases and evaluated the expression and intensity of estrogen receptor (ER)-α, ER-β, and progesterone receptor by immunohistochemistry., Results: Among the 12 ER-α-positive cases, median tumor ER-α expression was 10% (range, 10%-50%). In contrast to ER-α, all cases were ER-β-positive. Median tumor ER-β expression was 90% (range, 20%-100%). Nearly all cases had ER-β expression of ≥ 90% (175 [55.9%] with 90% and 103 [32.9%] with 100%). However, the intensity of ER-β staining varied from focal to moderate to marked in 64 (20.5%), 167 (53.4%), and 82 (26.2%) cases, respectively. Progesterone receptor expression was noted to be negative in all cases., Conclusions: ER-β is highly expressed in bladder cancer. Prospective validation of these data might further elucidate the utility of ER-β as a marker for prognosis or possible target for therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Although the kidney is a primary organ for vitamin D metabolism, the association between vitamin D and renal cell cancer (RCC) remains unclear., Methods: We prospectively evaluated the association between predicted plasma 25-hydroxyvitamin D [25(OH)D] and RCC risk among 72,051 women and 46,380 men in the period from 1986 to 2008. Predicted plasma 25(OH)D scores were computed using validated regression models that included major determinants of vitamin D status (race, ultraviolet B flux, physical activity, body mass index, estimated vitamin D intake, alcohol consumption, and postmenopausal hormone use in women). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. All statistical tests were two-sided., Results: During 22 years of follow-up, we documented 201 cases of incident RCC in women and 207 cases in men. The multivariable hazard ratios between extreme quintiles of predicted 25(OH)D score were 0.50 (95% CI = 0.32 to 0.80) in women, 0.59 (95% CI = 0.37 to 0.94) in men, and 0.54 (95% CI = 0.39 to 0.75; P trend<.001) in the pooled cohorts. An increment of 10 ng/mL in predicted 25(OH)D score was associated with a 44% lower incidence of RCC (pooled HR = 0.56, 95% CI = 0.42 to 0.74). We found no statistically significant association between vitamin D intake estimated from food-frequency questionnaires and RCC incidence., Conclusion: Higher predicted plasma 25(OH)D levels were associated with a statistically significantly lower risk of RCC in men and women. Our findings need to be confirmed by other prospective studies using valid markers of long-term vitamin D status., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Clear-cell renal-cell carcinomas display divergent clinical behaviours. However, the molecular genetic events driving these behaviours are unknown. We discovered that BAP1 is mutated in about 15% of clear-cell renal-cell carcinoma, and that BAP1 and PBRM1 mutations are largely mutually exclusive. The aim of this study was to investigate the clinicopathological significance of these molecular subtypes and to determine whether patients with BAP1-mutant and PBRM1-mutant tumours had different overall survival., Methods: In this retrospective analysis, we assessed 145 patients with primary clear-cell renal-cell carcinoma and defined PBRM1 and BAP1 mutation status from the University of Texas Southwestern Medical Center (UTSW), TX, USA, between 1998 and 2011. We classified patients into those with BAP1-mutant tumours and those with tumours exclusively mutated for PBRM1 (PBRM1-mutant). We used a second independent cohort (n=327) from The Cancer Genome Atlas (TCGA) for validation. In both cohorts, more than 80% of patients had localised or locoregional disease at presentation. Overall both cohorts were similar, although the TCGA had more patients with metastatic and higher-grade disease, and more TCGA patients presented before molecularly targeted therapies became available., Findings: The median overall survival in the UTSW cohort was significantly shorter for patients with BAP1-mutant tumours (4·6 years; 95% CI 2·1-7·2), than for patients with PBRM1-mutant tumours (10·6 years; 9·8-11·5), corresponding to a HR of 2·7 (95% CI 0·99-7·6, p=0·044). Median overall survival in the TCGA cohort was 1·9 years (95% CI 0·6-3·3) for patients with BAP1-mutant tumours and 5·4 years (4·0-6·8) for those with PBRM1-mutant tumours. A HR similar to the UTSW cohort was noted in the TCGA cohort (2·8; 95% CI 1·4-5·9; p=0·004). Patients with mutations in both BAP1 and PBRM1, although a minority (three in UTSW cohort and four in TCGA cohort), had the worst overall survival (median 2·1 years, 95% CI 0·3-3·8, for the UTSW cohort, and 0·2 years, 0·0-1·2, for the TCGA cohort)., Interpretation: Our findings identify mutation-defined subtypes of clear-cell renal-cell carcinoma with distinct clinical outcomes, a high-risk BAP1-mutant group and a favourable PBRM1-mutant group. These data establish the basis for a molecular genetic classification of clear-cell renal-cell carcinoma that could influence treatment decisions in the future. The existence of different molecular subtypes with disparate outcomes should be considered in the design and assessment of clinical studies., Funding: Cancer Prevention and Research Institution of Texas and National Cancer Institute., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Physical activity may decrease renal cancer risk by reducing obesity, blood pressure, insulin resistance, and lipid peroxidation. Despite plausible biologic mechanisms linking increased physical activity to decreased risk for renal cancer, few epidemiologic studies have been able to report a clear inverse association between physical activity and renal cancer, and no meta-analysis is available on the topic., Methods: We searched the literature using PubMed and Web of Knowledge to identify published non-ecologic epidemiologic studies quantifying the relationship between physical activity and renal cancer risk in individuals without a cancer history. Following the PRISMA guidelines, we conducted a systematic review and meta-analysis, including information from 19 studies based on a total of 2,327,322 subjects and 10,756 cases. The methodologic quality of the studies was examined using a comprehensive scoring system., Results: Comparing high vs low levels of physical activity, we observed an inverse association between physical activity and renal cancer risk (summary relative risk (RR) from random-effects meta-analysis=0.88; 95% confidence interval (CI)=0.79-0.97). Summarising risk estimates from high-quality studies strengthened the inverse association between physical activity and renal cancer risk (RR=0.78; 95% CI=0.66-0.92). Effect modification by adiposity, hypertension, type 2 diabetes, smoking, gender, or geographic region was not observed., Conclusion: Our comprehensive meta-analysis provides strong support for an inverse relation of physical activity to renal cancer risk. Future high-quality studies are required to discern which specific types, intensities, frequencies, and durations of physical activity are needed for renal cancer risk reduction., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Clinical and experimental findings suggest that female hormonal and reproductive factors could influence kidney cancer development. To evaluate this association, we conducted analyses in 2 large prospective cohorts (the National Institutes of Health-AARP Diet and Health Study (NIH-AARP), 1995-2006, and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), 1993-2010). Cohort-specific and aggregated hazard ratios and 95% confidence intervals relating reproductive factors and kidney cancer risk were computed by Cox regression. The analysis included 792 incident kidney cancer cases among 283,952 postmenopausal women. Women who had undergone a hysterectomy were at a significantly elevated kidney cancer risk in both NIH-AARP (hazard ratio = 1.28, 95% confidence interval: 1.09, 1.50) and PLCO (hazard ratio = 1.41, 95% confidence interval: 1.06, 1.88). Similar results were observed for both cohorts after analyses were restricted to women who had undergone a hysterectomy with or without an oophorectomy. For the NIH-AARP cohort, an inverse association was observed with increasing age at menarche (P for trend= 0.02) and increasing years of oral contraceptive use (P for trend = 0.02). No clear evidence of an association with parity or other reproductive factors was found. Our results suggest that hysterectomy is associated with increased risk of kidney cancer. The observed associations with age at menarche and oral contraceptive use warrant further investigation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the role of cytoreductive radiofrequency ablation (cRFA) in patients with metastatic renal cell carcinoma (RCC) with small primary tumours treated with immuno- or targeted therapy. To assess the efficacy of sunitinib in patients with metastatic RCC with unresected small primary tumours., Patients and Methods: Three parallel single-arm prospective studies were conducted. Eligibility criteria were nearly identical for all trials and included: histopathologically confirmed RCC; metastatic measurable disease; size of primary tumour <5cm; good or intermediate prognosis according to the Memorial Sloan-Kettering Cancer Center model; and no previous therapy. Study 1: Patients were treated with percutaneous cRFA under computed tomography guidance followed by interferon (IFN)-α, 9 MIU, s.c., three times per week. Study 2: Patients received cRFA followed by sunitinib in repeated 6-week cycles of 50mg/day orally for 4 weeks, then 2 weeks off treatment. Study 3: Patients with unresected primary RCC received sunitinib alone. The primary endpoint was progression-free survival (PFS)., Results: Baseline patient characteristics (age, gender, histology, Eastern Cooperative Oncology Group performance status, metastatic sites, primary tumour size) were similar in all three studies. Efficacy data for 114 evaluable patients showed an objective response rate of 8% (95% confidence interval [CI] 4.5, 10.5) for study 1, 28.9% (95% CI 15.2, 34) for study 2, and 31.6% (95% CI 20.3, 38.9) for study 3. The median (95% CI) PFS times were 9.1 (6.9, 10.2), 13.4 (9.8, 14.4) and 12.7 (11.3, 13.5) months for studies 1, 2 and 3, respectively. Objective response rate was significantly higher and PFS significantly longer in the sunitinib trials than in study 1 (P<0.01 all differences); no differences were found between studies 2 and 3 (objective response rate, P = 0.1; PFS, P = 0.6). Study 1 met its primary endpoint, showing that PFS was significantly longer than the expected 5 months (P = 0.02). The median (95% CI) objective survival (OS) times were greater in study 2 (cRFA/sunitinib) and study 3 (sunitinib-alone) than in study 1 (IFN-α) at 27.2 (22.6, 31.8) and 22.5 (20.7, 24.3) vs 19.5 (16.3, 22.7) months, respectively. Differences were significant (study 1 vs 2, hazard ratio [HR] = 0.55; P = 0.003; study 1 vs study 3 HR = 0.6, P = 0.01). OS was significantly longer in the cRFA/sunitinib group compared with the sunitinib-alone group (HR = 0.71; P = 0.04). There were no unexpected toxicities of medical treatment or complications of cRFA., Conclusions: cRFA is a safe and effective approach for select patients with metastatic RCC treated with immunotherapy. The cRFA technique did not improve PFS in patients treated with sunitinib; cRFA probably has impact on OS in these patients. This needs to be tested in a larger trial. Sunitinib was effective in patients with metastatic RCC with unresected small primary tumours., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Data regarding the natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) and adjuvant radiotherapy (aRT) are limited., Objective: To evaluate cancer-specific (CSM) and other-cause mortality (OCM) in prostate cancer patients with BCR after RP and aRT., Design, Setting, and Participants: We identified 336 patients with BCR treated between 1990 and 2006 at two tertiary care centers., Intervention: All patients underwent RP plus aRT., Outcome Measurements and Statistical Analysis: Cox regression analyses were used to evaluate the association between clinicopathologic variables and CSM. The coefficients of CSM-independent predictors were used to develop a novel nomogram. Patients were stratified into groups according to nomogram-calculated CSM probability and median age. Competing-risks survival analyses were used to estimate CSM and OCM for each group., Results and Limitations: Ten-year CSM and OCM were 21.5 and 21.7%, respectively. On multivariable analyses, short time to BCR, pathologic Gleason score ≥ 8, and positive lymph node count of more than two at RP were significantly associated with increased CSM rate (all p ≤ 0.01). These variables were used to develop a novel nomogram, which was used to stratify patients according to their 10-yr, nomogram-calculated, CSM probability: ≤ 10% versus >10-30% versus >30%. On competing-risks analysis, 10-yr CSM rate for these groups was 6%, 15%, and 42%, respectively, for patients aged ≤ 68 yr, versus 8%, 19%, and 42% for patients aged >68 yr. Likewise, 10-yr OCM rate was 24%, 9%, and 10%, respectively, for patients aged ≤ 68 yr, versus 37%, 20%, and 28%, respectively, for patients aged >68 yr. The study is limited by its retrospective design., Conclusions: Short time to BCR, pathologic Gleason score ≥ 8, and more than two positive lymph nodes were independent predictors of CSM in patients with BCR after RP and aRT. Men with these features may benefit from additional secondary therapies, ideally, in a clinical trial setting., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the affect of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC. Eight hundred and two patients (457 nonsmokers and 345 smokers) who had up to 232 months of follow-up were compared for differences in their clinicopathologic features and survival outcomes. Immunohistochemical differences in p53 expression were correlated with smoking status. Smokers presented more commonly with pulmonary comorbidities (P <0.0001) and cardiac comorbidities (P = 0.014) and with a worse performance status (P = 0.031) than nonsmokers. Smoking was associated significantly with tumor multifocality (P = 0.022), higher pathologic tumor classification (P = 0.037), an increased risk of bulky lymph node metastases (P = 0.031), and the presence of distant metastases (P <0.0001), especially lung metastases (P <0.0001). Both overall survival (62.37 months vs. 43.64 months; P = 0.001) and cancer-specific survival (CSS) (87.43 months vs. 56.57 months; P = 0.005) were significantly worse in patients who smoked. The number of pack-years was retained as an independent predictor of CSS and overall survival in patients with nonmetastatic disease. Mean expression levels of p53 were significantly higher in current smokers compared with former smokers and nonsmokers (P = 0.012). In patients with RCC, a history of smoking was associated with worse pathologic features and survival outcomes, and with an increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in patients with RCC who have a history of smoking is indicated., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We evaluated the morbidity of nephrectomy in patients older than 80 years of age. Between June 2002 and March 2011, 2,530 patients underwent surgery for renal tumor at 5 French academic centers. Of these patients, 180 (7.1%) were 80 years of age or older; 22 (12%) and 158 (88%) patients underwent partial and radical nephrectomy, respectively, and 47 (26.1%) of whom were treated with a laparoscopic approach. Mean patient age was 82.3 years. Median Charlson score was 4. Mean preoperative glomerular filtration rate was 47 ml/min. A total of 136 complications were recorded in 70 patients (38.8% of all patients). Of these patients, 28 (15.5%), 25 (13.9%), and 17 (9.4%) experienced 1, 2, and 3 or more complications, respectively. According to the modified Clavien classification grade I, II, III, IV, and V complications were observed in 7, 81, 19, 23, and 6 patients, respectively. The transfusion rate was 31.1% (56). On logistic regression analysis, the parameters of Eastern Cooperative Oncology Group Performance Status 2 to 4 (P = 0.035) and preoperative glomerular filtration rate less than 30 ml/min (P = 0.03) were independent predictive factors of morbidity. Morbidity and mortality are significant in the octogenarian population. The risk of complications should be considered in decision making for patients with renal cell carcinoma who were older than age 80 years., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Study type-therapy (case series). Level of evidence 4. What's known on the subject? And what does the study add? Minimizing renal ischemia and reperfusion injury is an area of active investigation and is particularly significant in cases of laparoscopic renal surgery where the kidney experiences warm ischemia. Reports of partial clamping, early unclamping, and off-clamp (OC) laparoscopic partial nephrectomy (LPN) have demonstrated potential technical modifications that can offer a protective role in preserving renal function. We investigated OC LPN for tumors with varying clinical stage to determine feasibility, perioperative outcomes, and renal functional changes when compared with a contemporary cohort of standard LPN with complete hilar clamping performed by a single surgeon. To compare the operative outcomes and oncological efficacy of OC LPN vs. complete hilar control (HC) LPN for stage T1a-T2 renal cell carcinoma. Retrospective review of all LPNs between June 2006 and March 2010 was performed, stratifying 390 patients by clinical T stage (cT1a = 313, cT1b = 62, cT2 = 15). Perioperative and postoperative parameters were analyzed comparing patients who underwent OC LPN (n = 126) with those who had HC LPN (n = 264) collectively and within each clinical stage cohort. There was no significant difference in the proportion of OC LPN for cT1a tumors compared with cT1b and cT2, P = 0.21. OC vs. HC LPN patients had a greater estimated blood loss but with no significant difference in perioperative blood transfusion rates. When compared by clinical stage, estimated blood loss was greater only for clinical stage T1a disease (P = 0.02) but not cT1b (P = 0.91) or cT2 (P = 0.42) tumors. There was no difference in the operative time or length of hospitalization between OC and HC LPN by stage: cT1a (P = 0.77 and P = 0.17), cT1b (P = 0.77 and P = 0.07) and cT2 (P = 0.42 and P = 0.66), respectively. In our series, 1 case (0.3%) of HC LPN had a positive margin on final pathology, 1 case was converted to open partial nephrectomy (0.3%), and 2 cases of OC LPN (1.6%) were intraoperatively converted to HC LPN. OC LPN is a feasible surgical option for patients with cT1-T2 renal cell carcinoma that completely avoids renal ischemic injury, with the benefits of minimally invasive surgery. LPN can be performed OC in patients with larger, more complex renal tumors without compromising the operative time, blood loss requiring transfusions, length of hospitalization, complication rates, or positive surgical margin rates compared with HC LPN., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Although partial nephrectomy is the preferred treatment for many patients with early-stage kidney cancer, recent clinical trial data, which demonstrate better survival for patients treated with radical nephrectomy, have generated new uncertainty regarding the comparative effectiveness of these treatment options. To compare long-term survival after partial vs. radical nephrectomy among a population-based patient cohort whose treatment reflects contemporary surgical practice. We performed a retrospective cohort study of Medicare beneficiaries with clinical stage T1a kidney cancer treated with partial or radical nephrectomy from 1992 to 2007. Using an instrumental variable approach to account for measured and unmeasured differences between treatment groups, we fit a 2-stage residual inclusion model to estimate the treatment effect of partial nephrectomy on long-term survival. Overall survival and kidney cancer-specific survival. Among 7,138 Medicare beneficiaries with early-stage kidney cancer, we identified 1,925 patients (27.0%) treated with partial nephrectomy and 5,213 patients (73.0%) treated with radical nephrectomy. During a median follow-up of 62 months, 487 (25.3%) and 2,164 (41.5%) patients died following partial or radical nephrectomy, respectively. Kidney cancer was the cause of death for 37 patients (1.9%) treated with partial nephrectomy, and 222 patients (4.3%) treated with radical nephrectomy. Patients treated with partial nephrectomy had a significantly lower risk of death (hazard ratio 0.54; 95% CI, 0.34-0.85). This corresponded with a predicted survival increase with partial nephrectomy of 5.6 (95% CI, 1.9-9.3), 11.8 (95% CI, 3.9-19.7), and 15.5 (95% CI, 5.0-26.0) percentage points at 2, 5, and 8 years post treatment (P <0.001). No difference was noted in kidney cancer-specific survival (hazard ratio 0.82; 95% CI, 0.19-3.49). Among Medicare beneficiaries with early-stage kidney cancer who were candidates for either surgery, treatment with partial rather than radical nephrectomy was associated with improved survival., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To investigate the use the sildenafil citrate, recognized as a first-line therapy for men with erectile dysfunction (ED), and which is safe and effective in men with various causes and severity of ED, including psychogenic ED, in a population of infertile men with sexual dysfunction., Patients and Methods: Infertility is a major source of life stress and might be associated with sexual dysfunction through the erosion of self-esteem and self-confidence, and in stimulating discord in a relationship. Men presenting for evaluation of fertility who on questioning by the physician reported the recent onset of sexual dysfunction, had a history taken, a physical examination, hormonal profile, and completed the International Index of Erectile Function (IIEF), a validated inventory for assessing sexual dysfunction. Thirty men with a score of <26 on the erectile function domain of the IIEF, or who complained of new onset rapid or delayed ejaculation, were treated with sildenafil with no randomization or placebo control. The evaluation was repeated and the IIEF completed again > or =3 months after starting treatment., Results: For men complaining of ED, subjective erectile rigidity, duration of erection, and the percentage of successful penetration attempts significantly improved with sildenafil. The mean (sd) IIEF domain scores for erection and satisfaction, at 18 (4) vs 27 (3), and 12 (2) vs 16 (3) (both P = 0.01), and orgasm, at 4 (1) vs 6 (3) (P = 0.001), respectively, significantly improved after treatment. In patients with ejaculatory dysfunction, the function improved in 64% after sildenafil therapy., Conclusions: We identified the nature of sexual dysfunction associated with male-factor infertility, and showed the efficacy of sildenafil therapy in men with this condition.

Purpose: We evaluated a large disease registry to determine the incidence of bladder cancer in patients with prostate cancer and investigate whether the type of treatment for prostate cancer increased the risk of bladder cancer., Materials and Methods: We analyzed the CaPSURE disease registry for men diagnosed with prostate cancer plus bladder cancer between 1989 and 2003. Demographics, comorbidities and prostate cancer treatment modalities were compared in patients with and without bladder cancer. A backward stepwise Cox proportional hazards regression model was used to predict bladder cancer onset after treatment for prostate cancer in patients who had bladder cancer 30 days or greater after prostate cancer treatment., Results: Of 9,780 patients from CaPSURE 143 (1.46%) also had bladder cancer. Patients with bladder cancer and prostate cancer were older (p<0.01) and more likely to be white (p=0.03), and they had lower levels of income (p<0.01) and education (p=0.04) than patients with prostate cancer only. Comorbidities did not differ between patients with and without bladder cancer. Patients treated with radical prostatectomy were approximately half as likely to have posttreatment bladder cancer as patients who underwent radiation therapy (HR 0.51, 95% CI 0.29-0.89). Patients who smoked had an independent increase in the risk of bladder cancer (HR 2.08, 95% CI 1.09-3.97), while smokers treated with radiation therapy were at almost 4-fold risk for bladder cancer (HR 3.65, 95% CI 1.45-9.16)., Conclusions: The incidence of bladder cancer in patients with prostate cancer was 1.5%. Radiation therapy and smoking increased the risk of bladder cancer.

Background: Men diagnosed with clinically localized prostate carcinoma have several treatment options. The investigation of these options may delay the initiation of definitive therapy. In the current study, the authors evaluated whether time from biopsy to radical prostatectomy (RP) was predictive of postoperative biochemical disease recurrence (BCR)., Methods: A total of 3149 consecutive patients who underwent RP as their initial treatment for prostate carcinoma within a year of diagnosis were identified. The time between diagnosis and RP was entered as a predictor in a multivariate logistic regression model predicting BCR at 3 years, 5 years, 8 years, and 10 years. The year surgery was performed and the nomogram-predicted probability of recurrence, which incorporates stage of disease, Gleason grade, and prostate-specific antigen (PSA) level, were used as covariates., Results: The authors found no clear evidence of a significant effect of delay to diagnosis on BCR. For those patients treated within 6 months (96% of the total sample) the odds ratio for each additional month of delay was 1.04, 1.07, 1.08, and 1.02, respectively, for 3-year, 5-year, 8-year, and 10-year BCR-free survival (P>0.2 for all analyses). However, the 95% confidence intervals were wide and included the possibility that even a minor delay in surgery might have a large impact on the probability of BCR., Conclusions: The time between biopsy and surgery does not appear to have a large effect on the risk of disease recurrence. Counseling patients on the importance of avoiding undue delay to surgery must be based on clinical judgment, particularly with respect to modifying advice based on the patient's risk., (Copyright (c) 2005 American Cancer Society.)

Purpose: Victor Fray Marshall (1913 to 2001) contributed to advancements in a variety of fields within urology, including incontinence, oncology, stone disease and pediatrics., Materials and Methods: We reviewed historical records from the New York Hospital archives as well as the original publications of Marshall. Personal experiences of former residents and others were recounted., Results: While Marshall may be most recognized for Marshall-Marchetti-Krantz vesicourethral suspension, designed to correct stress urinary incontinence, he was among the earliest advocates of surgical extirpation for bladder cancer and helped introduce the use of urinary cytology for the diagnosis of urothelial malignancy. At the same time Marshall contributed to the development of ureteroscopy for stone disease. His contributions to pediatric urology include the description of a nonrefluxing ureteral re-implantation technique for the surgical correction of reflux as well as his investigation of the embryology and surgical repair of bladder exstrophy., Conclusions: The contributions of Victor Marshall to urology are notable in breadth and significance.

Objectives: To investigate whether a delay in nephroureterectomy for patients with transitional cell carcinoma of the upper urinary tract owing to ureteroscopic biopsy and/or laser tumor ablation affects postoperative disease status., Methods: Of 155 patients diagnosed with upper tract transitional cell carcinoma at our institution from 1993 to 2003, 121 underwent nephroureterectomy. We compared the postoperative disease status of patients who underwent nephroureterectomy on the basis of positive cytology findings and filling defect on contrast imaging (no ureteroscopy; n = 34) to patients who underwent nephroureterectomy after ureteroscopic biopsy (n = 75) and patients who underwent nephroureterectomy after ureteroscopic biopsy and laser tumor ablation (n = 12)., Results: At a mean follow-up of 38.7 months, 29 (85.3%) of 34 patients who underwent nephroureterectomy on the basis of contrast imaging and urinary cytology alone were disease free compared with 61 (81.3%) of 75 patients who underwent ureteroscopic biopsy before nephroureterectomy (P = 0.18). The mean time from biopsy to nephroureterectomy for these 75 patients was 28 days, and the mean follow-up after nephroureterectomy was 40.1 months. Finally, 10 (83.3%) of 12 patients who underwent ureteroscopic biopsy and laser tumor ablation before nephroureterectomy were disease free at a mean follow-up of 37.2 months. The mean time from ureteroscopic biopsy to nephroureterectomy in this group was 196 days. No significant difference was found in the postoperative disease status between patients undergoing nephroureterectomy after ablation and those who proceeded to nephroureterectomy after endoscopic biopsy or those who did not undergo ureteroscopy before nephroureterectomy (P = 0.16)., Conclusions: Ureteroscopy with biopsy and/or tumor ablation before nephroureterectomy did not adversely affect the postoperative disease status.

Retinoids, which include vitamin A (retinol) and its derivatives, have previously been investigated as potential chemopreventive and chemotherapeutic agents in bladder cancer. We examined mRNA expression of the retinoid receptors RARalpha, RARbeta2, RARgamma and RXRalpha, as well as two putative RARbeta2 target genes, DAB2 and Midkine, in normal and malignant bladder tissue specimens from human patients. We evaluated 24 normal and malignant bladder specimens for retinoid receptor, DAB2 and Midkine mRNA expression using RT-PCR. We also examined the effects of retinoic acid and retinol on the expression of these genes in five human bladder cancer cell lines. Expression of RARalpha, RARbeta2, RARgamma and RXRalpha mRNA was detected in all of the non-neoplastic patient bladder specimens. RARbeta2 mRNA expression was undetectable in 7/13 tumors, RARalpha in 3/13, RARgamma in 1/13 and RXRalpha in 2/13. DAB2 mRNA was expressed in all non-neoplastic and all tumor specimens, while Midkine mRNA was detected in 8/11 non-neoplastic specimens versus 11/13 tumors. Two of the five bladder cancer cell lines expressed RARbeta2 independent of retinoid exposure; in three cell lines RARbeta2 expression was induced by retinoids. RARalpha, RARgamma and RXRalpha mRNA expression was detected in 5/5 cell lines, independent of retinoid exposure. We found a reduction in retinoid receptor mRNA expression, particularly for RARbeta2, in human bladder cancer specimens. We also demonstrated induction of RARbeta2 mRNA expression in some of the retinoid-treated bladder cancer cell lines. We suggest that restoration of RARbeta2 expression may be a reasonable biomarker for developing bladder cancer preventive and/or therapeutic drugs.

Background and Purpose: Endoscopic management of transitional-cell carcinoma (TCC) of the upper urinary tract remains associated with a significant rate of recurrence. We evaluated the impact of selective upper-tract cytology findings on tumor recurrence and renal salvage rate after ureteroscopic laser tumor ablation., Patients and Methods: From 1993 though 2003, 38 patients with upper-tract TCC underwent ureteroscopic laser tumor ablation. Cytology specimens were collected from the upper urinary tract prior to ablation. "Abnormal cytology" was defined as the presence of malignant or atypical cells. Patients with abnormal cytology results were compared with patients with those having negative findings for tumor recurrence and renal salvage rates using the X (2) test., Results: Of the 38 patients, 26 (68.4%) experienced at least one recurrence at a mean follow-up of 37.2 months. Pretreatment upper-tract cytology results were available in 34 of these patients: 17 (50%) were negative, and 17 were abnormal. Sixteen of the patients (94.1%) with abnormal cytology results had tumor recurrence after ablation, compared with 8 of the 17 (47.1%) with negative cytology findings (P = 0.0026). Twelve patients (31.5%) underwent nephroureterectomy during follow-up: 8 of the 17 (47.1%) with abnormal cytology, and 4 of the 17 (23.5%) with negative cytology (P = 0.15)., Conclusion: Abnormal selective cytology results were associated with a significantly higher rate of tumor recurrence and a trend toward increased renal loss in patients with upper-tract TCC treated with ureteroscopic ablation. These findings suggest a prognostic value for upper-tract cytology analysis in patients undergoing endoscopic therapy.

Objectives: To evaluate the expression of the androgen receptor (AR) in transitional cell carcinoma (TCC) of the bladder, and to assess whether its expression correlated with pathologic tumor stage. TCC of the bladder is three times more common in males than in females. The origin of this sex difference in incidence is unknown., Methods: We evaluated tumor specimens from 49 consecutive patients treated for TCC of the bladder at our institution between July 2002 and June 2003. Immunohistochemistry was performed using a monoclonal mouse anti-AR antibody on paraffin-embedded tissue sections of tumors obtained from transurethral resection, radical cystectomy, or resection of metastases. Specimens were assessed for AR expression, and, in tumors that demonstrated AR staining, the percentage of nuclei that stained positive was recorded., Results: Of the 49 tumors, 26 (53.1%) expressed the AR. The percentage of tumors that expressed the AR decreased with increasing pathologic stage, from 88.9% of pTa lesions to 0% of pT3 tumors. Overall, 75% of superficial tumors (pTa + pT1 + carcinoma in situ) expressed the AR compared with 21.4% of invasive tumors (pT2 + pT3; P = 0.002). In addition, among AR-expressing tumors, the mean percentage of nuclei that stained positive for the AR was significantly greater in pTa tumors (62.5%) than in pT1 (31%) or pT2 (20%) tumors (P = 0.005)., Conclusions: We found a decrease in AR protein expression in tumors with increased pathologic stage. Our data suggest that the loss of AR expression is associated with invasive bladder cancer.

Purpose: Retinoids, which include vitamin A (retinol; ROL) and its derivatives, have been investigated in the treatment of bladder cancer. We have shown that expression of the enzyme lecithin:ROL acyltransferase (LRAT), which converts ROL to retinyl esters, is reduced in several human cancers. Here we evaluated expression of LRAT protein and mRNA in normal and malignant bladder tissue specimens from human patients. We also examined the effect of retinoids on LRAT expression in bladder cancer cell lines., Experimental Design: We evaluated 49 bladder cancer specimens for LRAT protein expression using immunohistochemistry with affinity-purified antibodies to human LRAT. LRAT mRNA expression was assessed using reverse transcription-PCR in bladder specimens from an additional 16 patients. We examined the effect of retinoic acid and ROL on LRAT mRNA expression in five human bladder cancer cell lines., Results: LRAT protein was detected throughout the nonneoplastic bladder epithelium in all of the specimens. In bladder tumors, LRAT protein expression was reduced compared with the nonneoplastic epithelium or was completely absent in 7 of 32 (21.9%) superficial tumors versus 16 of 17 (94.1%) invasive tumors (P < 0.001). All of the non-neoplastic bladder specimens tested (11 of 11) showed LRAT mRNA expression, compared with 5 of 8 (62%) superficial tumors and 0 of 5 (0%) invasive tumors (P = 0.001). Three of five human bladder cancer cell lines expressed LRAT mRNA independent of retinoid exposure, whereas in two cell lines LRAT mRNA expression was induced by retinoid treatment., Conclusions: We report a significant reduction in LRAT expression in bladder cancer. Moreover, we demonstrate an inverse correlation of LRAT mRNA and protein expression with increasing tumor stage. These data suggest that loss of LRAT expression is associated with invasive bladder cancer.

Background: Laparoscopic live donor nephrectomy (LLDN) is increasingly used by transplantation centers worldwide. As in open live donor nephrectomy, the left kidney is preferred for LLDN; however, not all potential donors have anatomy conducive to left nephrectomy. The purpose of our study, therefore, was to report on a large, single-institution experience with right LLDN performed using a hand-assisted, transperitoneal approach., Methods: We performed a retrospective review of 40 consecutive patients who underwent transperitoneal right hand-assisted LLDN at our institution. Information on donor age, relation to recipient, and indication for right-sided donation was collected. Surgical demographics included operative time, warm ischemia time, and estimated blood loss. Recipients were followed for graft loss and for long-term renal allograft function., Results: The indications for right-sided donor nephrectomy were a difference in split renal function of greater than 10%, multiple left renal vessels, and right renal cysts. The mean surgical time in our series was 115.8 min, with a mean estimated blood loss of 85.7 mL and a warm ischemia time of 116.0 seconds. Surgical and postoperative complications were limited. Mean serum creatinine levels in the recipients were 1.6 mg/dL on day 7, 1.4 mg/dL on day 30, and 1.4 mg/dL at 1 year after transplantation., Conclusions: Right LLDN using a hand-assisted, transperitoneal technique was performed with minimal morbidity and favorable graft function. We believe that offering hand-assisted LLDN to patients with an indication for right-sided donation can safely and effectively increase the pool of donor organs available to patients with end-stage renal disease.

Purpose: We studied the impact of the interval from vasectomy to reversal and presence of sperm granuloma on outcomes of reversal., Materials and Methods: A total of 213 microsurgical vasectomy reversals performed by a single surgeon were stratified according to obstructive intervals of less than 5 years, 5 to 10 years, 10 to 15 years and greater than 15 years. The effects of obstructive interval on patency and pregnancy rates were assessed using multivariate logistical regression. The impact of sperm granuloma on patency and pregnancy was assessed using the chi-square test., Results: Patency did not change with increasing obstructive intervals as can be seen with 91% patency at less than 5 years, 88% at 5 to 10 years, 91% at 10 to 15 and 89% at greater than 15 years. There was no difference in pregnancy rates (89%, 82% or 86%) at obstructive intervals of 0 to 5, 5 to 10 or 10 to 15 years, respectively. Pregnancy rates were significantly lower (44%, p <0.05) with obstructive intervals greater than 15 years. Men with at least unilateral sperm granuloma had patency of 95% vs 78% without granulomas, a trend which did not quite reach statistical significance (p = 0.07). There was no difference in pregnancy rates with or without granulomas., Conclusions: Vasectomy reversal patency rates are high regardless of time since vasectomy. Pregnancy rates are lower more than 15 years after vasectomy. Sperm granuloma had a favorable impact on patency. Our data indicate that for obstructive intervals less than 15 years vasectomy reversal yields much higher pregnancy rates than in vitro fertilization and intracytoplasmic sperm injection, and that even for intervals greater than 15 years reversal outcomes equal or exceed those of in vitro fertilization and intracytoplasmic sperm injection.

The use of testosterone supplementation for elderly men has increased markedly over the last decade due to a recognized gradual decline in serum testosterone, which may lead to decreased bone mass, muscle strength, and libido. Testosterone supplementation is also used widely to treat some forms of erectile dysfunction, androgen deficiency, and infertility. However, long-term exogenous testosterone therapy has been associated with several complications, such as fluid retention, nitrogen retention, and hypertension. Due to these problems, alternate treatment modalities, involving more physiological and longer-acting systems for androgen delivery, have been pursued. Alginate-poly-L-lysine-encapsulated Leydig cell microspheres were used as a novel method for the delivery of testosterone in vivo. Encapsulated Leydig cells, which were stimulated with human chorionic gonadotropin, secreted high levels of testosterone in culture. Unencapsulated cells injected i.p. or s.c. failed to produce any testosterone levels, even with human chorionic gonadotropin stimulation. Castrated rats that were administered encapsulated Leydig cells i.p. or s.c. maintained a serum testosterone level between 0.23 and 0.51 ng/ml. Similar levels of testosterone were obtained for 43 d when the encapsulated Leydig cells were injected s.c. (0.28-0.48 ng/ml). Approximately 10% of a normal adult rat Leydig cell population was injected into each castrated animal; however, this resulted in serum testosterone levels of up to 40% of normal. Clinically, testosterone is usually delivered for supplementation and not for full replacement therapy. Therefore, the findings of this study suggest that microencapsulated Leydig cells may be a viable option as a therapeutic modality involving testosterone supplementation.

A 60-year-old Asian woman presented with a 1-year history of painless gross hematuria. She had no prior urologic history and no other medical problems. Her physical examination, urine cytology, and computed tomography scan were normal. Cystoscopy demonstrated several punctate areas of erythema within the bladder. Biopsies revealed amyloidosis, and immunohistochemical staining of the specimens defined the process as amyloid AA (often called secondary amyloidosis). The workup for systemic conditions associated with amyloid AA was negative. This represents an unusual case of primary localized AA-type amyloidosis of the bladder.