Malignant Urological Diseases Research Articles

Possibilities and limitations of using low biomass samples for urologic disease and microbiome research.

With the dogma of sterile urine no longer held as truth, numerous studies have implicated distinct changes in microbial diversity and composition to diseased subgroups in both benign and malignant urological diseases, ranging from overactive bladder to bladder and prostate cancer. Further facilitated by novel and effective techniques of urine culture and sequencing, analysis of the genitourinary microbiome holds high potential to identify biomarkers for disease and prognosis. However, the low biomass of samples included in microbiome studies of the urinary tract challenge researchers to draw definitive conclusions, confounded by technical and procedural considerations that must be addressed. Lack of samples and adequate true negative controls can lead to overestimation of microbial influence with clinical relevance. As such, results from currently available studies and assessment of their limitations required a thorough understanding. The purpose of this narrative review was to summarize notable microbiome studies in the field of urology with a focus on significant findings and limitations of study design. Methodological considerations in future research are also discussed.

Tobacco Screening and Treatment during Outpatient Urology Office Visits in the United States.

Tobacco use is a causative or exacerbating risk factor for benign and malignant urological disease. However, it is not well known how often urologists screen for tobacco use and provide tobacco cessation treatment at the population level. We sought to evaluate how often urologists see patients for tobacco-related diagnoses in the outpatient setting and how often these visits include tobacco use screening and treatment. We used the National Ambulatory Medical Care Survey public use files for the years 2014-2016 to identify all outpatient urology visits with adults 18 years old or older. Clinic visit reasons were categorized according to diagnoses associated with the encounter: all urological diagnoses, a tobacco-related urological condition or a urological cancer. Our primary outcome was the percentage of visits during which tobacco screening was reported. Secondary outcomes included reported delivery of cessation counseling and provision of cessation pharmacotherapy. We identified 4,625 unique urological outpatient encounters, representing a population-weighted estimate of 63.9 million visits over 3 years. Approximately a third of all urology visits were for a tobacco-related urological diagnosis and 15% were for urological cancers. An estimated 1.1 million visits over 3 years were with patients who identified as current tobacco users. Of all visits, 70% included tobacco screening. However, only 7% of visits with current smokers included counseling and only 3% of patients were prescribed medications. No differences in screening and treatment were observed between visit types. Urologists regularly see patients for tobacco-related conditions and frequently, although not universally, screen patients for tobacco. However, urologists rarely offer counseling or cessation treatment. These findings may represent missed opportunities to decrease the morbidity associated with tobacco use.

Ureteral stent-associated complications--where we are and where we are going.

Ureteral stents are one of the most commonly used devices in the treatment of benign and malignant urological diseases. However, they are associated with common complications including encrustation, infection, pain and discomfort caused by ureteral tissue irritation and possibly irregular peristalsis. In addition, stent migration and failure due to external compression by malignancies or restenosis occur, albeit less frequently. As these complications restrict optimal stent function, including maintenance of adequate urine drainage and alleviation of hydronephrosis, novel stent materials and designs are required. In recent years, progress has been made in the development of drug-eluting expandable metal stents and biodegradable stents. New engineering technologies are being investigated to provide stents with increased biocompatibility, decreased susceptibility to encrustation and improved drug-elution characteristics. These novel stent characteristics might help eliminate some of the common complications associated with ureteral stenting and will be an important step towards understanding the behaviour of stents within the urinary tract.

1289 ACUTE IMAGING FOR HEMATURIA IN THE UNITED STATES: COSTS AND PREDICTORS FROM THE NATIONWIDE EMERGENCY DEPARTMENT SAMPLE

prospectively collected and maintained on a Microsoft Access database for research and analysis. RESULTS: 190 patients under 40 years with visible haematuria were referred during the study period. The follow-up duration was 6.9 / 2.5 years (median / SD; range 3–11.5 years). The male/female ratio was 3.2:1 with a mean age of 30 (14 39) years. There were 42 smokers (35 males and 7 females). No pathology was found in 166 (87%) patients. Malignant urological disease was found in 6 (3.2%) patients: bladder tumour (5) and renal tumour (1). Of these one was a smoker, three were non-smokers and two of unknown smoking history. The rest had benign pathology as shown in table. No patient developed recurrent or persistent haematuria. CONCLUSIONS: 87% of patients under the age of 40 with visible haematuria do not have any pathology. The proportion of patients with malignant urological disease was small (3.2%), in contrast with the general cohort of patients of all ages who present with visible haematuria. Smoking did not seem to be a contributing factor.

Genistein Sensitizes Bladder Cancer Cells to HCPT Treatment In Vitro and In Vivo via ATM/NF-κB/IKK Pathway-Induced Apoptosis

Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-κB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-κB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy.

Half of Visible and Half of Recurrent Visible Hematuria Cases Have Underlying Pathology: Prospective Large Cohort Study With Long-Term Followup

Visible hematuria has a cancer yield of up to 24.2%. A large proportion of cases will have no etiology. In this study we determined the incidence of pathology (benign and malignant) in patients with visible hematuria and those with persistent and recurrent visible hematuria, and evaluated the policy for investigations. Data were prospectively collected for 1,804 patients with visible hematuria at a United Kingdom teaching hospital from January 1999 to September 2007. In October 2010 the comprehensive hospital electronic database was checked for every individual patient to ensure no urological pathology was missed. All patients underwent standard hematuria investigations, including renal tract ultrasound and excretory urography or contrast enhanced computer tomography urogram, flexible cystoscopy and urine cytology. The male-to-female ratio was 4.8:1. Median age ± SD was 67 ± 17.0 years (range 21 to 109). Median followup was 6.6 ± 2.5 years (range 1.5 to 11.6). No urological pathology was found in 965 (53.5%) patients. Malignant urological disease was found in 386 (21.4%) patients, of whom 329 had bladder tumors. There were 32 patients with persistent visible hematuria and no malignancy. Repeat investigation was performed in 69 patients reporting recurrence. Of these patients 35 received a significant urological diagnosis, including 12 (17.4%) urological malignancies, while 34 (49.3%) still had no diagnosis. Limitations include the possibility of missing pathology. Almost 50% of patients presenting with visible hematuria will have a diagnosis. Therefore, all cases of visible hematuria require full standard investigations. Patients with no diagnosis can be discharged from followup. Recurrent visible hematuria after full initial negative findings requires repeat full standard investigations because 11.6% will have malignant pathology.

Validação de construção de tissue microarray para estudo da displasia intraepitelial tubular renal

INTRODUÇÃO E OBJETIVO: O carcinoma de células renais (CCR) é umas das doenças urológicas de maior malignidade, correspondendo a 1%-3% de todos os tumores sólidos dos adultos. As lesões pré-malignas do CCR ainda não foram totalmente descritas. Achados de displasia intraepitelial tubular renal (DIETR) em áreas próximas ao tumor, livres de neoplasia, sugerem que esta alteração possa ser a precursora biológica de alguns tipos de CCR. O objetivo deste estudo é avaliar a possibilidade do uso de tissue microarray (TMA) no estudo da DIETR e do CCR e os parâmetros para sua utilização imuno-histoquímica (IHQ) utilizando os anticorpos anti-Ki-67 e p53 para confirmar a evidência de DIETR como precursora biológica do CCR. MATERIAL E MÉTODOS: O estudo foi realizado em 10 peças cirúrgicas de nefrectomias realizadas em pacientes com diagnóstico de CCR selecionadas no período de 2000 a 2005, em material arquivado no Instituto Nacional de Câncer (INCA). DISCUSSÃO: A utilização da técnica de TMA permite amostragem de várias áreas e realização da IHQ utilizando apenas duas lâminas, uma para cada marcador. Como não há na literatura descrição de utilização de TMA para estudo da DIETR, foi necessário inicialmente realizar estudo de validação para saber se haveria representatividade de lesões focais no TMA. RESULTADOS: A análise estatística não mostrou diferença entre a utilização de TMA com dois ou quatro cilindros de tecido ou o corte inteiro. CONCLUSÃO: O teste de validação de técnica artesanal de TMA autorizou o uso de dois cilindros de 1 mm² por caso.

Loss of p27(Kip1) CDKI is a predictor of poor recurrence-free and cancer-specific survival in patients with renal cancer

The importance of cyclin-dependent kinase inhibitors (CDKI) in benign and malignant urological diseases is a subject of intense ongoing investigation. The goal of the current study was to analyze the expression of p27((Kip1))CDKI in benign and malignant renal cells and assess their possible association with different clinical parameters. Expression of p27((Kip1)) was evaluated and compared in 24 normal human kidneys and in 52 renal cell carcinoma (RCC) tissue samples. Intensity of the expression was compared between the groups and association was analyzed with cancer clinical parameters. The expression of the marker was significantly higher in normal than in RCC samples (P = 0.0045). Intensity of p27((Kip1)) expression in RCC was negatively correlated with tumor size (Rho = -0.438, P = 0.0051) and associated with pathological stage and grade (P = 0.0488 and < 0.0001, respectively). The patients with symptomatic disease had significantly less marker expression than incidentally discovered tumors (P = 0.0301). Loss of p27((Kip1)) expression, pathological stage, grade and tumor size were the risk-factors for disease recurrence (P = 0.0072, 0.0011, 0.0467 and < 0.0001, respectively) and patient survival (P = 0.0021, 0.0106, 0.0151 and 0.0021, respectively). With Cox multivariate analysis loss of p27((Kip1)) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. Expression of p27((Kip1)) is significantly decreased in RCC as compared with normal kidney tissue. Intensity of the expression is associated with clinical parameters: tumor size, stage, grade and disease presentation. Loss of p27((Kip1)) expression is a risk-factor for disease recurrence and the strongest predictor of cancer-specific survival.

Urinary tissue factor levels in patients with bladder andprostate cancer

Aims Coagulation activation is a recognized complication of cancer in which increased tissue factor (TF) is implicated. TF can be detected in urine (uTF). This study assesses uTF levels in benign and malignant urological disease and correlates the results with conventional markers of tumour progression. Methods Using a simple and reproducible kinetic chromogenic assay, we determined uTF levels in controls (normal volunteers (n=57) and patients with renal stones (n=30)), benign and malignant bladder (n=75) or prostate (n=106) disease and in patients with or without recurrent bladder cancer (n=30). Each benign disease group was stratified as inflammatory (cystitis or prostatitis) or non-inflammatory (negative cystoscopy following haematuria or benign prostatic hypertrophy). Results The controls and the benign non-inflammatory results were indistinguishable. The malignant and inflammatory groups showed raised uTF levels over controls (P<0.001 bladder and P<0.01 prostate). The difference between malignant and benign inflammatory disease was only significant for the bladder group. uTF levels were significantly related to histological tumour grading, prostate serum specific antigen, static bone scan images and recurrence status. Conclusions uTF levels can distinguish, statistically but not without overlap, patients with malignancy from normal controls and benign non-inflammatory conditions. Discrimination between inflammatory and malignant disease has only been demonstrated in the bladder. uTF levels showed a significant association with markers of tumour progression or metastasis and may be useful in predicting bladder tumour recurrence.

Urinary gonadotropin peptide (UGP) in Egyptian patients with benign and advanced malignant urological disease

Urinary gonadotropin peptide (UGP) levels were determined in urine samples from 450 Egyptian subjects to determine its relative level of expression in benign and malignant urological disease, and normal individuals. The mean UGP level in patients with bladder cancer was 44-fold higher than in patients with benign disease, and 81-fold higher than in normal individuals. At specificities of 95% and 100%, overall sensitivities of 73% and 60%, respectively, were observed for the detection of malignant disease. Mean UGP levels in patients with bladder cancer were significantly correlated with the stage and grade of malignant disease but did not vary significantly when stratified according to histological type of disease, nodal involvement or bilharzial association. UGP could be a potentially useful marker for the differentiation of benign from malignant urological disease.

Urinary 28-kD calbindin-D as a new marker for damage to distal renal tubules caused by cisplatin-based chemotherapy.

Calbindin-D, a vitamin D-dependent calcium-binding protein of 28 kD, is found predominantly in the distal tubules of the kidney and central nervous system tissues in humans. To evaluate damage to the renal tubules caused by cisplatin-based chemotherapy, levels of urinary and serum calbindin-D were determined in patients treated with cisplatin- or carboplatin-based chemotherapies using a highly sensitive enzyme immunoassay system developed in our laboratory. Levels of urinary 28-kD calbindin-D were also determined in patients with benign and malignant urological diseases. The mean urinary calbindin-D level was 2.44 + or - 0.31 (mean + or - SE) ng/mg creatinine in 40 healthy subjects. Urinary calbindin-D levels were elevated (>10 ng/mg creatinine) in 2 of 33 patients (6%) with benign and 1 of 50 (2%) with malignant urological diseases. Urinary calbindin-D levels were significantly increased after cisplatin-based chemotherapy in 14 patients, with peaks (71.8 + or - 13.5 ng/mg creatinine) being found 8 days after administration of cisplatin, and then a gradual return to the baseline. On the other hand, 7 patients receiving carboplatin-based chemotherapy demonstrated no significant elevation (highest level 7.7 + or - 2.5 ng/mg creatinine). In 7 patients treated with cisplatin-based chemotherapy the serum calbindin-D level was also raised after treatment, with a good correlation to urinary values. These findings suggest that urinary and serum calbindin-D may be kidney-derived and that 28-kDa calbindin-D is a useful marker for damage to the distal renal tubules associated with cisplatin-based chemotherapy.

泌尿器悪性腫瘍の診断における尿 Basic fetoprotein (BFP) の意義

Basic fetoprotein (BFP) was measured by enzyme immunoassay in the urine of healthy adults and patients with benign or malignant urological diseases. Urinary BFP level in 34 healthy donors was very low (2.75 +/- 2.27 ng/ml). Since the BFP-positive rate is under 5% in healthy donors and, considering diagnostic efficiency for urological malignancies, a urinary BFP-concentration of 15 ng/ml was used as the cut off value. Urinary BFP was positive in 17.0% of 106 patients with benign urological diseases, in 51.9% of 52 patients with bladder cancer, in 75.0% of 8 patients with renal pelvic or ureteral cancer, in 25.0% of 20 patients with prostate cancer, and in 19.0% of 21 patients with renal cell carcinoma. In 60 patients with urothelial carcinomas, urinary BFP was higher in invasive diseases (greater than pT1) than in superficial diseases (p less than 0.05). The BFP level in urine also increased with a higher histological grade. The positive rate of urinary BFP was 78.9% in patients with invasive diseases and 66.7% in patients with grade 3 diseases. In 44 patients with urothelial carcinomas who underwent urinary cytological examination the positive rate was improved from 38.6% (17/44) to 81.4% (37/44) when measurement of urinary BFP was added. BFP in urine was found to be useful as a tumor marker for urothelial carcinomas. In addition, it was demonstrated that combined examination of urinary cytology with urinary BFP was more efficient for diagnosis of urothelial carcinomas.