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Kymora B Scotland, Dirk Lange Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada Abstract: Urosepsis is a potentially life-threatening phenomenon that may occur after an ureteroscopic procedure. With the increasingly widespread adoption of ureteroscopy, there is a concern that the rates of urosepsis may increase. This review examines the current work being undertaken to minimize postprocedure infections both in the field of device development and in clinical care. Guidelines for the diagnosis and management of urosepsis will be discussed. Keywords: urosepsis, sepsis, urinary tract infection, ureteroscopy, ureteroscope, ureteral stent

Purpose: Flank pain associated with stone disease is typically caused by a stone that obstructs urine flow. However, it is plausible that nonobstructing kidney stones may still cause pain. We performed a multicenter, observational trial to evaluate whether treatment of small nonobstructing calyceal stones improves pain and kidney stone-specific health-related quality of life., Materials and Methods: Patients aged 18 years or older with nonobstructing renal stone(s) up to 10 mm in longest diameter and moderate to severe pain were recruited. All participants completed 3 questionnaires: the Brief Pain Inventory (BPI), the Patient-Reported Outcomes Measurement Information System pain interference form 6a, and the Wisconsin Stone Quality of Life questionnaire. Thereafter, all participants underwent ureteroscopy for renal stone treatment. All 3 questionnaires were repeated at 2, 6 to 8, and at 12 weeks postprocedure. The primary outcomes were change in preoperative to 12-week postoperative mean BPI score and worst BPI pain score., Results: A total of 43 patients with nonobstructing kidney stones and associated flank pain were recruited. All stones were removed. Preoperatively, BPI scores for mean pain and worst pain were 5.5 and 7.2, respectively which decreased to 1.8 and 2.8 respectively at 12 weeks postoperatively. Wisconsin Stone Quality of Life questionnaire mean score increased from 70.4 to 115.3 at 12 weeks postoperatively. A total of 86% and 69% of patients had at least a 20% and 50% reduction in their mean pain scores, respectively., Conclusions: This study determined that patients benefit significantly from the removal of calyceal nonobstructing kidney stones for at least 12 weeks with a reduction in pain and an increase in quality of life. Therefore, surgical removal of these stones in this patient population should be offered as a treatment option.

Background: The COVID-19 pandemic drastically reduced opportunities for surgical skill sharing between high-income and low to middle-income countries. Augmented reality (AR) technology allows mentors in one country to virtually train a mentee in another country during surgical cases without international travel. We hypothesize that AR technology is an effective live surgical training and mentorship modality., Methods: Three senior urologic surgeons in the US and UK worked with four urologic surgeon trainees across the continent of Africa using AR systems. Trainers and trainees individually completed post-operative questionnaires evaluating their experience., Results: Trainees rated the quality of virtual training as equivalent to in-person training in 83% of cases (N = 5 of 6 responses). Trainers reported the technology's visual quality as "acceptable" in 67% of cases (N = 12 of 18 responses). The audiovisual capabilities of the technology had a "high" impact in the majority of the cases., Conclusion: AR technology can effectively facilitate surgical training when in-person training is limited or unavailable., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To develop a standardised tool to evaluate flexible ureterorenoscopes (fURS)., Materials and Methods: A three-stage consensus building approach based on the modified Delphi technique was performed under guidance of a steering group. First, scope- and user-related parameters used to evaluate fURS were identified through a systematic scoping review. Then, the main categories and subcategories were defined, and the expert panel was selected. Finally, a two-step modified Delphi consensus project was conducted to firstly obtain consensus on the relevance and exact definition of each (sub)category necessary to evaluate fURS, and secondly on the evaluation method (setting, used tools and unit of outcome) of those (sub)categories. Consensus was reached at a predefined threshold of 80% high agreement., Results: The panel consisted of 30 experts in the field of endourology. The first step of the modified Delphi consensus project consisted of two questionnaires with a response rate of 97% (n = 29) for both. Consensus was reached for the relevance and definition of six main categories and 12 subcategories. The second step consisted of three questionnaires (response rate of 90%, 97% and 100%, respectively). Consensus was reached on the method of measurement for all (sub)categories., Conclusion: This modified Delphi consensus project reached consensus on a standardised grading tool for the evaluation of fURS - The Uniform grading tooL for flexIble ureterorenoscoPes (TULIP) tool. This is a first step in creating uniformity in this field of research to facilitate future comparison of outcomes of the functionality and handling of fURS., (© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To investigate global changes in ureters at the transcriptional, translational and functional levels, both while stents are indwelling and after removal and recovery, and to study the effects of targeting pathways that play a potential role., Methods: Pig ureters were stented for varying amounts of time (48 h, 72 h, 14 days) and the impact on peristalsis, dilatation and hydronephrosis were assessed. RNAseq, proteomic, histological and smooth muscle (SM) function analyses were performed on ureteric and kidney tissues to assess changes induced by stenting and recovery. Pathway analysis was performed using Ingenuity Pathway Analysis software. To study the impact of possible interventions, the effects of erythropoeitin (EPO) and a Gli1 inhibitor were assessed., Results: Stenting triggers massive ureteric dilatation, aperistalsis and moderate hydronephrosis within 48 h. Pathways associated with obstruction, fibrosis and kidney injury were upregulated by stenting. Increased expression of GLI1, clusterin-α (a kidney injury marker) and collagen 4A2 (a fibrosis marker) was found in stented vs contralateral unstented ureters. EPO did not improve peristalsis or contraction force but did decrease non-purposeful spasming seen exclusively in stented ureters. Tamsulosin administration increased contractility but not rate of peristalsis in stented ureters., Conclusions: Ureters respond to stents similarly to how they respond to an obstruction, that is, with activation of pathways associated with hydronephrosis, fibrosis and kidney injury. This is driven by significant dilatation and associated ureteric SM dysfunction. EPO and tamsulosin induced mild favourable changes in SM physiology, suggesting that targeting specific pathways has potential to address stent-induced complications., (© 2022 BJU International.)

Purpose of Review: The persistent rise in kidney stone prevalence in recent decades has prompted much speculation as to the causes. There has been some discussion about the effect of heat on nephrolithiasis. Here, we review recent data and postulate that heat may play a role in stone formation on a large scale and among African-Americans in particular., Recent Findings: African-Americans are the race/ancestry group with faster rates of increasing incidence and prevalence of kidney stones. We make the observation that urban heat islands in the United States have resulted in part from the effects of redlining, a practice of systematic segregation and racism in housing that led to the development of neighborhoods with substantial disparities in environmental conditions., Summary: In this thought experiment, we propose that the disproportionate rise in the prevalence of nephrolithiasis in minoritized populations correlates with increased temperatures specifically in neighborhoods adversely affected by the practice of redlining. We discuss phenomena in support of this hypothesis and ongoing work to test this theory., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Treatment of struvite kidney stones requires complete surgical stone removal combined with antibiotic therapy to eliminate urinary tract infections and preventive measures to reduce stone recurrence. The optimal duration of antibiotic therapy is unknown. We sought to determine if 2- or 12-weeks of antibiotics post percutaneous nephrolithotomy (PNL) for infection stones resulted in better outcomes for stone recurrence and positive urine cultures., Material and Methods: This multi-center, prospective randomized trial evaluated patients with the clinical diagnosis of infection stones. Patients were randomized to 2- or 12-weeks of postoperative oral antibiotics (nitrofurantoin or culture-specific antibiotic) and included if residual fragments were ≤4 mm on computed tomography imaging after PNL. Imaging and urine analyses were performed at 3-, 6-, and 12-months post-procedure., Results: Thirty-eight patients were enrolled and randomized to either 2-weeks (n = 20) or 12-weeks (n = 18) of antibiotic therapy post-PNL. Eleven patients were excluded due to residual fragments >4 mm, and 3 patients were lost to follow-up. The primary outcome was the stone-free rate (SFR) at 6 months post-PNL. At 3-, 6-, and 12-months follow-up, SFRs were 72.7% versus 80.0%, 70.0% versus 57.1%, 80.0% versus 57.1% (p = ns), between 2- and 12-week-groups, respectively. At 3-, 6-, and 12-months follow-up, positive urine cultures were 50.0% versus 37.5%, 50.0% versus 83.3%, and 37.5% versus 100% between 2- and 12-week groups, respectively (p = ns)., Conclusions: For patients with stone removal following PNL, neither 2-weeks nor 12-weeks of postoperative oral antibiotics is superior to prevent stones and recurrent positive urine cultures., (© 2022 The Japanese Urological Association.)

Objective: To assess the effect of 2 over-the-counter alkalizing agents on 24 hour urinary parameters., Materials and Methods: Ten healthy volunteers without a history of kidney stones were recruited to complete a baseline 24 hour urinalysis with a 4 day diet inventory. Participants then maintained the same diet on either LithoLyte (20 mEq 2 times per day) or KSPtabs (1 tablet 2 times per day) and submitted another 24 hour urinalysis. The process was repeated with the other supplement. Urinary alkali parameters were compared to baseline, and side effects were elicited with a questionnaire., Results: LithoLyte intake resulted in a non-significant increase in citrate (597-758 mg/day, P =.058, an increase in urine pH (6.46-6.66, P =.028), and a decrease in urine ammonium (41-36 mmol/day, P =.005) compared to baseline. KSPtabs resulted in an increase in citrate (597-797 mg/day, P =.037) and urine pH (6.46-6.86, P =.037), with a non-significant decrease in ammonium (41-34 mmol/day, P =.059). No significant differences were seen comparing urinary analytes between LithoLyte and KSPtabs. With Litholyte, no side effects, mild, moderate, and severe side effects were seen in 50%, 40%, 10%, and 0%, respectively. With KSPtabs, rates were 60%, 20%, 10%, and 10%, respectively., Conclusion: In healthy participants without a history of kidney stones, LithoLyte and KSPtabs are effective over-the-counter alkali supplements, with a similar side effect profile to prescription potassium citrate., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Urolithiasis is a global phenomenon. Cystolithiasis is common in parts of Africa due to low protein intake and dehydration from endemic diarrhoeal illnesses. Nephrolithiasis is less prevalent than in high-income countries, probably due to a variety of lifestyle issues, such as a more elemental diet, higher physical activity, and less obesity. Although renal stones are less common in low- and middle-income countries (LMICs), the social and economic impacts of nephrolithiasis are still considerable; many stones present late or with complications such as upper urinary tract obstruction or urosepsis. These may lead to the development of chronic kidney disease, or end-stage renal failure in a small proportion of cases, conditions for which there is very poor provision in most LMICs. Early treatment of nephrolithiasis by the least invasive method possible can, however, reduce the functional consequences of urinary stone disease. Although extracorporeal lithotripsy is uncommon, and endoscopic interventions for stone are not widespread in most of Africa, percutaneous nephrolithotomy and ureteroscopic renal surgery are viable techniques in those regional centres with infrastructure to support them. Longitudinal mentoring has been shown to be a key step in the adoption of these minimally invasive procedures by local surgeons, something that has been difficult during the coronavirus disease 2019 (COVID-19) pandemic due to travel restriction. Augmented reality (AR) technology is an alternative means of providing remote mentoring, something that has been trialled by Urolink, the MediTech Trust and other global non-governmental organisations during this period. Our preliminary experience suggests that this is a viable technique for promulgating skills in LMICs where appropriate connectivity exists to support remote communication. AR may also have long-term promise for decreasing the reliance upon short-term surgical visits to consolidate competence, thereby reducing the carbon footprint of global surgical education., (© 2022 BJU International.)

Migration time fluctuation strongly affects peak alignment and identification of unknown compounds, making migration time correction an essential step in capillary electrophoresis (CE)-based metabolomics. To obtain more reliable information, metabolites with different apparent mobilities are analyzed by tandem mass spectrometry. Applying a small pressure is a common practice for reducing the analysis time of anions in a positive mode CE, known as the pressure-assisted CE. However, applying pressure may reduce the separation efficiency and can be undesirable for cation analysis. A simple way to address this issue is to increase the pressure after a certain time, during the separation. We term this practice as dual pressure CE. However, changing the pressure during the CE separation complicates migration time correction. Previous migration time correction methods were established based on a consistent electroosmotic flow and a constant pressure-driven bulk-flow velocity. We proposed a new correction method to support the peak alignment when dual pressure CE is used. A Python-based script was developed to implement dual pressure CE migration time correction for semi-targeted metabolomics study performed by a multiple reaction monitoring-based method. This script can help select suitable endogenous metabolites as correction markers, perform migration time correction, and conduct peak alignment. A case study showed that migration time precision of 156 metabolites in 32 samples can be improved from 4.8 to 11.4%RSD (relative standard deviation) to less than 1.8%RSD., (© 2022 Wiley-VCH GmbH.)

An increasing number of patients are utilizing the internet to answer their medical questions. Given the lack of verified stone treatment resources on the web, we sought to evaluate online interest in kidney stone surgical interventions and assess the quality of the most popular resources on social media. Google Trends was used to evaluate public interest in different kidney stone interventions between March 2016 and February 2021 and reported as search volume index (SVI). Next, the social media analysis tool, BuzzSumo, was used to identify stone surgery content online on the social media platforms, YouTube, Instagram, Pinterest, Reddit, and Twitter. To evaluate the quality of health information presented in the online resources, the DISCERN instrument was employed by three individual raters. Ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), and extracorporeal shockwave lithotripsy (SWL) were identified as the top search terms on Google Trends with mean SVIs of 47.75, 42.98, and 45.74, respectively ( p  = 0.012). On YouTube, URS, PCNL, and SWL had 12,549, 116,222, and 20,717 views, respectively. Nine articles and fifteen videos were chosen for analysis using the DISCERN tool with a mean score of 2.82 and 2.27, respectively, among three independent evaluators. The result of our study suggests that online users are interested in URS but engaged more often with PCNL content on social media platforms. We found that the quality of online resources related to stone surgery highlights the need for involvement of urologists in creation of engaging high-quality content and sharing of accurate information in a social media-driven society.

The medical and surgical management of kidney stones is one of the most common functions of the urologist. Management choices are often nuanced, involving the decision to embark on one surgical plan among several options. As the wider medical community critically evaluates the care we provide to an increasingly diverse population, it will be important to examine patient outcomes with a particular focus on ensuring equitable care. This review examines the influence of social parameters on the care of kidney stone patients. The dearth of literature in this area warrants rigorous studies on the relationship between race as well as socioeconomic status and the management of kidney stone disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Patients suffering from progressive symptoms of benign prostatic hyperplasia (BPH) increasingly turn to the internet for information on invasive and minimally invasive surgical therapies (MIST). This study aimed to identify online articles accessed by patients seeking guidance on said options and to evaluate the quality and readability of their content. Methods: Social media analytics tool Buzzumo was used to identify the most shared articles on Facebook, Twitter, Reddit, and Pinterest related to BPH surgical treatments from 2016 to 2021. The content quality was graded using the DISCERN tool; a questionnaire that assesses the quality of written information on treatment choices for a health problem. An online Automatic Readability Checker was used to evaluate the readability of the written transcripts. Google Trends data were used to evaluate search term popularity for BPH procedures from 2016 to 2021. Google Trends data and DISCERN ratings were analyzed with ANOVA and paired t -test, respectively. Results: Thirty-nine percent of identified articles were rated as low quality, 39% as moderate quality, and 22% as high quality using the DISCERN tool, with no significant difference among reviewer ratings ( p  = 0.0561). The median reading level of all articles was 12th grade. Google Trends data illustrated a rising popularity of MIST such as Rezūm and urethral lift (Urolift), exceeding interest in more invasive procedures such as Holmium laser enucleation of the prostate (HoLEP) and laser surgery. Transurethral resection of the prostate (TURP) remained popular with no significant difference between MIST and TURP on Google Trends ( p  = 3.46). Conclusions: The most accessed articles on BPH treatments have important shortcomings, including risks of treatment and other available options for treatment. Article transcripts exceed the reading level of the average adult patient. TURP has remained a popular procedure online, but there is a notable rising interest in MIST, especially Urolift.

Introduction: The novel coronavirus disease (COVID-19) pandemic has had a significant impact on the care of patients with urolithiasis. Recommendations and prioritization of endourologic surgical procedures vary among regions, and a comprehensive overall international directive is needed. We used the Delphi method to obtain international consensus on managing urolithiasis patients during the pandemic. Methods: A three-round Delphi process was used to elicit expert consensus (53 global key opinion leaders within the Endourological Society from 36 countries) on an extensive survey on management of endourologic patients in a pandemic. Questions addressed general management, inpatient and outpatient procedures, clinic visits, follow-up care, and best practices for suspension and resumption of routine care. Results: Consensus was achieved in 64/84 (76%) questions. Key consensus findings included the following: consultations should be delivered remotely when possible. Invasive surgical procedures for urolithiasis patients should be reserved for high-risk situations (infection, renal failure, etc.). To prevent aerosolization, spinal anesthesia is preferred over general, whenever feasible. Treatment of asymptomatic renal stones should be deferred. Primary definitive treatment of obstructing or symptomatic stones (both renal and ureteral) is preferred over temporizing drainage. Extracorporeal shockwave lithotripsy should be continued for obstructive ureteral stones. There was consensus on treatment modalities and drainage strategies depending on location and size of the stone. Conclusion: International endourologist members of the Endourological Society participated in this Delphi initiative to provide expert consensus on management of urolithiasis during a pandemic. These results can be applied currently and during a future pandemic.

Background: Ureteral contractility is a poorly understood process. Contractions have been demonstrated to occur in the smooth muscle layers of the ureter. Previous work suggests the involvement of Gli family proteins and erythropoietin (EPO) in regulating mammalian ureteral smooth muscle contraction. We sought to devise a method by which the effects of these proteins and tamsulosin on distal human ureteral tissue contractility could be investigated to better understand mechanisms regulating human ureteral function., Methods: IRB approval was obtained to procure portions of extraneous distal ureteral tissue from living donor renal transplants. Contractility was measured by placing the tissue in Krebs buffer and stimulating via a uniform electric current. Contractile force was recorded with each stimulation with and without the presence of a Gli inhibitor (GANT61) or EPO. Each ureteral specimen was subsequently fixed and tested by immunohistochemistry to determine Gli, EPO and alpha-adrenergic receptor activity., Results: Electrical field stimulation successfully elicited contractions in the ureteral tissue. Administering tamsulosin decreased force and duration of ureteral contractions. Inhibiting Gli signaling decreased contractility and EPO decreased ureteral contractile forces within 5 minutes of administration versus untreated controls. Staining confirmed Gli1 protein and α-adrenergic receptor expression in ureteral smooth muscle and epithelial tissue with EPO receptor expression confined to the epithelial layer., Conclusions: Distal ureteral contractile forces are decreased by inhibition of Gli family proteins and the α-adrenergic receptor. EPO acts within five minutes, suggesting ion channel involvement instead of changes in gene expression. Continuing work will elucidate the role of these proteins in coordinating ureteral contractions. This has implications for the use of pharmacologic methods to address ureteral contractility and dysfunctional peristalsis during stone passage, ureteroscopy, in transplant patients and potentially to reduce symptoms from ureteral stents., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tau-20-1342). The authors have no conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

Kidney stone disease (KSD) is a complex disease. Besides the high risk of recurrence, its association with systemic disorders contributes to the burden of disease. Sufficient water intake is crucial for prevention of KSD, however, the mineral content of water might influence stone formation, bone health and cardiovascular (CVD) risk. This study aims to analyse the variations in mineral content of bottled drinking water worldwide to evaluate the differences and describes the possible impact on nephrological and urological diseases. The information regarding mineral composition (mg/L) on calcium, bicarbonate, magnesium, sodium and sulphates was read from the ingredients label on water bottles by visiting the supermarket or consulting the online shop. The bottled waters in two main supermarkets in 21 countries were included. The evaluation shows that on a global level the mineral composition of bottled drinkable water varies enormously. Median bicarbonate levels varied by factors of 12.6 and 57.3 for still and sparkling water, respectively. Median calcium levels varied by factors of 18.7 and 7.4 for still and sparkling water, respectively. As the mineral content of bottled drinking water varies enormously worldwide and mineral intake through water might influence stone formation, bone health and CVD risk, urologists and nephrologists should counsel their patients on an individual level regarding water intake.

Introduction: Health-related quality of life (HRQOL) is decreased in patients with kidney stones at all stages of stone disease, even when asymptomatic. Stress is thought to contribute to HRQOL, although there has been minimal investigation into the effect of stress on stone-related quality of life (QOL). We used the Wisconsin Stone Quality of Life Questionnaire (WISQOL) to assess the relationship of stress to stone-related QOL in kidney stone patients., Methods: As part of the WISQOL Research Consortium, patients were approached in outpatient clinics and completed the WISQOL and the Perceived Stress Scale 10-item questionnaire (PSS-10). Patients with stones at enrollment were divided into those with symptoms and those without, while patients with no current stones formed another group. Questionnaire scores from each group were compared statistically and correlations between the groups were calculated., Results: Patients (n=704) were enrolled from six centers. The WISQOL successfully discriminated between patients with current stones and those without (p<0.0001), while the PSS-10 did not (p=0.0869). The PSS-10 revealed patients with symptomatic kidney stones experienced higher levels of general stress than asymptomatic subjects (p<0.0001). However, a Pearson correlation test comparing the responses from each instrument revealed no overall correlation between general stress and HRQOL (r=0.05)., Conclusions: Symptomatic kidney stones increase general stress, as these patients demonstrate higher PSS-10 scores. Despite this, no correlation exists between general stress and stone-related QOL in patients with stone disease regardless of their stone and symptom status. This implies the existence of other factors impacting QOL in these patients, which warrants further exploration.

Catheter-associated urinary tract infections (CAUTIs) are one of the most commonly occurring hospital-acquired infections. Current coating strategies to prevent catheter-associated biofilm formation are limited by their poor long-term efficiency and limited applicability to diverse materials. Here, the authors report a highly effective non-fouling coating with long-term biofilm prevention activity and is applicable to diverse catheters. The thin coating is lubricous, stable, highly uniform, and shows broad spectrum prevention of biofilm formation of nine different bacterial strains and prevents the migration of bacteria on catheter surface. The coating method is adapted to human-sized catheters (both intraluminal and extraluminal) and demonstrates long-term biofilm prevention activity over 30 days in challenging conditions. The coated catheters are tested in a mouse CAUTI model and demonstrate high efficiency in preventing bacterial colonization of both Gram-positive and Gram-negative bacteria. Furthermore, the coated human-sized Foley catheters are evaluated in a porcine CAUTI model and show consistent efficiency in reducing biofilm formation by Escherichia coli (E. coli) over 95%. The simplicity of the coating method, the ability to apply this coating on diverse materials, and the high efficiency in preventing bacterial adhesion increase the potential of this method for the development of next generation infection resistant medical devices., (© 2021 Wiley-VCH GmbH.)

Purpose: This study aims to identify clinical factors that may predispose struvite stone patients to urosepsis following percutaneous nephrolithotomy (PCNL)., Materials and Methods: A retrospective review was conducted on patients who received PCNL for struvite stones. The Systemic Inflammatory Response Syndrome (SIRS) criteria and quick-Sepsis Related Organ Failure Assessment (q-SOFA) criteria were used to identify patients who were at an increased risk for urosepsis. Statistical analysis was performed using Fisher's exactness test, Wilcoxon rank test, and logistic regression., Results: Chart review identified 99 struvite stone patients treated with PCNL. Post-operatively, 40 patients were SIRS positive (≥2 criteria) and/or q-SOFA positive (score ≥2). Using SIRS as an approximation for urosepsis, longer operative times (p<0.001), higher pre-operative white blood cell counts (p=0.01), greater total stone surface area (p<0.0001), and pre-operative stenting (OR, 5.75; p=0.01) were identified as independent risk factors for urosepsis. Multivariate analysis demonstrated pre-operative stenting (OR, 1.46; p=0.01) to be a risk factor. With q-SOFA, univariable analysis found that antibiotic use within 3 months prior to a PCNL (OR, 4.44; p=0.04), medical comorbidities (OR, 4.80; p=0.02), longer operative times (p<0.001), lengthier post-operative hospitalization (p<0.01), and greater total stone surface area (p<0.0001) were risk factors for urosepsis. Multivariate analysis revealed that bladder outlet obstruction (OR, 2.74; p<0.003) and pre-operative stenting (OR, 1.27; p=0.01) significantly increased odds of being q-SOFA positive., Conclusions: Several risk factors for urosepsis following PCNL for struvite stones have been identified. These risk factors should be taken into consideration in peri-operative care to mitigate the risks of urosepsis., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Objective: To compare the health-related quality of life (HRQOL) of patients with residual fragments after surgical intervention for kidney stones to patients that are stone-free using the disease-specific Wisconsin stone quality of life (WISQOL) questionnaire. Kidney stones contribute to impaired HRQOL, which is increasingly recognized as an important healthcare outcome measurement., Materials and Methods: With institutional review board approval, 313 adult patients who underwent surgical intervention for kidney stones at 4 sites completed a WISQOL questionnaire. We retrospectively collected surgical data including presence of residual fragments on post-operative imaging. We calculated standardized WISQOL total and domain scores (0-100), which included items related to social functioning (D1), emotional functioning (D2), stone-related impact (D3), and vitality (D4). Scores were compared between patients with residual fragments to those who were stone-free after surgical intervention., Results: Demographics did not differ between groups, overall mean age 54.6 ± 13.5 and 55.4% female. There was no significant difference in total WISQOL score for patients with residual fragments (n = 124) compared to patients that were stone-free (n = 189), 110.5 ± 27.8 vs 115.4 ± 23.6 respectively, (P = .12). Interestingly, patients with residual fragments who underwent secondary surgery were found to have significantly lower total WISQOL score (88.4 ± 30.1 vs 116.6 ± 25.0, P <.0001)., Conclusion: Stone-free status after surgical intervention is not associated with better HRQOL when compared with patients whose surgeries left residual fragments. Indeed, further surgical intervention on residual fragments to achieve stone-free status may actually result in worse HRQOL., (Copyright © 2020 Elsevier Inc. All rights reserved.)

INTRODUCTION To assess the relationship between pain after ureteral stent removal and patient and procedural factors., Materials and Methods: A validated survey designed to assess the relationship between quality of life and treatment decisions in kidney stone disease was randomly distributed to patients with a history of a ureteral stent in seven medical centers across North America participating in an endourology research collaborative between July 2016 and June 2018. The primary outcome was increased pain after ureteral stent removal. Statistical analyses were performed using Chi-square and multiple logistic regression., Results: A total of 327 surveys were analyzed. Twenty seven percent of patients reported increased pain in the hours after ureteral stent removal. Patients with a stent ≤ 7 days were significantly more likely to experience pain after stent removal compared to those with a stent > 7 days (33.3% versus 22.8%, p = 0.04). Female gender (OR: 2.41, 95% CI: 1.42-4.10) was associated with increased pain after stent removal, while increasing age was inversely associated (OR: 0.52, 95% CI: 0.36-0.74). After adjustment, patients with a stent > 7 days were significantly less likely to report pain in the hours after removal (OR: 0.59, 95% CI: 0.35-0.99)., Conclusions: Approximately one in four patients will experience increased pain after ureteral stent removal. Female patients, younger patients, and patients with a stent ≤ 7 days were more likely to experience an increase in pain immediately following stent removal. Understanding factors associated with post-stent removal pain may be helpful in counseling patients at high risk stent removal morbidity.

Objectives: Upper tract urothelial carcinoma (UTUC) is relatively rare. While nephroureterectomy is considered the gold standard for treatment, endoscopic nephron- sparing techniques have emerged for select cases with equivalent cancer specific survival (CSS). We present the largest series with longest follow-up to date of retrograde ureteroscopy as the primary treatment of UTUC., Methods: A retrospective review was performed of 258 patients diagnosed with UTUC who were initially evaluated and managed by a single surgeon. Patients were followed from 1994 to 2017. Clinical records were evaluated for patient and tumor characteristics, operative parameters and outcomes. Statistical analysis was performed to identify risk of recurrence, progression, cancer and overall survival., Results: Following exclusion criteria, 168 patients were evaluated. Average tumor size on initial excision was 16.8mm. Mean age of the cohort was 70 years, with mean follow-up of 5.53 years. The 5-year overall survival was 80.9%, but CSS was 92.6%. Recurrence free survival was 30% with average tumor size on recurrence of 6.39mm. Progression free survival was 75% with a renal preservation rate of 71.4%., Conclusions: Ureteroscopic management of UTUC is a successful alternative to nephroureterectomy in select cases of UTUC. With strict surveillance protocols to manage frequent local recurrence rates, it is possible to achieve high renal preservation rates with acceptable CSS, even in the long-term., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Metabolic syndrome (MetS) is a cluster of metabolic diseases that is linked to atherosclerotic cardiovascular disease. MetS has also been linked to increased nephrolithiasis. However, limited research has been conducted on MetS and its impact on stone-specific health-related quality of life (HRQOL). This study aims to examine the hypothesis that the presence of MetS is associated with decreased HRQOL. Materials and Methods: The Wisconsin Stone Quality of Life Questionnaire, a stone-specific HRQOL questionnaire, was used to survey 3051 patients with kidney stones. Medical history was collected from patients. These data were used to distinguish MetS patients from non-MetS patients. Among patients with current stones, a Wilcoxon rank sum test was used to compare HRQOL scores from MetS patients and non-MetS patients. HRQOL from patients with and without individual MetS components were also compared, and a multivariate analysis was conducted. Results: Statistical comparison between MetS patients (median score 102/140) and non-MetS patients (median score 106/140) demonstrated a lower stone-specific HRQOL in patients with MetS ( p  = 0.049). Among individual MetS components, patients with diabetes mellitus (DM) or body mass index (BMI) >30 had significantly lower HRQOL than patients without DM or BMI <30 ( p  = 0.028 and p  < 0.001, respectively). The multivariate analysis supported this trend as MetS remained a significant predictor of decreased HRQOL ( p  = 0.002) after controlling for other variables assessed. Conclusions: This study indicates an association between MetS and a lower stone-specific QOL. This has important implications for stone prevention strategies in patients with MetS. Clinical Trial Registration number: H14-01143.

Despite routine implementation in urology, indwelling ureteral stents pose as a nidus for infection. Conditioning film accumulates on stents, which prime pathogen adhesion, promoting infectious biofilm formation. However, the extent to which conditioning film components play a role in facilitating bacterial adhesion and biofilm formation remains largely unknown. Here, we examined the interaction of previously identified stent-bound conditioning film components (fibrinogen, uromodulin, and albumin) with bacterial uropathogens. Cytoscopically removed stents were incubated with common uropathogens ( Escherichia coli , Enterococcus faecalis , and Staphylococcus aureus ). Immunofluorescent double staining was performed to study the localization of uropathogens relative to stent-bound conditioning film proteins. Conditioning film components were identified on the external stent surface with some deposition in the inner lumen. Bacteria co-localized with fibrinogen, uromodulin, and albumin, suggesting a potential mechanism for stent-associated infections. Here, we determine strong co-localization between common uropathogenic bacterial species with prominent conditioning film components on ureteral stents. Further functional validation of interactions amongst these uropathogens and conditioning film proteins may enhance clinical management for stent-associated infections and development of improved stent technologies.

Ureteral stents are the most widely used surgical implant in urology. However, they may cause adverse effects to patients, including pain, discomfort, and inflammation. In this work, the inflammatory effect of stent placement and the associated elevation of cyclooxygenase-2 (COX-2) expression were observed. Furthermore, a capillary electrophoresis mass spectrometry (CE-MS) based approach was subsequently developed to quantify urinary prostaglandin E 2 (PGE 2 ), a COX-2 metabolite known to contribute to inflammatory renal diseases, to further interrogate the role of this pathway. Urine samples were cleaned and preconcentrated by solid-phase extraction (SPE), and an on-line sample stacking method was used for the enrichment of analytes. The accuracy, precision, and specificity of this method were validated. Standard addition methods were performed to assess the reliability of using deuterated internal standards (IS) in compensating the remaining matrix effect after SPE as well as the detector fluctuation. Through the analysis of 32 pig urine samples, a statistically significant increase of PGE 2 was observed in the stented group compared to the unstented (P = 0.01) and the recovered (P = 0.004) groups. This work determined that stent placement may contribute to COX-2-dependent inflammation and developed a reliable CE-MS based methodology to quantify PGE 2 in stented individuals that may further understand the biology of stent-associated inflammation and inform urologic patient management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this paper, the development of a simple dilute-and-shoot method for quantifying urinary creatinine by CE-ESI-MS was described. The creatinine analysis time was about 7 min/sample by conventional single injection (SI) method and can be significantly reduced to less than 2 min/sample with multi-segment injection (MSI). In addition, the standard addition analysis of 5-hydroxyindole-3-acetic acid (5-HIAA) and creatinine normalization was performed within one run by the MSI technique, and the total analysis time was 14-min faster compared to the SI method for analyzing the same set of samples. The uses of isotopic and non-isotopic internal standards (ISs) were compared. Creatinine-(methyl- 13 C) and 5-hydroxyindole-4,6,7-D 3 -3-acetic-D 2 acid (5-HIAA-D 5 ) used as isotopic ISs can provide both accurate and precise results. In contrast, 1,5,5-trimethylhydantoin (1,5,5-TH) used as the non-isotopic IS for creatinine may cause a bias of over 13% in SI method and even worse when the MSI technique was used. Another compound, 2-methyl-3-indoleacetic acid (2-MIAA), was determined not suitable for MSI analysis of 5-HIAA due to endogenous interferences despite its acceptable performance in conventional methods of analysis., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Kidney stones affect 1 in every 11 people in the United States each year. There is a significant high recurrence rate without a stone prevention protocol. Alkali citrate is beneficial in decreasing stone recurrence, but because of the cost and gastrointestinal side effects there is a low adherence rate. This study aims to serve as a review of some of the most commonly used alkalizing over-the-counter supplements that are advertised to prevent and treat kidney stones. Methods: Data were gathered by a comprehensive online literature search and company inquiries for kidney stone prevention supplements. An additional informal poll of the authors selected supplements that are most commonly taken by their patients. A total of eight supplements were evaluated for cost, alkali equivalent provided, dosing, and regulatory information. Results: Eight of the most commonly used supplements were reviewed with a focus on alkalizing agents. Information reviewed revealed dosing recommendations resulting in decreased citrate alkali equivalents per day compared with prescription-strength potassium citrate. Cost, peer-reviewed study results, and regulatory data were reviewed, tabulated, and analyzed. Cost per alkali equivalent was substantially decreased for each supplement compared with the prescribed drug. All supplements were found to be readily available online. Conclusion: Over-the-counter alkalizing agents are available to patients and may be an appropriate alternative to cost-prohibitive potassium citrate when treating urolithiasis patients. Additional testing will be necessary in the future to determine the efficacy of these supplements in the treatment and prevention of urinary stone disease.

Introduction: Current American Urological Association guidelines recommend ureteroscopy (URS) as primary management of distal ureteral stones and shock wave lithotripsy (SWL) as a secondary option. Utilization of SWL in the management of nephrolithiasis in North America has decreased. We hypothesized that SWL continues to be an effective option in the management of distal ureteral calculi and studied data from our center in patients who received SWL for distal ureteral stones. Methods: A retrospective review was performed of 104 patients treated initially with SWL for distal ureteral calculi between 2011 and 2018 at this institution. The success rate of SWL was assessed through radiologic imaging and if subsequent procedures were required to render patients stone free. Results: Operative note and chart review identified 104 patients who presented with distal ureteral stones and were treated with SWL as the initial form of management. Average patient age was 52.2 ± 15.3 years, average BMI was 27.4 ± 5.7, and average total axial stone surface area was 25.96 ± 14.32 mm 2 . Of these patients, 78.8% ( n  = 82) were stone free following one SWL and required no subsequent procedures. Of these patients, 87.5% ( n  = 91) were stone free following a second SWL, and 87.5% ( n  = 91) were stone free following a secondary URS. After the initial SWL, residual stones were identified in 21.2% of patients ( n  = 22). Four patients, 3.8%, required a salvage URS following a failed second SWL to achieve stone-free status. Conclusion: One SWL procedure offers a stone-free rate (SFR) of 78.8% and after two SWLs an 87.5% SFR. Only 12.5% of patients undergoing SWL at our center required URS to achieve a stone-free status. SWL is an effective modality in the treatment of distal ureteral stones.

Ureteral stents are an indispensable tool in contemporary urologic patient care. They have become first-line devices for maintenance of ureteral patency postoperatively and in cases of ureteral narrowing. Despite their widespread use, these implants are associated with multiple complications including stent colic, infection, and encrustation. There is no ideal ureteric stent currently available. The aim of most recent stent innovation has been to make steps toward properties of an ideal stent. This article reviews recent technological advances in stent design and how they have attempted to tackle issues that urologists and patients face with ureteral stents., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Flexible ureteroscopy has become an important tool in the urologist's armamentarium. Until recently, reusable ureteroscopes were the only tools available to perform ureteroscopy. However, in recent years, single-use flexible and semirigid ureteroscopes have been developed as an alternative to reusable ureteroscopes. These disposable ureteroscopes were designed to mitigate problems associated with the use of reusable ureteroscopes, including the high costs related to ureteroscope acquisition, maintenance, processing, sterilization, and repairs. In this review, we provide an overview of currently available single-use flexible ureteroscopes, which include LithoVue, Uscope, NeoFlex, and Shaogang, as well as the Neoscope semirigid ureteroscope. The functional capabilities (deflection, irrigation, and optical properties) of each ureteroscope are also discussed.

Ureteral stents are commonly used devices in hospital settings. However, their usage is often complicated by associated urinary tract infections as a result of bacterial adhesion onto the indwelling implant surfaces, followed by the formation of layers of biofilm. Once formed, the biofilm is exceedingly difficult to remove, potentially leading to further morbidity and even urosepsis. Urosepsis, where pathogens from the urinary tract enter the bloodstream, has a mortality rate of up to 50% of severely infected patients. Hence, it is important to understand its pathogenesis. In this review, ureteral stent-associated urinary tract infection and urosepsis will be addressed. In particular, the bacterial mechanisms involved, as well as the prevention and treatment of these infections will be discussed.

Purpose: Patients with cystinuria are often treated with medical alkalization and shock wave lithotripsy, although each treatment is hypothesized to increase the risk of calcium phosphate stones. We performed a multicenter retrospective review to evaluate whether stones of another composition develop in patients with cystinuria and with what frequency., Materials and Methods: We retrospectively reviewed the records of a multi-institutional cohort of patients with cystinuria. We assessed medications, stone analyses, 24-hour urinalyses and types of procedures. We compared patients who formed only cystine stones vs those with noncystine stones., Results: We identified 125 patients from a total of 5 institutions who were followed a mean of 5.2 years (range 0 to 26). Stones with noncystine components were submitted by 37 patients (29.6%). Potassium citrate medication was not associated with a noncystine composition (p = 0.1877). Regarding surgical management 18 patients (13%) underwent at least 1 shock wave lithotripsy session (range 0 to 9) and 79 (63%) underwent percutaneous nephrolithotomy at least once (range 0 to 10). When stratified based on pure cystine vs converted stones, the average total number of shock wave lithotripsy and percutaneous nephrolithotomy procedures was higher in the group with cystine and subsequent noncystine stone compositions (0.94 vs 0.10, p <0.0001, and 1.7 vs 1.5, p = 0.0053, respectively). On logistic regression male gender (OR 3.1, p = 0.0280) and the number of shock wave lithotripsy sessions (OR 3.0, p = 0.0170) were associated with an increased likelihood of the development of stones with a noncystine composition., Conclusions: Stones with noncystine components develop in more than 25% of patients with cystinuria, underscoring the importance of continued stone analysis. In this study prior shock wave lithotripsy was associated with conversion to a noncystine stone composition while urinary alkalization therapy was not associated., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effectiveness of ureteroscopy (URS) with laser ablation as an alternative treatment for upper tract urothelial carcinoma (UTUC) lesions larger than 2 cm. Traditionally, patients with large UTUC are treated with radical nephroureterectomy (RNU). However, in patients with pre-existing renal disease, a solitary kidney, or those who decline RNU, management of UTUC may prove challenging METHODS: An institutional database review identified 80 patients with biopsy proven low-grade UTUC who had at least one lesion larger than 2 cm. We collected clinical data including demographics, operative parameters, and pathologic features. Follow-up for all patients was standardized and included cystoscopy and URS every 3 months until clear, every 6 months through the fifth year, and yearly thereafter. We calculated rates of recurrence, progression, and overall survival., Results: In total, 86 unique lesions ≥2cm were identified in the 80 qualifying patients; mean tumor size was 3.04 cm. Median follow-up was 43.6 months. During follow-up of patients treated curatively, 90.5% of tumors had ipsilateral recurrence and 31.7% progressed in grade at a median of 26.3 months. RNU was performed in 16 patients (20%); mean time to surgery was 23.2 months. Overall survival was 75%, and cancer specific survival was 84% at 5-year follow-up., Conclusion: Under strict surveillance, ureteroscopic management of large (≥ 2cm) UTUC lesions is a viable treatment alternative to RNU. While recurrence is common, URS can potentially preserve renal units in patients with large lesions., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To define the need for emergent intervention between patients with simultaneous bilateral ureteral calculi (SBUC) compared to unilateral ureteral calculi (UUC). Patients with SBUC represent a potential urological emergency due to possible anuria or electrolyte imbalance. While conventional practice mandates immediate intervention in these patients, little data exist to define the rate of these events., Methods: Records of all patients with ureteral stones treated ureteroscopically over an 11-year period were reviewed to identify those with SBUC. Patient presenting characteristics, time from diagnosis to intervention, and postoperative outcomes were noted. To determine the need for emergent intervention, we compared metabolic and infectious parameters between SBUC patients and age- and sex-matched patients with UUC., Results: A total of 3800 patients presented with ureteral calculi including 42 (1.1%) with SBUC. Two-thirds of patients with SBUC had an established diagnosis of nephrolithiasis. Among the 42 patients with SBUC, 11 (26.2%) were considered emergent due to metabolic (5 of 11, 45.5%), infectious (1 of 11, 9.1%), or both metabolic and infectious indications (5 of 11, 45.5%). No patients required acute dialysis before surgical intervention. Compared to patients with UUC, those with SBUC were significantly more likely to require emergent management (P = .03, odds ratio 2.3). Univariate and multivariate analyses showed this to be due to anuria (P = .001) and acidosis (P = .003)., Conclusion: SBUC is an uncommon condition and, in this series, only the minority of patients presented emergently. Therefore, patients with SBUC can often be managed electively if counseled on clinical signs warranting emergent medical attention. Appropriately selected patients have excellent outcomes following single stage bilateral ureteroscopy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Advances in flexible ureteroscope design and accessory instrumentation have allowed for more challenging cases to be treated ureteroscopically. Here, we evaluate our experience with ureteroscopy (URS) for the management of large renal calculi (≥2 cm) and provide a concise review of recent reports., Methods: A retrospective review was undertaken of all URS cases between 2004 and 2014 performed by the endourologic team at a single academic tertiary care institution. We identified patients with at least one stone ≥2 cm managed with retrograde URS. Stone size was defined as the largest linear diameter of the index stone. Small diameter flexible ureteroscopes were used primarily with holmium laser. Patient demographics, intraoperative data, and postoperative outcomes were evaluated., Results: We evaluated 167 consecutive patients who underwent URS for large renal stones ≥2 cm. The initial reason for choosing URS included patient preference (29.5%), failure of other therapies (8.2%), anatomic considerations/body habitus (30.3%), and comorbidities (28.8%). Mean patient age was 55.5 years (22-84). The mean stone size was 2.75 cm with mean number of procedures per patient of 1.65 (1-6). The single session stone-free rate was 57.1%, two-stage procedure stone-free rate was 90.2% and three-stage stone-free rate was 94.0%. Access sheaths were used in 47% of patients. An association was identified between stone size and patient outcomes; smaller stones correlated with decreased number of procedures. Postoperative complications were minor., Conclusions: Single or multi-stage retrograde ureteroscopic lithotripsy is a safe and effective mode of surgical management of large renal calculi. Total stone burden is a reliable predictor of the need for a staged procedure and of stone-free rate.

Purpose: Intracorporeal lithotripsy is becoming the most commonly used surgical method of stone treatment in Urology. The five major types of intracorporeal lithotripters are ultrasonic, ballistic, and combination lithotripters as well as laser and electrohydraulic lithotripters. The advantages and disadvantages of choosing each of these treatment modalities are reviewed., Methods: Extensive review of literature was performed to identify the types of intracorporeal lithotripters. An investigation was undertaken of the early development of each modality of intracorporeal lithotripsy and/or the mechanism of action. Challenges of each technique were identified and presented. Finally, a determination was made of how these lithotripters compare on the basis of effectiveness of action and cost based on information provided in primary literature as well as previous reviews of these modalities., Results: Contemporary lithotripters have found widespread use in the management of urinary lithiasis. Holmium laser lithotripsy has become one of the most commonly used tools for intracorporeal lithotripsy., Conclusion: There is a wide variety of intracorporeal lithotripters which can be chosen based on the characteristics of each modality and the requirements of the urologist.

Objectives: Shock wave lithotripsy (SWL) remains the only effective truly non-invasive treatment for nephrolithiasis. While single-treatment success rates may not equal those of ureteroscopy and percutaneous nephrolithotomy, it has an important role to play in the management of stones. In this paper, we outline the latest evidence-based recommendations for maximizing SWL outcomes, while minimizing complications., Materials and Methods: A comprehensive review of the current literature was performed regarding maximizing SWL outcomes., Results: Several different considerations need to be made regarding patient selection with respect to body habitus, body mass index, anatomical location and underlying urologic abnormalities. Stone composition and stone density (Hounsfield Units) are important prognostic variables. Patient positioning is critical to allow for adequate stone localization with either fluoroscopy or ultrasound. Coupling should be optimized with a low viscosity gel applied to the therapy head first and patient movement should be limited. SWL energy should be increased slowly and shockwave rates of 60 or 90 Hz should be used. Medical expulsive therapy with alpha-blockers after SWL treatment has shown benefit, particularly with stones greater than 10 mm., Conclusion: While single-treatment success rates may not equal those of ureteroscopy or percutaneous nephrolithotomy, with proper patient selection, optimization of SWL technique, and use of adjunctive treatment after SWL, success rates can be maximized while further reducing the already low rate of serious complications. SWL remains an excellent treatment option for calculi even in 2017.

Background: Radical prostatectomy is a standard surgical treatment of clinically localized prostate cancer. Margin status has been found to be an independent predictor of biochemical recurrence (BCR) after open radical prostatectomy in several large series but this is still controversy in Robotic Assisted Radical Prostatectomy (RARP) series. We therefore wanted to investigate the prognostic significance of positive surgical margin (PSM) and other pathological factors on BCR in patients treated with RARP by a single surgeon., Methods: Prospectively collected data of 439 patients treated with RARP between October 2005 and June 2013 by a single surgeon at a single institution were analyzed. BCR was defined as follow-up PSA level > 0.2 ng/ml on two separate occasions or patients who had to undergo salvage therapy. Kaplan Meier curves and Log Rank test were used to compare the risk of BCR. Univariate and Multivariate Cox Regression analyses were performed to determine the prognostic impact of age, BMI, prostate weight, PSA prior to surgery, pathological T-stage, pathological Gleason sum, PSM and operative period., Results: In this study period, 34 out of 439 had BCR, giving an overall BCR rate of 7.7% for this cohort. Overall 2- and 3-year BCR-free survival rates were 93% and 88%, respectively. Patients with a PSM had a 2-year BCR free survival of 88% compared to 94% in those with negative margins (p < .0001). On the multivariate analysis, PSM as well as pathological Gleason sum > = 8, PSA, pathological stage and operative period were significantly associated with BCR., Conclusions: In our case series of RARP performed by a single surgeon, PSM as well as pathological Gleason sum, PSA, pathological stage and early operative period for this surgeon were the independent predictors of BCR.

Bladder cancer is three times more common in men than in women. However, the physiological basis of the male predominance of bladder cancer remains poorly understood. A higher than expected association of prostate and bladder cancers has also been reported which may indicate a common mechanism of carcinogenesis. Consistent with this, androgens and the androgen receptor (AR) play essential roles in prostate carcinogenesis and are believed to play a role in bladder carcinogenesis. There is also evidence implicating cancer stem cells in prostate and bladder cancers. Indeed putative prostate and bladder cancer stem cells share some common molecular features. We highlight key proteins (CD49f, CD133, PTEN, CD44) which are implicated in both prostate and bladder cancers and are enriched in putative prostate and bladder cancer stem cells. We examine published chromatin immuno-precipitation studies analyzing the genome-wide distribution of the AR to identify AR association with, and by inference potential AR-regulation of, these loci. We discuss recent evidence indicating a role for the AR in the splicing of the key urological stem cell protein CD44. We propose a model whereby aberrant AR regulation of these putative stem cell proteins contributes to malignant transformation of prostate and bladder cells. For these reasons we propose that the relationship between androgens and cancer stem cell associated proteins warrants further investigation.

Coordinated transcription factor networks have emerged as the master regulatory mechanisms of stem cell pluripotency and differentiation. Many stem cell-specific transcription factors, including the pluripotency transcription factors, OCT4, NANOG, and SOX2 function in combinatorial complexes to regulate the expression of loci, which are involved in embryonic stem (ES) cell pluripotency and cellular differentiation. This review will address how these pathways form a reciprocal regulatory circuit whereby the equilibrium between stem cell self-renewal, proliferation, and differentiation is in perpetual balance. We will discuss how distinct epigenetic repressive pathways involving polycomb complexes, DNA methylation, and microRNAs cooperate to reduce transcriptional noise and to prevent stochastic and aberrant induction of differentiation. We will provide a brief overview of how these networks cooperate to modulate differentiation along hematopoietic and neuronal lineages. Finally, we will describe how aberrant functioning of components of the stem cell regulatory network may contribute to malignant transformation of adult stem cells and the establishment of a "cancer stem cell" phenotype and thereby underlie multiple types of human malignancies.