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OBJECTIVE - To estimate effective dose of kidney-ureter-bladder (KUB) radiographs in a contemporary population of patients with urolithiasis.
METHODS - A retrospective review was performed to identify patients visiting a urology clinic for urolithiasis where a KUB was obtained and whom had a recent computed tomography (CT). Effective dose for KUBs was estimated using a Monte Carlo based simulation program and for CT utilizing the reported dose-length-product. Age, gender, body mass index, and abdominal diameter were analyzed for association with effective dose. KUBs performed at outside facilities in referred patient were compared to those obtained locally when available.
RESULTS - Fifty-four patients were identified meeting criteria. The majority (92.6%) of KUBs contained multiple radiographs. Mean effective dose was 2.15 mSv ± 1.67 mSv. Only 26% of examinations effective dose was under 1 mSv. Body mass index, abdominal thickness, and image count were all associated with an increase in dose (P < .01 each). Similar to local KUBs, 88% of outside examinations contained multiple images.
CONCLUSION - KUB examinations in this contemporary setting are associated with a 2-fold higher effective dose then is often referenced. Increased effective dose is associated with increased patient size and number of images acquired. Nearly 1 in 5 patient's KUB effective dose was similar to a low-dose CT. KUBs role should be re-examined given its limited sensitivity, specificity, associated radiation, and other available imaging options.
Copyright © 2018. Published by Elsevier Inc.

OBJECTIVE - To identify nonclinical factors affecting postoperative complication rates in patients with neurogenic bladder undergoing benign genitourinary (GU) reconstruction.
METHODS - Adult patients with neurogenic bladder undergoing benign GU reconstruction between October 2010 and November 2015 were included. Patients were excluded if a diversion was performed for malignancy, if patients had a history of radiation or if a new bowel segment was not utilized at the time of the operation. Clinical and nonclinical factors were abstracted from the patients' electronic medical records. Health literacy was assessed via the Brief Health Literacy Screen (BHLS), a validated 3-question assessment. Education, marital status, and distance from the medical center were also queried.
RESULTS - Forty-nine patients with a neurogenic bladder undergoing complex GU reconstruction met inclusion and exclusion criteria. On average, patients lived 111 miles (standard deviation 89) from the hospital. Overall, mean BHLS score was 10.4 (standard deviation 4.6) with 35% of patients scoring a BHLS of ≤9. Mean years of educational attainment was 9.7, and only 31% of patients completed high school education. In the first month after surgery, 37 patients (76%) experienced a complication, and 22% were readmitted; however, analysis of complication data did not identify an association between any nonclinical variables and complication rates.
CONCLUSION - Nonclinical factors including unmarried status, poor health literacy, and marked distance from quaternary care are prevalent in patients with neurogenic bladder undergoing complex GU reconstruction. To mitigate these potential risk factors, the authors recommend acknowledgment of these factors and multidisciplinary support perioperatively to counteract them.
Copyright © 2018. Published by Elsevier Inc.

PURPOSE - The objective of this study was to assess toileting behaviors in community dwelling women.
MATERIALS AND METHODS - Women 18 years old or older were recruited through a national registry of research volunteers. They were asked to complete validated questionnaires assessing urinary symptoms and toileting behaviors, specifically place preference for voiding, convenience voiding, delayed voiding, straining during voiding and position preference for voiding. The PPBC (patient perception of bladder condition) was administered to assess the participant impression of bladder health. Analyses were done to determine the prevalence of each toileting behavior reported to occur sometimes or more often as well as differences in toileting behaviors in women with vs without self-perceived bladder problems based on the PPBC response.
RESULTS - The 6,695 women who completed the questionnaires were 18 to 89 years old (mean ± SD age 41.4 ± 15). Of the women 79.9% identified as white and 71.0% were college educated. Of the women 6,613 (98.8%) reported a place preference for voiding. The 3,552 women (53.1%) who reported a bladder problem were more likely to report convenience voiding, delayed voiding and strained voiding behaviors. While 6,657 women (99.4%) reported sitting to void at home only 5,108 (76.2%) reported sitting when using public toilets.
CONCLUSIONS - Certain toileting behaviors, of which some may be considered unhealthy, were common in this sample of women and most were associated with a perception of bladder problems. Voiding positions other than sitting were frequently used when away from home. These data have important implications for defining bladder health and implementing behavior based interventions for women with lower urinary tract symptoms.

PURPOSE - We investigated the relationship of painful bladder filling and urinary urgency to somatic and chronic pain symptoms in women with overactive bladder without an interstitial cystitis/bladder pain syndrome diagnosis.
MATERIALS AND METHODS - Women who met overactive bladder criteria based on symptoms were recruited, including 183 (83.9%) from the community and 35 (16.1%) from the urology clinic to complete validated questionnaires assessing urinary symptoms, somatic symptoms and pain syndromes. Participants were categorized into 1 of 3 groups, including 1) neither symptom, 2) either symptom or 3) both symptoms, based on their reports of painful urinary urgency and/or painful bladder filling. Multivariable regression analyses were performed to determine factors predictive of having painful urgency and/or painful filling.
RESULTS - Of 218 women with overactive bladder 101 (46%) had neither painful bladder filling nor urinary urgency, 94 (43%) had either symptom and 23 (11%) had both symptoms. When controlling for age, women with either or both urological pain symptoms were more likely to have irritable bowel syndrome, chronic pelvic pain and temporomandibular disorder than women in the neither group. Additionally, these women had higher pain intensity and somatic symptoms scores than women with neither symptom.
CONCLUSIONS - The majority of women with overactive bladder who had not been diagnosed with interstitial cystitis/bladder pain syndrome reported painful urgency and/or painful filling. Experiencing painful urgency and/or filling was associated with an increased somatic symptom burden and greater pain intensity. These findings support the hypothesis that overactive bladder and interstitial cystitis/bladder pain syndrome diagnoses may represent a continuum of bladder hypersensitivity.
Copyright © 2018. Published by Elsevier Inc.

PURPOSE - We sought to determine whether women with overactive bladder who required third line therapy would demonstrate greater central sensitization, indexed by temporal summation to heat pain stimuli, than those with overactive bladder.
MATERIALS AND METHODS - We recruited 39 women with overactive bladder from the urology clinic who were planning to undergo interventional therapy for medication refractory overactive bladder with onabotulinumtoxinA bladder injection or sacral neuromodulation. We also recruited 55 women with overactive bladder who were newly seen at our urology clinic or who responded to advertisements for study participation. Participants underwent quantitative sensory testing using a thermal temporal summation protocol. The primary study outcome was the degree of temporal summation as reflected in the magnitude of positive slope of the line fit to the series of 10 stimuli at a 49C target temperature. We compared the degree of temporal summation between the study groups using linear regression.
RESULTS - Women in the group undergoing third line therapy showed significantly higher standardized temporal summation slopes than those in the nontreatment group (β = 1.57, 95% CI 0.18-2.96, t = 2.25, p = 0.027). On exploratory analyses a history of incontinence surgery or hysterectomy was associated with significantly greater temporal summation.
CONCLUSIONS - In this study the degree of temporal summation was elevated in women undergoing third line overactive bladder therapy compared to women with overactive bladder who were not undergoing that therapy. These findings suggest there may be pathophysiological differences, specifically in afferent nerve function and processing, in some women with overactive bladder.
Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.
Copyright © 2017 Elsevier Inc. All rights reserved.

OBJECTIVE - LithoVue™ is a novel, single-use, digital flexible ureteroscope that was released to the US market in January 2016. There are scant data regarding its performance in humans. Procedural outcomes comparing LithoVue with reusable ureteroscopes are presented in patients undergoing ureteroscopy for upper urinary tract pathology.
PATIENTS AND METHODS - Clinical outcomes between two groups of patients undergoing flexible ureteroscopy for upper urinary tract pathology were analyzed. The first group underwent surgery utilizing LithoVue, and the second group used reusable fiber-optic flexible ureteroscopes. Differences in procedural outcomes, operative times, and time spent in hospital were analyzed using two-tailed t-tests and chi-squared and Fisher's exact tests.
RESULTS - One hundred fifteen cases utilizing LithoVue and 65 cases utilizing reusable ureteroscopes were included in this study. Demographics, surgical indications, stone size, location, total stone burden, composition, procedural outcomes, and complications were comparable between groups. For all cases, LithoVue procedures lasted 54.1 ± 25.7 minutes compared with 64.5 ± 37.0 minutes for reusable scope procedures (p < 0.05) and for stone removal cases, 57.3 ± 25.1 vs 70.3 ± 36.9 minutes, respectively (p < 0.05). Scope failure occurred in 4.4% of LithoVue cases and 7.7% of reusable cases (p = 0.27).
CONCLUSIONS - LithoVue represents a feasible alternative to reusable ureteroscopes with a low rate of scope failure comparable with reusable ureteroscopes. Its use shortens procedure duration, a finding that warrants further investigation.

Radical cystectomy remains the gold standard treatment for organ-confined high-grade recurrent or muscle-invasive bladder cancer. Orthotopic neobladder urinary diversion following cystectomy represents an option for patients wishing for continent urinary diversion. Female patients who undergo radical cystectomy with orthotopic bladder substitution are at risk for developing both common and neobladder-specific disorders of the pelvic floor, including urinary incontinence, hypercontinence, vaginal prolapse, and neobladder-vaginal fistula. Each of these sequelae can have significant impact on the patient's quality of life. Due to the increased frequency of orthotopic neobladder creation in women, subspecialty urologists are more likely to confront such pelvic floor disorders in bladder cancer survivors. This review presents the most current information on the treatment of pelvic floor disorders after orthotopic bladder substitution.

The construction of tissue microarrays (TMAs) with cores from a large number of paraffin-embedded tissues (donors) into a single paraffin block (recipient) is an effective method of analyzing samples from many patient specimens simultaneously. For the TMA to be successful, the cores within it must capture the correct histologic areas from the donor blocks (technical accuracy) and maintain concordance with the tissue of origin (analytical accuracy). This can be particularly challenging for tissues with small histological features such as small islands of carcinoma in situ (CIS), thin layers of normal urothelial lining of the bladder, or cancers that exhibit intratumor heterogeneity. In an effort to create a comprehensive TMA of a bladder cancer patient cohort that accurately represents the tumor heterogeneity and captures the small features of normal and CIS, we determined how core size (0.6 vs 1.0 mm) impacted the technical and analytical accuracy of the TMA. The larger 1.0 mm core exhibited better technical accuracy for all tissue types at 80.9% (normal), 94.2% (tumor), and 71.4% (CIS) compared with 58.6%, 85.9%, and 63.8% for 0.6 mm cores. Although the 1.0 mm core provided better tissue capture, increasing the number of replicates from two to three allowed with the 0.6 mm core compensated for this reduced technical accuracy. However, quantitative image analysis of proliferation using both Ki67+ immunofluorescence counts and manual mitotic counts demonstrated that the 1.0 mm core size also exhibited significantly greater analytical accuracy (P=0.004 and 0.035, respectively, r=0.979 and 0.669, respectively). Ultimately, our findings demonstrate that capturing two or more 1.0 mm cores for TMA construction provides superior technical and analytical accuracy over the smaller 0.6 mm cores, especially for tissues harboring small histological features or substantial heterogeneity.

Proteins involved in tumor cell migration can potentially serve as markers of invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes adhesion, while shedding of its extracellular domain is associated with migration. We hypothesized that shed ALCAM in biofluids could be predictive of progressive disease. ALCAM expression in tumor (n = 198) and shedding in biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy cohorts by immunofluorescence and enzyme-linked immunosorbent assay, respectively. The primary outcome measure was accuracy of predicting 3-year overall survival (OS) with shed ALCAM compared to standard clinical indicators alone, assessed by multivariable Cox regression and concordance-indices. Validation was performed by internal bootstrap, a cohort from a second institution (n = 64), and treatment of missing data with multiple-imputation. While ALCAM mRNA expression was unchanged, histological detection of ALCAM decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was elevated 17.0-fold (P < 0.0001) above non-cancer controls, correlated positively with tumor stage (P = 0.018), was an independent predictor of OS after adjusting for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03-2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5% vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy (HR, 1.10; 95% CI, 1.02-1.19; P = 0.011). In conclusion, shed ALCAM may be a novel prognostic biomarker in bladder cancer, although prospective validation studies are warranted. These findings demonstrate that markers reporting on cell motility can act as prognostic indicators.