Budgetary Impact of Including the Urinary Genomic Marker Cxbladder Detect in the Evaluation of Microhematuria Patients.

INTRODUCTION: Current AUA guidelines mandate a risk-stratified approach for the evaluation of microhematuria. Urine genomic tests with high negative predictive value could further reduce unnecessary diagnostic testing and morbidity, but the economic impact is unknown. This study modeled the financial impact of Cxbladder Detect on microhematuria evaluations. METHODS: A decision tree analysis was constructed by Coreva Scientific comparing 1-year costs of the standard microhematuria evaluation using the AUA guidelines vs an algorithm incorporating Cxbladder Detect. Cxbladder Detect-positive patients had cystoscopy and imaging, whereas patients with negative tests were reevaluated in 6 months. Patients with positive diagnostic testing underwent cystoscopy, and positive cystoscopies led to transurethral resection of bladder tumor. Test performance was based on published literature, and costs were based on Medicare allowable fees. RESULTS: Using the decision tree model, the average savings of using Cxbladder Detect was $559 compared with the standard of care, with an average reduction of 0.38 procedures per patient. Probabilistic analysis showed statistical significance with a median reduction in the total cost of $498 per patient (95% CrI [-1356, -2]) and a significant median reduction in diagnostic procedures per patient of 0.36 (95% CrI [-0.52, -0.16]) without impact on the number of cancers diagnosed. CONCLUSIONS: This model-based study demonstrates the potential economic value of using a Cxbladder-driven protocol for microhematuria evaluations.

Adverse Urinary System Outcomes among Older Women with Endometrial Cancer.

PURPOSE OF THE STUDY: Endometrial cancer and its treatment may cause damage to the urinary system, but few large-scale studies have examined the incidence of urinary-related outcomes among endometrial cancer survivors. We investigated the risk of several urinary disease diagnoses among older women with endometrial cancer compared to women without a cancer history. METHODS: Women ages 66 years and older with an endometrial cancer diagnosis during 2004-2017 (N=44,386) and women without a cancer history (N=221,219) matched 5:1 on age, race/ethnicity, and state were identified in the Surveillance, Epidemiology, and End Results-Medicare linked data. ICD-9 and -10 diagnosis codes were used to identify urinary outcomes in the Medicare claims data. Cumulative incidences (IP) of urinary outcomes were estimated among women with and without endometrial cancer. Multivariable Cox proportional hazards regression models were used to estimate hazards ratios (HR) for urinary outcomes comparing women with and without endometrial cancer. HRs were also used to identify characteristics associated with urinary outcomes among endometrial cancer survivors. RESULTS: Relative to women without cancer, endometrial cancer survivors had an increased risk of urinary system diagnoses, including renal failure (5-year IP: 25% vs 14%; HR=1.50; 95% CI: 1.47-1.53), chronic kidney disease (5-year IP: 20% vs 14%; HR=1.25; 95% CI: 1.22-1.28), calculus of the urinary tract (5-year IP: 7% vs 4%; HR=1.55; 95% CI: 1.50-1.61), lower urinary tract infection (5-year IP: 55% vs 33%; HR=1.75; 95% CI: 1.72, 1.78), and bladder diseases (5-year IP: 10% vs 6%; HR=1.57; 95% CI: 1.52, 1.62). These associations persisted in analyses limited to 1+ and 5+ years after endometrial cancer diagnosis. Non-Hispanic Black or Hispanic race/ethnicity, higher comorbidity index, higher stage or grade cancer, non-endometrioid histology, and treatment with chemotherapy and/or radiation were often predictors of urinary outcomes among women with endometrial cancer. CONCLUSIONS: Our results suggest that, among older women, the risk of urinary outcomes is elevated after endometrial cancer. Monitoring for urinary diseases may be a critical part of long-term survivorship care for older women with an endometrial cancer history.

Urobiome in Gender-Related Diversities of Bladder Cancer.

Bladder cancer (BC) remains the most common malignancy of urinary tract. Sex-related differences in BC epidemiology, diagnosis, therapy, and outcomes have been reported. Throughout the recent years, extensive research has been devoted to genetic and molecular alterations in BC. Apart from the molecular background, another related concept which has been speculated to contribute to gender diversities in BC is the role of urinary pathogens in bladder carcinogenesis. Microbiome studies, fueled by the availability of high-throughput DNA-based techniques, have shown that perturbation in the microbiome is associated with various human diseases. The aim of this review is to comprehensively analyze the current literature according to sex-related differences in the microbiome composition in BC.

Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts.

Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) is often regarded as one entity and is managed generally with similar principles. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is an established standard of care in UCB, strong evidence for a similar approach is lacking in UTUC. The longest survival is seen in patients with complete response (pT0) on pathological examination of the RC specimen, but impact of delayed RC in nonresponders may be detrimental. The rate of pT0 following NAC in UTUC is considerably lower than that in UCB due to differences in access and instrumentation. Molecular markers have been evaluated to try to predict response to chemotherapy to reduce unnecessary treatment and expedite different treatment for nonresponders. A variety of potential biomarkers have been evaluated to predict response to cisplatin based chemotherapy including DNA repair genes (ATM, RB1, FANCC, ERCC2, BRCA1, and ERCC1), regulators of apoptosis (survivin, Bcl-xL, and emmprin), receptor tyrosine kinases (EGFR and erbB2), genes involved in cellular efflux (MDR1 and CTR1), in addition to molecular subtypes (Basal, luminal, and p53-like). The current state of the literature on the prediction of response to NAC based on the presence of these biomarkers is discussed in this review.

Imaging response assessment of immunotherapy in patients with renal cell and urothelial carcinoma.

PURPOSE OF REVIEW: Recent advances in anticancer immunotherapy have revolutionized the treatment of metastatic renal cell (RCC) and urothelial carcinoma. In this review, we discuss the mechanisms of action of these new therapeutic approaches, explicate the common adverse events, and highlight different imaging-based response criteria. RECENT FINDINGS: The recent introduction of immune-checkpoint inhibitors led to substantial advances in therapy of metastatic RCC and urothelial carcinoma. Because of the distinct effector mechanisms of these new substances, atypical response patterns such as transient enlargements of tumor lesions, appearance of new lesions after therapy, no measurable decrease in tumor size, or delayed responses are observed in medical imaging studies. This indicates that the established imaging-based response assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines has shortcomings to comprehensively evaluate treatment effects. SUMMARY: While monitoring response to immunotherapy still relies on RECIST criteria, immune-related response criteria have been established to better address the imaging changes occurring under immunotherapy. Further studies with long-term follow-up are needed to properly identify and predict response after treatment beyond progression. Because of the expanding clinical use of immune checkpoint inhibitors, radiologists, urologist, and oncologists should be familiar with common imaging findings under this respective therapy.

The global burden of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: A systematic review and meta-analysis.

Benign prostatic hyperplasia is a common non-malignant condition among older men, but the epidemiology is poorly characterised. We summarised and determined the global prevalence of benign prostatic hyperplasia. A systematic search on PubMed, EMBASE and CENTRAL was performed up until 31st July 2016. Studies that described the epidemiology of benign prostatic hyperplasia were included and cumulative plots of prevalence estimates were calculated. A total of 31 prevalence rate estimates from 25 countries were identified. The combined prevalence estimates showed that the lifetime prevalence of BPH was 26.2% (95% CI: 22.8-29.6%). We found that there was an increasing prevalence of BPH with age. However, we found no significant difference between (a) rural, urban or mixed sites, (b) different countries, (c) respondent representativeness. (d) sample size or (e) study quality. We also found no significant change in the prevalence over the past 20 years. While there is substantial variation between sites estimates, results suggest that nearly 1 in 4 men will suffer from BPH over their lifetime. The study revealed there are significant gaps in knowledge, which provides opportunities for future research to further enrich the epidemiological landscape with data.

A practice pattern assessment of members of the Society of Pediatric Urology for evaluation and treatment of urinary tract dilation.

INTRODUCTION: Over the last decade the literature, including a multidisciplinary consensus statement, has supported a paradigm shift in management of urinary tract dilation, yet the impact on practice patterns has not been well documented. OBJECTIVE: This study aims to elucidate specific practice patterns for treatment of prenatal unilateral urinary tract dilation and to assess surgical intervention patterns for ureteropelvic junction obstruction. STUDY DESIGN: An online survey was distributed to 234 pediatric urologists through the Society of Pediatric Urology. The survey was composed of five clinical case scenarios addressing evaluation and management of unilateral urinary tract dilation. RESULTS: The response rate was 71% (n = 168). Circumcision status, gender, and grade were significant factors in recommending prophylactic antibiotics for newborn urinary tract dilation. Prophylactic antibiotic use in the uncircumcised male and female was twice that of a circumcised male for grade 3 (Table). This difference was minimized for grade 4. Use of VCUG was high for circumcised males with grade 3 or 4 (Table). The choice of minimally invasive surgery for ureteropelvic junction repair increased with age from 19% for a 5-month-old, 49% for a 2-year-old, and 85% for a 10-year-old. Notably, 44% of respondents would observe a 10-year-old with intermittent obstruction. Retrograde pyelography was recommended in conjunction with repair in 65% of respondents. Antegrade stent placement was the most common choice (38-47%) for urinary diversion after pyeloplasty. Regarding postoperative imaging, only 5% opted for routine renal scan whereas most would perform renal ultrasound alone. DISCUSSION: Practice patterns seen for use of prophylactic antibiotics are in agreement with the literature, which promotes selective use in those at highest risk for urinary tract infections. Interestingly, use of aggressive screening was not concordant with this literature. Several studies have indicated an increased usage of robotic pyeloplasty; however, results indicate that minimally invasive surgery is not preferred in those younger than 6 months. Study limitations include use of clinical case scenarios as opposed to actual clinical practice. CONCLUSION: Practice patterns for prophylactic antibiotic use for neonatal urinary tract dilation are dependent on gender, circumcision status, and grade. The use of minimally invasive surgery for ureteropelvic junction repair increased with patient age, with 50% preferring this modality at 2 years.

Trends in the utilization of imaging for upper tract urothelial carcinoma.

OBJECTIVES: To evaluate the changes in use of the different imaging modalities for diagnosing upper tract urothelial carcinoma (UTUC) and assess how these changes have affected tumor stage at the time of surgery. MATERIALS AND METHODS: We assessed the Surveillance, Epidemiology, and End Results (SEER) cancer registry and linked Medicare claims data (1992-2009) for 5377 patients who underwent surgery for UTUC. We utilized International Classification of Disease-Oncology 3 codes to identify UTUC. International Classification of Disease, ninth Revision, Clinical Modification and Current Procedure Terminology codes identified surgical treatment and imaging modalities. We assessed for use of intravenous pyelography, retrograde pyelography (RGP), computed tomography urography (CTU), magnetic resonance urography (MRU), and endoscopy. For each modality, patients were categorized as having received the modality at least once or not at all. Patient characteristics were compared using chi-squared tests. Usage of imaging modalities and tumor stage was trended using Cochran-Armitage tests. We stratified our data into 2 multivariate logistic regression models to determine the effect of imaging modalities on tumor stage: 1992 to 1999 with all modalities except MRU, and 2000 to 2009 with all modalities. RESULTS: Our patient population was predominantly White males of more than 70 years old. Intravenous pyelography and RGP declined in use (62% and 72% in 1992 vs. 6% and 58% in 2009, respectively) while computed tomography urography, MRU, and endoscopy increased in use (2%, 0%, and 37% in 1992 vs. 44%, 6%, and 66% in 2009, respectively). In both regression analyses, endoscopy was associated with lower-stage tumors. In the 2000 to 2009 model, RGP was associated with lower-stage tumors, and MRU was associated with higher-stage tumors. Finally, our data showed an increasing number of modalities utilized for each patient (1% receiving 4 modalities in 1992 vs. 20% in 2009). CONCLUSIONS: We found trends toward the utilization of newer imaging modalities to diagnose UTUC and more modalities per patient. Endoscopy and RGP were associated with smaller tumors, whereas MRU was associated with larger tumors. Further studies are needed to evaluate the utility of the different modalities in diagnosing UTUC.

The diagnosis and management of lower urinary tract symptoms in multiple sclerosis patients.

Sixty-five percent of multiple sclerosis patients have moderate to severe urinary symptoms and up to 14% initially present with urinary symptomatology. Urinary retention, neurogenic detrusor overactivity, and detrusor sphincter dyssynergia, all increase the risk for urinary tract infections in patients with multiple sclerosis, and these infections may exacerbate their immune response, leading to symptom progression. Fewer than half of the patients with urinary symptoms have seen a specialist and only half have been treated for their neurogenic detrusor overactivity. Several treatments including pelvic floor muscle therapy, pelvic floor electrical stimulation, anticholinergics, desmopressin, sacral nerve neuromodulation, posterior tibial nerve stimulation, cannabinoids, and intravesical therapy with vanniloids, as well as botulinum toxin, have all been shown to be effective in treating urinary symptoms in those with multiple sclerosis. Clean intermittent catheterization is invaluable in patients with persistent urinary retention to avoid infection and upper tract dysfunction. Indwelling transurethral catheterization should be avoided because of the high risk of infection. Identification and successful treatment of these urinary conditions will improve the health and quality of life for these men and women.

Analytical chemistry, toxicology, epidemiology and health impact assessment of melamine in infant formula: recent progress and developments.

This review summarizes the most recent scientific literature and regulations regarding analytical chemistry, toxicology, epidemiology, exposure, and risk assessment of melamine in infant formula. For analyses, enzyme-linked immunosorbent assay, high-performance liquid chromatography, capillary electrophoresis, gas chromatography coupled with mass spectrometry and liquid chromatography coupled with tandem mass spectrometry have commonly been used. Organization of proficiency test programs provided good evidence to facilitate granting laboratories accreditation and to ascertain the measurement reliability of melamine methods. Metabolic studies demonstrated that melamine is predominantly restricted to blood or extracellular fluid and is not extensively distributed to organs and tissues. Studies of human renal histopathology and clinical diagnoses indicated that melamine-related obstructive nephropathy derives from melamine precipitation in the lower urinary tract, with stones that are thought to be melamine-uric acid complexes. Epidemiologic studies showed that the occurrence of melamine-related urolithiasis is related to both the concentration of melamine in ingested milk products and the duration of ingestion. Long-term follow-up cohort studies should be continued to further investigate the epidemic and chronic hazard of melamine-induced nephrotoxicity. The World Health Organization set a tolerable daily intake of 0.2 mg/kg bw/day to be applied to "the whole population including infants". Other authorities and research institutes have set/proposed lower values.

Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men: assessment using colour Doppler ultrasonography.

OBJECTIVES: To investigate, using transrectal colour Doppler ultrasonography, (TRCDUS) whether perfusion of the bladder and prostate is reduced in elderly patients with lower urinary tract symptoms (LUTS), common in later life, as experimental data suggest that chronic ischaemia has a key role in the development of LUTS. PATIENTS, SUBJECTS AND METHODS: In 32 elderly patients with LUTS (12 women, mean age 82.3 years, group 1; and 20 men, 79.4 years, group 2) perfusion of the bladder neck (in women) and of the bladder neck and prostate (in men) was measured using TRCDUS and the resistive index (RI) and colour pixel density (CPD) determined, assessed by a TRUS unit and special software. To assess the age-related effect two control groups of 10 young healthy women (mean age 42.3 years, group 3) and 10 age-matched healthy men (mean age 41.5 years, group 4) were also enrolled. RESULTS: Irrespective of gender, there was markedly lower bladder perfusion in elderly patients with LUTS than in the younger subjects. The mean (SD) RI of the bladder neck in group 1, of 0.88 (0.06), and group 2, of 0.80 (0.08), was higher than in control groups 3, of 0.62 (0.05), and group 4, of 0.64 (0.09). The results were similar for the CPD measurements. The frequency of daily and nightly micturition showed a strong negative correlation with perfusion in the urinary bladder. CONCLUSION: In elderly patients with LUTS there was decreased perfusion of the bladder neck and prostate when assessed using TRCDUS. Therefore, decreased perfusion in the urinary bladder might be responsible for the development of LUTS with advancing age.

Descripción de una técnica mínimamente invasiva, sencilla y de bajo costo para la resolución de estenosis de la vía urinaria superior: experiencia inicial / Minimally invasive and low cost approach for the treatment of upper urinary tract stenosis: surgical techniques and initial experience

El avance de las técnicas mínimamente invasivas y la aparición de nuevos dispositivos han llegado a resolver muchas de las patologías urológicas actuales, sin embargo, estas técnicas no siempre son simples de realizar y suelen asociarse a un aumento en los costos de insumos y equipos, limitando su uso. En el presente trabajo describimos nuestra experiencia inicial en el manejo de estenosis de la vía urinaria superior utilizando una técnica endoscópica con papilótomo y precut (instrumental gastroenterológico para ERCP) bajo visión fluoroscópica. Se presentan tres casos clínicos, dos de ellos con estenosis del cuello del cáliz superior (CCS) izquierdo y uno con una estenosis pieloureteral derecha recidivada luego de una pieloplastía laparoscópica. En los tres pacientes se logró abrir las zonas estenóticas obteniendoimágenes fluoroscópicas satisfactorias. No hubo complicaciones durante la cirugía ni en el postoperatorio.El alta se dio entre las 24 y 72 hrs posprocedimiento. La técnica empleada permite corregir estenosis de la vía urinaria superior, con equipos e insumos que se encuentran disponibles en la mayoría de los centros públicos y privados del país, de manera sencilla, económica, segura y mínimamente invasiva. Si bien los resultados iniciales obtenidos son muy alentadores, se debe tener presente que las estenosis de la vía urinaria tienden a recidivar, por lo que el éxito a largo plazo y el porcentaje de reestenosis es aún desconocido.

Minimally invasive techniques (MIT) are both difficult to perform and costly in terms of equipment and supplies. The latter has limited the expansion of MIT. Herein, we describe a technique for management of upper tract urinary estenosis with the deploy of endoscopic retrograde colangiopancreatoscopy equipment (ERCP) and radiologic assistance. Three cases were treated with the technique. Two cases with superior calyx estenosis and 1 case with recidivated ureteropelvic stenosis. All three patients were solved with the proposed technique with adequate radiographic results verified at the end of the procedure. There were no perioperative complications and patients were discharged between 24 and 72 hours after the procedure. The technique offers a safe, reliable and low cost approach for the urinary tract stenosis. Follow-up is mandatory.

The pathology of primary blast overpressure injury.

Primary blast injury occurs in civilian and military detonations and from the firing of weapon systems. The pathology of primary blast injury has been reported for the last 70 years and has primarily been limited to descriptions of gross pathology and histology. Commonly accepted tenets have not been confirmed as blast overpressure experiments in enclosures and with multiple detonations have been conducted. Organ systems other than the ear and the lung are playing a greater role in injury definition and research importance. This paper is an overview and update of the current understanding of the pathology of primary blast injury.

Neurophysiologic assessment of urinary dysfunction in children with thoracic syringomyelia.

Isolated syringomyelia of the thoracic portion of the spinal cord is relatively uncommon. In children, signs and symptoms may involve only the urinary system. Five children who presented for evaluation of urinary tract dysfunction were found to have syringomyelia of the thoracic cord not associated with any other central nervous system abnormality on radiographic imaging. Each child underwent a complete neurologic examination and a complete electrophysiologic/urodynamic evaluation. One patient underwent surgical drainage of the syrinx due to progression of neurologic deficit, with slight improvement; three patients were treated pharmacologically to control the urinary dysfunction.

Organ-limited autopsies. Obtaining permission for postmortem examination of the urinary tract.

OBJECTIVE: To develop a systematic pre- and postmortem program for obtaining permission for autopsies limited to the urinary tract. DESIGN: Comparison versus historical control of autopsy permission using a new process comprising premortem education, modification of the permission process, and autopsy limited to the urinary tract. PARTICIPANTS AND SETTING: Patients, family members, and healthcare providers associated with a nursing home. INTERVENTION: Education of healthcare providers and family members and modification of autopsy consent and performance. MAIN OUTCOME MEASURE: Permission rate and demographic characteristics of patients and family members giving permission. RESULTS: Of the 361 patients who died during the study, we received permission for postmortem examination of the urinary tract for 129 (36%). This was substantially better than the autopsy rate in the year prior to the study, 0.6%. A significantly higher permission rate was associated with patients and contact persons of white race, a higher level of education of the contact person, a nonrelative contact person, and two or fewer individuals making the decision. CONCLUSION: Permission for organ-limited autopsies can be obtained with a systematic approach.

Assessment of the urinary system.

History and physical examination alone will most often provide conclusive evidence of urinary tract disorders in ruminants. Detailed examination of the urinary system is described, and examples of disease are presented. Ancillary testing may be indicated to confirm the diagnosis, direct treatment, or clarify the prognosis. Serum chemistry interpretation, urinalysis, urinary tract endoscopy and radiography, ultrasonography, abdominocentesis, and renal biopsy are discussed.