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Compared to a Western diet, the Mediterranean diet moves away from red meat and processed foods. Universally regarded as a healthier dietary alternative, the Mediterranean diet has garnered scientific endorsement for its ability to confer an array of compelling benefits. These health benefits encompass not only a lowered incidence of Type 2 diabetes with a reduction in obesity, but also a robust protective effect on cardiovascular health. Extensive literature exists to corroborate these health benefits; however, the impact of a Mediterranean diet on urologic diseases, specifically sexual dysfunction, lower urinary tract symptoms, stone disease, and urologic cancers are not well studied. Understanding how dietary habits may impact these urologic conditions can contribute to improved prevention and treatment strategies.A total of 955 papers from PubMed and Embase were systematically reviewed and screened. After exclusion of disqualified and duplicated studies, 58 studies consisting of randomized controlled trials, cohort studies, cross sectional studies, reviews and other meta-analyses were included in this review. 11 primary studies were related to the impact of a Mediterranean diet on sexual dysfunction, 9 primary studies regarding urinary symptoms, 8 primary studies regarding stone disease, and 9 primary studies regarding urologic cancers. All primary studies included were considered of good quality based on a New-Castle Ottawa scale. The results demonstrate a Mediterranean diet as an effective means to prevent as well as improve erectile dysfunction, nephrolithiasis, lower urinary tract symptoms, and urinary incontinence. The review highlights the need for additional research to study the impact of diet on urologic cancers and other urologic conditions such as premature ejaculation, loss of libido, female sexual dysfunction, and overactive bladder., (© 2024. The Author(s).)

Purpose: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics., Methods: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5., Results: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825., Conclusion: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer., (© 2023. The Author(s).)

Background: Nephroureterectomy remains the gold standard treatment for upper tract urothelial carcinoma (UTUC). Considering the high risk of developing renal function impairment after surgery, the rationale for nephron sparing approaches in treatment of UTUC has been raised. In this case, renal cryoablation was able to achieve successful oncologic control while preserving renal function during 5 years of follow up without intraoperative or post operative complications., Case Presentation: A 79 year old male presents after three months of macroscopic hematuria. Imaging revealed a 3.6 × 3.1 × 2.7 cm endophytic mass in the interpolar region of the left kidney and an atrophic right kidney. After weighing the lesion's location with the patient's of complex medical history, he was counselled to undergo a minimally invasive percutaneous cryoablation as treatment for his solitary renal mass. A diagnostic dilemma was encountered as imaging suggested a diagnosis of renal cell carcinoma. However, the pre-ablation biopsy established an alternative diagnosis, revealing UTUC. Percutaneous cryoablation became an unorthodox treatment modality for the endophytic component of his UTUC followed by retrograde ureteroscopic laser fulguration. The patient was followed in 3 months, 6 months, then annually with cross sectional imaging by MRI, cystoscopy, urine cytology and renal function testing. After five years of follow-up, the patient did not encountered recurrence of UTUC or deterioration in renal function, thereby maintaining a stable eGFR., Conclusion: Although evidence for nephron-sparing modalities for UTUC is mounting in recent literature, limited data still exists on cryotherapy as a line of treatment for urothelial carcinoma. We report successful management of a low-grade UTUC using cryoablation with the crucial aid of an initial renal biopsy and long-term follow-up. Our results provide insight into the role of cryoablation as a nephron-sparing approach for UTUC., (© 2023. The Author(s).)

Background: Metabolic factors underlying the recent increase in stone prevalence over the past decades are not well understood. Herein, we evaluate temporal, geographic and gender-specific trends in metabolic risk factors in recurrent kidney stone formers., Patients and Methods: A systematic literature review of metabolic risk factors for stone formation was conducted, inclusive of the last four decades. Studies with inadequate 24 h urine metabolic data, pediatric or those with less than 50 patients were excluded. The primary outcome was prevalence of each metabolic risk factor, compared between studies published prior to the year 2000 vs those following. Geographic and gender differences were secondary outcomes., Results: Twenty-eight articles met inclusion criteria, of which 10 ( n  = 1578) were published prior to the year 2000 and 18 ( n  = 8747) were published thereafter. Comparing these groups, an increase in hyperoxaluria (29% vs 33%; p  = 0.002), hypercalciuria (35 vs 36%; p  = 0.446), hyperuricosuria (17% vs 22%; p  < 0.0001), low urine volume (28 vs 38%; p  < 0.0001) and hypocitraturia (23% vs 44%; p  < 0.0001) was observed. The prevalence of hyperoxaluria, hypercalciuria, hyperuricosuria and hypocitraturia were significantly higher in males. There were also significant geographical differences, with higher prevalence of hyperoxaluria and hypocitraturia in non-Western countries and higher prevalence of hypercalciuria in Western countries. Prevalence of hyperoxaluria is increasing in the US., Conclusion: Prevalence of metabolic risk factors for nephrolithiasis significantly increased in recent years. These findings are hypothesis-generating and may provide valuable insight into the epidemiology, prevention and management of recurrent stone disease. Dietary modifications and innovative medical therapies are needed to decrease metabolic risk factors underlying nephrolithiasis.

Objective: To evaluate metabolic risk factors in calcium kidney stone formers from two different decades, comparing changes in metabolic profiles over time., Methods: A retrospective analysis was performed of calcium kidney stone formers who underwent metabolic evaluation of urolithiasis with 24-hour urine collections at a single institution. There were 309 patients evaluated from 1988 to 1994 (Group A), and 229 patients from 2007 to 2010 (Group B). A comparison between both groups was performed to assess changes in demographics and in metabolic stone profiles., Results: Comparing Group A to Group B, the percentage of females increased from 43 to 56%, obese patients (BMI ≥ 30) increased from 22 to 35%, and patients ≥ 50 years increased from 29 to 47% (all p  < 0.005). A greater percentage of patients had hypocitraturia in the recent cohort (46-60%, p  = 0.001), with hypocitraturia significantly more frequent in obese patients ( p  = 0.005). Hyperoxaluria was also increased in Group B compared to Group A (23-30% p  = 0.07), a finding that was significant in males (32-53%, p  = 0.001)., Conclusions: Urolithiasis has increased in females, obese, and older patients, consistent with population-based studies. We report a rising incidence of hypocitraturia and hyperoxaluria in the contemporary cohort, particularly in obese patients and in males, respectively. Further studies are needed to better characterize the metabolic changes corresponding to the increase in stone disease.

Introduction: We evaluated epidemiologic trends and survival for bladder cancer histologic subtypes in California patients by comparing urothelial carcinoma of the bladder (UCB) and non-urothelial subtypes including squamous cell carcinoma (SCC), adenocarcinoma (ADC), and small-cell carcinoma (SmCC)., Materials and Methods: The California Cancer Registry (CCR) was queried for incident bladder cancer cases from 1988 to 2012. Epidemiologic trends based on tumor histology were described. The primary outcome was disease-specific survival (DSS). Kaplan-Meier and multivariable Cox regression survival analyses were performed., Results: A total of 72,452 bladder cancer cases (66,260 UCB, 1390 SCC, 587 ADC, 370 SmCC, and 3845 other) were included. The median age was 72 years (range, 18-109 years). ADC was more common in younger patients. Male:female ratios varied among cancer types (3.1:1 in UCB, 2.9:1 in SmCC, 1.6:1 in ADC, and 0.9:1 in SCC). Most non-urothelial cases (> 60%) presented at advanced stages, whereas most UCB cases (80.6%) were localized. Kaplan-Meier analysis revealed the best 5-year DSS and overall survival (OS) in UCB, whereas the worst outcomes were seen with SCC and SmCC (P < .0001). Multivariable analysis controlling for age, gender, tumor stage, and grade demonstrated that non-urothelial histologic subtypes were associated with significantly worse DSS compared with UCB (SCC hazard ratio [HR], 2.612; SmCC HR, 1.641; and ADC HR, 1.459; P < .0001)., Conclusions: Non-urothelial bladder cancers have worse oncologic outcomes than UCB in California patients. SCC and SmCC are associated with the worst DSS based on univariable and multivariable analyses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To examine the California Cancer Registry (CCR) for bladder cancer survival disparities based on race, socioeconomic status (SES), and insurance in California patients., Patients and Methods: The CCR was queried for bladder cancer cases in California from 1988 to 2012. The primary outcome was disease-specific survival (DSS), defined as the time interval from date of diagnosis to date of death from bladder cancer. Survival analyses were performed to determine the prognostic significance of racial and socioeconomic factors., Results: A total of 72,452 cases were included (74.5% men, 25.5% women). The median age was 72 years (range, 18-109 years). The racial distribution among the patients was 81% white, 3.8% black, 8.8% Hispanic, 5.2% Asian, and 1.2% from other races. In black patients, tumors presented more frequently with advanced stage and high grade. Medicaid patients tended to be younger and had more advanced-stage, higher-grade tumors compared to patients with Medicare or managed care (P < .0001). Kaplan-Meier analysis demonstrated significantly poorer 5-year DSS in black, low SES, and Medicaid patients (P < .0001). When controlling for stage, grade, age, and gender, multivariate analysis revealed that black race (DSS hazard ratio = 1.295; 95% confidence interval, 1.212-1.384), low SES (DSS hazard ratio = 1.325; 95% confidence interval, 1.259-1.395), and Medicaid insurance (DSS hazard ratio = 1.349; 95% confidence interval, 1.246-1.460) were independent prognostic factors (P < .0001)., Conclusion: An analysis of the CCR demonstrated that black race, low SES, and Medicaid insurance portend poorer DSS. These findings reflect a multifaceted socioeconomic and public health conundrum, and efforts to reduce inequalities should be pursued., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Checkpoint inhibitors are approved for the treatment of urothelial bladder cancer. However, there have been no reports on the prognostic value of programmed-death receptor ligand 1 (PD-L1) expression in squamous cell carcinoma (SCC) of the bladder. We assessed the relationship between PD-L1 expression, clinicopathological features, and oncologic outcomes in bladder SCC., Methods and Materials: Immunohistochemistry of PD-L1 was performed on 151 radical cystectomy specimens with pure SCC treated in Mansoura, Egypt from 1997 to 2004., Results: Median patient age was 52 years (range: 36-74 years) and median length of follow up was 63 months (range: 1-100 months). Schistosomiasis was present in 81% of the specimens and 93% had muscle-invasive disease on pathologic staging. PD-L1 expression was negative in 50 (33%) of the specimens. Negative PD-L1 expression was associated with higher pathologic tumor stage (P = 0.04), higher grade lesions (P = 0.01), and the presence of lymphovascular invasion (P < 0.01). Kaplan-Meier analyses showed that negative PD-L1 expression is associated with worse recurrence-free (P = 0.01) and worse cancer-specific survival (P = 0.01). Multivariable Cox regression analyses showed negative PD-L1 expression was an independent predictor of disease recurrence (hazards ratio 2.05, 95% confidence interval 1.06-3.96, P = 0.03) and cancer-specific mortality (hazards ratio 2.89, 95% confidence interval 1.22-6.82, P = 0.02)., Conclusions: Negative PD-L1 expression is associated with higher pathologic tumor stage, higher grade lesions, presence of lymphovascular invasion, and worse oncologic outcomes after radical cystectomy for SCC. These findings support the need for the inclusion of patients with bladder SCC into immunotherapy clinical trials., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate differences in pathological features and prognostics across four bladder cancer histopathological types: urothelial carcinoma (UC), urothelial carcinoma with variant histology (UCV), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), utilizing a large cohort of radical cystectomy (RC) patients., Methods: A retrospective analysis of patients who underwent RC at a single institution in Egypt between 1997 and 2004 was performed. Kaplan-Meier and multivariable analyses were performed to evaluate the prognostic significance of pathological features including tumor stage, grade, lymphovascular invasion (LVI), and lymph node (LN) involvement in the different subtypes on disease-free survival (DFS)., Results: 1238 patients (975 male, 263 female) were included, of whom 577 (47%) had UC, 174 (14%) UCV, 398 (32%) SCC, and 89 (7%) ADC. Median age was 54 (20-87) years and median follow-up was 40 months (0-110). There were significant differences in stage, grade, LVI, LN involvement, and presence of schistosomiasis across the subtypes (all p < 0.05). The prognostic significance of LVI was more evident in SCC (HR 2.14, p = 0.003) and ADC (HR 2.17, p = 0.044) than in UC (HR 1.66, p = 0.008). LN involvement was the strongest prognostic factor in UCV (HR 2.14, p = 0.012)., Conclusions: There are significant differences in clinicopathological features and their prognostic impact across bladder cancer subtypes. The prognostic significance of LVI is more evident in SCC and ADC, while LN involvement is more prognostic in UCV. Determining independent predictors in individual subtypes can guide multimodal treatment selection and clinical trial design.

Introduction: Ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) are common procedures performed to treat kidney stones. Despite advances in technology/technique, serious infectious complications can occur. To better understand the preoperative antibiotic administration patterns and adherence to guidelines from the American Urological Association (AUA) and the European Association of Urology (EAU), members of the Endourological Society were sent a clinical vignette-based survey to assess the antibiotic use in a variety of pre-URS and pre-PCNL scenarios., Methods: Endourological Society members were e-mailed a survey that queried antibiotic therapy duration before uncomplicated URS and PCNL with negative and asymptomatic positive preoperative urine cultures (PUCs). For negative PUC questions, selecting more perioperative antibiotics was considered a "prolonged" course as it extends past the maximum of 24-hour perioperative prophylaxis recommended by both the AUA and EAU., Results: The response rate was 16.3% for a total of 326 responders. Twenty-one percent to 39% of respondents reported giving prolonged courses of preoperative antibiotics before a URS or PCNL with a negative PUC (p < 0.0001). When presented with a negative PUC, more prolonged antibiotic courses were reported with the following hierarchy: PCNL for 2 cm intrarenal stones (39%) > URS for 12 mm renal pelvis stone (28%) > URS for 7 mm distal ureteral stones (21%) (p < 0.0001). In both negative and positive PUC questions, differences were noted in preoperative antibiotic prescribing patterns among site of practice (United States, Canada, Europe, Asia, South America, and Others), type of practice (academic vs all others), years in practice (<10 or ≥10 years), and surgical volume (URS and PCNL >100 or ≤100 annual cases)., Conclusions: Adherence to guidelines on antibiotic administration before PCNL and URS with a negative PUC varies by scenario and provider. In 21% to 39% of negative PUC cases, reported antibiotic use before a URS or PCNL is not consistent with recommendations from the AUA and EAU. Before a positive PUC URS or PCNL, nearly all surveyed provide preoperative antibiotics; however, the regimen length is variable.

Bladder cancer is the most prevalent malignancy of the urinary tract and is associated with significant morbidity and mortality. Preventative efforts to reduce the medical and financial burdens of bladder cancer are highly desirable. However, the utilization of natural and pharmaceutical products for the prevention and treatment of bladder cancer remains largely controversial. Herein, we review the current body of evidence surrounding a number of natural dietary substances and their roles in chemoprevention of bladder cancer. Possible chemopreventative properties of several pharmaceutical agents are also reviewed. Overall, the current body of evidence is insufficient to establish a clear link between these proposed chemopreventive agents and risk of bladder cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: To determine the impact of skin-to-tumor (STT) distance on the risk for treatment failure following percutaneous cryoablation (PCA)., Methods: We retrospectively reviewed patients who underwent PCA with documented T1a recurrent renal cell carcinoma (RCC) at 2 academic centers between 2005 and 2015. Patient demographics, tumor characteristics, and perioperative and postoperative course variables were collected. Additionally, we measured the STT distance by averaging the distance from the skin to the center of the tumor at 0°, 45°, and 90° on preoperative computed tomography imaging., Results: We identified 86 patients with documented T1a RCC. The mean age at the time of surgery was 69 years (range: 37-91 years), and the mean tumor size was 2.7 cm (range: 1.0-4.0 cm). With a mean follow-up of 24 months (range: 3-63 months), 11 (12.8%) treatment failures occurred. Patients with treatment failure had significantly higher mean STT distance than those without: 11.0 cm (range: 6.3-20.1 cm) compared to 8.4 cm (range: 4.4-15.2 cm), respectively (P = .002). STT distance was an independent predictor of treatment failure (odds ratio: 1.32, 95% confidence interval: 1.04-1.69, P = .029). STT distance greater than 10 cm had a fourfold increased risk of tumor treatment failure (odds ratio: 4.43, 95% confidence interval: 1.19-16.39, P = .018). Tumor size, R.E.N.A.L. Nephrometry score, and number of cryoprobes placed were not associated with treatment failure., Conclusion: STT, an easily measured preoperative variable, may inform the risk of RCC treatment failure following PCA., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Previous studies suggested that patients with pure struvite calculi rarely have underlying metabolic abnormalities. Therefore, most of these patients do not undergo metabolic studies. We report our experience with these patients and their response to directed medical therapy. Between 1/2005 and 9/2012, 75 patients treated with percutaneous nephrolithotomy for struvite stones were identified. Of these, 7 had pure struvite stones (Group 1), 32 had mixed struvite stones (Group 2), both with metabolic evaluation, and 17 had pure struvite stones without metabolic evaluation (Group 3). The frequency of metabolic abnormalities and stone activity (defined as stone growth or stone-related events) was compared between groups. The median age was 55 years and 64 % were female. No significant difference in race, infection history, family history, stone location or volume existed between groups. Metabolic abnormalities were found in 57 % of Group 1 and 81 % of Group 2 patients. A similar proportion of Group 1 and 2 patients received modification to or continuation of metabolic therapy, whereas no Group 3 patients received any directed therapy. In patients with >6 months follow-up, the stone activity rate between Groups 1 and 2 appeared similar whereas Group 3 trended towards higher stone activity rate. Metabolic abnormalities in pure struvite stone formers appear to be more common than previously reported. Directed medical therapy in these patients may reduce stone activity. The role of metabolic evaluation and directed medical therapy needs reconsideration in patients with pure struvite stones.

Purpose: To investigate the prognostic significance of tumor location on survival outcomes in patients with urinary bladder adenocarcinoma (BAC)., Methods: We retrospectively analyzed cases of BAC with known tumor location from the Surveillance, Epidemiology, and End Results database from 1973 to 2012. Data regarding patient demographics, tumor characteristics, and oncological and survival outcomes were collected. Patients were subgrouped according to tumor location into urachal/dome (dome and urachus [UD]), lateral wall (anterior, posterior, and lateral bladder walls [LW]), and base (trigone, ureteral orifices, and bladder neck [BL])., Results: A total of 1,361 cases of BAC with known tumor location were identified. More UD tumors were low grade (grade I and II; 51%) than LW (33%) and BL (43%) tumors (P<0.0001). UD lesions were the most likely to have metastatic spread (23% vs. 17% for LW and 15% for BL) (P<0.0001). The 5-year overall survival (OS) and disease-specific survival (DSS) rates were 37.3% and 49.0%, respectively, for all BAC. Furthermore, the 5-year OS rates were 42.3%, 35.9%, and 28.4% for UD, LW, and BL lesions, respectively (P<0.0001), whereas the 5-year DSS rates were 50.2%, 51.7%, and 42.1% for UD, LW, and BL lesions, respectively (P = 0.0097). Multivariate Cox regression analysis controlling for tumor stage and grade demonstrated that both tumors of the LW (hazards ratio [HR] = 1.52 for OS and 1.30 for DSS) and BL (HR = 1.71 for OS and 1.57 for DSS) conferred a worse prognosis relative to those of the UD (P< 0.05)., Conclusions: Tumor location of BAC is an independent prognostic factor for disease outcome. Our results suggest that the urachal and dome locations are associated with relatively favorable survival and oncological outcomes, whereas basal location confers poorer outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate the association of lymphovascular invasion (LVI) with oncologic outcomes of squamous cell carcinoma (SCC) of the urinary bladder following radical cystectomy (RC)., Patients and Methods: We performed a retrospective analysis of 1,280 patients who underwent RC for invasive bladder cancer between 1997 and 2003 in Mansoura, Egypt. Only patients with pure urothelial carcinoma of the bladder (UCB) or SCC pathology were included. Using multivariate Cox regression analyses and Kaplan-Meier analyses, prognostic significance of LVI in disease-free survival and cancer-specific survival was evaluated for patients with UCB and SCC., Results: Our cohort included 519 (59%) patients with UCB and 360 (41%) with SCC. Median patient age and follow-up were 55 years (20-87) and 64 months (0-128), respectively. Median number of lymph nodes (LN) retrieved was 19 (4-70). LVI was present in 288 (32.8%) patients (241 [46.4%] UCB vs. 47 [13.1%] SCC; P<0.001). LVI was an independent predictor of oncologic outcomes in both UCB and SCC groups; however, LVI had more prognostic significance in SCC. LN negative, LVI positive (LVI+/LN-) patients with SCC had higher risk of recurrence and cancer-specific mortality compared to LN positive, LVI negative (LVI-/LN+) patients with SCC (hazard ratio = 2.8 vs. 1.9 and hazard ratio = 3.6 vs. 2.2, respectively)., Conclusion: The presence of LVI is an independent predictor of poor oncologic outcomes after RC and had greater prognostic significance in patients with SCC compared to UCB., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To highlight the current understanding of the epidemiology, clinicopathological characteristics, and management of squamous cell carcinoma (SCC) of the bladder, as it accounts for 2-5% of bladder tumours, with a focus on non-bilharzial-associated SCC (NB-SCC). The standard treatment for bladder SCC remains radical cystectomy (RC). We present an updated clinical profile of bladder SCC and a review of NB-SCC therapeutic approaches, including RC, neoadjuvant and adjuvant treatments, radiotherapy, chemotherapy, and immunotherapy., Methods: Using search terms relating to SCC, urinary bladder, and treatment modalities, we performed a search of the PubMed and Embase databases to identify NB-SCC treatment approaches and outcomes. Peer-reviewed English language reports from 1975 to present assessing SCC management were included. Two authors independently screened and extracted the data., Results: Of the 806 articles screened, 10 met the pre-defined inclusion criteria. RC was performed in seven of the 10 studies. Although radiotherapy alone yielded poor outcomes, preoperative radiotherapy and RC were associated with improved survival. There is little evidence supporting the use of chemotherapy in NB-SCC, and its efficacy in relation to RC is not known., Conclusion: Based on current literature, there is insufficient evidence to provide a treatment recommendation for NB-SCC. Whilst RC is the standard of care, the role of preoperative radiotherapy should be revisited and compared to RC alone. Additional studies incorporating multimodal approaches, contemporary radiation techniques, and systemic therapies are warranted. Immunotherapy as a treatment for bladder SCC has yet to be investigated.

Background and Purpose: Struvite stones have been associated with significant morbidity and mortality, yet there has not been a report on the medical management of struvite stones in almost 20 years. We report on the contemporary outcomes of the surgical and medical management of struvite stones in a contemporary series., Patients and Methods: A retrospective review of patients who were treated with percutaneous nephrolithotomy (PCNL) for struvite stones at Duke University Medical Center between January 2005 and September 2012 identified a total of 75 patients. Of these, 43 patients had adequate follow-up and were included in this analysis. Stone activity, defined as either stone recurrence or stone-related events, and predictors of activity were evaluated after combined surgical and medical treatment., Results: The study included 43 patients with either pure (35%) or mixed (65%) struvite stones with a median age of 55±15 years (range 21-89 years). The stone-free rate after PCNL was 42%. Stone recurrence occurred in 23% of patients. Postoperatively, 30% of patients had a stone-related event, while 60% of residual stones remained stable with no growth after a median follow-up of 22 months (range 6-67 mos). Kidney function remained stable during follow-up. Independent predictors of stone activity included the presence of residual stones >0.4 cm(2), preoperative large stone burden (>10 cm(2)), and the presence of medical comorbidities (P<0.05)., Conclusions: Struvite stones can be managed safely with PCNL followed by medical therapy. The majority of patients with residual fragments demonstrated no evidence of stone growth on medical therapy. With careful follow-up and medical management, kidney function can be maintained and stone morbidity can be minimized. Initial large stone burden, residual stones after surgery, and associated medical comorbidities may have deleterious effect on stone recurrence or residual stone-related events.

Purpose: To compare the costs associated with ultrasound (US)-guided hospital-based (UGHB), CT-guided hospital-based (CTG), and US-guided office-based (UGOB) percutaneous renal biopsy (PRB) for small renal masses (SRMs)., Methods: We retrospectively analyzed patient demographics, tumor characteristics, R.E.N.A.L. nephrometry scores, and cost data of patients undergoing PRB for SRM at our institution from May 2012 to September 2015. Cost data, including facility costs, professional fees, and pathology, were obtained from the departments of urology, radiology, and pathology., Results: A total of 78 patients were included in our analysis: 19, 31, and 28 UGHB, CTG, and UGOB, respectively. There was no difference in age, gender distribution, or tumor size among the three groups (p-values 0.131, 0.241, and 0.603, respectively). UGOB tumors had lower R.E.N.A.L. nephrometry scores (p=0.008). There were no differences in nondiagnostic rates between the UGHB, CTG, and UGOB groups [4 (21%), 5 (16%), and 6 (21%)] (p=0.852). There were no differences in final tumor treatment strategies utilized among the UGHB, CTG, and UGOB groups (p=0.447). There were 0, 2 (6%), and 0 complications in the UGHB, CTG, and UGOB biopsy groups. Total facility costs were $3449, $3280, and $1056 for UGHB, CTG, and UGOB PRB, respectively (p<0.0001). There was no difference between the urologist's and radiologist's professional fees (p=0.066). Total costs, including facility costs, pathology fees, and professional fees, were $4598, $4470, and $2129 for UGHB, CTG, and UGOB renal biopsy, respectively (p<0.0001)., Conclusion: For select patients with less anatomically complex, exophytic, and posteriorly located tumors, UGOB PRB provides equivalent diagnostic and complication rates while being significantly more cost-effective than either UGHB or CTG renal biopsy.

Purpose: To report chronological trends and geographical distributions related to the prevalence of hyperoxaluria in stone-forming patients., Materials and Methods: We systematically reviewed the existing literature between 1982 and 2013 seeking studies that assessed for hyperoxaluria (>45 mg/day [499.5 μmol/24 hour]) in recurrent stone formers. Studies that performed 24-hour urine analysis for urine oxalate in patients with recurrent urinary stones were included. Studies were divided chronologically and by geographical region, and prevalence rates of hyperoxaluria were compared between groups., Results: Our literature search provided 22 peer-reviewed articles involving 3636 patients in total. Ten studies were performed between 1982 and 2000, and 12 studies were performed between 2001 and 2013. The prevalence of hyperoxaluria in stone-forming patient cohorts was 24.8% and 45.1% (p = 0.019) in studies performed between 1982 and 2000 and 2001 and 2013, respectively. Hyperoxaluria rates were significantly higher in non-American cohorts compared with American cohorts (40.7% vs 23.0%; p = 0.018). Reported hyperoxaluria rates were higher in Asian countries compared with Western countries (56.8% and 23.8%; p < 0.001)., Conclusions: The prevalence of hyperoxaluria in stone-forming patients has increased over the past two decades and may be a contributing factor to the rising global prevalence of urolithiasis. A geographical disparity in hyperoxaluria may exist between Asian and Western countries. Future studies are needed to explain these trends and their consequences.

Objective: Digital tomosynthesis (DT) is a new X-ray-based imaging technique that allows image enhancement with minimal increase in radiation exposure. The purpose of this study was to compare DT with noncontrast computed tomography (NCCT) and to evaluate its potential role for the follow-up of patients with nephrolithiasis in a nonemergent setting., Methods: A retrospective review of patients with nephrolithiasis at our institution that underwent NCCT and DT from July 2012 to September 2013 was performed. Renal units (RUs) that did not undergo treatment or stone passage were randomly assigned to two blinded readers, who recorded stone count, size area (mm(2)), maximum stone length (mm), and location, for both DT and NCCT. Mean differences per RU were compared. Potential variables affecting stone detection rate, including stone size and body mass index (BMI), were evaluated. Interobserver agreement was determined using the intraclass correlation coefficient to measure the consistency of measurements made by the readers., Results: DT and NCCT demonstrated similar stone detection rates in terms of stone counts and stone area mm(2). Of the 79 RUs assessed, 41 RUs showed exact stone counts on DT and NCCT. The mean difference in stone area was 16.5 mm(2) (-4.6 to 38.5), p = 0.121. The mean size of the largest stone on NCCT and DT was 9.27 and 8.87 mm, respectively. Stone size and BMI did not cause a significant difference in stone detection rates. Interobserver agreement showed a strong correlation between readers and adequate reproducibility., Conclusion: We found DT to be a comparable imaging modality to NCCT for the detection of intrarenal stones, without a significant effect from stone size and BMI and adequate reproducibility between multiple readers. DT appears to be an ideal alternative for following patients with nephrolithiasis due to its acceptable stone detection rates, low radiation exposure, and decreased cost compared to NCCT.

Withdrawn by the publisher.

Purpose: To determine the effect of obesity on radiation exposure during simulated ureteroscopy., Methods: A validated anthropomorphic adult male phantom with a body mass index (BMI) of approximately 24 kg/m(2), was positioned to simulate ureteroscopy. Padding with radiographic characteristics of human fat was placed around the phantom to create an obese model with BMI of 30 kg/m(2). Metal oxide semiconductor field effect transistor (MOSFET) dosimeters were placed at 20 organ locations in both models to measure organ dosages. A portable C-arm was used to provide fluoroscopic x-ray radiation to simulate ureteroscopy. Organ dose rates were calculated by dividing organ dose by fluoroscopy time. Effective dose rate (EDR, mSv/sec) was calculated as the sum of organ dose rates multiplied by corresponding ICRP 103 tissue weighting factors., Results: The mean EDR was significantly increased during left ureteroscopy in the obese model at 0.0092 ± 0.0004 mSv/sec compared with 0.0041 ± 0.0003 mSv/sec in the nonobese model (P < 0.01), as well as during right ureteroscopy at 0.0061 ± 0.0002 and 0.0036 ± 0.0007 mSv/sec in the obese and nonobese model, respectively (P < 0.01). EDR during left ureteroscopy was significantly greater than right ureteroscopy in the obese model (P = 0.02)., Conclusions: Fluoroscopy during ureteroscopy contributes to the overall radiation dose for patients being treated for nephrolithiasis. Obese patients are at even higher risk because of increased exposure rates during fluoroscopy. Every effort should be made to minimize the amount of fluoroscopy used during ureteroscopy, especially with obese patients.

Purpose: We sought to create a 3-dimensional reconstruction of the autonomic nervous tissue innervating the bladder using male and female cadaver histopathology., Materials and Methods: We obtained bladder tissue from a male and a female cadaver. Axial cross sections of the bladder were generated at 3 to 5 mm intervals and stained with S100 protein. We recorded the distance between autonomic nerves and bladder mucosa. We manually demarcated nerve tracings using ImageScope software (Aperio, Vista, California), which we imported into Blender™ graphics software to generate 3-dimensional reconstructions of autonomic nerve anatomy., Results: Mean nerve density ranged from 0.099 to 0.602 and 0.012 to 0.383 nerves per mm2 in female and male slides, respectively. The highest concentrations of autonomic innervation were located in the posterior aspect of the bladder neck in the female specimen and in the posterior region of the prostatic urethra in the male specimen. Nerve density at all levels of the proximal urethra and bladder neck was significantly higher in posterior vs anterior regions in female specimens (0.957 vs 0.169 nerves per mm2, p<0.001) and male specimens (0.509 vs 0.206 nerves per mm2, p=0.04)., Conclusions: Novel 3-dimensional reconstruction of the bladder is feasible and may help redefine our understanding of human bladder innervation. Autonomic innervation of the bladder is highly focused in the posterior aspect of the proximal urethra and bladder neck in male and female bladders., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We created a prognostic tool for the prediction of oncologic outcomes after radical nephroureterectomy (RNU) for high-grade non-metastatic upper tract urothelial carcinoma (UTUC)., Methods: UTUC collaboration was utilized to include 586 patients who underwent RNU for non-metastatic high-grade UTUC. Survival outcomes were compared according to a score defined based on the sum of the independent prognostic variables., Results: The study included 382 males with a median age 70 years (range 28-97). Independent prognostic factors included: T (t stage), A (architecture), LVI (lympho-vascular invasion) and L (lymphadenectomy). TALL score (1-7) was the sum of T (≤T1 = 1, T2 = 2, T3 = 3 and T4 = 4), A (papillary = 0 and sessile = 1), LVI (absent = 0 and present = 1) and L (lymphadenectomy = 0 and no lymphadenectomy = 1). Five-year disease-free survival (DFS) and cancer-specific survival (CSS) were stratified into four risk categories according to the TALL score: low (TALL 0-2; 86 % DFS and 90 % CSS), intermediate (TALL = 3; 71 % DFS and 75 % CSS), high (TALL = 4; 57 % DFS and 58 % CSS) and very high risk (TALL ≥ 5; 34 % DFS and 38 % CSS) using Kaplan-Meier survival analyses. TALL score was externally validated in a single-center cohort of 85 UTUC patients., Conclusions: We developed a multivariable prognostic tool for the prediction of oncological outcomes after RNU for high-grade UTUC. The score can be used for patient counseling, selection for adjuvant systemic therapies and design of clinical trials.

A rapid expansion in the medical applications of three-dimensional (3D)-printing technology has been seen in recent years. This technology is capable of manufacturing low-cost and customisable surgical devices, 3D models for use in preoperative planning and surgical education, and fabricated biomaterials. While several studies have suggested 3D printers may be a useful and cost-effective tool in urological practice, few studies are available that clearly demonstrate the clinical benefit of 3D-printed materials. Nevertheless, 3D-printing technology continues to advance rapidly and promises to play an increasingly larger role in the field of urology. Herein, we review the current urological applications of 3D printing and discuss the potential impact of 3D-printing technology on the future of urological practice., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the ignition and burn risk associated with contemporary fiberoptic and distal sensor endoscopic technologies., Materials and Methods: We used new and used SCB Xenon 300 light sources to illuminate a 4.8 mm fiberoptic cable, 10 mm laparoscope, 5 mm laparoscope, rigid cystoscope, semirigid ureteroscope, flexible cystoscope, flexible fiberoptic ureteroscope, distal sensor cystoscope, and a distal sensor ureteroscope (Karl Storz, Inc., Tuttlingen, Germany). We measured peak temperatures at the distal end of each device. We then evaluated each device on a flat and folded surgical drape to establish ignition risk. Finally, we evaluated the effects of all devices on human cadaver skin covered by surgical drape., Results: Peak temperatures recorded for each device ranged from 26.9°C (flexible fiberoptic ureteroscope) to 194.5°C (fiberoptic cable). Drape ignition was noted when the fiberoptic cable was placed against a fold of drape. Contact with the fiberoptic cable, 10 mm laparoscope, 5 mm laparoscope, and distal sensor cystoscope resulted in cadaver skin damage. Cadaver skin damage occurred despite little or no visible change to the surgical drape. Rigid and flexible fiberoptic cystoscopes and flexible fiberoptic ureteroscopes had no effect on surgical drapes or cadaver skin., Conclusions: Fiberoptic light cables and some endoscopic devices have the potential to cause thermal injury and drape ignition. Thermal injury may occur without visible damage to drapes. Surgeons should remain vigilant regarding the risks associated with these devices and take necessary safety precautions to prevent patient injury.

Background: We evaluated the association of fibroblast growth factor (FGF2) expression with pathologic features and clinical outcomes of squamous cell carcinoma (SCC) of the urinary bladder., Methods: Immunohistochemistry of FGF2 was performed on radical cystectomy specimens with pure SCC from 1997 to 2003. The relationship between FGF2 and pathologic parameters and oncological outcome was assessed., Results: The study included 151 patients with SCC (98 men) with a median age of 52 years (range: 36-74 y). Schistosomal infection was found in 81% of patients. Pathologic category was T2 and T3 in 88% of patients and the grade was low in>50%. Lymph node invasion and lymphovascular invasion were found in 30.5% and 16%. Altered FGF2 was associated with tumor grade (P = 0.014), lymph node invasion, and lymphovascular invasion (P = 0.042). Altered FGF2 was associated with both disease recurrence and cancer-specific mortality (P≤0.001) in Kaplan-Meier analyses and was an independent predictor of cancer recurrence (hazard ratio = 2.561, P = 0. 009) and cancer-specific mortality (hazard ratio = 2.679, P = 0. 033) in multivariate Cox regression analyses. Adding FGF2 to a model including standard clinicopathologic prognostics (pathologic T category, lymph node status, and grade) showed a significant improvement (6%) in accuracy of prediction poor oncological outcome., Conclusions: FGF2 overexpression is associated with aggressive pathologic features and worse outcomes after radical cystectomy for SCC, suggesting a good prognostic and possible therapeutic role., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We evaluated the association of multiple biomarkers with clinical outcomes in patients treated with radical cystectomy for squamous cell carcinoma of the bladder to identify the best prognostic panel of markers., Materials and Methods: Immunohistochemistry for 14 biomarkers was performed on tissue microarray sections of 151 radical cystectomy specimens showing squamous cell carcinoma. Biomarker alterations, pathological features and oncologic outcomes were evaluated. The panel of biomarkers that best predicted the oncologic outcome was determined. Outcomes were stratified based on a prognostic score according to the number of altered biomarkers. The accuracy of oncologic outcome prediction was evaluated by ROC curves., Results: The study included 151 patients. Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients. Median followup was 63.2 months. The best prognostic panel of markers included COX-2, FGF-2, p53, Bax and EGFR. On multivariate Cox regression analysis a prognostic score based on marker alterations was an independent predictor of intermediate and high risk of disease recurrence (HR 3.2, p = 0.008 and HR 15.5, p ≤ 0.001) and bladder cancer specific mortality (HR 5.2, p = 0.009 and HR 19.4, p ≤ 0.001, respectively). A multivariate prognostic model incorporating the prognostic score demonstrated significantly better performance to predict the outcome compared to clinicopathological parameters only (0.78 vs 0.64)., Conclusions: Biomarkers have significant potential to predict the outcome of radical cystectomy for squamous cell carcinoma. An increased number of altered markers may identify patients at high risk who might benefit from multimodal treatment approaches., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To prospectively evaluate the feasibility of obtaining a reliable histochemical assessment of cell cycle biomarkers from endoscopic biopsy specimens of patients with upper tract urothelial cancer., Methods: Overall, 17 patients were identified who had an available biopsy as well as those who underwent subsequent radical nephroureterectomy (RNU) or segmental ureterectomy (SU) for clinically localized high-grade upper tract urothelial cancer of the renal pelvis or ureter. Of those 17 patients, 15 (88%) had sufficient tissue to undergo immunohistochemical staining. Biopsies were obtained using various endoscopic techniques. Tumor characteristics were recorded and prospectively evaluated for immunohistochemical expression of 5 biomarkers: p21, p27, p53, cyclin E, and Ki67/pRb. Unfavorable prognostic score (PS) was defined as>2 altered markers., Results: The median age of the patients was 68 years (range: 53-82y) with 87% being males. Of the 15 specimens, 9 (60%) tumors were organ confined (T≤2 and N0), and all were high grade. Of the 15 patients, 4 (27%), 7 (46.6%), 3 (20%), and 1 (6.7%) individuals had 1, 2, 3, and 5 markers altered on biopsy marker profiling, respectively, with Ki67 being the most frequent alteration (13/15; 87.7%). An overall concordance rate of 60% (9/15) was seen between biopsy and RNU/SU PS. Those patients with favorable biopsy biomarker PS were less likely to display adverse pathological features, with organ-confined disease in 7/11 (63.6%) patients and 9/11 (81.8%) being free of carcinoma in situ in the final specimen. Additionally, 10/11 (91%) had no evidence of necrosis and 7/11 (64%) had no evidence of lymphovascular invasion on final pathologic evaluation., Conclusions: Preliminary results suggest that obtaining interpretable biomarker profile of ureteroscopic biopsy specimens is feasible. Tumor heterogeneity and limited biopsy material may account for the discordance between biopsy and RNU/SU specimens. Meaningful biopsy biomarker profiling could serve as a powerful tool for individualizing treatment regimens and augmenting current predictive variables. Further studies are needed to evaluate clinical applicability., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Purpose: The outcomes of ureteroscopy (URS) after urgent decompression and antibiotics for patients who initially present with urosepsis because of obstructive urolithiasis have not been previously evaluated. The aim of this study was to compare the outcomes and complications of URS in patients with a recent history of sepsis with those without sepsis., Methods: The study included 138 patients who underwent URS for stone removal from January 2004 to September 2011 at a university medical center. A matched-pair analysis was performed using three parameters (age, sex, and race) to compare outcomes and complications between 69 patients who had sepsis vs a matched cohort who did not have sepsis before URS., Results: The study included 138 patients, 88 (64%) females and 50 (36%) males with a median age of 57.5 years (range 18-88 years). Patients with previous sepsis had similar patient characteristics and stone-free rates (81% vs 77%) compared with patients without previous sepsis (P>0.05). Patients with previous sepsis, however, had a significantly higher complications rate (20% vs 7%), longer hospital length of stay (LOS), and longer courses of postoperative antibiotics after URS (P<0.05). Sepsis developed postoperatively in two patients with diabetes (one with and one without previous sepsis), and postoperative fever developed in five patients with previous sepsis., Conclusions: URS after decompression for urolithiasis-related sepsis has similar success but higher complication rates, greater LOS, and longer course of postoperative antibiotics. This is important in counseling patients who present for definitive URS after urgent decompression for urolithiasis-related sepsis.

Purpose: Upper tract urothelial carcinoma is rare and less well studied than bladder cancer. It remains questionable if findings in bladder cancer can safely be extrapolated to upper tract urothelial carcinoma. We prospectively evaluate molecular profiles of upper tract urothelial carcinoma and bladder cancer using a cell cycle biomarker panel., Materials and Methods: Immunohistochemical staining for p21, p27, p53, cyclin E and Ki-67 was prospectively performed for 96 patients with upper tract urothelial carcinoma and 159 patients with bladder cancer with nonmetastatic high grade urothelial carcinoma treated with extirpative surgery. Data were compared between the groups according to pathological stage. Primary outcome was assessment of differences in marker expression. Secondary outcome was difference in survival according to marker status., Results: During a median followup of 22.0 months 31.2% of patients with upper tract urothelial carcinoma and 28.3% of patients with bladder cancer had disease recurrence, and 20.8% and 27.7% died of upper tract urothelial carcinoma and bladder cancer, respectively. The number of altered markers was not significantly different between the study groups. Overall 34 patients (35.4%) with upper tract urothelial carcinoma and 62 (39.0%) with bladder cancer had an unfavorable marker score (more than 2 markers altered). There were no significant differences between upper tract urothelial carcinoma and bladder cancer in the alteration status of markers, the number of altered markers and biomarker score when substratified by pathological stage. There were no significant differences in survival outcomes between patients with upper tract urothelial carcinoma and those with bladder cancer according to the number of altered markers and biomarker score., Conclusions: Our results demonstrate the molecular similarity of upper tract urothelial carcinoma and bladder cancer in terms of cell cycle and proliferative tissue markers. These findings have important implications and support the further extrapolation of treatment paradigms established in bladder cancer to upper tract urothelial carcinoma., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To validate the impact of Ki67 expression on oncological outcomes of patients treated for clinically localized clear-cell renal cell carcinoma (ccRCC)., Patients and Methods: Immunohistochemistry for Ki67 was performed on tissue microarray constructs of patients treated with radical or partial nephrectomy for clinically localized (M0) ccRCC and Ki67 expression >10% was considered abnormal. Clinical and pathological data elements were entered into an institutional review board-approved database. The Kaplan-Meier method and Cox regression models were used to analyse disease-free survival (DFS) and cancer-specific survival (CSS) probabilities., Results: Of 401 patients, 59.6% were males. The median (range) age was 58 (17-85) years, follow-up was 22 (0-150) months and time to death was 27 (0-150) months. A total of 20.2% of patients had advanced stage (pT3-T4) and 31% had advanced grade (3-4) disease. Abnormal expression of Ki67 was seen in 6.5% of our cohort and was associated with adverse pathological features (P < 0.05). Patients with high expression of Ki67 were found to have 5-year DFS and CSS rates of 67 and 84%, respectively, vs 87 and 95%, respectively, in those with normal expression (P < 0.001 and P < 0.05, respectively). In multivariable analyses, adjusting for stage and grade, abnormal Ki67 expression was an independent predictor of DFS (hazard ratio [HR] 3.77, P = 0.011, 95% confidence interval [CI] 1.35-10.52), but not of CSS (HR 3.51 P = 0.137, 95% CI 0.671-18.35)., Conclusions: Our findings support the role of Ki67 as a powerful independent predictor of inferior oncological outcomes in patients with ccRCC. Further prospective studies are needed to determine the clinical applicability of these findings., (© 2013 The Authors. BJU International © 2013 BJU International.)

Background: Squamous cell carcinoma (SCC) and transitional carcinoma with squamous differentiation (SCC/TCC) are rare in western countries. Chronic inflammation and irritation of the urothelium are common risk factors for the development of SCC and TCC/SCC. Tumour biology of squamous cell cancer and precancerous squamous lesions is different from transitional cell cancer (TCC). Recent advances in molecular analysis of benign and malignant squamous cell lesions indicate that they are closely associated and might lead to improved bladder cancer subclassification in the future., Aim: At present, the clinical management and therapy of SCC remains challenging, as scientific evidence based on prospective clinical trials is not available. We performed an analysis of available literature on natural history, treatment, and prognosis of SCC, SCC/TCC and metaplastic lesions. Furthermore, recent findings in molecular cancer biology are discussed with a focus on their relevance for SCC carcinogenesis.

Background: To determine whether patients found to have hematuria by their primary care physicians are evaluated according to best practice policy., Materials and Methods: The University of Texas Southwestern Medical Center maintains institutional outpatient electronic medical records (EMR) that are used by all providers in all specialties. We conducted an Institutional Review Board approved observational study of patients found to have more than 5 red blood cells/high power field between March 2009 and February 2010., Results: There were 449 patients of whom the majority were female (82%), Caucasian (39%), with microscopic hematuria (MH) (85%). Almost 58% of patients were initially symptomatic with urinary symptoms or pain. Evaluation for the source of hematuria was limited and included imaging (35.6%), cystoscopy (9%, and cytology (7.3%). Only 36% of men and 8% of women were referred to a urologist. No abnormality was found in 32% and 51% of patients with gross hematuria and MH, respectively (P = 0.004). There were 4 bladder tumors and 1 renal mass detected. Male gender, ethnicity and gross (vs. microscopic) hematuria were associated with higher rate of urological referral. Advanced age, smoking, provider practice type, and the presence of urinary symptoms were not associated with an increase rate of urological referral. No additional cancers were diagnosed with 29-month follow-up., Conclusions: While urinalysis remains a common diagnostic tool, most cases of both microscopic and gross hematuria are not fully evaluated according to guidelines. Use of cystoscopy, cytology, and upper tract imaging is limited. Further studies will be needed to determine the extent of the problem and impact on morbidity and survival., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Bladder squamous cell carcinoma, squamous metaplasia, and transitional cell carcinoma with squamous differentiation are infrequent findings in Western countries. A common risk factor for their development consists of chronic bladder irritation and inflammation. The prognostic and clinical relevance and natural history of squamous cell lesions has been under investigation, revealing individual premalignant characteristics. Recent developments in molecular characterization of squamous alterations of the urinary tract indicate pathogenetic similarities and interrelations and might lead to more precise tumor classification and risk stratification in the future. Nevertheless, current clinical management of patients with premalignant and malignant bladder squamous cell lesions remains challenging, as high evidence level studies are not available and prognosis of invasive squamous carcinoma is poor. Our review summarizes the available data on clinical presentation, treatment, and outcome of bladder squamous cell carcinoma, metaplastic lesions, and transitional cell carcinoma with squamous differentiation and discusses implementable current advances in the understanding of bladder cancer tumorigenesis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: We determined the association of the proliferation marker Ki-67 with pathological parameters and oncologic outcomes in patients with high grade upper tract urothelial carcinoma., Materials and Methods: Immunohistochemical staining for Ki-67 was done prospectively in 101 consecutive patients undergoing radical nephroureterectomy/ureterectomy for high grade upper tract urothelial carcinoma. Data were compared based on Ki-67 status (normal vs over expressed). Survival was assessed by the Kaplan-Meier method. Cox regression analysis was done to identify independent predictors of time dependent outcomes., Results: Median patient age was 70.0 years and median followup was 22.0 months (range 1 to 77). Overall, 30.2% of the population experienced recurrence and 24.8% died of upper tract urothelial carcinoma. Organ confined disease (T2 or less and lymph node negative), lymphovascular invasion and sessile architecture were present in 56.3%, 33.3% and 20.8% of patients, respectively. Ki-67 was over expressed in 73.3% of patients and associated with adverse pathological features. Patients with over expressed Ki-67 had significantly worse recurrence-free survival (43.2 vs 69.0 months, p = 0.006) and cancer specific survival (48.9 vs 68.9 months, p = 0.031) than patients with normal Ki-67. Patients with nonmetastatic disease similarly had worse recurrence-free survival (40.7 vs 71.8 months, p = 0.003) and cancer specific survival (41 months vs not attained, p = 0.008) for over expressed vs normal Ki-67. After adjusting for the effects of organ vs nonorgan confined disease Ki-67 over expression was an independent predictor of recurrence-free survival in the total cohort (HR 4.3, p = 0.05) and in patients with nonmetastatic disease (HR 8.5, p = 0.038)., Conclusions: Ki-67 over expression was associated with adverse pathological features in cases of upper tract urothelial carcinoma. It was also an independent predictor of recurrence-free survival in patients with high grade upper tract urothelial carcinoma., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

GATA-3 is a newly described marker that labels urothelial and breast carcinoma. However, no prior study has evaluated the expression of GATA-3 in primary bladder adenocarcinoma. Tissue microarrays (TMAs) containing 46 primary bladder adenocarcinomas were constructed. They contained 19 signet ring cell (SRC) and 27 conventional adenocarcinomas. Three additional cases of SRC using routine sections were included resulting in a total of 22 SRCs. In addition, TMAs containing 32 primary gastric signet ring adenocarcinomas and 36 primary lobular breast carcinomas were evaluated. The TMAs were subjected to immunohistochemical analysis for GATA-3, with nuclear labeling scored by intensity and percentage labeling. Breast and urothelial TMAs were also labeled for estrogen receptor, progesterone receptor, and gross cystic duct fluid protein. Diffuse nuclear GATA-3 labeling was seen in 9/22 (41.0%) SRCs and in 2/27 (7.0%) conventional adenocarcinomas (P=0.01). Extracellular mucin production was seen in 12 SRCs. One of 12 (8.0%) SRCs with extracellular mucin was GATA-3 positive, and 8/10 SRCs without extracellular mucin was GATA-3 positive (P=0.005). No nuclear GATA-3 labeling was seen in any gastric signet ring carcinoma. Diffuse, moderate to strong nuclear GATA-3 labeling was seen in 36/36 (100%) primary lobular breast carcinomas. Nuclear GATA-3 labeling is a useful marker for primary adenocarcinomas of the urinary bladder with signet ring features and can be helpful in distinguishing primary signet ring carcinomas of the urinary bladder from gastric signet ring carcinomas. GATA-3 is rarely positive in bladder adenocarcinomas that lack signet ring features and in SRCs displaying extracellular mucin production.

Purpose: Cell cycle regulatory molecules are implicated in various stages of carcinogenesis. In this proof of principle study we systematically evaluate the association of aberrant expression of cell cycle regulators and proliferative markers and their effect on oncologic outcomes of patients with clear cell renal carcinoma., Materials and Methods: Immunohistochemistry for Cyclin D, Cyclin E, p16, p21, p27, p53, p57 and Ki67 was performed on tissue microarray constructs of 452 patients treated with extirpative therapy for clear cell renal cell carcinoma between 1997 and 2010. Clinical and pathological data elements were collected. A prognostic marker score was defined as unfavorable if more than 4 biomarkers were altered. The relationship between marker score and pathological features and oncologic outcomes was evaluated., Results: Median age was 57 years (range 17 to 85) and median followup was 24 months (range 6 to 150). An unfavorable marker score was found in 55 (12.2%) patients and was associated with adverse pathological features. A significant correlation between unfavorable marker score and disease-free survival (HR 26.62, 95% CI 43.38-100.04, p=0.000) and with cancer specific survival (HR 8.15, 95% CI 74.42-101.56, p=0.004) was demonstrated on Kaplan-Meier survival analysis. On multivariate analysis an unfavorable marker score was an independent predictor of disease-free survival (HR 2.63, 95% CI 1.08-6.38, p=0.033)., Conclusions: The cumulative number of aberrantly expressed cell cycle and proliferative biomarkers correlates with aggressive pathological features and inferior oncologic outcomes in patients with clear cell renal cell carcinoma. Our findings indicate that interrogation of cell cycle and proliferative markers is feasible, and further prospective pathway based exploration of biomarkers is needed., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes., Materials and Methods: Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU., Results: The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06)., Conclusions: Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC.

Purpose: Patients with renal cell carcinoma who present with pulmonary embolism and venous thrombus may not be offered surgery because of presumed poor postoperative outcomes. In this multicenter study we evaluated perioperative mortality, recurrence and cancer specific survival in patients with renal cell carcinoma and venous thrombus diagnosed with preoperative pulmonary embolism., Materials and Methods: We reviewed consecutive patient records from our 3 tertiary hospitals to identify patients with renal cell carcinoma and venous thrombus treated with surgery from 2000 to 2011. Univariate and multivariate Cox proportional hazards analysis was used to evaluate whether preoperative pulmonary embolism or other clinical variables were associated with postoperative disease recurrence or cancer specific survival., Results: Pulmonary embolism was identified preoperatively in 35 of 782 patients (4.4%) with renal cell carcinoma. Those with pulmonary embolism preoperatively were more likely to have higher level thrombus and higher T stage (p <0.01). No differences were found in other clinical or pathological features between the groups. There was no difference in 90-day mortality in patients diagnosed with pulmonary embolism preoperatively. Of 395 patients without metastasis preoperatively 147 (37.2%) showed metastatic renal cell carcinoma at a median followup of 22 months. There was no difference in the recurrence rate of renal cell carcinoma in patients with pulmonary embolism (p = 0.36). Recurrence in the lung was not more common in patients with vs without pulmonary embolism preoperatively (p = 0.71). Also, preoperative pulmonary embolism was not predictive of worse cancer specific survival (p = 0.58)., Conclusions: Preoperative pulmonary embolism is not associated with worse early mortality, recurrence or cancer specific survival in patients with renal cell carcinoma and tumor thrombus., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The natural history of urothelial carcinoma arising at the uretero-enteric junction (UEJ) is poorly defined, and the data guiding clinical management of these patients is limited. Therefore, we evaluated oncologic outcomes of patients treated for urothelial carcinoma at the UEJ., Methods: Utilizing a multi-institutional database of patients treated with radical nephroureterectomy (RNU), we assessed the clinicopathologic parameters and oncologic outcomes of UEJ tumors compared with other upper tract urothelial carcinomas (UTUC). Survival analyses were performed to determine independent predictors of disease recurrence and cancer-specific mortality after RNU., Results: The study included 1,363 patients, 921 men and 442 women with 36 months median follow-up after RNU. Compared with UTUC in the kidney or ureter, UEJ tumors (n = 22) were more likely to demonstrate features of advanced disease, which were proved to be independent predictors of disease recurrence and cancer-specific mortality after RNU. The 5 year disease-free survival (DFS) and cancer-specific survival (CSS) rates were 25% and 39% in those with UEJ tumors vs. 69% and 73% in those with UTUC in the kidney or ureter (P = 0.001 and P = 0.008, respectively)., Conclusions: UEJ tumors harbor features of locally advanced disease associated with high risk of systemic recurrence and death from cancer after RNU. Our findings suggest the need for integration of systemic therapy into the management paradigm of these patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To evaluate the association of the altered expression of the mammalian target of rapamycin (mTOR) pathway components with oncologic outcomes in patients with nonmetastatic clear cell renal cell carcinoma (ccRCC)., Materials and Methods: Immunohistochemistry for phosphorylated-S6, phosphorylated-mTOR, mTOR, phosphorylated-AKT, hypoxia inducible factor-1α, Raptor, phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and phosphorylated 4E-binding protein-1 was performed on tissue microarray constructs of patients treated for nonmetastatic kidney cancer from 1997 to 2010. The relationship between individual altered marker expression and a prognostic marker score (low, intermediate, and high, defined as ≤ 3, 4-5, >5 altered biomarkers, respectively) and oncologic outcome was assessed., Results: The study included 419 patients with nonmetastatic ccRCC, with a median follow-up period of 26 months (range 6-150). The tumors were nonorgan confined (pT3-T4) in 86 (20.5%) and high Fuhrman nuclear grade (3-4) in 131 (31%). A low, intermediate, and high prognostic marker score was found in 214 (51%), 152 (36%), and 53 (13%) patients, respectively. Kaplan-Meier analysis demonstrated a statistically significant correlation between the risk groups and disease recurrence and cancer-specific survival. In a multivariate Cox regression analysis controlling for tumor stage and grade, a high marker score was an independent predictor of disease recurrence (hazard ratio 3.3, 95% confidence interval 1.33-8.39, P = .01), and a combination of a high and an intermediate score was an independent predictor of survival (hazard ratio 4.8, 95% confidence interval 1.27-4.78, P = .008)., Conclusion: The cumulative number of aberrantly expressed biomarkers correlated with aggressive tumor biology and inferior oncologic outcomes in patients with ccRCC. Our data support prospective pathway-based exploration of the mTOR signaling cascade to augment current clinicopathologic predictors of oncologic outcomes in patients with ccRCC., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Residual fragments following ureteroscopy for calculi may contribute to stone growth, symptoms or additional interventions. We reviewed our experience with ureteroscopy for calculus disease to define the incidence and establish factors predictive of residual fragments., Materials and Methods: Records associated with 667 consecutive ureteroscopic lithotripsy procedures for upper urinary calculi were reviewed. In 265 procedures (40%) computerized tomography was done between 30 and 90 days postoperatively. They comprised the study group. Residual fragments were defined as any residual ipsilateral stone greater than 2 mm., Results: Included in the study were 121 men and 127 women with a mean age of 47 years. Mean target stone diameter was 7.6 mm. The stone location was the kidney in 30% of cases, ureter in 50%, and kidney and ureter in 20%. Residual fragments were detected on computerized tomography after 101 of 265 procedures (38%). Pretreatment stone size was associated with residual fragments at a rate of 24%, 40% and 58% for stones 5 or less, 6 to 10 and greater than 10 mm, respectively (p <0.001). Additionally, stone location in the kidney (p <0.001) or the kidney and ureter (p = 0.044), multiple calculi (p = 0.003), longer operative time (p = 0.008) and exclusive use of flexible ureteroscopy (p = 0.029) were associated with residual fragments. In a multivariate model only pretreatment stone diameter greater than 5 mm was independently associated with residual fragments after ureteroscopy (diameter 6 to 10 and greater than 10 mm OR 2.03, p = 0.03 and OR 3.74, p = 0.003, respectively)., Conclusions: Of patients who underwent ureteroscopic lithotripsy for calculi 38% had residual fragments by computerized tomography criteria, including more than 50% with stones 1 cm or greater. Such data may guide expectations regarding the success of ureteroscopy in attaining stone-free status., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Unlabelled: What's known on the subject? and What does the study add? Shock wave lithotripsy and flexible ureterorenoscopy are acceptable treatment options for lower pole stones smaller than 10 mm, while percutaneous nephrolithotomy is the favoured treatment for stones larger than 20 mm. For treatment of lower pole stones of 10-20 mm, flexible ureterorenoscopy has a significantly higher stone-free rate and lower retreatment rate than shock wave lithotripsy., Objective: To compare the outcomes of flexible ureterorenoscopy (F-URS) and extracorporeal shock wave lithotripsy (ESWL) for treatment of lower pole stones of 10-20 mm., Patients and Methods: The database of patients with a single lower pole stone of 10-20 mm was examined to obtain two matched groups who were treated with F-URS or ESWL. Matching criteria were stone length, side and patient gender. Stone-free rates were evaluated 3 months after the last treatment session by non-contrast computed tomography. Both groups were compared for retreatment rate, complications and stone-free rate., Results: The matched groups included 37 patients who underwent F-URS and 62 patients who underwent ESWL. Retreatment rate was significantly higher for ESWL (60% vs 8%, P < 0.001). Complications were more after F-URS (13.5% vs 4.8%), but the difference was not significant (P= 0.146). All complications were grade II or IIIa on modified Clavien classification. The stone-free rate was significantly better after F-URS (86.5% vs 67.7%, P= 0.038). One failure of F-URS (2.7%) and five failures (8%) of ESWL were treated with percutaneous nephrolithotomy. Significant residual fragments in three patients (8%) after F-URS were treated with ESWL, while significant residual fragments after ESWL in five patients (8%) were treated with F-URS. Residual fragments (<4 mm) were followed every 3 months in one patient (2.7%) after F-URS and in 10 patients (16%) after ESWL., Conclusions: For treatment of lower pole stones of 10-20 mm, F-URS provided significantly higher stone-free rate and lower retreatment rate compared with ESWL. The incidence of complications after F-URS was not significantly more than after ESWL., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)